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Find video protocols related to scientific articles indexed in Pubmed.
Does oral Coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in Chronic Fatigue Syndrome?
Antioxid. Redox Signal.
PUBLISHED: 11-12-2014
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Chronic Fatigue Syndrome (CFS) is a chronic and extremely debilitating illness characterized by prolonged fatigue and multiple symptoms with unknown cause, diagnostic test, or universally effective treatment. Inflammation, oxidative stress, mitochondrial dysfunction, and CoQ10 deficiency have been well documented in CFS. We conducted an 8-weeks randomized, double-blind, placebo-controlled trial to evaluate the benefits of oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation on fatigue and biochemical parameters in 73 Spanish CFS patients. This study was registered in ClinicalTrials.gov (NCT02063126). A significant improvement of fatigue showing a reduction in FIS total score (p< 0.05) was reported in treated group vs. placebo. In addition, a recovery of the biochemical parameters was also reported. NAD+/NADH (p< 0.001), CoQ10 (p< 0.05), ATP (p< 0.05) and citrate synthase (p< 0.05) were significantly higher and lipoperoxides (p< 0.05) were significantly lower in blood mononuclear cells (BMCs) of the treated group. These observations lead to the hypothesis that the oral CoQ10 plus NADH supplementation could confers potential therapeutic benefits on fatigue and biochemical parameters in CFS. Larger sample trials are warranted to confirm these findings.
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Spontaneous regression of multiple melanocytic nevi after melanoma: report of 3 cases.
Am J Dermatopathol
PUBLISHED: 10-25-2014
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: Complete spontaneous regression of multiple melanocytic nevi after melanoma is an extremely rare phenomenon. We report 3 cases of patients with a history of melanoma that showed regression of almost all melanocytic nevi over time. One of the patients had 2 simultaneous primary cutaneous melanomas without metastasis. In the other 2 patients, regression of the melanocytic nevi was seen after the development of metastasis in lymph nodes. These patients had spontaneously developed an efficient immune response against melanocytes, and they would represent paradigmatic examples of the spontaneous immune responses in melanoma patients. Better understanding of the mechanisms involved in the complete regression of melanocytic lesions would lead to a better selection of melanoma patients for immunotherapy.
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Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine.
Hum. Gene Ther.
PUBLISHED: 10-03-2014
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Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 10(7) MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2-treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally.
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Identification and Characterization of Hundreds of Potent and Selective Inhibitors of Trypanosoma brucei Growth from a Kinase-Targeted Library Screening Campaign.
PLoS Negl Trop Dis
PUBLISHED: 10-01-2014
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In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.
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Mixtec Mexican Amerindians: an HLA Alleles Study for America Peopling, Pharmacogenomics and Transplantation.
Immunol. Invest.
PUBLISHED: 09-25-2014
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HLA-A, -B and -DRB1 alleles have been studied in a Mixtec Mexican Amerindian population by indirect DNA sequencing. HLA relatedness has been tested by comparing results with other Amerindians and worldwide populations; a total of 15,681 chromosomes have been used. Genetic distances between populations, Neighbour Joining (NJ) dendrograms and correspondence analyses have been carried out. Conclusions are: 1) Our Mixtec sample from Oaxaca Coastal Mexican area shows an HLA profile different to that of Oaxaca Central Mountains area showing that genes and languages do not correlate which is inferred both by plane genetic distances and NJ dendrograms and correspondence analyses. 2) Genetic distances and NJ dendrograms join together Mazatecan Mexican Amerindians with our studied Coastal Mixtec group; it fits with the historical relationship between Mixtec and Mazatecans. 3) A*24:02-B*35:14-DRB1*04:11, A*02:01-B*15:15-DRB1*04:11 and A*68:03-B*39:08-DRB1*08:02 extended HLA haplotypes have been "de novo" found in our Mixtec Coastal sample. 4) Shared HLA alleles are found between our Pacific Coast Mixtec Amerindians and Pacific Islanders. 5) These results are useful for establishing a future area transplantation waiting list, for the study of HLA linked diseases epidemiology and for pharmacogenomics in certain drug therapy.
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Genomic footprints of speciation in Atlantic eels (Anguilla anguilla and A. rostrata).
Mol. Ecol.
PUBLISHED: 09-22-2014
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The importance of speciation-with-geneflow scenarios is increasingly appreciated. However, the specific processes and the resulting genomic footprints of selection are subject to much discussion. We studied the genomics of speciation between the two panmictic, sympatrically spawning sister species; European (Anguilla anguilla) and American eel (A. rostrata). Divergence is assumed to have initiated more than 3 Ma, and although low gene flow still occurs, strong postzygotic barriers are present. Restriction-site-associated DNA (RAD) sequencing identified 328 300 SNPs for subsequent analysis. However, despite the presence of 3757 strongly differentiated SNPs (FST > 0.8), sliding window analyses of FST showed no larger genomic regions (i.e. hundreds of thousands to millions of bases) of elevated differentiation. Overall FST was 0.041, and linkage disequilibrium was virtually absent for SNPs separated by more than 1000 bp. We suggest this to reflect a case of genomic hitchhiking, where multiple regions are under directional selection between the species. However, low but biologically significant gene flow and high effective population sizes leading to very low genetic drift preclude accumulation of strong background differentiation. Genes containing candidate SNPs for positive selection showed significant enrichment for gene ontology (GO) terms relating to developmental processes and phosphorylation, which seems consistent with assumptions that differences in larval phase duration and migratory distances underlie speciation. Most SNPs under putative selection were found outside coding regions, lending support to emerging views that noncoding regions may be more functionally important than previously assumed. In total, the results demonstrate the necessity of interpreting genomic footprints of selection in the context of demographic parameters and life-history features of the studied species.
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Haptically Assisted Connection Procedure for the Reconstruction of Dendritic Spines.
IEEE Trans Haptics
PUBLISHED: 09-10-2014
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Dendritic spines are thin protrusions that cover the dendritic surface of numerous neurons in the brain and whose function seems to play a key role in neural circuits. The correct segmentation of those structures is difficult due to their small size and the resulting spines can appear incomplete. This paper presents a four-step procedure for the complete reconstruction of dendritic spines. The haptically driven procedure is intended to work as an image processing stage before the automatic segmentation step giving the final representation of the dendritic spines. The procedure is designed to allow both the navigation and the volume image editing to be carried out using a haptic device. A use case employing our procedure together with a commercial software package for the segmentation stage is illustrated. Finally, the haptic editing is evaluated in two experiments; the first experiment concerns the benefits of the force feedback and the second checks the suitability of the use of a haptic device as input. In both cases, the results shows that the procedure improves the editing accuracy.
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Risk assessment of particle dispersion and trace element contamination from mine-waste dumps.
Environ Geochem Health
PUBLISHED: 09-05-2014
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In this study, a model to delimit risk zones influenced by atmospheric particle dispersion from mine-waste dumps is developed to assess their influence on the soil and the population according to the concentration of trace elements in the waste. The model is applied to the Riotinto Mine (in SW Spain), which has a long history of mining and heavy land contamination. The waste materials are separated into three clusters according to the mapping, mineralogy, and geochemical classification using cluster analysis. Two of the clusters are composed of slag, fresh pyrite, and roasted pyrite ashes, which may contain high concentrations of trace elements (e.g., >1 % As or >4 % Pb). The average pollution load index (PLI) calculated for As, Cd, Co, Cu, Pb, Tl, and Zn versus the baseline of the regional soil is 19. The other cluster is primarily composed of sterile rocks and ochreous tailings, and the average PLI is 3. The combination of particle dispersion calculated by a Gaussian model, the PLI, the surface area of each waste and the wind direction is used to develop a risk-assessment model with Geographic Information System GIS software. The zone of high risk can affect the agricultural soil and the population in the study area, particularly if mining activity is restarted in the near future. This model can be applied to spatial planning and environmental protection if the information is complemented with atmospheric particulate matter studies.
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Natural selection on coding and noncoding DNA sequences is associated with virulence genes in a plant pathogenic fungus.
Genome Biol Evol
PUBLISHED: 09-04-2014
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Natural selection leaves imprints on DNA, offering the opportunity to identify functionally important regions of the genome. Identifying the genomic regions affected by natural selection within pathogens can aid in the pursuit of effective strategies to control diseases. In this study, we analyzed genome-wide patterns of selection acting on different classes of sequences in a worldwide sample of eight strains of the model plant-pathogenic fungus Colletotrichum graminicola. We found evidence of selective sweeps, balancing selection, and positive selection affecting both protein-coding and noncoding DNA of pathogenicity-related sequences. Genes encoding putative effector proteins and secondary metabolite biosynthetic enzymes show evidence of positive selection acting on the coding sequence, consistent with an Arms Race model of evolution. The 5' untranslated regions (UTRs) of genes coding for effector proteins and genes upregulated during infection show an excess of high-frequency polymorphisms likely the consequence of balancing selection and consistent with the Red Queen hypothesis of evolution acting on these putative regulatory sequences. Based on the findings of this work, we propose that even though adaptive substitutions on coding sequences are important for proteins that interact directly with the host, polymorphisms in the regulatory sequences may confer flexibility of gene expression in the virulence processes of this important plant pathogen.
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Enhanced association for C70 over C60 with a metal complex with corannulene derivate ligands.
Dalton Trans
PUBLISHED: 09-03-2014
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The geometry imposed by the coordination sphere around the metal, together with the choice of the "arms" can be advantageously used to build corannulene-based molecular tweezers, which show great affinities for C60 and C70, as revealed by NMR titration experiments, mass spectroscopy, DFT calculations and the single crystal X-ray structural analysis of the compound C60 ? .
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[Impact of plasma pro-B-type natriuretic peptide amino-terminal and galectin-3 levels on the predictive capacity of the LIPID Clinical Risk Scale in stable coronary disease.]
Clin Investig Arterioscler
PUBLISHED: 08-12-2014
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At present, there is no tool validated by scientific societies for risk stratification of patients with stable coronary artery disease (SCAD). It has been shown that plasma levels of monocyte chemoattractant protein-1 (MCP-1), galectin-3 and pro-B-type natriuretic peptide amino-terminal (NT-proBNP) have prognostic value in this population.
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Galectin-3, a biomarker linking oxidative stress and inflammation with the clinical outcomes of patients with atherothrombosis.
J Am Heart Assoc
PUBLISHED: 08-07-2014
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Galectin-3 (Gal-3) participates in different mechanisms involved in atherothrombosis, such as inflammation, proliferation, or macrophage chemotaxis. Thus, there have been committed intensive efforts to elucidate the function of Gal-3 in cardiovascular (CV) diseases. The role of Gal-3 as a circulating biomarker has been demonstrated in patients with heart failure, but its importance as a biomarker in atherothrombosis is still unknown.
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[Alcohol drinking patterns in Spain: a country in transition].
Rev. Esp. Salud Publica
PUBLISHED: 08-05-2014
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Alcohol consumption in Mediterranean countries is in a transition period. The objective is to describe in the Spanish adult population the pattern of alcohol consumption by major sociodemographic variables.
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Interobserver variance in myelodysplastic syndromes with less than 5 % bone marrow blasts: unilineage vs. multilineage dysplasia and reproducibility of the threshold of 2 % blasts.
Ann. Hematol.
PUBLISHED: 07-27-2014
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Previous studies have shown the reproducibility of the 2008 World Health Organization (WHO) classification in myelodysplastic syndromes (MDS), especially when multilineage dysplasia or excess of blasts are present. However, there are few data regarding the reproducibility of MDS with unilineage dysplasia. The revised International Prognostic Scoring System R-IPSS described two new morphological categories, distinguishing bone marrow (BM) blast cell count between 0-2 % and >2-?
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What are carotenoids signaling? Immunostimulatory effects of dietary vitamin E, but not of carotenoids, in Iberian green lizards.
Naturwissenschaften
PUBLISHED: 07-25-2014
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In spite that carotenoid-based sexual ornaments are one of the most popular research topics in sexual selection of animals, the antioxidant and immunostimulatory role of carotenoids, presumably signaled by these colorful ornaments, is still controversial. It has been suggested that the function of carotenoids might not be as an antioxidant per se, but that colorful carotenoids may indirectly reflect the levels of nonpigmentary antioxidants, such as melatonin or vitamin E. We experimentally fed male Iberian green lizards (Lacerta schreiberi) additional carotenoids or vitamin E alone, or a combination of carotenoids and vitamin E dissolved in soybean oil, whereas a control group only received soybean oil. We examined the effects of the dietary supplementations on phytohaemagglutinin (PHA)-induced skin-swelling immune response and body condition. Lizards that were supplemented with vitamin E alone or a combination of vitamin E and carotenoids had greater immune responses than control lizards, but animals supplemented with carotenoids alone had lower immune responses than lizards supplemented with vitamin E and did not differ from control lizards. These results support the hypothesis that carotenoids in green lizards are not effective as immunostimulants, but that they may be visually signaling the immunostimulatory effects of non-pigmentary vitamin E. In contrast, lizards supplemented with carotenoids alone have higher body condition gains than lizards in the other experimental groups, suggesting that carotenoids may be still important to improve condition.
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Gorgan (Turkmen in Iran) HLA genetics: transplantation, pharmacogenomics and anthropology.
Immunol. Invest.
PUBLISHED: 07-25-2014
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HLA class I and II alleles have been studied in a population from Gorgan (North East Iranian city bordering Turkmenistan). This population is composed of mainly Turkmen who speak Oghuz Turkish language. Comparison of Gorgan people HLA profile has been carried out with about 7984 HLA chromosomes from other worldwide populations; extended haplotypes and three dimension genetic distances have been calculated by using neighbor-joining and correspondence relatedness analyses. Most frequent extended HLA haplotypes show a Siberian/Mediterranean admixture and closest populations are Chuvashians (North Caspian Sea, Russia) and other geographically close populations like Siberian Mansi, Buryats and other Iranians. New extended HLA haplotypes have been found, such as: A*31:01-B*35:01-DRB1*15:01-DQB1*03:01, A*01:01-B*35:01-DRB1*03:01-DQB1*02:01. Relationships of Turkmen with Kurgan (Gorgan) archaeological mounds, Scythians and Sarmatians are discussed. This study is also useful for a future transplantation Gorgan waiting list, Gorgan HLA and disease epidemiology and HLA pharmacogenomics.
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Infrared thermography is useful for ruling out fractures in paediatric emergencies.
Eur. J. Pediatr.
PUBLISHED: 06-05-2014
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Musculoskeletal injuries are a leading cause of paediatric injuries and emergency department visits in Western countries. Diagnosis usually involves radiography, but this exposes children without fractures to unnecessary ionising radiation. We explored whether infrared thermography could provide a viable alternative in trauma cases. We compared radiography and thermal images of 133 children who had been diagnosed with a trauma injury in the emergency unit of a Spanish hospital. As well as the thermal variables in the literature, we introduced a new quantifier variable, the size of the lesion. Decision tree models were built to assess the technique's accuracy in diagnosing whether a bone had been fractured or not. Infrared thermography had a sensitivity of 0.91, a specificity of 0.88 and a negative predictive value of 0.95. The new lesion size variable introduced appeared to be of main importance to the discriminatory power of the method. Conclusion: The high negative predictive value of infrared thermography suggests that it is a promising method for ruling out fractures.
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Complete Chemical Hydrolysis of Cellulose into Fermentable Sugars through Ionic Liquids and Antisolvent Pretreatments.
ChemSusChem
PUBLISHED: 05-26-2014
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This work describes a relatively simple methodology for efficiently deconstructing cellulose into monomeric glucose, which is more easily transformed into a variety of platform molecules for the production of chemicals and fuels. The approach undertaken herein first involves the dissolution of cellulose in an ionic liquid (IL), followed by a second reconstruction step aided by an antisolvent. The regenerated cellulose exhibited strong structural and morphological changes, as revealed by XRD and SEM analyses. These changes dramatically affect the hydrolytic reactivity of cellulose with dilute mineral acids. As a consequence, the glucose yield obtained from the deconstructed-reconstructed cellulose was substantially higher than that achieved through hydrolysis of the starting cellulose. Factors that affect the hydrolysis reaction include the type of cellulose substrate, the type of IL used in pretreatment, and the type of acid used in the hydrolysis step. The best results were obtained by treating cellulose with IL and using phosphotungstic acid (0.067?mol?L(-1) ) as a catalyst at 413?K. Under these conditions, the conversion of cellulose was almost complete (>99?%), with a glucose yield of 87?% after only 5?h of reaction.
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Haplo-Cord Transplantation Using CD34(+) Cells from a Third-Party Donor to Speed Engraftment in High-Risk Patients with Hematologic Disorders.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-18-2014
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Among the strategies to optimize engraftment of cord blood (CB) stem cell transplantation (SCT), single CB with the coinfusion of CD34(+) stem cells from an HLA-mismatched auxiliary donor (haplo-cord) provides a valid alternative for adult patients without a suitable donor. A total of 132 high-risk adult patients with hematological malignancies from 3 Spanish institutions underwent myeloablative haplo-cord SCT. The median age was 37 years and median weight was 70 kg; 37% had active disease. The median number of postprocessing CB total nucleated and CD34(+) cells was 2.4 × 10(7)/kg (interquartile range [IQR], 1.8 to 2.9) and 1.4 × 10(5)/kg (IQR, .9 to 2), respectively. Neutrophil engraftment occurred in a median of 11.5 days (IQR, 10.5 to 16.5) and platelet engraftment at 36 days (IQR, 25.5 to 77). Graft failure was 2% overall and only 9% for CB. Cumulative incidence of acute graft-versus-host disease (GHVD) grades II to IV was 21% and cumulative incidence of chronic GVHD was 21%. Median follow-up was 60 months (range, 3.5 to 163). Overall survival was 43.5%, event-free survival was 38.3%, nonrelapse mortality was 35%, and relapse was 20% at 5 years. Myeloablative haplo-cord SCT results in fast engraftment of neutrophils and platelets, low incidences of acute and chronic GVHD, and favorable long-term outcomes using single CB units with relatively low cell content. Moreover, CB cell dose had no impact on CB engraftment and survival in this study. Therefore, haplo-cord SCT expands donor availability while reducing CB cell dose requirements.
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Relationship between physiological parameters and performance during a half-ironman triathlon in the heat.
J Sports Sci
PUBLISHED: 05-13-2014
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Triathlon is a popular outdoor endurance sport performed under a variety of environmental conditions. The aim of this study was to assess physiological variables before and after a half-ironman triathlon in the heat and to analyse their relationship with performance. Thirty-four well-trained triathletes completed a half-ironman triathlon in a mean dry temperature of 29 ± 3ºC. Before and within 1 min after the end of the race, body mass, core temperature, maximal jump height and venous blood samples were obtained. Mean race time was 315 ± 40 min, with swimming (11 ± 1%), cycling (49 ± 2%) and running (40 ± 3%) representing different amounts of the total race time. At the end of the competition, body mass changed by -3.8 ± 1.6% and the change in body mass correlated positively with race time (r = 0.64; P < 0.001). Core temperature increased from 37.5 ± 0.6ºC to 38.8 ± 0.7ºC (P < 0.001) and post-race core temperature correlated negatively with race time (r = -0.47; P = 0.007). Race time correlated positively with the decrease in jump height (r = 0.38; P = 0.043), post-race serum creatine kinase (r = 0.55; P = 0.001) and myoglobin concentrations (r = 0.39; P = 0.022). In a half-ironman triathlon in the heat, greater reductions in body mass and higher post-competition core temperatures were present in faster triathletes. In contrast, slower triathletes presented higher levels of muscle damage and decreased muscle performance.
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Honest sexual signaling in turtles: experimental evidence of a trade-off between immune response and coloration in red-eared sliders Trachemys scripta elegans.
Naturwissenschaften
PUBLISHED: 05-09-2014
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Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade-off between maintaining the immune system and the elaboration of ornaments. This hypothesis has been experimentally tested in some groups of animals but not in others such as turtles. We experimentally challenged the immune system of female red-eared sliders Trachemys scripta elegans, with a bacterial antigen (lipopolysaccharide (LPS)) without pathogenic effects to explore whether the immune activation affected visual colorful ornaments of the head. The LPS injection altered the reflectance patterns of color ornaments. In comparison to the control animals, the yellow chin stripes of injected animals exhibited (1) reduced brightness, (2) lower long wavelength (>470 nm) reflectance, and (3) lower values for carotenoid chroma. The postorbital patches of injected individuals also showed reduced very long wavelength (>570 nm) reflectance but did not change in carotenoid chroma. Thus, experimental turtles showed darker and less "yellowish" chin stripes and less "reddish" postorbital patches at the end of the experiment, whereas control turtles did not change their coloration. This is the first experimental evidence supporting the existence of a trade-off between the immune system and the expression of visual ornaments in turtles. We suggest that this trade-off may allow turtles to honestly signal individual quality via characteristics of coloration, which may have an important role in intersexual selection processes.
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Changes in the gene expression profiles of the brains of male European eels (Anguilla anguilla) during sexual maturation.
BMC Genomics
PUBLISHED: 04-03-2014
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The vertebrate brain plays a critical role in the regulation of sexual maturation and reproduction by integrating environmental information with developmental and endocrine status. The European eel Anguilla anguilla is an important species in which to better understand the neuroendocrine factors that control reproduction because it is an endangered species, has a complex life cycle that includes two extreme long distance migrations with both freshwater and seawater stages and because it occupies a key position within the teleost phylogeny. At present, mature eels have never been caught in the wild and little is known about most aspects of reproduction in A. anguilla. The goal of this study was to identify genes that may be involved in sexual maturation in experimentally matured eels. For this, we used microarrays to compare the gene expression profiles of sexually mature to immature males.
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Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation.
Eur. J. Haematol.
PUBLISHED: 04-02-2014
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Allogeneic stem cell transplantation (allo-SCT) has become the treatment of choice in patients with intermediate-risk and high-risk acute myeloid leukemia (AML). The quality of response to treatment, assessed in terms of detection of minimal residual disease (MRD), has been consistently associated with prognosis and clinical outcome in patients with AML. The aim of the present study was to evaluate the prognostic impact of analyzing MRD in bone marrow using 4-color multiparametric flow cytometry (MFC) in 29 patients with AML before and after allo-SCT. Eighteen patients who were shown to be MRD-negative [?0.1% leukemia-associated immunophenotypes (LAIPs)] by MFC at transplantation and underwent allo-SCT had lower rates of relapse (15% vs. 66%, P = 0.045), better overall 1-yr survival (83% vs. 52%, P = 0.021) and a lower cumulative incidence of relapse (P = 0.032) than patients who were MRD-positive (>0.1%). All post-transplant MRD-positive patients underwent a therapeutic intervention after transplant (tapering of immunosuppression, donor lymphocyte infusion, or re-transplant) with the intention of preventing relapse. Disease was controlled and MRD disappeared in five of these patients. Disease recurred in the other seven patients. We can conclude that follow-up with MFC for the detection of MRD in AML before and after SCT is useful for predicting relapse. In the post-transplant setting, monitoring of MRD by MFC could be a key preemptive intervention.
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Condition-dependent chemosignals in reproductive behavior of lizards.
Horm Behav
PUBLISHED: 03-28-2014
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Many lizards have diverse glands that produce chemosignals used in intraspecific communication and that can have reproductive consequences. For example, information in chemosignals of male lizards can be used in intrasexual competition to identify and assess the fighting potential or dominance status of rival males either indirectly through territorial scent-marks or during agonistic encounters. Moreover, females of several lizard species "prefer" to establish or spend more time on areas scent-marked by males with compounds signaling a better health or body condition or a higher genetic compatibility, which can have consequences for their mating success and inter-sexual selection processes. We review here recent studies that suggest that the information content of chemosignals of lizards may be reliable because several physiological and endocrine processes would regulate the proportions of chemical compounds available for gland secretions. Because chemosignals are produced by the organism or come from the diet, they should reflect physiological changes, such as different hormonal levels (e.g. testosterone or corticosterone) or different health states (e.g. parasitic infections, immune response), and reflect the quality of the diet of an individual. More importantly, some compounds that may function as chemosignals also have other important functions in the organism (e.g. as antioxidants or regulating the immune system), so there could be trade-offs between allocating these compounds to attending physiological needs or to produce costly sexual "chemical ornaments". All these factors may contribute to maintain chemosignals as condition-dependent sexual signals, which can inform conspecifics on the characteristics and state of the sender and allow making behavioral decisions with reproductive consequences. To understand the evolution of chemical secretions of lizards as sexual signals and their relevance in reproduction, future studies should examine what information the signals are carrying, the physiological processes that can maintain the reliability of the message and how diverse behavioral responses to chemosignals may influence reproductive success.
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Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer.
Tumour Biol.
PUBLISHED: 03-27-2014
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Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an increasingly recognized role in tumour biology. The aim of this study was to explore the role of DUSP6 expression in the prognosis of human non-small cell lung cancer (NSCLC). DUSP6 expression levels were evaluated by real-time quantitative reverse transcription polymerase chain reaction (PCR) in 60 NSCLC samples from patients who underwent pulmonary resection at 12 de Octubre University Hospital. We performed a statistical analysis to investigate the correlation of DUSP6 expression and the clinical outcomes. We found that 66.7 % of the tumour samples show the downregulation of DUSP6 at the messenger RNA (mRNA) levels compared to benign epithelial lung tissues and 55 % of them show at least twofold downregulation of DUSP6 gene expression. Patients were classified into three groups according to their DUSP6 expression levels and those with very low levels (at least twofold downregulation) had the worst outcomes. Using the value of twice below the mean value in benign epithelial lung tissue as a cutoff, the overall survival of patients with very low DUSP6 levels was significantly lower than that in the rest of patients (31.9?±?18.8 months vs. not reached, P?=?0.049). This was most pronounced in adenocarcinoma histology and high-stage tumour samples. Our results suggest that DUSP6 gene expression in tumour samples may be a prognostic marker in NSCLC.
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Do North Atlantic eels show parallel patterns of spatially varying selection?
BMC Evol. Biol.
PUBLISHED: 03-27-2014
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The two North Atlantic eel species, the European and the American eel, represent an ideal system in which to study parallel selection patterns due to their sister species status and the presence of ongoing gene flow. A panel of 80 coding-gene SNPs previously analyzed in American eel was used to genotype European eel individuals (glass eels) from 8 sampling locations across the species distribution. We tested for single-generation signatures of spatially varying selection in European eel by searching for elevated genetic differentiation using FST-based outlier tests and by testing for significant associations between allele frequencies and environmental variables.
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Hemodynamic changes in patients undergoing carotid endarterectomy under cervical block and general anesthesia.
Ann Vasc Surg
PUBLISHED: 03-19-2014
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The objective of this study was to assess differences in hemodynamic stability for patients undergoing carotid endarterectomy (CEA) under general anesthesia (GA) as compared with cervical block anesthesia (CBA).
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Patterns of Alcohol Consumption in the Older Population of Spain, 2008-2010.
J Acad Nutr Diet
PUBLISHED: 03-11-2014
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Older adults are a growing segment of the European population and alcohol is an important cause of disease burden; thus, it is noteworthy that little information is available on alcohol intake among older adults in Europe.
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Crk adaptors negatively regulate actin polymerization in pedestals formed by enteropathogenic Escherichia coli (EPEC) by binding to Tir effector.
PLoS Pathog.
PUBLISHED: 03-01-2014
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Infections by enteropathogenic Escherichia coli (EPEC) cause diarrhea linked to high infant mortality in developing countries. EPEC adheres to epithelial cells and induces the formation of actin pedestals. Actin polymerization is driven fundamentally through signaling mediated by Tir bacterial effector protein, which inserts in the plasma membrane of the infected cell. Tir binds Nck adaptor proteins, which in turn recruit and activate N-WASP, a ubiquitous member of the Wiskott-Aldrich syndrome family of proteins. N-WASP activates the Arp2/3 complex to promote actin polymerization. Other proteins aside from components of the Tir-Nck-N-WASP pathway are recruited to the pedestals but their functions are unknown. Here we investigate the function of two alternatively spliced isoforms of Crk adaptors (CrkI/II) and the paralog protein CrkL during pedestal formation by EPEC. We found that the Crk isoforms act as redundant inhibitors of pedestal formation. The SH2 domain of CrkII and CrkL binds to phosphorylated tyrosine 474 of Tir and competes with Nck to bind Tir, preventing its recruitment to pedestals and thereby inhibiting actin polymerization. EPEC infection induces phosphorylation of the major regulatory tyrosine in CrkII and CrkL, possibly preventing the SH2 domain of these proteins from interacting with Tir. Phosphorylated CrkII and CrkL proteins localize specifically to the plasma membrane in contact with EPEC. Our study uncovers a novel role for Crk adaptors at pedestals, opening a new perspective in how these oncoproteins regulate actin polymerization.
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A phase I/II, multiple-dose, dose-escalation study of siltuximab, an anti-interleukin-6 monoclonal antibody, in patients with advanced solid tumors.
Clin. Cancer Res.
PUBLISHED: 02-21-2014
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This phase I/II study evaluated safety, efficacy, and pharmacokinetics of escalating, multiple doses of siltuximab, a chimeric anti-interleukin (IL)-6 monoclonal antibody derived from a new Chinese hamster ovary (CHO) cell line in patients with advanced/refractory solid tumors.
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Assessment of SOX11 expression in routine lymphoma tissue sections: characterization of new monoclonal antibodies for diagnosis of mantle cell lymphoma.
Am. J. Surg. Pathol.
PUBLISHED: 02-08-2014
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The diagnosis of mantle cell lymphoma (MCL) can be difficult, especially when no t(11;14) translocation and cyclin D1 overexpression can be detected. In such cases, the transcription factor SOX11 represents an important diagnostic marker, as it is expressed in most MCLs and, in particular, in all cyclin D1-negative MCLs reported so far. A reliable anti-SOX11 antibody is therefore a very useful tool for routine diagnosis. Here, we characterize the new monoclonal anti-SOX11 antibodies, suitable for Western blot assay and immunohistochemistry (IHC) on formalin-fixed paraffin-embedded tissue; we tested them on a large series of primary lymphoid tumors and compared these results with those of other routinely used antibodies. Moreover, we show that IHC results depend on transcription levels of SOX11, which suggests that posttranscriptional and posttranslational modifications do not significantly affect cutoff levels for IHC detection of SOX11.
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Label-free quantitative proteomic analysis of human plasma-derived microvesicles to find protein signatures of abdominal aortic aneurysms.
Proteomics Clin Appl
PUBLISHED: 01-31-2014
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To find potential biomarkers of abdominal aortic aneurysms (AAA), we performed a differential proteomic study based on human plasma-derived microvesicles.
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Evaluation of novel trans-sulfonamide platinum complexes against tumor cell lines.
Eur J Med Chem
PUBLISHED: 01-30-2014
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Platinum-based drugs, mainly cisplatin, are employed for the treatment of solid malignancies. However, cisplatin treatment often results in the development of chemoresistance, leading to therapeutic failure. Here, the antitumor activity of different trans-sulfonamide platinum complexes in a panel of human cell lines is presented. The cytotoxicity profiles and cell cycle analyses of these platinum sulfonamide complexes were different from those of cisplatin. These studies showed that complex 2b with cyclohexyldiamine and dansyl moieties had the best antitumoral activities.
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Captive breeding programs based on family groups in polyploid sturgeons.
PLoS ONE
PUBLISHED: 01-01-2014
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In species with long life cycles and discontinuous availability of individuals to reproduction, implementing a long-term captive breeding program can be difficult or impossible. In such cases, managing diversity among familiar groups instead of individuals could become a suitable approach to avoid inbreeding and increase the possibility to accomplish a breeding scheme. This is the case of several sturgeon species including the Adriatic sturgeon, whose recovery depends on the management of a few captive stocks directly descended from the same group of wild parents. In the present study, relatedness among 445 potential breeders was inferred with a novel software for pedigree reconstruction in tetraploids ("BreedingSturgeons"). This information was used to plan a breeding scheme considering familiar groups as breeding units and identifying mating priorities. A two-step strategy is proposed: a short-term breeding program, relying on the 13 remaining F0 individuals of certain wild origin; and a long-term plan based on F1 families. Simulations to evaluate the loss of alleles in the F2 generation under different pairing strategies and assess the number of individuals to breed, costs and logistical aquaculture constraints were performed. The strategy proposed is transferable to the several other tetraploid sturgeon species on the brink of extinction.
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Is the physician's behavior in dyslipidemia diagnosis in accordance with guidelines? Cross-sectional ESCARVAL study.
PLoS ONE
PUBLISHED: 01-01-2014
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Clinical inertia has been defined as mistakes by the physician in starting or intensifying treatment when indicated. Inertia, therefore, can affect other stages in the healthcare process, like diagnosis. The diagnosis of dyslipidemia requires ?2 high lipid values, but inappropriate behavior in the diagnosis of dyslipidemia has only previously been analyzed using just total cholesterol (TC).
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Transcriptome characterization by RNA sequencing identifies a major molecular and clinical subdivision in chronic lymphocytic leukemia.
Genome Res.
PUBLISHED: 11-21-2013
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Chronic lymphocytic leukemia (CLL) has heterogeneous clinical and biological behavior. Whole-genome and -exome sequencing has contributed to the characterization of the mutational spectrum of the disease, but the underlying transcriptional profile is still poorly understood. We have performed deep RNA sequencing in different subpopulations of normal B-lymphocytes and CLL cells from a cohort of 98 patients, and characterized the CLL transcriptional landscape with unprecedented resolution. We detected thousands of transcriptional elements differentially expressed between the CLL and normal B cells, including protein-coding genes, noncoding RNAs, and pseudogenes. Transposable elements are globally derepressed in CLL cells. In addition, two thousand genes-most of which are not differentially expressed-exhibit CLL-specific splicing patterns. Genes involved in metabolic pathways showed higher expression in CLL, while genes related to spliceosome, proteasome, and ribosome were among the most down-regulated in CLL. Clustering of the CLL samples according to RNA-seq derived gene expression levels unveiled two robust molecular subgroups, C1 and C2. C1/C2 subgroups and the mutational status of the immunoglobulin heavy variable (IGHV) region were the only independent variables in predicting time to treatment in a multivariate analysis with main clinico-biological features. This subdivision was validated in an independent cohort of patients monitored through DNA microarrays. Further analysis shows that B-cell receptor (BCR) activation in the microenvironment of the lymph node may be at the origin of the C1/C2 differences.
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Sexually dichromatic coloration reflects size and immunocompetence in female Spanish terrapins, Mauremys leprosa.
Naturwissenschaften
PUBLISHED: 09-26-2013
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Many studies have shown the importance of colorful ornamentation in mate choosiness or intrasexual conflict. However, research on color ornaments has focused mainly on birds, lizards or fish, but remains practically unknown in other animal groups such as turtles. In addition, female ornaments and their relation with sexual selection also remain almost unknown. Here, we measured the coloration of the shell and the limb stripes of male and female Spanish terrapins Mauremys leprosa and explored the existence of sexual dichromatism and the relation of color characteristics with body size and health state estimated from the immune response to the injection of an antigen (phytohaemagglutinin test). Our results showed that shell coloration, which could be constrained by natural selection to be cryptic, changed with body size, but did not differ between sexes. In contrast, females had brighter and less ultraviolet-saturated and more orange-saturated limb stripes than males. In females, interindividual variation in limb stripe coloration was related with body size and immune response suggesting that this coloration may inform honestly about multiple traits that could be important in sexual selection. In contrast, coloration of limb stripes of males was duller than in females, and was not related with any trait suggesting that coloration is not important in sexual selection for males.
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Usefulness of a Combination of Monocyte Chemoattractant Protein-1, Galectin-3, and N-Terminal Probrain Natriuretic Peptide to Predict Cardiovascular Events in Patients With Coronary Artery Disease.
Am. J. Cardiol.
PUBLISHED: 09-05-2013
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Patients with coronary artery disease may develop not only ischemic events but also heart failure and death due to previous myocardial damage. The purpose of this study was to test the prognostic value of a panel of plasma biomarkers related to vascular (monocyte chemoattractant protein-1 [MCP-1] and soluble tumor necrosis factor-like weak inducer of apoptosis) and myocardial damage (galectin-3, N-terminal fragment of brain natriuretic peptide [NT-proBNP], and neutrophil gelatinase-associated lipocalin) in 706 patients with chronic coronary artery disease followed for 2.2 ± 0.99 years. Secondary outcomes were the incidence of acute ischemic events (ST elevation myocardial infarction, non-ST elevation acute coronary syndrome, stroke, or transient ischemic attack) and death or heart failure. The primary outcome was the combination of the secondary outcomes. Cox proportional hazards model was used for analysis. Fifty-three patients developed acute ischemic events. Increasing MCP-1 plasma levels (p = 0.002), age, and body mass index predicted this outcome independently. Thirty-three patients developed death and/or heart failure. Galectin-3 (p = 0.007), NT-proBNP plasma levels (p = 0.004), hypertension, glomerular filtration rate, and the use of nitrates and anticoagulants were associated with this outcome independently. The development of the primary outcome was predicted independently by MCP-1 (p <0.001), NT-proBNP (p = 0.005), and galectin-3 (p = 0.019); hypertension; atrial fibrillation; and treatment with nitrates. Every biomarker with a value above the median increased the risk of developing this outcome by 1.832 (95% confidence interval 1.356 to 2.474, p <0.001). High-sensitivity C-reactive protein and lipid levels were not associated with any outcome. In conclusion, increasing MCP-1, galectin-3, and NT-proBNP plasma levels are associated with a greater incidence of cardiovascular events.
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Chemical compounds from the preanal gland secretions of the male tree agama (Acanthocercus atricollis) (fam. Agamidae).
Z. Naturforsch., C, J. Biosci.
PUBLISHED: 08-09-2013
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Chemical signals have an important role in the reproductive behaviour of many lizards. However, the compounds secreted by their femoral or preanal glands, which may be used as sexual signals, are mainly known for lizard species within the Scleroglossa clade, whereas compounds in secretions of lizards within the Iguania clade are much less studied. Based on mass spectra, obtained by GC-MS, we found 60 lipophilic compounds in preanal gland secretions of the male tree agama (Acanthocercus atricollis) (fam. Agamidae), including steroids (mainly cholesterol, cholest-3-ene, and some of their derivatives), fatty acids ranging between n-C12 and n-C18 (mainly hexadecanoic and octadecenoic acids), ketones from n-C17 to n-C25, and other minor compounds, such as tocopherol, squalene, waxy esters, and furanones. We compare the compounds found with those present in other lizard species and discuss their potential function in social behaviour.
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Medicinal plants of Chile: evaluation of their anti-Trypanosoma cruzi activity.
Z. Naturforsch., C, J. Biosci.
PUBLISHED: 08-09-2013
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The extracts of several plants of Central Chile exhibited anti-Trypanosoma cruzi trypomastigotes activity. Most active extracts were those obtained from Podanthus ovatifolius, Berberis microphylla, Kageneckia oblonga, and Drimys winteri. The active extract of Drimys winteri (IC50 51.2 microg/mL) was purified and three drimane sesquiterpenes were obtained: polygodial, drimenol, and isodrimenin. Isodrimenin and drimenol were found to be active against the trypomastigote form of T. cruzi with IC50 values of 27.9 and 25.1 microM, respectively.
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A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
Hum. Mol. Genet.
PUBLISHED: 06-04-2013
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Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
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Could mitochondrial dysfunction be a differentiating marker between chronic fatigue syndrome and fibromyalgia?
Antioxid. Redox Signal.
PUBLISHED: 05-29-2013
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Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are complex and serious illnesses that affect approximately 2.5% and 5% of the general population worldwide, respectively. The etiology is unknown; however, recent studies suggest that mitochondrial dysfunction has been involved in the pathophysiology of both conditions. We have investigated the possible association between mitochondrial biogenesis and oxidative stress in patients with CFS and FM. We studied 23 CFS patients, 20 FM patients, and 15 healthy controls. Peripheral blood mononuclear cell showed decreased levels of Coenzyme Q10 from CFS patients (p<0.001 compared with controls) and from FM subjects (p<0.001 compared with controls) and ATP levels for CFS patients (p<0.001 compared with controls) and for FM subjects (p<0.001 compared with controls). On the contrary, CFS/FM patients had significantly increased levels of lipid peroxidation, respectively (p<0.001 for both CFS and FM patients with regard to controls) that were indicative of oxidative stress-induced damage. Mitochondrial citrate synthase activity was significantly lower in FM patients (p<0.001) and, however, in CFS, it resulted in similar levels than controls. Mitochondrial DNA content (mtDNA/gDNA ratio) was normal in CFS and reduced in FM patients versus healthy controls, respectively (p<0.001). Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A, mitochondrial by immunoblotting were significantly lower in FM patients (p<0.001) and were normal in CFS subjects compared with healthy controls. These data lead to the hypothesis that mitochondrial dysfunction-dependent events could be a marker of differentiation between CFS and FM, indicating the mitochondria as a new potential therapeutic target for these conditions.
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Aberrant DNA methylation profile of chronic and transformed classic Philadelphia-negative myeloproliferative neoplasms.
Haematologica
PUBLISHED: 05-28-2013
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Most DNA methylation studies in classic Philadelphia-negative myeloproliferative neoplasms have been performed on a gene-by-gene basis. Therefore, a more comprehensive methylation profiling is needed to study the implications of this epigenetic marker in myeloproliferative neoplasms. Here, we have analyzed 71 chronic (24 polycythemia vera, 23 essential thrombocythemia and 24 primary myelofibrosis) and 13 transformed myeloproliferative neoplasms using genome-wide DNA methylation arrays. The three types of chronic Philadelphia-negative myeloproliferative neoplasms showed a similar aberrant DNA methylation pattern when compared to control samples. Differentially methylated regions were enriched in a gene network centered on the NF-?B pathway, indicating that they may be involved in the pathogenesis of these diseases. In the case of transformed myeloproliferative neoplasms, we detected an increased number of differentially methylated regions with respect to chronic myeloproliferative neoplasms. Interestingly, these genes were enriched in a list of differentially methylated regions in primary acute myeloid leukemia and in a gene network centered around the IFN pathway. Our results suggest that alterations in the DNA methylation landscape play an important role in the pathogenesis and leukemic transformation of myeloproliferative neoplasms. The therapeutic modulation of epigenetically-deregulated pathways may allow us to design targeted therapies for these patients.
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Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.
BMC Med. Genet.
PUBLISHED: 05-08-2013
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Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition.
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Enhanced labelling on alcoholic drinks: reviewing the evidence to guide alcohol policy.
Eur J Public Health
PUBLISHED: 05-08-2013
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Consumer and public health organizations have called for better labelling on alcoholic drinks. However, there is a lack of consensus about the best elements to include. This review summarizes alcohol labelling policy worldwide and examines available evidence to support enhanced labelling.
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microRNA expression profiles identify subtypes of mantle cell lymphoma with different clinicobiological characteristics.
Clin. Cancer Res.
PUBLISHED: 05-02-2013
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microRNAs (miRNA) are posttranscriptional gene regulators that may be useful as diagnostic and/or prognostic biomarkers. We aim to study the expression profiles of a high number of miRNAs and their relationship with clinicopathologic and biologic relevant features in leukemic mantle cell lymphomas (MCL).
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HLA in Georgians (Caucasus) and their relationship with Eastern Mediterraneans.
Mol. Biol. Rep.
PUBLISHED: 04-12-2013
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HLA-A, -B, -DQB1, and -DRB1 typing has been performed in a sample of Georgian population (South Caucasus). Allele frequencies, neighbour joining and correspondence relatedness analyses and extended HLA haplotypes have been obtained with comparison with other Middle East and Mediterranean populations. Our Georgian sample tends to be genetically related in these analyses with Eastern Mediterraneans and Middle East people. This is important for future regional transplant programs, and Georgian HLA and disease epidemiology and pharmacogenomics.
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Lack of association between the protein tyrosine phosphatase non-receptor type 22 R263Q and R620W functional genetic variants and endogenous non-anterior uveitis.
Mol. Vis.
PUBLISHED: 03-18-2013
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Endogenous uveitis is a major cause of visual loss mediated by the immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell receptor (TCR) signaling. Two independent functional missense single nucleotide polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been associated with different autoimmune disorders. We aimed to analyze for the first time the influence of these PTPN22 genetic variants on endogenous non-anterior uveitis susceptibility.
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The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma.
Histopathology
PUBLISHED: 03-05-2013
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Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression.
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[Pd(Fmes)2(tmeda)]: a case of intermittent C-H···F-C hydrogen-bond interaction in solution.
Chemistry
PUBLISHED: 02-01-2013
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The X-ray structure of the title compound [Pd(Fmes)2 (tmeda)] (Fmes=2,4,6-tris(trifluoromethyl)phenyl; tmeda=N,N,N,N-tetramethylethylenediamine) shows the existence of uncommon C?H???F?C hydrogen-bond interactions between methyl groups of the TMEDA ligand and ortho-CF3 groups of the Fmes ligand. The (19) F?NMR spectra in CD2 Cl2 at very low temperature (157?K) detect restricted rotation for the two ortho-CF3 groups involved in hydrogen bonding, which might suggest that the hydrogen bond is responsible for this hindrance to rotation. However, a theoretical study of the hydrogen-bond energy shows that it is too weak (about 7?kJ?mol(-1) ) to account for the rotational barrier observed (?H(?) =26.8?kJ?mol(-1) ), and it is the steric hindrance associated with the puckering of the TMEDA ligand that should be held responsible for most of the rotational barrier. At higher temperatures the rotation becomes fast, which requires that the hydrogen bond is continuously being split up and restored and exists only intermittently, following the pulse of the conformational changes of TMEDA.
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DICER1, DROSHA and miRNAs in patients with non-small cell lung cancer: implications for outcomes and histologic classification.
Carcinogenesis
PUBLISHED: 01-24-2013
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The clinical and functional significance of RNA-interference machinery in lung cancer is poorly understood. Besides, microRNAs (miRNA) have the potential to serve both as biomarkers and therapeutic agents, by personalizing diagnosis and therapy. In this study, we investigated whether the expression levels of DICER1 and DROSHA, components of the RNA-interference machinery, can predict survival, and whether the miRNA expression profiles can differentiate histologic subtypes in non-small cell lung cancer (NSCLC). Levels of DICER1, DROSHA and five different miRNAs were measured in NSCLC specimens (N = 115) by qRT-PCR assay and correlated with clinical outcomes. Low expression of DROSHA was associated with an increased median survival (154.2 versus 39.8 months, P = 0.016). Also, high DROSHA expression was associated with decreased median survival in the following subgroups: adenocarcinoma (P = 0.011), grade III tumors (P = 0.038) and low-stage patients (P = 0.014). In multivariate analyses, we found two independent predictors of reduced disease-specific survival: high DROSHA expression [hazards ratio = 2.24; P = 0.04] and advanced tumor stage (hazards ratio = 1.29, P = 0.02). In general, the overall tumor miRNA expression was downregulated in our cohort compared with normal tissues. Expression levels of hsa-let-7a (P = 0.005) and miR-16 (P = 0.003) miRNA were significantly higher in squamous cell carcinoma than in adenocarcinoma samples. This study supports the value of the expression profiling of the components of the miRNA-processing machinery in the prognosis of NSCLC patients, especially DROSHA expression levels. In addition, differential expression of miRNAs, such as hsa-let-7a and miR-16 may be helpful tools in the histologic subclassification of NSCLC.
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The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis.
PLoS ONE
PUBLISHED: 01-23-2013
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Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P ?=?1.34×10(-8), OR ?=?1.22, CI 95% ?=?1.14-1.30; rs2004640: P ?=?4.60×10(-7), OR ?=?0.84, CI 95% ?=?0.78-0.90; rs10488631: P ?=?7.53×10(-20), OR ?=?1.63, CI 95% ?=?1.47-1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P ?=?0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P ?=?9.04×10(-22), OR ?=?1.75, CI 95% ?=?1.56-1.97) better explained the observed association (likelihood P-value ?=?1.48×10(-4)), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific.
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Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma.
Clin. Cancer Res.
PUBLISHED: 01-21-2013
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Signaling through the fibroblast growth factor (FGF) pathway may account for tumor resistance to antiangiogenic therapies targeting the VEGF pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial.
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SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma.
Blood
PUBLISHED: 01-15-2013
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Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms whose pathogenesis is not fully understood. The neural transcription factor SOX11 is overexpressed in most MCL but is not detected in other mature B-cell lymphomas or normal lymphoid cells. The specific expression of SOX11 in MCL suggests that it may be an important element in the development of this tumor, but its potential function is not known. Here, we show that SOX11 promotes tumor growth in a MCL-xenotransplant mouse model. Using chromatin immunoprecipitation microarray analysis combined with gene expression profiling upon SOX11 knockdown, we identify target genes and transcriptional programs regulated by SOX11 including the block of mature B-cell differentiation, modulation of cell cycle, apoptosis, and stem cell development. PAX5 emerges as one of the major SOX11 direct targets. SOX11 silencing downregulates PAX5, induces BLIMP1 expression, and promotes the shift from a mature B cell into the initial plasmacytic differentiation phenotype in both primary tumor cells and an in vitro model. Our results suggest that SOX11 contributes to tumor development by altering the terminal B-cell differentiation program of MCL and provide perspectives that may have clinical implications in the diagnosis and design of new therapeutic strategies.
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Prevalence of black stain and associated risk factors in preschool Spanish children.
Pediatr Int
PUBLISHED: 01-13-2013
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In pediatric clinical practice, it is common to be asked about the presence of black stains on teeth in children and teenagers. According to controversial etiology, it is known to be related to a low rate of caries. The aim of this study was to determine the prevalence of black stain and associated risk factors in Spanish preschool children.
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Responses of female rock lizards to multiple scent marks of males: effects of male age, male density and scent over-marking.
Behav. Processes
PUBLISHED: 01-05-2013
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Scent-marked substrates may inform conspecifics on the characteristics of territorial males. Scent-marks of male Carpetan rock lizards (Iberolacerta cyreni) affect space use of females, which by selecting an area may increase the probability of mating with the male that has scent-marked that area. However, males do not hold exclusive territories, and scent-marks of different individual males are often together. This may provide complex information from multiple sources on the social structure. Here, we examined female preference in response to scent marks of various males and combinations in a laboratory experiment. Females preferred areas scent-marked by territorial old males against those scent-marked by young satellite-sneaker males. This reflected the known preference of females for mating with old males. In a second experiment, females preferred areas scent-marked by two males to areas of similar size marked by a single male. This may increase the probability of obtaining multiple copulations with different males, which may favour sperm competition and cryptic female choice, or may be a way to avoid infertile males. Finally, when we experimentally over-marked the scent-marks of an old male with scent-marks of a young male, females did not avoid, nor prefer, the over-marked area, suggesting that the quality of the old male may override the presence of a satellite male. We suggest that, irrespective of the causes underlying why a female selects a scent-marked area, this strategy may affect her reproductive success, which may have the same evolutionary consequences that "direct" mate choice decisions of other animals.
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Selecting deep brain stimulation or infusion therapies in advanced Parkinsons disease: an evidence-based review.
J. Neurol.
PUBLISHED: 01-05-2013
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Motor complications in Parkinsons disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.
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No Evidence of Association between Common Autoimmunity STAT4 and IL23R Risk Polymorphisms and Non-Anterior Uveitis.
PLoS ONE
PUBLISHED: 01-01-2013
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STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes.
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Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis.
PLoS ONE
PUBLISHED: 01-01-2013
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Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes.
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A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations.
Hum. Mol. Genet.
PUBLISHED: 11-10-2011
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A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P(MH)= 1.92 × 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P(MH)= 4.84 × 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P(?2) = 2.82 × 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P(MH)= 2.82 × 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
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Feeding status and basking requirements of freshwater turtles in an invasion context.
Physiol. Behav.
PUBLISHED: 10-19-2011
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Thermoregulatory behavior and feeding status are strongly related in ectotherms. A trade-off between maintenance of energy balance and digestion efficiency has been recently proposed to affect thermoregulation in these animals. On the other hand, competition for basking sites has been described between Iberian turtles and the introduced red-eared slider (Trachemys scripta elegans). T. scripta negatively interferes with basking behavior of native turtles and benefits from a greater capacity to retain body heat, which may likely result in thermoregulatory advantages for the introduced sliders. Consequently, complex effects and alterations in metabolic rates of native turtles might derive from a deficient basking behavior. We compared the basking requirements of the endangered native Spanish terrapin (Mauremys leprosa) and those of the introduced red-eared slider, analyzing the upper set point temperature (USP) (defined as the body temperature at which basking ceased) of both native and introduced turtles, under feeding and fasting conditions. We found higher values of USP in the native species, and a reduction of this temperature associated with food deprivation in the two turtle species. This adjustment of thermoregulatory behavior to the nutritional status found in freshwater turtles suggests that ectotherms benefit from metabolic depression as an adaptive mechanism to preserve energy during periods of fasting. However, a reduction in metabolic rates induced by competition with sliders might lead M. leprosa to a prolonged deficiency of their physiological functions, thus incurring increased predation risk and health costs, and ultimately favoring the recession of this native species in Mediterranean habitats.
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Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region.
J. Rheumatol.
PUBLISHED: 10-01-2011
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The PTPN22 rs2476601 genetic variant has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. Some reports suggest that this single-nucleotide polymorphism (SNP) may not be the only causal variant in the region of PTPN22. Our aim was to identify new independent RA-associated common gene variants in the PTPN22 region.
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Chemical constituents of the femoral gland secretions of male tegu lizards (Tupinambis merianae) (Family teiidae).
Z. Naturforsch., C, J. Biosci.
PUBLISHED: 09-29-2011
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In spite of the importance of chemical signals (pheromones) in the reproductive behaviour of lizards, the chemical compounds secreted by their femoral glands, which may be used as sexual signals, are only known for a few lizard species. Based on mass spectra, obtained by GC-MS, we found 49 lipophilic compounds in femoral gland secretions of male tegu lizards (Tupinambis merianae) (fam. Teiidae), including a very high proportion of carboxylic acids and their esters ranging between n-C8 and n-C20 (mainly octadecanoic and 9,12-octadecadienoic acids), with much less proportions of steroids, tocopherol, aldehydes, and squalene. We discuss the potential function of these compounds in secretions, and compare the compounds found here with those documented for other lizard species.
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Proteomic analysis of polymorphonuclear neutrophils identifies catalase as a novel biomarker of abdominal aortic aneurysm: potential implication of oxidative stress in abdominal aortic aneurysm progression.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 09-22-2011
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Polymorphonuclear neutrophils (PMNs) play a main role in abdominal aortic aneurysm (AAA) progression. We have analyzed circulating PMNs isolated from AAA patients and controls by a proteomic approach to identify proteins potentially involved in AAA pathogenesis.
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The social nature of chronic noncommunicable diseases and how to tackle them through communication technology, training, and outreach.
J Health Commun
PUBLISHED: 09-16-2011
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As world leaders prepare for the United Nations High Level Meeting on Noncommunicable Diseases, to take place in September 2011, international organizations, nongovernmental organizations, and economic and business fora have created new alliances and initiatives to accelerate research, advocacy, and political commitment. This article argues that the time is propitious to reflect on the social nature of the most common behavioral noncommunicable disease determinants, including tobacco and alcohol use, physical inactivity, and unhealthy diet. Evidence is presented related to the fact that these diseases are profoundly rooted in social and community ties and points to the need for a modern communication strategy to serve as a linchpin of any successful action to address these public health threats. Several proposals, aimed at promoting health literacy, strengthening health workforce skills, capturing the power of new media and technologies, and targeting vulnerable groups, are discussed.
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Reconciling deep calibration and demographic history: bayesian inference of post glacial colonization patterns in Carcinus aestuarii (Nardo, 1847) and C. maenas (Linnaeus, 1758).
PLoS ONE
PUBLISHED: 09-11-2011
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A precise inference of past demographic histories including dating of demographic events using bayesian methods can only be achieved with the use of appropriate molecular rates and evolutionary models. Using a set of 596 mitochondrial cytochrome c oxidase I (COI) sequences of two sister species of European green crabs of the genus Carcinus (C. maenas and C. aestuarii), our study shows how chronologies of past evolutionary events change significantly with the application of revised molecular rates that incorporate biogeographic events for calibration and appropriate demographic priors. A clear signal of demographic expansion was found for both species, dated between 10,000 and 20,000 years ago, which places the expansions events in a time frame following the Last Glacial Maximum (LGM). In the case of C. aestuarii, a population expansion was only inferred for the Adriatic-Ionian, suggestive of a colonization event following the flooding of the Adriatic Sea (18,000 years ago). For C. maenas, the demographic expansion inferred for the continental populations of West and North Europe might result from a northward recolonization from a southern refugium when the ice sheet retreated after the LGM. Collectively, our results highlight the importance of using adequate calibrations and demographic priors in order to avoid considerable overestimates of evolutionary time scales.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.