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Find video protocols related to scientific articles indexed in Pubmed.
Polarization transition between sunlit and moonlit skies with possible implications for animal orientation and Viking navigation: anomalous celestial twilight polarization at partial moon.
Appl Opt
PUBLISHED: 10-17-2014
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Using full-sky imaging polarimetry, we measured the celestial distribution of polarization during sunset and sunrise at partial (78% and 72%) and full (100%) moon in the red (650 nm), green (550 nm), and blue (450 nm) parts of the spectrum. We investigated the temporal change of the patterns of degree p and angle ? of linear polarization of sunlit and moonlit skies at dusk and dawn. We describe here the position change of the neutral points of sky polarization, and present video clips about the celestial polarization transition at moonlit twilight. We found that at partial moon and at a medium latitude (47° 15.481' N) during this transition there is a relatively short (10-20 min) period when (i) the maximum of p of skylight decreases, and (ii) from the celestial ? pattern neither the solar-antisolar nor the lunar-antilunar meridian can be unambiguously determined. These meridians can serve as reference directions of animal orientation and Viking navigation based on sky polarization. The possible influence of these atmospheric optical phenomena during the polarization transition between sunlit and moonlit skies on the orientation of polarization-sensitive crepuscular/nocturnal animals and the hypothesized navigation of sunstone-aided Viking seafarers is discussed.
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Seasonality and daily activity of male and female tabanid flies monitored in a Hungarian hill-country pasture by new polarization traps and traditional canopy traps.
Parasitol. Res.
PUBLISHED: 09-06-2014
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Blood-sucking female tabanid flies cause serious problems for animals and humans. For the control of tabanids, the knowledge about their seasonality and daily activity is of great importance. Earlier, only traditional traps capturing exclusively female tabanids have been used to survey tabanid activity. The data of such temporal trapping do not reflect correctly the activity of male and female tabanid flies. Our major aim was to monitor the trapping numbers of male and female tabanids during a 3-month summer survey in Hungary. We used (i) conventional canopy traps with liquid traps on the ground beneath the canopy and (ii) L-shaped sticky traps with vertical and horizontal components. Our other goal was to compare the efficiencies of the two components of each trap type used. We observed two greater peaks of the trapping number of tabanids. These peaks started with increased catches of female tabanids captured by the canopy traps and the vertical sticky traps and ended with a dominance of male and female tabanids caught by the liquid traps and the horizontal sticky traps. The swarming periods were interrupted by rainy/cool days, when the number of tabanids decreased drastically. Among the 17 species, six dominated and composed 89.4 % of the captured tabanids: Haematopota pluvialis, Tabanus tergestinus, Tabanus bromius, Tabanus maculicornis, Tabanus bovinus and Atylotus loewianus. The number of water-seeking male and female tabanids rose up to 12-13 h and then decreased but had a secondary peak at about 17 h. The stochastic weather change and the communities of different species resulted in large standard deviations of the averaged number of tabanids in the course of a day. The horizontally polarizing (liquid and horizontal sticky) traps captured both male and female specimens and were about three times more efficient than the canopy and vertical sticky traps that caught only females. The results of the horizontal sticky traps corresponded to those of the liquid traps, while the catches of the vertical sticky traps corresponded to those of the canopy traps. The catches of the used trap types reflected well the species and water/host-seeking composition of tabanids.
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Accuracy of sun localization in the second step of sky-polarimetric Viking navigation for north determination: a planetarium experiment.
J Opt Soc Am A Opt Image Sci Vis
PUBLISHED: 08-15-2014
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It is a widely discussed hypothesis that Viking seafarers might have been able to locate the position of the occluded sun by means of dichroic or birefringent crystals, the mysterious sunstones, with which they could analyze skylight polarization. Although the atmospheric optical prerequisites and certain aspects of the efficiency of this sky-polarimetric Viking navigation have been investigated, the accuracy of the main steps of this method has not been quantitatively examined. To fill in this gap, we present here the results of a planetarium experiment in which we measured the azimuth and elevation errors of localization of the invisible sun. In the planetarium sun localization was performed in two selected celestial points on the basis of the alignments of two small sections of two celestial great circles passing through the sun. In the second step of sky-polarimetric Viking navigation the navigator needed to determine the intersection of two such celestial circles. We found that the position of the sun (solar elevation ?(S), solar azimuth ?(S)) was estimated with an average error of +0.6°????+8.8° and -3.9°????+2.0°. We also calculated the compass direction error when the estimated sun position is used for orienting with a Viking sun-compass. The northern direction (?(North)) was determined with an error of -3.34°???(North)?+6.29°. The inaccuracy of the second step of this navigation method was high (??(North)=-16.3°) when the solar elevation was 5°??(S)?25°, and the two selected celestial points were far from the sun (at angular distances 95°??(1), ?(2)?115°) and each other (125°???145°). Considering only this second step, the sky-polarimetric navigation could be more accurate in the mid-summer period (June and July), when in the daytime the sun is high above the horizon for long periods. In the spring (and autumn) equinoctial period, alternative methods (using a twilight board, for example) might be more appropriate. Since Viking navigators surely also committed further errors in the first and third steps, the orientation errors presented here underestimate the net error of the whole sky-polarimetric navigation.
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The B? regulatory subunit of protein phosphatase 2A mediates the dephosphorylation of rice retinoblastoma-related protein-1.
Plant Mol. Biol.
PUBLISHED: 05-05-2014
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The phosphorylation of plant retinoblastoma-related (RBR) proteins by cyclin-dependent kinases (CDKs) is well documented, but the counteracting phosphatases have not been identified yet. We report here that rice retinoblastoma-related protein-1 (OsRBR1) interacted with the B? subunit of rice protein phosphatase 2A (OsPP2A B?) and underwent reversible phosphorylation during the cell division cycle. The OsRBR1-OsPP2A B" association required B domain in OsRBR1 and the C-terminal region of OsPP2A B?. We found by immunoprecipitation that OsPP2A B?, OsPP2A catalytic subunit subtype II, PSTAIRE-type CDK and OsRBR1 were in the same protein complex, indicating a physical association between the phosphatase, the kinase and their common substrate. OsPP2A B? contains three predicted CDK phosphorylation sites: Ser95, Ser102 and Ser119. The in vitro phosphorylation of Ser95 and Ser119 with PSTAIRE-kinases was verified by mass spectrometry. We generated a series of phosphorylation site mutants to mimic the dephosphorylated or phosphorylated states of OsPP2A B?, and confirmed that all of the three predicted sites can be phosphorylated. Yeast two-hybrid experiments suggested that the phosphorylation of OsPP2A B? promoted the formation of the OsPP2A holoenzyme. A triple phosphorylation mimicking OsPP2A B? mutant containing holoenzyme showed higher activity in phosphatase assays. Our data collectively show that the phosphatase activity of OsPP2A against OsRBR1 is regulated by the phosphorylation of its B? regulatory subunit. However, the analysis of the effect of okadaic acid, a phosphatase inhibitor, in rice cell suspension cultures revealed that the dephosphorylation of OsRBR1 was completely inhibited only by high dose (300 nM) of the okadaic acid during the cell cycle progression. Therefore the role of the protein phosphatase 1 should be considered as an additional post translational regulatory component of RBR protein function in higher plants.
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Short-term response of metabolic hormones to coronary artery bypass surgery.
Adv Med Sci
PUBLISHED: 04-14-2014
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To explore the response pattern of plasma adipokine and ghrelin levels to coronary artery bypass graft (CABG) surgery in patients with (on-pump) and without (off-pump) cardiopulmonary bypass (CPB).
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[Diagnosis and treatment of chronic hepatitis B and D. Hungarian national consensus guideline].
Orv Hetil
PUBLISHED: 03-18-2014
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Diagnosis and treatment of hepatitis B and D virus infections mean that the patient is able to maintain working capacity, increase quality of life, prevent cancer, and prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2014, which is agreed on a consensus meeting of specialists involved in the treatment of the above diseases. The prevalence of hepatitis B virus infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline emphasizes the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection.
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[Diagnosis, treatment, and follow-up of hepatitis C-virus related liver disease. Hungarian national consensus guideline].
Orv Hetil
PUBLISHED: 03-18-2014
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Approximately 70 000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. Early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases (liver cirrhosis and liver cancer) and its complications. In addition, it may increase work productivity and life expectancy of infected individual, and can prevent further viral transmission. Early recognition can substantially reduce the long term financial burden of related morbidity from socioeconomic point of view. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can kill the virus in 40-45% of previously not treated (naïve), and in 5-21% of previous treatment-failure patients. Addition of two direct acting first generation protease inhibitor drugs (boceprevir and telaprevir) to the dual therapy increased the chance of sustained clearance of virus to 63-75% and 59-66%, respectively. These two protease inhibitor drugs are available and financed for a segment of Hungarian patients since May 2013. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. For initiation of treatment as well as for on-treatment decisions accurate and timely molecular biology tests are mandatory. Staging of liver damage (fibrosis) non-invasive methods (transient elastography and biochemical methods) are acceptable to avoid concerns of patients related to liver biopsy. Professional decision for treatment is balanced against budget limitations in Hungary, and priority is given to those with urgent need using a national Priority Index system reflecting stage of liver disease as well as additional factors (activity and progression of liver disease, predictive factors and other special circumstances). All naïve patients are given a first chance with dual therapy. Those with genotype 1 infection and with on-treatment or historic failure to dual therapy are eligible to receive protease inhibitor based triple therapy provided, they reach financial cutoff eligibility based on Priority Index. Duration of therapy is usually 48 weeks in genotype 1 with a response-guided potential to reduce duration for non-cirrhotic patients. Patients with non-1 genotypes are treated with dual therapy (without protease inhibitors) for a genotype and response driven duration of 16, 24, 48, or 72 week. Careful monitoring for early recognition and management of side-effects as well as viral response and potential breakthrough during protease-inhibitor therapy are recommended.
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How could the Viking Sun compass be used with sunstones before and after sunset? Twilight board as a new interpretation of the Uunartoq artefact fragment.
Proc. Math. Phys. Eng. Sci.
PUBLISHED: 02-27-2014
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Vikings routinely crossed the North Atlantic without a magnetic compass and left their mark on lands as far away as Greenland, Newfoundland and Baffin Island. Based on an eleventh-century dial fragment artefact, found at Uunartoq in Greenland, it is widely accepted that they sailed along chosen latitudes using primitive Sun compasses. Such instruments were tested on sea and proved to be efficient hand-held navigation tools, but the dimensions and incisions of the Uunartoq find are far from optimal in this role. On the basis of the sagas mentioning sunstones, incompatible hypotheses were formed for Viking solar navigation procedures and primitive skylight polarimetry with dichroic or birefringent crystals. We describe here a previously unconceived method of navigation based on the Uunartoq artefact functioning as a 'twilight board', which is a combination of a horizon board and a Sun compass optimized for use when the Sun is close to the horizon. We deduced an appropriate solar navigation procedure using a twilight board, a shadow-stick and birefringent crystals, which bring together earlier suggested methods in harmony and provide a true skylight compass function. This could have allowed Vikings to navigate around the clock, to use the artefact dial as a Sun compass during long parts of the day and to use skylight polarization patterns in the twilight period. In field tests, we found that true north could be appointed with such a medieval skylight compass with an error of about ±4° when the artificially occluded Sun had elevation angles between +10° and -8° relative to the horizon. Our interpretation allows us to assign exact dates to the gnomonic lines on the artefact and outlines the schedule of the merchant ships that sustained the Viking colony in Greenland a millennium ago.
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Phototaxis and polarotaxis hand in hand: night dispersal flight of aquatic insects distracted synergistically by light intensity and reflection polarization.
Naturwissenschaften
PUBLISHED: 01-30-2014
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Based on an earlier observation in the field, we hypothesized that light intensity and horizontally polarized reflected light may strongly influence the flight behaviour of night-active aquatic insects. We assumed that phototaxis and polarotaxis together have a more harmful effect on the dispersal flight of these insects than they would have separately. We tested this hypothesis in a multiple-choice field experiment using horizontal test surfaces laid on the ground. We offered simultaneously the following visual stimuli for aerial aquatic insects: (1) lamplit matte black canvas inducing phototaxis alone, (2) unlit shiny black plastic sheet eliciting polarotaxis alone, (3) lamplit shiny black plastic sheet inducing simultaneously phototaxis and polarotaxis, and (4) unlit matte black canvas as a visually unattractive control. The unlit matte black canvas trapped only a negligible number (13) of water insects. The sum (16,432) of the total numbers of water beetles and bugs captured on the lamplit matte black canvas (7,922) and the unlit shiny black plastic sheet (8,510) was much smaller than the total catch (29,682) caught on the lamplit shiny black plastic sheet. This provides experimental evidence for the synergistic interaction of phototaxis (elicited by the unpolarized direct lamplight) and polarotaxis (induced by the strongly and horizontally polarized plastic-reflected light) in the investigated aquatic insects. Thus, horizontally polarizing artificial lamplit surfaces can function as an effective ecological trap due to this synergism of optical cues, especially in the urban environment.
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Unexpected attraction of polarotactic water-leaving insects to matt black car surfaces: mattness of paintwork cannot eliminate the polarized light pollution of black cars.
PLoS ONE
PUBLISHED: 01-01-2014
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The horizontally polarizing surface parts of shiny black cars (the reflection-polarization characteristics of which are similar to those of water surfaces) attract water-leaving polarotactic insects. Thus, shiny black cars are typical sources of polarized light pollution endangering water-leaving insects. A new fashion fad is to make car-bodies matt black or grey. Since rough (matt) surfaces depolarize the reflected light, one of the ways of reducing polarized light pollution is to make matt the concerned surface. Consequently, matt black/grey cars may not induce polarized light pollution, which would be an advantageous feature for environmental protection. To test this idea, we performed field experiments with horizontal shiny and matt black car-body surfaces laid on the ground. Using imaging polarimetry, in multiple-choice field experiments we investigated the attractiveness of these test surfaces to various water-leaving polarotactic insects and obtained the following results: (i) The attractiveness of black car-bodies to polarotactic insects depends in complex manner on the surface roughness (shiny, matt) and species (mayflies, dolichopodids, tabanids). (ii) Non-expectedly, the matt dark grey car finish is much more attractive to mayflies (being endangered and protected in many countries) than matt black finish. (iii) The polarized light pollution of shiny black cars usually cannot be reduced with the use of matt painting. On the basis of these, our two novel findings are that (a) matt car-paints are highly polarization reflecting, and (b) these matt paints are not suitable to repel polarotactic insects. Hence, the recent technology used to make matt the car-bodies cannot eliminate or even can enhance the attractiveness of black/grey cars to water-leaving insects. Thus, changing shiny black car painting to matt one is a disadvantageous fashion fad concerning the reduction of polarized light pollution of black vehicles.
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[Fractionated conformal stereotactic irradiation of recurrent sacral tumour. Case report and first description of the method in Hungary].
Magy Onkol
PUBLISHED: 10-11-2013
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Non-invasive procedures completing traditional surgical treatment play an increasing role in the management of central nervous system malignancies. Conformal stereotactic irradiation (radiosurgery) has become a routine method in intracranial malignancies. However, application of this modality in tumours of the spinal cord and spinal column is much more difficult to perform. It is because extracranial organs can be only inaccurately fixed, and radio-sensitivity of the spinal cord and risks of radionecrosis with ensuing paraplegia are high. A recurrent sacrum chordoma treated by means of this modality - first reported in Hungary - has been chosen for case presentation as the criteria for radiotherapy such as high dose to target volume, minimal dose to neighbouring structures highly sensitive to radiation are best met in these tumours by means of conformal stereotactic radiotherapy. On the basis of further 13 extracranial cases treated with this method one can conclude that high precision stereotactic conformal radiotherapy offers up-grade to traditional radiotherapy despite the fact that it is a time-consuming procedure. The oncological efficiency, the reduced risks of side effects and the improved quality of life due to this treatment modality compensate duly for the increased labour input.
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Orientation with a Viking sun-compass, a shadow-stick, and two calcite sunstones under various weather conditions.
Appl Opt
PUBLISHED: 10-03-2013
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It is widely accepted that Vikings used sun-compasses to derive true directions from the cast shadow of a gnomon. It has been hypothesized that when a cast shadow was not formed, Viking navigators relied on crude skylight polarimetry with the aid of dichroic or birefringent crystals, called "sunstones." We demonstrate here that a simple tool, that we call "shadow-stick," could have allowed orientation by a sun-compass with satisfying accuracy when shadows were not formed, but the sun position could have reliably been estimated. In field tests, we performed orientation trials with a set composed of a sun-compass, two calcite sunstones, and a shadow-stick. We show here that such a set could have been an effective orientation tool for Vikings only when clear, blue patches of the sky were visible.
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RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.
J. Exp. Med.
PUBLISHED: 09-30-2013
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Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products (RAGE) promoted DNA uptake into endosomes and lowered the immune recognition threshold for the activation of Toll-like receptor 9, the principal DNA-recognizing transmembrane signaling receptor. Structural analysis of RAGE-DNA complexes indicated that DNA interacted with dimers of the outermost RAGE extracellular domains, and could induce formation of higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable to mount a typical inflammatory response to DNA in the lung, indicating that RAGE is important for the detection of nucleic acids in vivo.
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Environmental enrichment decreases asphyxia-induced neurobehavioral developmental delay in neonatal rats.
Int J Mol Sci
PUBLISHED: 09-14-2013
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Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.
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Middle East respiratory syndrome coronavirus accessory protein 4a is a type I interferon antagonist.
J. Virol.
PUBLISHED: 09-11-2013
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Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory infection with as yet unclear epidemiology. We previously showed that MERS-CoV counteracts parts of the innate immune response in human bronchiolar cells. Here we analyzed accessory proteins 3, 4a, 4b, and 5 for their abilities to inhibit the type I interferon response. Accessory protein 4a was found to block interferon induction at the level of melanoma differentiation-associated protein 5 (MDA5) activation presumably by direct interaction with double-stranded RNA.
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Exposure to enriched environment decreases neurobehavioral deficits induced by neonatal glutamate toxicity.
Int J Mol Sci
PUBLISHED: 07-19-2013
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Environmental enrichment is a popular strategy to enhance motor and cognitive performance and to counteract the effects of various harmful stimuli. The protective effects of enriched environment have been shown in traumatic, ischemic and toxic nervous system lesions. Monosodium glutamate (MSG) is a commonly used taste enhancer causing excitotoxic effects when given in newborn animals. We have previously demonstrated that MSG leads to a delay in neurobehavioral development, as shown by the delayed appearance of neurological reflexes and maturation of motor coordination. In the present study we aimed at investigating whether environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal MSG treatment. Newborn pups were treated with MSG subcutaneously on postnatal days 1, 5 and 9. For environmental enrichment, we placed rats in larger cages, supplemented with different toys that were altered daily. Normal control and enriched control rats received saline treatment only. Physical parameters such as weight, day of eye opening, incisor eruption and ear unfolding were recorded. Animals were observed for appearance of reflexes such as negative geotaxis, righting reflexes, fore- and hindlimb grasp, fore- and hindlimb placing, sensory reflexes and gait. In cases of negative geotaxis, surface righting and gait, the time to perform the reflex was also recorded daily. For examining motor coordination, we performed grid walking, footfault, rope suspension, rota-rod, inclined board and walk initiation tests. We found that enriched environment alone did not lead to marked alterations in the course of development. On the other hand, MSG treatment caused a slight delay in reflex development and a pronounced delay in weight gain and motor coordination maturation. This delay in most signs and tests could be reversed by enriched environment: MSG-treated pups kept under enriched conditions showed no weight retardation, no reflex delay in some signs and performed better in most coordination tests. These results show that environmental enrichment is able to decrease the neurobehavioral delay caused by neonatal excitotoxicity.
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[Organizational characteristics of treatment for chronic hepatitis in Hungary: Hepatitis Registry and Priority Index].
Orv Hetil
PUBLISHED: 07-16-2013
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Hepatitis Registry was developed by the Hepatology Section of the Hungarian Gastroenterology Society with the contribution of the Foundation for Liver Patients. The main task was to register all interferon based treatments of chronic hepatitis C and B and to facilitate the preauthorization process. The registry helped to clarify the number and characteristics of hepatitis C patients waiting for triple therapy; 3000 previously failed patients are still eligible for protease inhibitor therapy, 40% of them already developed cirrhosis stage and 40% are null responders to the previous therapy. As a file is created for treatment authorization, the system counts automatically the Priority Index according to the calculation set in the guideline. Priority Index reflects the urgency of treatment. The most prominent parameter of the Index is the degree of fibrosis, but it also takes into account the progression rate, prognostic factors, and special situations.
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[Interdisciplinary aspects of and new drugs for chronic hepatitis B].
Orv Hetil
PUBLISHED: 07-16-2013
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Hepatitis B virus infection is a significant health problem worldwide. The prevalence of HBsAg positivity is about 0.5-0.7% in Hungary. Liver cirrhosis and/or hepatocellular carcinoma develops in 15-40% of chronic hepatitis B virus infected patients without treatment. The ultimate goal of treatment would be to clear the virus from the infected subject; however, in practice, we can usually achieve long term suppression of viral replicaton with consequent prevention of the progression of liver disease, and reduction of the risk of the development of liver cirrhosis and hepatocellular carcinoma. Currently, there are two different treatment strategies for patients with chronic hepatitis B virus infection: therapy of finite duration with interferon or long-term treatment with nucleot(s)ide analogues. Entecavir and tenofovir are the two most effective nucleot(s)ide analogues with high barrier to resistance, thus, they can be confidently used as first-line treatments. Lamivudine engenders very high rates of resistance; adefovir is less efficacious than entecavir or tenofovir, and also engendering higher rates of resistance, thus none of them are recommended for initiation of a new treatment. Tenofovir is the treatment option in cases with lamivudine resistance, because entecavir has an unfavourable resistance-profile in this group of patients. Interferon is contraindicated during pregnancy. Should treatment of chronic hepatitis B virus infection be necessary during pregnancy, tenofovir, listed by the FDA as pregnancy category B drug, is to be preferred. Nucleot(s)ide analogues may be used to reduce the risk of intra-uterine and perinatal transmission of hepatitis B virus, which may occur in a proportion of newborns from highly viremic mothers, despite active and passive immunization. Similarly, tenofovir is recommended in the last trimester of pregnancy for women with high viremia. The risk of reactivation of chronic hepatitis B virus infection is high in HBsAg positive patients, and in patients with occult hepatitis B virus infection during and after chemotherapy or immunosuppressive treatment, including biological response modifiers (particularly related to rituximab therapy). Therefore, all candidates for these treatments should be screened for HBsAg and anti-HBc. Pre-emptive nucleot(s)ide analogues therapy should be initiated in patients with HBsAg positivity, and patients with occult hepatitis B virus infection. The role of general practitioners and occupational health physicians in the identification and the prevention of hepatitis B virus infection is stressed. Issues of high risk population groups, candidacy for vaccination, and methodology of active and passive immunisation are also reviewed in this paper.
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[Non-alcoholic fatty liver disease and steatohepatitis].
Orv Hetil
PUBLISHED: 07-16-2013
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Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.
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ASC speck formation as a readout for inflammasome activation.
Methods Mol. Biol.
PUBLISHED: 07-16-2013
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All inflammasomes require the adapter protein apoptosis associated speck-like protein containing a CARD (ASC) for the activation of caspase-1. After inflammasome activation, ASC assembles into a large protein complex, which is termed "speck". ASC specks can be observed as they reach a size of around 1 ?m and in most cells only one speck forms upon inflammasome activation. Hence, ASC speck formation can be used as a simple upstream readout for inflammasome activation. Here, we describe a method for analyzing inflammasome activation by ASC speck visualization. First, we describe the generation of a clonal inflammasome reporter macrophage cell line overexpressing fluorescently tagged ASC. We then discuss stimulation conditions and the microscopic evaluation of ASC speck formation.
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Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP.
Nature
PUBLISHED: 06-24-2013
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The innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert non-infected cells to the possibility of pathogen challenge. Moreover, in conjunction with chemokines they can instruct specialized immune cells to contain and eradicate microbial infection. Several receptors and signalling pathways exist that couple pathogen sensing to the induction of cytokines, whereas cytosolic recognition of nucleic acids seems to be exquisitely important for the activation of type I IFNs, master regulators of antiviral immunity. Cytosolic DNA is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses the synthesis of the second messenger cGAMP(2-5). This molecule in turn activates the endoplasmic reticulum (ER)-resident receptor STING, thereby inducing an antiviral state and the secretion of type I IFNs. Here we find in murine and human cells that cGAS-synthesized cGAMP(2-5) is transferred from producing cells to neighbouring cells through gap junctions, where it promotes STING activation and thus antiviral immunity independently of type I IFN signalling. In line with the limited cargo specificity of connexins, the proteins that assemble gap junction channels, most connexins tested were able to confer this bystander immunity, thus indicating a broad physiological relevance of this local immune collaboration. Collectively, these observations identify cGAS-triggered cGAMP(2-5) transfer as a novel host strategy that serves to rapidly convey antiviral immunity in a transcription-independent, horizontal manner.
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Gender-dependent effects of enriched environment and social isolation in ischemic retinal lesion in adult rats.
Int J Mol Sci
PUBLISHED: 06-06-2013
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Exposure to an enriched environment has been shown to have many positive effects on brain structure and function. Numerous studies have proven that enriched environment can reduce the lesion induced by toxic and traumatic injuries. Impoverished environment, on the other hand, can have deleterious effects on the outcome of neuronal injuries. We have previously shown that enriched conditions have protective effects in retinal injury in newborn rats. It is well-known that the efficacy of neuroprotective strategies can depend on age and gender. The aim of the present study, therefore, was to examine the effects of environmental enrichment and social isolation in retinal ischemia. We used bilateral common carotid artery occlusion to induce retinal hypoperfusion in adult Wistar rats of both genders. Groups were housed in standard, enriched or impoverished conditions. Impoverished environment was induced by social isolation. Retinas were processed for histological analysis after two weeks of survival. In the present study, we show that (1) enriched environment has protective effects in adult ischemic retinal lesion, while (2) impoverished environment further increases the degree of ischemic injury, and (3) that these environmental effects are gender-dependent: females are less responsive to the positive effects of environmental enrichment and more vulnerable to retinal ischemia in social isolation. In summary, our present study shows that the effects of both positive and negative environmental stimuli are gender-dependent in ischemic retinal lesions.
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Stripes disrupt odour attractiveness to biting horseflies: battle between ammonia, CO?, and colour pattern for dominance in the sensory systems of host-seeking tabanids.
Physiol. Behav.
PUBLISHED: 05-01-2013
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As with mosquitoes, female tabanid flies search for mammalian hosts by visual and olfactory cues, because they require a blood meal before being able to produce and lay eggs. Polarotactic tabanid flies find striped or spotted patterns with intensity and/or polarisation modulation visually less attractive than homogeneous white, brown or black targets. Thus, this reduced optical attractiveness to tabanids can be one of the functions of striped or spotty coat patterns in ungulates. Ungulates emit CO2 via their breath, while ammonia originates from their decaying urine. As host-seeking female tabanids are strongly attracted to CO2 and ammonia, the question arises whether the poor visual attractiveness of stripes and spots to tabanids is or is not overcome by olfactory attractiveness. To answer this question we performed two field experiments in which the attractiveness to tabanid flies of homogeneous white, black and black-and-white striped three-dimensional targets (spheres and cylinders) and horse models provided with CO2 and ammonia was studied. Since tabanids are positively polarotactic, i.e. attracted to strongly and linearly polarised light, we measured the reflection-polarisation patterns of the test surfaces and demonstrated that these patterns were practically the same as those of real horses and zebras. We show here that striped targets are significantly less attractive to host-seeking female tabanids than homogeneous white or black targets, even when they emit tabanid-luring CO2 and ammonia. Although CO2 and ammonia increased the number of attracted tabanids, these chemicals did not overcome the weak visual attractiveness of stripes to host-seeking female tabanids. This result demonstrates the visual protection of striped coat patterns against attacks from blood-sucking dipterans, such as horseflies, known to transmit lethal diseases to ungulates.
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Molecular evidence of Ehrlichia canis and Rickettsia massiliae in ixodid ticks of carnivores from South Hungary.
Acta Vet. Hung.
PUBLISHED: 02-27-2013
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To monitor the emergence of thermophilic, Mediterranean ixodid tick species and tick-borne pathogens in southern Hungary, 348 ticks were collected from shepherd dogs, red foxes and golden jackals during the summer of 2011. Golden jackals shared tick species with both the dog and the red fox in the region. Dermacentor nymphs were collected exclusively from dogs, and the sequence identification of these ticks indicated that dogs are preferred hosts of both D. reticulatus and D. marginatus nymphs, unlike previously reported. Subadults of three ixodid species were selected for reverse line blot hybridisation (RLB) analysis to screen their vector potential for 40 pathogens/groups. Results were negative for Anaplasma, Babesia and Theileria spp. Investigation of D. marginatus nymphs revealed the presence of Ehrlichia canis, Rickettsia massiliae and Borrelia afzelii for the first time in this tick species. These findings broaden the range of those tick-borne agents, which are typically transmitted by Rhipicephalus sanguineus, but may also have Dermacentor spp. as potential or alternative vectors. Ehrlichiacanis was also newly detected in Ixodes canisuga larvae from red foxes. In absence of transovarial transmission in ticks this implies that Eurasian red foxes may play a reservoir role in the epidemiology of canine ehrlichiosis.
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Natural IS711 insertion causing omp31 gene inactivation in Brucella ovis.
J. Vet. Diagn. Invest.
PUBLISHED: 02-12-2013
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The present report describes an atypical Brucella ovis strain (Bo10) isolated from the epididymis and testis of an infected ram. Macroscopic and microscopic lesions characteristic for the infection, including positive Brucella immunostaining, were observed within lesions in the genital organs. Compared to other isolates, strain Bo10 required an additional day (a total of 96 hr) of incubation to form visible colonies, showed a distinct carbon source utilization profile, agglutinated only weakly with rough (R) serum, but showed a high capacity for autoagglutination. Isolate Bo10 failed to produce the 1,071-bp fragment in the outer membrane protein (omp) 31 gene-based part of the "Bruce-ladder" multiplex polymerase chain reaction system but did produce a 1,915-bp amplicon, thus presenting a profile similar to Brucella abortus. Sequence analysis of the 1,915-bp fragment revealed an 842-bp long insertion sequence (IS)711 transposon element inserted into the promoter region of the omp31 gene, immediately upstream from the ribosome binding site (-10 box/Pribnow box). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of a whole-cell lysate showed the absence in Bo10 of the approximately 31-kDa protein fragment associated with omp31. The results demonstrate a natural inactivation of omp31 and, consequently, the absence of the Omp31 protein in this B. ovis isolate. The novel location of IS711 within the genome of a naturally occurring B. ovis strain supports the hypothesis that IS711 could be an active transposon in this Brucella species.
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A new tabanid trap applying a modified concept of the old flypaper: linearly polarising sticky black surfaces as an effective tool to catch polarotactic horseflies.
Int. J. Parasitol.
PUBLISHED: 02-02-2013
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Trapping flies with sticky paper sheets is an ancient method. The classic flypaper has four typical characteristics: (i) its sticky paper is bright (chamois, light yellow or white), (ii) it is strip-shaped, (iii) it hangs vertically, and (iv) it is positioned high (several metres) above ground level. Such flypapers, however, do not trap horseflies (tabanids). There is a great need to kill horseflies with efficient traps because they are vectors of dangerous diseases, and due to their continuous annoyance livestock cannot graze, horses cannot be ridden, and meat and milk production from cattle is drastically reduced. Based on earlier findings on the positive polarotaxis (attraction to linearly polarised light) in tabanid flies and modifying the concept of the old flypaper, we constructed a new horsefly trap called "horseflypaper". In four field experiments we showed that the ideal horseflypaper (i) is shiny black, (ii) has an appropriately large (75×75 cm(2)) surface area, (iii) has sticky black vertical and horizontal surfaces in an L-shaped arrangement, and (iv) its horizontal surface should be at ground level for maximum effectiveness. Using imaging polarimetry, we measured the reflection-polarisation characteristics of this new polarisation tabanid trap. The ideal optical and geometrical characteristics of this trap revealed in field experiments are also explained. The horizontal part of the trap captures water-seeking male and female tabanids, while the vertical part catches host-seeking female tabanids.
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TripleFRET measurements in flow cytometry.
Cytometry A
PUBLISHED: 01-23-2013
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A frequently used method for viewing protein interactions and conformation, Förster (fluorescence) resonance energy transfer (FRET), has traditionally been restricted to two fluorophores. Lately, several methods have been introduced to expand FRET methods to three species. We present a method that allows the determination of FRET efficiency in three-dye systems on a flow cytometer. TripleFRET accurately reproduces energy transfer efficiency values measured in two-dye systems, and it can indicate the presence of trimeric complexes, which is not possible with conventional FRET methods. We also discuss the interpretation of energy transfer values obtained with tripleFRET in relation to spatial distribution of labeled molecules, specifically addressing the limitations of using total energy transfer to determine molecular distance.
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Albuterol modulates its own transepithelial flux via changes in paracellular permeability.
Am. J. Respir. Cell Mol. Biol.
PUBLISHED: 12-08-2011
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Although inhaled bronchodilators are commonly used in the treatment of airway disease to dilate airway smooth muscle, little is known regarding the mechanisms that regulate albuterol movement across the epithelium to reach its target, the airway smooth muscle. Because the rate of onset depends on the transepithelial transport of albuterol, to determine the mechanisms that regulate the transepithelial movement of albuterol is essential. Human bronchial epithelial cells, fully redifferentiated in culture at the air-liquid interface, were used to study the cellular uptake and total transepithelial flux of (3)H-albuterol from the apical to the basolateral surfaces. (3)H-mannitol and transepithelial electrical resistance were used to quantify changes in paracellular permeability. The majority of albuterol flux across the epithelium occurred via the paracellular route. The cellular uptake of albuterol was found to be saturable, whereas transepithelial flux was not. Cellular uptake could be inhibited by the amino acids lysine and histidine, with no effect on net transepithelial flux. Transepithelial flux was altered by maneuvers that collapsed or disrupted intercellular junctions. Acidification, usually seen in exacerbations of airway disease, decreased albuterol flux. In addition, albuterol increased its own paracellular permeability. The ability of albuterol to modulate paracellular permeability was blocked by the ?(2)-adrenergic receptor-selective antagonist ICI 118551. Albuterol mainly crosses the epithelium via the paracellular pathway, but has the ability to modulate its own permeability through changes in the leakiness of tight junctions, which is modulated through the signaling of the ?(2)-adrenergic receptor.
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Imaging polarimetry of the fogbow: polarization characteristics of white rainbows measured in the high Arctic.
Appl Opt
PUBLISHED: 10-22-2011
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The knowledge on the optics of fogbows is scarce, and their polarization characteristics have never been measured to our knowledge. To fill this gap we measured the polarization features of 16 fogbows during the Beringia 2005 Arctic polar research expedition by imaging polarimetry in the red, green and blue spectral ranges. We present here the first polarization patterns of the fogbow. In the patterns of the degree of linear polarization p, fogbows and their supernumerary bows are best visible in the red spectral range due to the least dilution of fogbow light by light scattered in air. In the patterns of the angle of polarization ? fogbows are practically not discernible because their ?-pattern is the same as that of the sky: the direction of polarization is perpendicular to the plane of scattering and is parallel to the arc of the bow, independently of the wavelength. Fogbows and their supernumeraries were best seen in the patterns of the polarized radiance. In these patterns the angular distance ? between the peaks of the primary and the first supernumerary and the angular width ? of the primary bow were determined along different radii from the center of the bow. ? ranged between 6.08° and 13.41°, while ? changed from 5.25° to 19.47°. Certain fogbows were relatively homogeneous, meaning small variations of ? and ? along their bows. Other fogbows were heterogeneous, possessing quite variable ?- and ?-values along their bows. This variability could be a consequence of the characteristics of the high Arctic with open waters within the ice shield resulting in the spatiotemporal change of the droplet size within the fog.
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No evidence for behavioral responses to circularly polarized light in four scarab beetle species with circularly polarizing exocuticle.
Physiol. Behav.
PUBLISHED: 09-26-2011
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The strongest known circular polarization of biotic origin is the left-circularly polarized (LCP) light reflected from the metallic shiny exocuticle of certain beetles of the family Scarabaeidae. This phenomenon has been discovered by Michelson in 1911. Although since 1955 it has been known that the human eye perceives a visual illusion when stimulated by circularly polarized (CP) light, it was discovered only recently that a stomatopod shrimp is able to perceive circular polarization. It is pertinent to suppose that scarab beetles reflecting LCP light in an optical environment (vegetation) being deficient in CP signals may also perceive circular polarization and use it to find each other (mate/conspecifics) as until now it has been believed. We tested this hypothesis in six choice experiments with several hundred individuals of four scarab species: Anomala dubia, Anomala vitis (Coleoptera, Scarabaeidae, Rutelinae), and Cetonia aurata, Potosia cuprea (Coleoptera, Scarabaeidae, Cetoniinae), all possessing left-circularly polarizing exocuticle. From the results of our experiments we conclude that the studied four scarab species are not attracted to CP light when feeding or looking for mate or conspecifics. We demonstrated that the light reflected by host plants of the investigated scarabs is circularly unpolarized. Our results finally solve a puzzle raised over one hundred years ago, when Michaelson discovered that scarab beetles reflect circularly polarized light.
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Intracellular sensing of microbes and danger signals by the inflammasomes.
Immunol. Rev.
PUBLISHED: 09-03-2011
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The cells of the innate immune system mobilize a coordinated immune response towards invading microbes and after disturbances in tissue homeostasis. These immune responses typically lead to infection control and tissue repair. Exaggerated or uncontrolled immune responses, however, can also induce acute of chronic inflammatory pathologies that are characteristic for many common diseases such as sepsis, arthritis, atherosclerosis, or Alzheimers disease. In recent years, the concerted efforts of many scientists have uncovered numerous mechanisms by which immune cells detect foreign or changed self-substances that appear in infections or during tissue damage. These substances stimulate signaling receptors, which leads to cellular activation and the induction of effector mechanisms. Here, we review the role of inflammasomes, a family of signaling molecules that form multi-molecular signaling platforms and activate inflammatory caspases and interleukin-1? cytokines.
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[Predictors of efficacy, mucosal healing and dose intensification during the first year of adalimumab therapy in patients with luminal and fistulizing Crohns disease. National data from Hungary].
Orv Hetil
PUBLISHED: 08-26-2011
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Adalimumab is a fully human monoclonal antibody targeting tumor necrosis factor with proven efficacy in the treatment of Crohns disease in clinical trials. The aim of the present study was to investigate the predictors of medium term clinical efficacy and mucosal healing during adalimumab therapy in patients with Crohns disease in specialized centers approved for biological therapy in Hungary.
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Synchronization of Medicago sativa cell suspension culture.
Methods Mol. Biol.
PUBLISHED: 07-15-2011
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Deepening our knowledge on the regulation of the plant cell division cycle depends on techniques that allow for the enrichment of cell populations in defined cell cycle phases. Synchronization of cell division can be achieved using different plant tissues; however, well-established cell suspension cultures provide the largest amount of biological sample for further analysis. Here we describe the methodology of the establishment, propagation, and analysis of a Medicago sativa suspension culture that can be used for efficient synchronization of the cell division and also the application and removal of hydroxyurea blocking agent. A novel method is used for the estimation of cell portion that enters S phase during the assay. The protocol can be used in the case of other species as well.
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Polarotaxis in non-biting midges: female chironomids are attracted to horizontally polarized light.
Physiol. Behav.
PUBLISHED: 05-25-2011
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Non-biting midges (Chironomidae, Diptera) are widely distributed aquatic insects. The short-living chironomid adults swarm in large numbers above water surfaces, and are sometimes considered a nuisance. They are vectors of certain bacteria, and have a key-role in benthic ecosystems. Optical cues, involving reflection-polarization from water, were found to be important in the habitat selection by three Mediterranean freshwater chironomid species. In this work we report on our multiple-choice experiments performed in the field with several other European freshwater chironomid species. We show that the investigated non-biting midges are positively polarotactic and like many other aquatic insects their females are attracted to horizontally polarized light. Our finding is important in the visual ecology of chironomids and useful in the design of traps for these insects.
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[New non-invasive tool for assessment of liver fibrosis: transient elastography].
Orv Hetil
PUBLISHED: 05-14-2011
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Formation of connective tissue causing liver fibrosis is the common trait of chronic liver diseases. The "gold-standard" of the evaluation of liver fibrosis is liver biopsy, but it is an invasive, painful procedure, and carries a significant, although small risk of life-threatening complications. It may have contraindications, and it is certainly not the ideal procedure for serially repeated assessment of disease progression. A new, non-invasive method for the assessment of liver fibrosis by measuring liver stiffness is the transient elastography. The velocity of the propagation of a shear wave is measured by ultrasound. The procedure is painless, rapid, and does not need any preparation. So far, transient elastography has been mostly validated in chronic hepatitis C, but it is applicable in liver diseases with other etiologies. The diagnostic accuracy of transient elastography increases with stage of fibrosis, and is more accurate in advanced fibrosis (F?2, Metavir score) and in cirrhosis. Indication of antiviral therapy for chronic viral hepatitis B and C are the main field of the application of the transient elastography, and it is also a useful tool for follow-up the disease progression. It is applicable for early, non-invasive detection of graft damage after liver transplantation. Evaluation of liver damage, the stage of liver fibrosis by transient elastography may have an important role in the decision before surgery, or application of potentially hepatotoxic drugs. Histological examination of the liver tissue is not substituted in every case by transient elastography, but liver biopsy is supplanted by measuring liver stiffness for evaluation of liver fibrosis in many cases.
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Molecular characterization of the interaction between sialylated Neisseria gonorrhoeae and factor H.
J. Biol. Chem.
PUBLISHED: 04-29-2011
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Human factor H (HufH), a key inhibitor of the alternative pathway of complement, binds to Neisseria gonorrhoeae and constitutes an important mechanism of human-specific complement evasion. The C-terminal domain 20 of HufH contains the binding site for sialylated gonococci. We exploited differences in amino acid sequences between human and non-binding chimpanzee fH domain 20 to create cross-species mutations to define amino acids important for binding to sialylated gonococci. We used fH/Fc fusion constructs that contained contiguous fH domains 18-20 fused to Fc fragments of murine IgG2a. The Fc region was used both as a tag for detection of each fusion molecule on the bacterial surface and as an indicator for complement-dependent killing. Arg-1203 was critical for binding to both porin (Por) B.1A and PorB.1B strains. Modeling of the R1203N human-to-chimpanzee mutation using the crystal structure of HufH19-20 as a template showed a loss of positive charge that protrudes at the C terminus of domain 20. We tested the functional importance of Arg-1203 by incubating sialylated gonococci with normal human serum, in the presence of wild-type HufH18-20/Fc or its R1203A mutant. Gonococci bound and were killed by wild-type HufH18-20/Fc but not by the R1203A mutant. A recombinant fH/Fc molecule that contained chimpanzee domain 20, humanized only at amino acid 1203 (N1203R) also bound to sialylated gonococci and restored killing. These findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics.
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A successful strategy for surgical treatment of Boerhaaves syndrome.
Surg Endosc
PUBLISHED: 04-18-2011
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This retrospective single-institution study presents a successful treatment strategy for Boerhaaves syndrome.
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Rapid nongenomic actions of inhaled corticosteroids on long-acting ?(2)-agonist transport in the airway.
Pulm Pharmacol Ther
PUBLISHED: 04-10-2011
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Corticosteroids inhibit organic cation transporters (OCTs) that play an important role in drug absorption, tissue distribution and elimination. Corticosteroid sensitivity of bronchodilator trafficking in the airway tissue, however, is poorly understood. To assess the effects of inhaled corticosteroids on airway absorption and disposal mechanisms of long-acting ?(2)-agonists, human airway epithelial and smooth muscle cell uptake of tritiated formoterol and salmeterol was measured in vitro. Corticosteroids caused a rapid, concentration-dependent inhibition of uptake of the cationic formoterol by airway smooth muscle cells, but not airway epithelial cells. Uptake of the non-charged lipophilic salmeterol was corticosteroid-insensitive in both cell types. In smooth muscle cells, inhaled corticosteroids inhibited formoterol uptake with a novel potency rank order: des-ciclesonide > budesonide > beclomethasone 17-monopropionate > beclomethasone dipropionate > ciclesonide > fluticasone. The inhibitory action was rapidly reversible, and was not enhanced by prolonged corticosteroid exposure or sensitive to a transcription inhibitor. Suppression of OCT3 expression using lentivirus-mediated production of shRNA reduced corticosteroid sensitivity of formoterol uptake by smooth muscle cells. Our data support a corticosteroid insensitive absorption and a corticosteroid-sensitive disposition mechanism for cationic long-acting ?(2)-agonist bronchodilators in the airway. Potency rank order and other classical features of anti-inflammatory effects do not apply to inhaled corticosteroids rapid drug transport actions.
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Cell-cycle control as a target for calcium, hormonal and developmental signals: the role of phosphorylation in the retinoblastoma-centred pathway.
Ann. Bot.
PUBLISHED: 03-25-2011
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During the life cycle of plants, both embryogenic and post-embryogenic growth are essentially based on cell division and cell expansion that are under the control of inherited developmental programmes modified by hormonal and environmental stimuli. Considering either stimulation or inhibition of plant growth, the key role of plant hormones in the modification of cell division activities or in the initiation of differentiation is well supported by experimental data. At the same time there is only limited insight into the molecular events that provide linkage between the regulation of cell-cycle progression and hormonal and developmental control. Studies indicate that there are several alternative ways by which hormonal signalling networks can influence cell division parameters and establish functional links between regulatory pathways of cell-cycle progression and genes and protein complexes involved in organ development.
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On the trail of Vikings with polarized skylight: experimental study of the atmospheric optical prerequisites allowing polarimetric navigation by Viking seafarers.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 02-02-2011
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Between AD 900 and AD 1200 Vikings, being able to navigate skillfully across the open sea, were the dominant seafarers of the North Atlantic. When the Sun was shining, geographical north could be determined with a special sundial. However, how the Vikings could have navigated in cloudy or foggy situations, when the Suns disc was unusable, is still not fully known. A hypothesis was formulated in 1967, which suggested that under foggy or cloudy conditions, Vikings might have been able to determine the azimuth direction of the Sun with the help of skylight polarization, just like some insects. This hypothesis has been widely accepted and is regularly cited by researchers, even though an experimental basis, so far, has not been forthcoming. According to this theory, the Vikings could have determined the direction of the skylight polarization with the help of an enigmatic birefringent crystal, functioning as a linearly polarizing filter. Such a crystal is referred to as sunstone in one of the Vikings sagas, but its exact nature is unknown. Although accepted by many, the hypothesis of polarimetric navigation by Vikings also has numerous sceptics. In this paper, we summarize the results of our own celestial polarization measurements and psychophysical laboratory experiments, in which we studied the atmospheric optical prerequisites of possible sky-polarimetric navigation in Tunisia, Finland, Hungary and the high Arctic.
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Overproduction of a rice aldo-keto reductase increases oxidative and heat stress tolerance by malondialdehyde and methylglyoxal detoxification.
Plant Mol. Biol.
PUBLISHED: 01-11-2011
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The accumulation of toxic compounds generated by the interaction between reactive oxygen species and polyunsaturated fatty acids of membrane lipids can significantly damage plant cells. A plethora of enzymes act on these reactive carbonyls, reducing their toxicity. Based on the chromosomal localization and on their homology with other stress-induced aldo-keto reductases (AKRs) we have selected three rice AKR genes. The transcription level of OsAKR1 was greatly induced by abscisic acid and various stress treatments; the other two AKR genes tested were moderately stress-inducible. The OsAKR1 recombinant protein exhibited a high nicotinamide adenine dinucleotide phosphate-dependent catalytic activity to reduce toxic aldehydes including glycolysis-derived methylglyoxal (MG) and lipid peroxidation-originated malondialdehyde (MDA). The function of this enzyme in MG detoxification was demonstrated in vivo in E. coli and in transgenic plants overproducing the OsAKR1 protein. Heterologous synthesis of the OsAKR1 enzyme in transgenic tobacco plants resulted in increased tolerance against oxidative stress generated by methylviologen (MV) and improved resistance to high temperature. In these plants lower levels of MDA were detected both following MV and heat treatment due to the activity of the OsAKR1 enzyme. The transgenic tobaccos also exhibited higher AKR activity and accumulated less MG in their leaves than the wild type plants; both in the presence and absence of heat stress. These results support the positive role of OsAKR1 in abiotic stress-related reactive aldehyde detoxification pathways and its use for improvement of stress tolerance in plants.
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Immunodetection of retinoblastoma-related protein and its phosphorylated form in interphase and mitotic alfalfa cells.
J. Exp. Bot.
PUBLISHED: 01-04-2011
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Plant retinoblastoma-related (RBR) proteins are primarily considered as key regulators of G(1)/S phase transition, with functional roles in a variety of cellular events during plant growth and organ development. Polyclonal antibody against the C-terminal region of the Arabidopsis RBR1 protein also specifically recognizes the alfalfa 115?kDa MsRBR protein, as shown by the antigen competition assay. The MsRBR protein was detected in all cell cycle phases, with a moderate increase in samples representing G(2)/M cells. Antibody against the human phospho-pRb peptide (Ser807/811) cross-reacted with the same 115?kDa MsRBR protein and with the in vitro phosphorylated MsRBR protein C-terminal fragment. Phospho-MsRBR protein was low in G(1) cells. Its amount increased upon entry into the S phase and remained high during the G(2)/M phases. Roscovitine treatment abolished the activity of alfalfa MsCDKA1;1 and MsCDKB2;1, and the phospho-MsRBR protein level was significantly decreased in the treated cells. Colchicine block increased the detected levels of both forms of MsRBR protein. Reduced levels of the MsRBR protein in cells at stationary phase or grown in hormone-free medium can be a sign of the division-dependent presence of plant RBR proteins. Immunolocalization of the phospho-MsRBR protein indicated spots of variable number and size in the labelled interphase nuclei and high signal intensity of nuclear granules in prophase. Structures similar to phospho-MsRBR proteins cannot be recognized in later mitotic phases. Based on the presented western blot and immunolocalization data, the possible involvement of RBR proteins in G(2)/M phase regulation in plant cells is discussed.
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Comparison between PACAP- and enriched environment-induced retinal protection in MSG-treated newborn rats.
Neurosci. Lett.
PUBLISHED: 07-29-2010
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Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This effect has been proven in different models of retinal degeneration. We have previously shown that PACAP protects against monosodium-glutamate (MSG)-induced damage in neonatal rats. The beneficial effects of enriched environment, another neuroprotective strategy, have long been known. Environmental enrichment has been shown to decrease different neuronal injuries. It also influences the development of the visual system. We have recently demonstrated that significant neuroprotection can be achieved in MSG-induced retinal degeneration in animals kept in an enriched environment. Combination of neuroprotective strategies often results in increased protection. Therefore, the aim of the present study was to compare the two neuroprotective strategies alone and in combination therapy. We found that both PACAP and environmental enrichment led to a similar degree of retinal protection, but the two treatments together did not lead to increased protection: their effects were not additive.
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[Better quality of life after surgery treatment in patients with colitis ulcerosa: what is the price].
Orv Hetil
PUBLISHED: 07-27-2010
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Exacerbations of ulcerative colitis (UC) have a great impact on patients quality of life. Only a few data is available about the effect of surgery on the quality of life in patients with UC. Aim: of our study was to evaluate the outcome and the impact of surgery on the quality of life of patients with UC. Patients and methods: 183 UC patients [mean age at the diagnosis: 33.23 years (12-69 years), female/male ratio: 95/88] were hospitalized in our tertiary clinic because of exacerbation of UC requiring parenteral corticosteroid therapy between 1998 and 2007. Data of 46 patients undergoing colectomy were analyzed retrospectively. Outcome of surgery, frequency of early and late complications, the alteration of the number of hospitalizations and outpatient visits, the number of medication, the income and the disability grade were assessed in detail. The patients were also asked to complete questionnaires to compare their quality of life before and after colectomy. The follow up period was 3.3 years. Data were analyzed using two-sample t-test and one-way analysis of variance. P value lower than 0.05 was considered statistically significant. Results: 74% of the colectomized patients underwent ileal pouch anal anastomosis procedure, 11 patients needed definitive ileostomy and in one case, ileorectal anastomosis was requested by the patient. Early complications occurred in 24, late complications in 23 patients (pouchitis in 13 cases). The need for hospitalization and the number of medication decreased significantly, while significant improvement was shown in the patients quality of life after colectomy compared to the preoperative condition. Colectomy did not have an impact on the patients income in 64.5% of the cases and no alteration of the disability grade was detected in 32% of the patients. Discussion: Our results show that surgery may results in a good quality of life in the majority of the patients, however, further management may be necessary due to the late postoperative complications.
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Decreased soluble adenylyl cyclase activity in cystic fibrosis is related to defective apical bicarbonate exchange and affects ciliary beat frequency regulation.
J. Biol. Chem.
PUBLISHED: 07-16-2010
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Human airway cilia contain soluble adenylyl cyclase (sAC) that produces cAMP upon HCO(3)(-)/CO(2) stimulation to increase ciliary beat frequency (CBF). Because apical HCO(3)(-) exchange depends on cystic fibrosis transmembrane conductance regulator (CFTR), malfunctioning CFTR might impair sAC-mediated CBF regulation in cells from patients with cystic fibrosis (CF). By Western blot, sAC isoforms are equally expressed in normal and CF airway epithelial cells, but CBF decreased more in CF than normal cells upon increased apical HCO(3)(-)/CO(2) exposure in part because of greater intracellular acidification from unbalanced CO(2) influx (estimated by 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) fluorescence). Importantly, ciliated cell-specific cAMP production (estimated by FRET fluorescence ratio changes of tagged cAMP-dependent protein kinase (PKA) subunits expressed under a ciliated cell-specific promoter) in response to increased apical HCO(3)(-)/CO(2) perfusion was higher in normal compared with CF cells. Inhibition of bicarbonate influx via CFTR (CFTR(inh)172) and inhibition of sAC (KH7) and PKA activation (H89) led to larger CBF declines in normal cells, now comparable with changes seen in CF cells. These inhibitors also reduced FRET changes in normal cells to the level of CF cells with the expected exception of H89, which does not prevent dissociation of the fluorescently tagged PKA subunits. Basolateral permeabilization and subsequent perfusion with HCO(3)(-)/CO(2) rescued CBF and FRET changes in CF cells to the level of normal cells. These results suggest that CBF regulation by sAC-produced cAMP could be impaired in CF, thereby possibly contributing to mucociliary dysfunction in this disease, at least during disease exacerbations when airway acidification is common.
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Pregnancy outcome in patients with inflammatory bowel disease according to the activity of the disease and the medical treatment: a case-control study.
Scand. J. Gastroenterol.
PUBLISHED: 07-05-2010
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There is limited data on pregnancy outcome in inflammatory bowel diseases (IBD) (Crohns disease [CD] and ulcerative colitis [UC]) from Eastern Europe. The aim of our multicenter study was to compare the pregnancy outcomes and the data of infants in pregnancies before and after the diagnosis of IBD.
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Outcomes of patients receiving clopidogrel prior to cardiac surgery.
Int. J. Cardiol.
PUBLISHED: 05-25-2010
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Clinical impact of the concomitant clopidogrel therapy on clinical outcomes in patients undergoing cardiac surgery is unclear. We aimed to pool and systematically analyze outcomes in clopidogrel-treated patients undergoing cardiac operations to achieve greater statistical power and to define precise effect-estimates.
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Agrin immunohistochemistry facilitates the determination of primary versus metastatic origin of liver carcinomas.
Hum. Pathol.
PUBLISHED: 05-14-2010
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In our earlier work, we demonstrated that agrin, a multifunctional heparan sulfate proteoglycan, accumulates in hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC). In addition, we proved the utility of agrin immumohistochemistry in discriminating between HCCs and benign parenchymal lesions. Here, we have examined the expression of agrin in metastatic liver carcinomas in comparison with primary liver tumors. Immunohistochemistry for agrin was performed on 25 HCC, 16 intrahepatic CCC, 20 colorectal cancer metastasis (CRCm), and 18 pancreatic ductal carcinoma metastasis (PDCm) samples and evaluated with both quantitative and qualitative methods. Agrin/CD34 double immunofluorescent staining was carried out on snap-frozen sections. Agrin mRNA expression was measured in 11 HCC, 7 CCC, 11 CRCm, and 12 normal liver tissues. Regardless of tumor grade, agrin immunostaining was strong in the microvessels of HCCs. As opposed to HCC, agrin immunostaining was faint or nearly absent from the CD34-positive microvessels of CCC, CRCm, and PDCm; rather, it was detected in the basement membranes surrounding tumor cell pseudoglandules. While agrin was preserved in the basement membranes of Grade III CCCs, it was nearly absent from poorly differentiated metastatic adenocarcinomas. Agrin mRNA levels were the highest in CCC and lower, but still elevated in HCC and CRCm. By qualitative evaluation of agrin immunoreactions, CCC was differentiated from CRCm and PDCm with a sensitivity of 0.81 and a specificity of 0.82. HCCs were unequivocally identified on the basis of microvascular agrin labeling. Thus, agrin immunohistochemistry may facilitate determination of primary versus metastatic origin in problematic liver cancer cases.
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Reducing the maladaptive attractiveness of solar panels to polarotactic insects.
Conserv. Biol.
PUBLISHED: 05-12-2010
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Human-made objects (e.g., buildings with glass surfaces) can reflect horizontally polarized light so strongly that they appear to aquatic insects to be bodies of water. Insects that lay eggs in water are especially attracted to such structures because these insects use horizontal polarization of light off bodies of water to find egg-laying sites. Thus, these sources of polarized light can become ecological traps associated with reproductive failure and mortality in organisms that are attracted to them and by extension with rapid population declines or collapse. Solar panels are a new source of polarized light pollution. Using imaging polarimetry, we measured the reflection-polarization characteristics of different solar panels and in multiple-choice experiments in the field we tested their attractiveness to mayflies, caddis flies, dolichopodids, and tabanids. At the Brewster angle, solar panels polarized reflected light almost completely (degree of polarization d ? 100%) and substantially exceeded typical polarization values for water (d ? 30-70%). Mayflies (Ephemeroptera), stoneflies (Trichoptera), dolichopodid dipterans, and tabanid flies (Tabanidae) were the most attracted to solar panels and exhibited oviposition behavior above solar panels more often than above surfaces with lower degrees of polarization (including water), but in general they avoided solar cells with nonpolarizing white borders and white grates. The highly and horizontally polarizing surfaces that had nonpolarizing, white cell borders were 10- to 26-fold less attractive to insects than the same panels without white partitions. Although solar panels can act as ecological traps, fragmenting their solar-active area does lessen their attractiveness to polarotactic insects. The design of solar panels and collectors and their placement relative to aquatic habitats will likely affect populations of aquatic insects that use polarized light as a behavioral cue.
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Prevalence of radiographic primary hip and knee osteoarthritis in a representative Central European population.
Int Orthop
PUBLISHED: 05-09-2010
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The aim of our study was to determine the radiographic prevalence of hip and knee osteoarthritis and compare our results with prevalence data reported by other studies, as no similar study had been performed in Hungary previously. Our aim was also to investigate the usefulness of the different radiological scoring methods for the definition of osteoarthritis. Patients who earlier reported complaints and gave written consent were asked to participate in a clinical follow-up. In the 682 participants Harris hip score, visual analogue pain scale values for both joints, Knee Society score and knee functional score were calculated. Weight-bearing radiographs were taken of both joints. Kellgren-Lawrence radiological evaluation was performed and osteoarthritis prevalence was defined. Hip osteoarthritis was found in 109 cases (16.49%), and knee osteoarthritis was found in 111 cases (16.54%). Harris hip score, Knee Society score, functional score and visual analogue scale values were significantly worse in people with radiographically proven osteoarthritis compared to the control group (p?
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Cadmium- and flood-induced anoxia stress in pea roots measured by electrical impedance.
Z. Naturforsch., C, J. Biosci.
PUBLISHED: 04-02-2010
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Electrical impedance measurement--complex resistance in the presence of alternating current--is a useful tool for the investigation of structural characteristics of solid materials but also for plant tissues. This measurement is easily done: only two electrodes are inserted into the plant tissue, so it can be considered as a non-invasive technique and it may be a successful method for detecting structural changes in plants caused by environmental stresses. The effects of flood and cadmium stress were investigated by electrical impedance measurement, because both of them cause structural changes in plant tissues. Apoplasmic resistance (Ra), symplasmic resistance (Rs), and membrane capacitance (Cm) of pea roots were calculated. In the first five days of flood treatment, the Rs and Cm values of roots decreased drastically. In case of cadmium treatment, the Rs and Cm values of roots showed an increasing tendency supposedly as a consequence of the enhanced membrane rigidity, the thickened cell walls and decreased growth phenomena caused by the heavy metal. There also was a remarkable difference in cadmium accumulation patterns and in the changes of the calculated parameters amongst anoxic and aerated seedlings. This initial work revealed that the development of stress caused by two environental stress agents, cadmium and flood, can be followed by electrical impedance measurement.
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Fatty acid composition of plasma lipid classes in chronic alcoholic pancreatitis.
Pancreatology
PUBLISHED: 02-13-2010
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Supplementation of n-3 long-chain polyunsaturated fatty acids (LCPUFA) is considered as adjuvant therapy in acute pancreatitis. We investigated plasma fatty acid status in chronic pancreatitis (CP).
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An unexpected advantage of whiteness in horses: the most horsefly-proof horse has a depolarizing white coat.
Proc. Biol. Sci.
PUBLISHED: 02-03-2010
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White horses frequently suffer from malign skin cancer and visual deficiencies owing to their high sensitivity to the ultraviolet solar radiation. Furthermore, in the wild, white horses suffer a larger predation risk than dark individuals because they can more easily be detected. In spite of their greater vulnerability, white horses have been highly appreciated for centuries owing to their natural rarity. Here, we show that blood-sucking tabanid flies, known to transmit disease agents to mammals, are less attracted to white than dark horses. We also demonstrate that tabanids use reflected polarized light from the coat as a signal to find a host. The attraction of tabanids to mainly black and brown fur coats is explained by positive polarotaxis. As the hosts colour determines its attractiveness to tabanids, this parameter has a strong influence on the parasite load of the host. Although we have studied only the tabanid-horse interaction, our results can probably be extrapolated to other host animals of polarotactic tabanids, as the reflection-polarization characteristics of the hosts body surface are physically the same, and thus not species-dependent.
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A rapid and robust assay for detection of S-phase cell cycle progression in plant cells and tissues by using ethynyl deoxyuridine.
Plant Methods
PUBLISHED: 01-28-2010
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Progress in plant cell cycle research is highly dependent on reliable methods for detection of cells replicating DNA. Frequency of S-phase cells (cells in DNA synthesis phase) is a basic parameter in studies on the control of cell division cycle and the developmental events of plant cells. Here we extend the microscopy and flow cytometry applications of the recently developed EdU (5-ethynyl-2-deoxyuridine)-based S-phase assay to various plant species and tissues. We demonstrate that the presented protocols insure the improved preservation of cell and tissue structure and allow significant reduction in assay duration. In comparison with the frequently used detection of bromodeoxyuridine (BrdU) and tritiated-thymidine incorporation, this new methodology offers several advantages as we discuss here.
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Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis.
Am. Heart J.
PUBLISHED: 01-16-2010
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A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates.
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[Prevalence of knee osteoarthritis in Hungary. Study conducted in a representative Hungarian population].
Orv Hetil
PUBLISHED: 01-15-2010
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In an earlier publication, authors have already reported the result of a survey conducted in a representative Hungarian population, where joint complaint prevalence data were presented, including those of the knee joint.
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Optics of sunlit water drops on leaves: conditions under which sunburn is possible.
New Phytol.
PUBLISHED: 01-08-2010
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*It is a widespread belief that plants must not be watered in the midday sunshine, because water drops adhering to leaves can cause leaf burn as a result of the intense focused sunlight. The problem of light focusing by water drops on plants has never been thoroughly investigated. *Here, we conducted both computational and experimental studies of this phyto-optical phenomenon in order to clarify the specific environmental conditions under which sunlit water drops can cause leaf burn. *We found that a spheroid drop at solar elevation angle theta approximately 23 degrees, corresponding to early morning or late afternoon, produces a maximum intensity of focused sunlight on the leaf outside the drops imprint. Our experiments demonstrated that sunlit glass spheres placed on horizontal smooth Acer platanoides (maple) leaves can cause serious leaf burn on sunny summer days. *By contrast, sunlit water drops, ranging from spheroid to flat lens-shaped, on horizontal hairless leaves of Ginkgo biloba and Acer platanoides did not cause burn damage. However, we showed that highly refractive spheroid water drops held in focus by hydrophobic wax hairs on leaves of Salvinia natans (floating fern) can indeed cause sunburn because of the extremely high light intensity in the focal regions, and the loss of water cooling as a result of the lack of intimate contact between drops and the leaf tissue.
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Prevalence of low back pain and lumbar spine degenerative disorders. Questionnaire survey and clinical-radiological analysis of a representative Hungarian population.
Int Orthop
PUBLISHED: 10-31-2009
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A cross-sectional epidemiological study via personal interviews was performed regarding low back pain and its related clinical aspects in a Hungarian sample of 10,000 people. Joining the international campaign of the "Bone and Joint Decade", our aim was to give data on low back pain prevalence and to explore the underlying possible clinical conditions in a Central European adult and adolescent population. Ten thousand people aged 14-65, selected randomly by the Hungarian central office of statistics from three counties of the south-western Hungarian region, were surveyed using a special questionnaire focusing on low back pain and other degenerative spinal symptoms. People with low back pain complaints and written consent were asked to participate in a further clinical investigation, where radiological and clinical assessment was performed. A total of 4,389 persons (44.1%) reported low back pain in the last month at the time of the survey. Work absenteeism due to low back pain affected 2,140 persons (21.5%). A total of 292 people (2.9%) had already undergone spinal surgery. Upon request 682 people came for a clinical follow-up, where thorough physical examination and radiological analysis was performed and results were statistically interpreted. The Oswestry disability index (ODI) in the examined group of patients averaged 35.1%; radiological degenerative signs were observed in 392/682 (57.5%). Individuals with signs of radiological degeneration had a statistically significant higher ODI value, age, and a higher, yet not significantly increased BMI value than radiographically negative patients (p?
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Efficacy and safety of infliximab induction therapy in Crohns Disease in Central Europe--a Hungarian nationwide observational study.
BMC Gastroenterol
PUBLISHED: 09-10-2009
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Infliximab (IFX) has proven to be an effective addition to the therapeutic arsenal for refractory, fistulizing, and steroid dependent Crohns disease (CD), with efficacy in the induction and maintenance of clinical remission of CD. Our objective in this study is to report the nationwide, multicenter experience with IFX induction therapy for CD in Hungary.
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Chemo-radiotherapy in locally advanced squamous cell oesophageal cancer--are upper third tumours more responsive?
Pathol. Oncol. Res.
PUBLISHED: 08-31-2009
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Before neoadjuvant therapy was widely applied, the prognosis of oesophageal cancer had been considered dependent on the location of the tumor, i.e. upper third cancers had had the worst prognosis. The aim of this retrolective study was to prove the efficiency of the neoadjuvant treatment, and to compare the response of esophageal cancer in different locations. Between January 1998 and September 2005, 102 patients with locally advanced squamous cell oesophageal cancer received preoperative chemo-radiotherapy. In 40 cases the tumor was located in the upper third and in 62 cases in the middle third of the oesophagus. After a four-week-long treatment free period restaging was carried out and patients considered resectable were submitted to surgery. From 40 patients with upper third oesophageal cancer 28 underwent oesophageal resection or pharyngo-laryngectomy. Thiry-five percent a complete histopathological remission was observed. From 62 patients with middle third oesophageal cancer 43 underwent oesophageal resection. Histological examination of the resected specimens documented complete response only in three patients. The median survival and the R0 resection rate were similar in the two groups. Although the resection rate, perioperative morbidity, mortality and the median survival were similar in the two groups, a significantly higher rate of complete response (p < 0,05) was observed in patients with upper third oesophageal cancer compared to patients with middle third oesophageal cancer. It seems that upper third oesophageal cancer has superior sensitivity to multimodal treatment therefore our results may support that upper third location is not an unfavorable prognostic factor any more.
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Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.
J. Immunol.
PUBLISHED: 07-01-2009
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The IL-1 family cytokines are regulated on transcriptional and posttranscriptional levels. Pattern recognition and cytokine receptors control pro-IL-1beta transcription whereas inflammasomes regulate the proteolytic processing of pro-IL-1beta. The NLRP3 inflammasome, however, assembles in response to extracellular ATP, pore-forming toxins, or crystals only in the presence of proinflammatory stimuli. How the activation of gene transcription by signaling receptors enables NLRP3 activation remains elusive and controversial. In this study, we show that cell priming through multiple signaling receptors induces NLRP3 expression, which we identified to be a critical checkpoint for NLRP3 activation. Signals provided by NF-kappaB activators are necessary but not sufficient for NLRP3 activation, and a second stimulus such as ATP or crystal-induced damage is required for NLRP3 activation.
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Degrees of polarization of reflected light eliciting polarotaxis in dragonflies (Odonata), mayflies (Ephemeroptera) and tabanid flies (Tabanidae).
J. Insect Physiol.
PUBLISHED: 05-24-2009
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With few exceptions insects whose larvae develop in freshwater possess positive polarotaxis, i.e., are attracted to sources of horizontally polarized light, because they detect water by means of the horizontal polarization of light reflected from the water surface. These insects can be deceived by artificial surfaces (e.g. oil lakes, asphalt roads, black plastic sheets, dark-coloured cars, black gravestones, dark glass surfaces, solar panels) reflecting highly and horizontally polarized light. Apart from the surface characteristics, the extent of such a polarized light pollution depends on the illumination conditions, direction of view, and the threshold p* of polarization sensitivity of a given aquatic insect species. p* means the minimum degree of linear polarization p of reflected light that can elicit positive polarotaxis from a given insect species. Earlier there were no quantitative data on p* in aquatic insects. The aim of this work is to provide such data. Using imaging polarimetry in the red, green and blue parts of the spectrum, in multiple-choice field experiments we measured the threshold p* of ventral polarization sensitivity in mayflies, dragonflies and tabanid flies, the positive polarotaxis of which has been shown earlier. In the blue (450nm) spectral range, for example, we obtained the following thresholds: dragonflies: Enallagma cyathigerum (0%
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Toll-like receptor interactions imaged by FRET microscopy and GFP fragment reconstitution.
Methods Mol. Biol.
PUBLISHED: 04-21-2009
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Protein-protein interactions regulate biological networks. The most proximal events that initiate signal transduction frequently are receptor dimerization or conformational changes in receptor complexes. Toll-like receptors (TLRs) are transmembrane receptors that are activated by a number of exogenous and endogenous ligands. Most TLRs can respond to multiple ligands and the different TLRs recognize structurally diverse molecules ranging from proteins, sugars, lipids, and nucleic acids. TLRs can be expressed on the plasma membrane or in endosomal compartments, and ligand recognition thus proceeds in different microenvironments. Not surprisingly, distinctive mechanisms of TLR receptor activation have evolved. A detailed understanding of the mechanisms of TLR activation is important for the development of novel synthetic TLR activators or pharmacological inhibitors of TLRs. Confocal laser scanning microscopy (LSM) combined with green fluorescent protein (GFP) technology allows the direct visualization of TLR expression in living cells. Fluorescence resonance energy transfer (FRET) measurements between two differentially tagged proteins permit the study of TLR interaction and distances between receptors in the range of molecular interactions can be measured and visualized. Additionally, FRET measurements combined with confocal microscopy provide detailed information about molecular interactions in different subcellular localizations. Bimolecular complementation using split fluorescent proteins (BiFC) represents an additional valuable method to study mechanisms of receptor activation in living cells. These techniques permit the dynamic visualization of early signaling events in living cells and can be utilized in pharmacological or genetic screens.
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Leaf hue measurements offer a fast, high-throughput initial screening of photosynthesis in leaves.
J. Plant Physiol.
PUBLISHED: 02-20-2009
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Experiments with tobacco and grapevine leaves having different color due to varying stages of senescence showed that leaf hue is significantly linearly correlated with chlorophyll content up to 80% loss of pigment. Samples from leaves with more pronounced loss of chlorophyll did not fit into this linear relationship, and the hue data set as a whole followed a saturating exponential dependence on chlorophyll content. In leaves with less than 80% chlorophyll loss, the hue parameter was also proportional to the photochemical yield of photosystem (PS) II measured in the light. These results suggest that leaf hue measurements offer a fast, high-throughput initial screening system to precede more specific but more time consuming photosynthesis measurements, with the possibility of applications not only for senescing plants, but also for stress conditions accompanied by chlorophyll loss.
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AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC.
Nature
PUBLISHED: 01-21-2009
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The innate immune system senses nucleic acids by germline-encoded pattern recognition receptors. RNA is sensed by Toll-like receptor members TLR3, TLR7 and TLR8, or by the RNA helicases RIG-I (also known as DDX58) and MDA-5 (IFIH1). Little is known about sensors for cytoplasmic DNA that trigger antiviral and/or inflammatory responses. The best characterized of these responses involves activation of the TANK-binding kinase (TBK1)-interferon regulatory factor 3 (IRF3) signalling axis to trigger transcriptional induction of type I interferon genes. A second, less well-defined pathway leads to the activation of an inflammasome that, via caspase-1, controls the catalytic cleavage of the pro-forms of the cytokines IL1beta and IL18 (refs 6, 7). Using mouse and human cells, here we identify the PYHIN (pyrin and HIN domain-containing protein) family member absent in melanoma 2 (AIM2) as a receptor for cytosolic DNA, which regulates caspase-1. The HIN200 domain of AIM2 binds to DNA, whereas the pyrin domain (but not that of the other PYHIN family members) associates with the adaptor molecule ASC (apoptosis-associated speck-like protein containing a caspase activation and recruitment domain) to activate both NF-kappaB and caspase-1. Knockdown of Aim2 abrogates caspase-1 activation in response to cytoplasmic double-stranded DNA and the double-stranded DNA vaccinia virus. Collectively, these observations identify AIM2 as a new receptor for cytoplasmic DNA, which forms an inflammasome with the ligand and ASC to activate caspase-1.
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Effects of maternal separation on the neurobehavioral development of newborn Wistar rats.
Brain Res. Bull.
PUBLISHED: 01-15-2009
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Animal models of neonatal stress, like maternal separation, may provide important correlation with human stress-related disorders. Early maternal deprivation has been shown to cause several short- and long-term neurochemical and behavioral deficits. Little is known about the early neurobehavioral development after postnatal stress. The aim of the present study was to investigate the development of reflexes and motor coordination in male and female pups subjected to maternal deprivation. Pups were removed from their mothers from postnatal day 1-14, for 3h daily. Somatic development (weight gain, eye opening, ear unfolding, incisor eruption) and reflex development was tested during the first 3 weeks. The appearance of the following reflexes was investigated: crossed extensor, grasping, placing, gait, righting and sensory reflexes, and negative geotaxis. Timely performance of negative geotaxis, righting and gait were also tested daily during the first 3 weeks. Motor coordination and open-field tests were performed on postnatal weeks 3-5 (rotarod, elevated grid-walk, footfault, rope suspension, inclined board and walk initiation tests). The results revealed that a 3-h-long daily maternal separation did not lead to a marked delay or enhancement in reflex development and motor coordination. A subtle enhancement was observed in the appearance of hindlimb grasp and gait reflexes, and a better performance in footfault test in male rats suffering from maternal deprivation. In contrast, female maternally deprived (MD) rats displayed a slight delay in forelimb grasp and air righting reflex appearance, and surface righting performance. Open-field activity was not changed in maternally deprived rats. In summary, our present observations indicate that maternal deprivation does not induce drastic changes in early neurodevelopment, therefore, further research is needed to determine the onset of behavioral alterations in subject with maternal deprivation history. Gender differences described in this study could help to understand how gender-specific differences in early life experience-induced stress-related disorders appear in adult life.
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Disease burden of psoriatic arthritis compared to rheumatoid arthritis, Hungarian experiment.
Rheumatol. Int.
PUBLISHED: 01-09-2009
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The objectives of this study were to assess the costs of psoriatic arthritis (PsA) in Hungary and to identify key cost drivers among demographic and clinical variables and to compare cost-of-illness of PsA and rheumatoid arthritis (RA). Cross-sectional retrospective survey of 183 consecutive patients from eight rheumatology centres was conducted. Mean direct medical, direct non medical, indirect and total costs were 1,876, 794, 2,904 and 5,574 euros/patient/year, respectively. Total costs were in significant linear relationship with health assessment questionnaire score and psoriatic area severity index. Costs of RA were higher in all domains than of PsA. Our study was the first from the Eastern European region that provides cost-of-illness data on PsA. Our study revealed that functional status and severity of skin symptoms were the key cost drivers. The costs of PsA in Hungary were lower than in the high-income European countries.
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Effects of perinatal asphyxia on the neurobehavioral and retinal development of newborn rats.
Brain Res.
PUBLISHED: 01-03-2009
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Perinatal asphyxia during delivery produces long-term deficits and represents a major problem in both neonatal and pediatric care. Several morphological, biochemical and behavioral changes have been described in rats exposed to perinatal asphyxia. The aim of the present study was to evaluate how perinatal asphyxia affects the complex early neurobehavioral development and retinal structure of newborn rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by cesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily during the first 3 weeks, and motor coordination tests were performed on postnatal weeks 3-5. After completion of the testing procedure, retinas were removed for histological analysis. We found that in spite of the fast catch-up-growth of asphyctic pups, nearly all examined reflexes were delayed by 1-4 days: negative geotaxis, sensory reflexes, righting reflexes, development of fore- and hindlimb grasp and placing, gait and auditory startle reflexes. Time to perform negative geotaxis, surface righting and gait reflexes was significantly longer during the first few weeks in asphyctic pups. Among the motor coordination tests, a markedly weaker performance was observed in the grid walking and footfault test and in the walk initiation test. Retinal structure showed severe degeneration in the layer of the photoreceptor and bipolar cell bodies. In summary, our present study provided a detailed description of reflex and motor development following perinatal asphyxia, showing that asphyxia led to a marked delay in neurobehavioral development and a severe retinal degeneration.
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Early postnatal enriched environment decreases retinal degeneration induced by monosodium glutamate treatment in rats.
Brain Res.
PUBLISHED: 01-02-2009
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Environmental enrichment is known to influence the development of the nervous system and it provides beneficial effects in various kinds of brain lesions. Enriched housing conditions also influence the development and functioning of the visual system. The aim of the present study was to investigate whether retinal degeneration induced by neonatal monosodium glutamate (MSG) in rats can be ameliorated by expanded cage size or enriched environment. Control rats were kept in a regular cage, another group of pups was kept in an expanded cage and a third group was kept under complex environmental enriched conditions from the first postnatal day. Half of the rats received MSG treatment on postnatal days 1, 5, and 9, while the other half of the groups received only saline treatment. Retinas were removed at 5 weeks of age and processed for histological analysis. Microscopical analysis revealed a substantial inner retinal degeneration in MSG-treated animals: the retinal thickness was less than 25% of the normal retinas, and the inner layers were completely fused. Expanded cage environment had a significant protective effect: the layers of the retina were well visible, and the thickness of the entire retina had a nearly 50% amelioration. Best results were obtained in retinas from rats living in enriched environment: the retina suffered only an approximately 25% reduction in thickness, and all layers were significantly thicker than in MSG-treated retinas. In summary, the present study showed that expanded field provided some degree of neuroprotection, while a complex environmental enrichment led to a manifest protection against retinal degeneration induced by neonatal MSG treatment in rats.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.