JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Microsecond folding and domain motions of a spider silk protein structural switch.
J. Am. Chem. Soc.
PUBLISHED: 11-11-2014
Show Abstract
Hide Abstract
Web spiders rapidly assemble protein monomers, so-called spidroins, into extraordinarily tough silk fibers. The process involves the pH-triggered self-association of the spidroin N-terminal domain (NTD), which contains a structural switch connecting spidroins to super-molecules. Single-molecule spectroscopy can detect conformational heterogeneity that is hidden to conventional methods, but motions of the NTD are beyond the resolution limit. Here, we engineered probes for 1-nm conformational changes based on the phenomenon of fluorescence quenching by photoinduced electron transfer into the isolated NTD of a spidroin from the nursery web spider Euprosthenops australis. Correlation analysis of single-molecule fluorescence fluctuations uncovered site-dependent nano-to-microsecond movement of secondary and tertiary structure. Kinetic amplitudes were most pronounced for helices that are part of the association interface and where structural studies show large displacements between monomeric and dimeric conformations. A single tryptophan at the center of the five-helix bundle toggled conformations in ~100 µs and in a pH-dependent manner. Equilibrium denaturation and temperature-jump relaxation experiments revealed cooperative and ultrafast folding in only 60 µs. We deduced a free-energy surface that exhibits native-state ruggedness with apparently similar barrier heights to folding and native motions. Observed equilibrium dynamics within the domain suggest a conformational selection mechanism in the rapid association of spidroins through their NTDs during silk synthesis by web spiders.
Related JoVE Video
Knowledge and Awareness of Human Papillomavirus (HPV), Cervical Cancer and HPV Vaccine among Women in Two Distinct Nepali Communities.
Asian Pac. J. Cancer Prev.
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
This study assessed human papillomavirus (HPV), cervical cancer, and HPV vaccine knowledge and awareness among women in two sub-populations in Nepal - Khokana, a traditional Newari village in the Lalitpur District about eight kilometers south of Kathmandu, and Sanphebagar, a village development committee within Achham District in rural Far-Western Nepal.
Related JoVE Video
Timing of Antiretroviral Therapy Initiation in a Nationally Representative Sample of HIV-Infected Adults Receiving Medical Care in the United States.
AIDS Patient Care STDS
PUBLISHED: 10-21-2014
Show Abstract
Hide Abstract
Abstract Early antiretroviral therapy (ART) initiation reduces the risk of disease progression and HIV transmission, but data on time from HIV care entry to ART initiation are lacking. Using data from the Medical Monitoring Project (MMP), a population-based probability sample of HIV-infected adults receiving medical care in the United States, we assessed time from care entry to ART initiation among persons diagnosed May 2004-April 2009 and used multivariable Cox proportional-hazards models to identify factors associated with time to ART initiation. Among 1094 MMP participants, 83.9% reported initiating ART, with median time to ART initiation of 10 months. In multivariable models, blacks compared to whites [hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.70-0.98], persons without continuous health insurance (HR 0.82; CI 0.70-0.97), heterosexual women and men who have sex with men compared to heterosexual men (HR 0.66; CI 0.51-0.85 and HR 0.71; CI 0.60-0.84, respectively), and persons without AIDS at care entry (HR 0.37; CI 0.31-0.43) had significantly longer times to ART initiation. Overall, time to ART initiation was suboptimal by current standards and significant disparities were noted among certain subgroups. Efforts to encourage prompt ART initiation should address delays among those without health insurance and among certain sociodemographic subgroups.
Related JoVE Video
Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of neuropeptide y signaling, and hypertension in adult life.
Hypertension
PUBLISHED: 09-29-2014
Show Abstract
Hide Abstract
Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (?3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1-5 and 6-10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ?50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (?9 months; 139±3 versus 126±3 mm Hg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease.
Related JoVE Video
The effect of liraglutide on endothelial function in patients with type 2 diabetes.
Diab Vasc Dis Res
PUBLISHED: 09-11-2014
Show Abstract
Hide Abstract
This single-centre, 12-week, double-blind, placebo-controlled trial assessed how the human glucagon-like-peptide 1 analogue liraglutide impacted endothelial function in adult patients (n?=?49) with type 2 diabetes and no overt cardiovascular disease. Patients were randomized to liraglutide, placebo or glimepiride. At baseline and Week 12, venous occlusion plethysmography was used to measure forearm blood flow (FBF) in response to acetylcholine (ACh) and sodium nitroprusside (SNP) before and after l-N(G)-monomethyl arginine (L-NMMA) infusion. At Week 12, ACh-mediated FBF increased with liraglutide and decreased with placebo; however, the between-treatment difference was not significant (p?=?0.055). Inhibition of ACh-mediated FBF after L-NMMA infusion increased with liraglutide and decreased with placebo; this between-treatment difference was also not significant (p?=?0.149). No change in FBF was observed with SNP. Liraglutide did not significantly impact endothelium-dependent vasodilation after 12?weeks; however, additional investigations looking at the effect of liraglutide on endothelial function in alternative vasculature and during the postprandial period are warranted.
Related JoVE Video
Endothelial-mesenchymal transition in normal human esophageal endothelial cells cocultured with esophageal adenocarcinoma cells: role of IL-1? and TGF-?2.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 08-27-2014
Show Abstract
Hide Abstract
Endothelial-mesenchymal transition (EndoMT) has been recognized as a key determinant of tumor microenvironment in cancer progression and metastasis. Endothelial cells undergoing EndoMT lose their endothelial markers, acquire the mesenchymal phenotype, and become more invasive with increased migratory abilities. Early stages of esophageal adenocarcinoma (EAC) are characterized by strong microvasculature whose impact in tumor progression remains undefined. Our aim was to determine the role of EndoMT in EAC by investigating the impact of tumor cells on normal primary human esophageal microvascular endothelial cells (HEMEC). HEMEC were either cocultured with OE33 adenocarcinoma cells or treated with IL-1? and transforming growth factor-?2 (TGF-?2) for indicated periods and analyzed for EndoMT-associated changes by real-time PCR, Western blotting, immunofluorescence staining, and functional assays. Additionally, human EAC tissues were investigated for detection of EndoMT-like cells. Our results demonstrate an increased expression of mesenchymal markers [fibroblast-specific protein 1 (FSP1), collagen1?2, vimentin, ?-smooth muscle actin (?-SMA), and Snail], decreased expression of endothelial markers [CD31, von Willebrand factor VIII (vWF), and VE-cadherin], and elevated migration ability in HEMEC following coculture with OE33 cells. The EndoMT-related changes were inhibited by IL-1? and TGF-?2 gene silencing in OE33 cells. Recombinant IL-1? and TGF-?2 induced EndoMT in HEMEC. Although the level of VEGF expression was elevated in EndoMT cells, the angiogenic property of these cells was diminished. In vivo, by immunostaining EndoMT-like cells were detected at the invasive front of EAC. Our findings underscore a significant role for EndoMT in EAC and provide new insights into the mechanisms and significance of EndoMT in the context of tumor progression.
Related JoVE Video
A bioinspired omniphobic surface coating on medical devices prevents thrombosis and biofouling.
Nat. Biotechnol.
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
Thrombosis and biofouling of extracorporeal circuits and indwelling medical devices cause significant morbidity and mortality worldwide. We apply a bioinspired, omniphobic coating to tubing and catheters and show that it completely repels blood and suppresses biofilm formation. The coating is a covalently tethered, flexible molecular layer of perfluorocarbon, which holds a thin liquid film of medical-grade perfluorocarbon on the surface. This coating prevents fibrin attachment, reduces platelet adhesion and activation, suppresses biofilm formation and is stable under blood flow in vitro. Surface-coated medical-grade tubing and catheters, assembled into arteriovenous shunts and implanted in pigs, remain patent for at least 8 h without anticoagulation. This surface-coating technology could reduce the use of anticoagulants in patients and help to prevent thrombotic occlusion and biofouling of medical devices.
Related JoVE Video
Spectroscopy and dynamics of the HOCO radical: insights into the OH + CO ? H + CO2 reaction.
Phys Chem Chem Phys
PUBLISHED: 08-08-2014
Show Abstract
Hide Abstract
After more than forty years of scrutiny, crucial new details regarding the elementary reaction OH + CO ? H + CO2 are still emerging from experimental and theoretical studies of the HOCO radical intermediate. In this perspective, previous studies of this elementary reaction and the structure and energetics of the HOCO radical will be briefly reviewed. Particular attention will be paid to the experimental techniques used in our laboratory to prepare excited HOCO radicals by both photodetachment and dissociative photodetachment of HOCO(-). These experiments directly probe the dynamics occurring on the ground and excited states of the HOCO radical, and are sensitive to both direct and tunneling-induced dissociation. Photoelectron-photofragment coincidence experiments on HOCO(-) in particular have been used to study tunneling from the HOCO well to form H + CO2 products. In addition, new experimental insights into the OH + CO entrance channel for the reaction will be presented. These studies have provided a number of constraints on the potential energy surface for this system from an energetic and dynamical perspective, and have helped spur a renewed effort to characterize the global potential energy surface and reaction dynamics of this fundamental chemical reaction. Outstanding questions and new directions for future work on the HOCO radical will be discussed.
Related JoVE Video
Associations of census-tract poverty with subsite-specific colorectal cancer incidence rates and stage of disease at diagnosis in the United States.
J Cancer Epidemiol
PUBLISHED: 08-03-2014
Show Abstract
Hide Abstract
Background. It remains unclear whether neighborhood poverty contributes to differences in subsite-specific colorectal cancer (CRC) incidence. We examined associations between census-tract poverty and CRC incidence and stage by anatomic subsite and race/ethnicity. Methods. CRC cases diagnosed between 2005 and 2009 from 15 states and Los Angeles County (N = 278,097) were assigned to 1 of 4 groups based on census-tract poverty. Age-adjusted and stage-specific CRC incidence rates (IRs) and incidence rate ratios (IRRs) were calculated. Analyses were stratified by subsite (proximal, distal, and rectum), sex, race/ethnicity, and poverty. Results. Compared to the lowest poverty areas, CRC IRs were significantly higher in the most impoverished areas for men (IRR = 1.14 95% CI 1.12-1.17) and women (IRR = 1.06 95% CI 1.05-1.08). Rate differences between high and low poverty were strongest for distal colon (male IRR = 1.24 95% CI 1.20-1.28; female IRR = 1.14 95% CI 1.10-1.18) and weakest for proximal colon. These rate differences were significant for non-Hispanic whites and blacks and for Asian/Pacific Islander men. Inverse associations between poverty and IRs of all CRC and proximal colon were found for Hispanics. Late-to-early stage CRC IRRs increased monotonically with increasing poverty for all race/ethnicity groups. Conclusion. There are differences in subsite-specific CRC incidence by poverty, but associations were moderated by race/ethnicity.
Related JoVE Video
Identification of host genes that affect acquisition of an integrative and conjugative element in Bacillus subtilis.
Mol. Microbiol.
PUBLISHED: 07-26-2014
Show Abstract
Hide Abstract
Conjugation, a major type of horizontal gene transfer in bacteria, involves transfer of DNA from a donor to a recipient using donor-encoded conjugation machinery. Using a high-throughput screen (Tn-seq), we identified genes in recipients that contribute to acquisition of the integrative and conjugative element ICEBs1 by Bacillus subtilis. We found that null mutations in some genes caused an increase, and others a decrease in conjugation efficiency. Some mutations affected conjugation only when present in recipients. Other mutations affected conjugation when present in donors or recipients. Most of the genes identified are known or predicted to affect the cell envelope. Several encode enzymes involved in phospholipid biosynthesis and one encodes a homologue of penicillin-binding proteins. Two of the genes identified also affected conjugation of Tn916, indicating that their roles in conjugation may be general. We did not identify any genes in recipients that were essential for ICEBs1 conjugation, indicating that if there are such genes, then these are either essential for cell growth or redundant. Our results indicate that acquisition of ICEBs1, and perhaps other conjugative elements, is robust and not easily avoided by mutation and that several membrane-related functions affect the efficiency of conjugation.
Related JoVE Video
Acute cyclooxygenase inhibition does not alter muscle sympathetic nerve activity or forearm vasodilator responsiveness in lean and obese adults.
Physiol Rep
PUBLISHED: 07-16-2014
Show Abstract
Hide Abstract
Obesity is often characterized by chronic inflammation that may contribute to increased cardiovascular risk via sympathoexcitation and decreased vasodilator responsiveness. We hypothesized that obese individuals would have greater indices of inflammation compared with lean controls, and that cyclooxygenase inhibition using ibuprofen would reduce muscle sympathetic nerve activity (MSNA) and increase forearm blood flow in these subjects. We measured MSNA, inflammatory biomarkers (C-reactive protein [CRP] and Interleukin-6 [IL-6]), and forearm vasodilator responses to brachial artery acetylcholine and sodium nitroprusside in 13 men and women (7 lean; 6 obese) on two separate study days: control (CON) and after 800 mg ibuprofen (IBU). CRP (1.7 ± 0.4 vs. 0.6 ± 0.3 mg/L; P < 0.05) and IL-6 (4.1 ± 1.5 vs. 1.0 ± 0.1pg/mL; P < 0.05) were higher in the obese group during CON and tended to decrease with IBU (IL-6: P < 0.05; CRP: P = 0.14). MSNA was not different between groups during CON (26 ± 4 bursts/100 heart beats (lean) versus 26 ± 4 bursts/100 heart beats (obese); P = 0.50) or IBU (25 ± 4 bursts/100 heart beats (lean) versus 30 ± 5 bursts/100 heart beats (obese); P = 0.25), and was not altered by IBU. Forearm vasodilator responses were unaffected by IBU in both groups. In summary, an acute dose of ibuprofen did not alter sympathetic nerve activity or forearm blood flow responses in healthy obese individuals, suggesting that the cyclooxygenase pathway is not a major contributor to these variables in this group.
Related JoVE Video
Novel microscale approaches for easy, rapid determination of protein stability in academic and commercial settings.
Biochim. Biophys. Acta
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
Chemical denaturant titrations can be used to accurately determine protein stability. However, data acquisition is typically labour intensive, has low throughput and is difficult to automate. These factors, combined with high protein consumption, have limited the adoption of chemical denaturant titrations in commercial settings. Thermal denaturation assays can be automated, sometimes with very high throughput. However, thermal denaturation assays are incompatible with proteins that aggregate at high temperatures and large extrapolation of stability parameters to physiological temperatures can introduce significant uncertainties. We used capillary-based instruments to measure chemical denaturant titrations by intrinsic fluorescence and microscale thermophoresis. This allowed higher throughput, consumed several hundred-fold less protein than conventional, cuvette-based methods yet maintained the high quality of the conventional approaches. We also established efficient strategies for automated, direct determination of protein stability at a range of temperatures via chemical denaturation, which has utility for characterising stability for proteins that are difficult to purify in high yield. This approach may also have merit for proteins that irreversibly denature or aggregate in classical thermal denaturation assays. We also developed procedures for affinity ranking of protein-ligand interactions from ligand-induced changes in chemical denaturation data, and proved the principle for this by correctly ranking the affinity of previously unreported peptide-PDZ domain interactions. The increased throughput, automation and low protein consumption of protein stability determinations afforded by using capillary-based methods to measure denaturant titrations, can help to revolutionise protein research. We believe that the strategies reported are likely to find wide applications in academia, biotherapeutic formulation and drug discovery programmes.
Related JoVE Video
Alterations in the cholinergic system of brain stem neurons in a mouse model of Rett syndrome.
Am. J. Physiol., Cell Physiol.
PUBLISHED: 07-09-2014
Show Abstract
Hide Abstract
Rett syndrome is an autism-spectrum disorder resulting from mutations to the X-linked gene, methyl-CpG binding protein 2 (MeCP2), which causes abnormalities in many systems. It is possible that the body may develop certain compensatory mechanisms to alleviate the abnormalities. The norepinephrine system originating mainly in the locus coeruleus (LC) is defective in Rett syndrome and Mecp2-null mice. LC neurons are subject to modulation by GABA, glutamate, and acetylcholine (ACh), providing an ideal system to test the compensatory hypothesis. Here we show evidence for potential compensatory modulation of LC neurons by post- and presynaptic ACh inputs. We found that the postsynaptic currents of nicotinic ACh receptors (nAChR) were smaller in amplitude and longer in decay time in the Mecp2-null mice than in the wild type. Single-cell PCR analysis showed a decrease in the expression of ?3-, ?4-, ?7-, and ?3-subunits and an increase in the ?5- and ?6-subunits in the mutant mice. The ?5-subunit was present in many of the LC neurons with slow-decay nAChR currents. The nicotinic modulation of spontaneous GABAA-ergic inhibitory postsynaptic currents in LC neurons was enhanced in Mecp2-null mice. In contrast, the nAChR manipulation of glutamatergic input to LC neurons was unaffected in both groups of mice. Our current-clamp studies showed that the modulation of LC neurons by ACh input was reduced moderately in Mecp2-null mice, despite the major decrease in nAChR currents, suggesting possible compensatory processes may take place, thus reducing the defects to a lesser extent in LC neurons.
Related JoVE Video
Related JoVE Video
Empirical tests of harvest-induced body-size evolution along a geographic gradient in Australian macropods.
J Anim Ecol
PUBLISHED: 07-04-2014
Show Abstract
Hide Abstract
Life-history theory predicts the progressive dwarfing of animal populations that are subjected to chronic mortality stress, but the evolutionary impact of harvesting terrestrial herbivores has seldom been tested. In Australia, marsupials of the genus Macropus (kangaroos and wallabies) are subjected to size-selective commercial harvesting. Mathematical modelling suggests that harvest quotas (c. 10-20% of population estimates annually) could be driving body-size evolution in these species. We tested this hypothesis for three harvested macropod species with continental-scale distributions. To do so, we measured more than 2000 macropod skulls sourced from wildlife collections spanning the last 130 years. We analysed these data using spatial Bayesian models that controlled for the age and sex of specimens as well as environmental drivers and island effects. We found no evidence for the hypothesized decline in body size for any species; rather, models that fit trend terms supported minor body size increases over time. This apparently counterintuitive result is consistent with reduced mortality due to a depauperate predator guild and increased primary productivity of grassland vegetation following European settlement in Australia. Spatial patterns in macropod body size supported the heat dissipation limit and productivity hypotheses proposed to explain geographic body-size variation (i.e. skull size increased with decreasing summer maximum temperature and increasing rainfall, respectively). There is no empirical evidence that size-selective harvesting has driven the evolution of smaller body size in Australian macropods. Bayesian models are appropriate for investigating the long-term impact of human harvesting because they can impute missing data, fit nonlinear growth models and account for non-random spatial sampling inherent in wildlife collections.
Related JoVE Video
Comparison of tensile strength of fibrin glue and suture in microflap closure.
Laryngoscope
PUBLISHED: 06-24-2014
Show Abstract
Hide Abstract
Suture closure and fibrin glue placement have been advocated as alternatives to healing by secondary intention. The aim of this study was to examine the tensile strength of these microflap closure techniques.
Related JoVE Video
Microhydration of contact ion pairs in M(2+)OH(-)(H2O)(n=1-5) (M = Mg, Ca) clusters: spectral manifestations of a mobile proton defect in the first hydration shell.
J Phys Chem A
PUBLISHED: 06-20-2014
Show Abstract
Hide Abstract
Vibrational predissociation spectra of D2-"tagged" Mg(2+)OH(-)(H2O)n=1-6 and Ca(2+)OH(-)(H2O)n=1-5 clusters are reported to explore how the M(2+)OH(-) contact ion pairs respond to stepwise formation of the first hydration shell. In both cases, the hydroxide stretching frequency is found to red-shift strongly starting with addition of the third water molecule, quickly becoming indistinguishable from nonbonded OH groups associated with solvent water molecules by n = 5. A remarkably broad feature centered around 3200 cm(-1) and spanning up to ?1000 cm(-1) appears for the n ? 4 clusters that we assign to a single-donor ionic hydrogen bond between a proximal first solvent shell water molecule and the embedded hydroxide ion. The extreme broadening is rationalized with a theoretical model that evaluates the range of local OH stretching frequencies predicted for the heavy particle configurations available in the zero-point vibrational wave function describing the low-frequency modes. The implication of this treatment is that extreme broadening in the vibrational spectrum need not arise from thermal fluctuations in the ion ensemble, but can rather reflect combination bands based on the OH stretching fundamental that involve many quanta of low-frequency modes whose displacements strongly modulate the OH stretching frequency.
Related JoVE Video
Behavioral and clinical characteristics of persons receiving medical care for HIV infection - Medical Monitoring Project, United States, 2009.
MMWR Surveill Summ
PUBLISHED: 06-19-2014
Show Abstract
Hide Abstract
As of December 31, 2009, an estimated 864,748 persons were living with human immunodeficiency virus (HIV) infection in the 50 U.S. states, the District of Columbia, and six U.S.-dependent areas. Whereas HIV surveillance programs in the United States collect information about persons with a diagnosis of HIV infection, supplemental surveillance systems collect in-depth information about the behavioral and clinical characteristics of persons receiving outpatient medical care for HIV infection. These data are needed to reduce HIV-related morbidity and mortality and HIV transmission.
Related JoVE Video
Communication: He-tagged vibrational spectra of the SarGlyH? and H?(H?O)(2,3) ions: quantifying tag effects in cryogenic ion vibrational predissociation (CIVP) spectroscopy.
J Chem Phys
PUBLISHED: 06-16-2014
Show Abstract
Hide Abstract
To assess the degree to which more perturbative, but widely used "tag" species (Ar, H2, Ne) affect the intrinsic band patterns of the isolated ions, we describe the extension of mass-selective, cryogenic ion vibrational spectroscopy to the very weakly interacting helium complexes of three archetypal ions: the dipeptide SarGlyH(+) and the small protonated water clusters: H(+)(H2O)(2,3), including the H5O2(+) "Zundel" ion. He adducts were generated in a 4.5 K octopole ion trap interfaced to a double-focusing, tandem time-of-flight photofragmentation mass spectrometer to record mass-selected vibrational predissociation spectra. The H2 tag-induced shift (relative to that by He) on the tag-bound NH stretch of the SarGlyH(+) spectrum is quite small (12 cm(-1)), while the effect on the floppy H5O2(+) ion is more dramatic (125 cm(-1)) in going from Ar (or H2) to Ne. The shifts from Ne to He, on the other hand, while quantitatively significant (maximum of 10 cm(-1)), display the same basic H5O2(+) band structure, indicating that the He-tagged H5O2(+) spectrum accurately represents the delocalized nature of the vibrational zero-point level. Interestingly, the He-tagged spectrum of H(+)(H2O)3 reveals the location of the non-bonded OH group on the central H3O(+) ion to fall between the collective non-bonded OH stretches on the flanking water molecules in a position typically associated with a neutral OH group.
Related JoVE Video
Novel calmodulin mutations associated with congenital arrhythmia susceptibility.
Circ Cardiovasc Genet
PUBLISHED: 06-10-2014
Show Abstract
Hide Abstract
Genetic predisposition to life-threatening cardiac arrhythmias such as congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations.
Related JoVE Video
FAD binding, cobinamide binding and active site communication in the corrin reductase (CobR).
Biosci. Rep.
PUBLISHED: 06-10-2014
Show Abstract
Hide Abstract
Adenosylcobalamin, the coenzyme form of vitamin B12, is one Nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. The aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from Co(II) to Co(I) before adenosylation can take place. A corrin reductase (CobR) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. Herein, we reveal how Brucella melitensis CobR binds its coenzyme FAD (flavin dinucleotide) and we also show that the enzyme can bind a corrin substrate consistent with its role in reduction of the cobalt of the corrin ring. Stopped-flow kinetics and EPR reveal a mechanistic asymmetry in CobR dimer that provides a potential link between the two electron reduction by NADH to the single electron reduction of Co(II) to Co(I).
Related JoVE Video
Ex utero intrapartum treatment of fetal micrognathia.
Mil Med
PUBLISHED: 06-06-2014
Show Abstract
Hide Abstract
Ex utero intrapartum treatment (EXIT) procedures have emerged as a viable option for potentially life-saving procedures in fetuses with predicted airway compromise at birth. The ability to maintain maternal-fetal uteroplacental perfusion allows for prolonged procedures in a stable fetal hemodynamic environment thereby avoiding neonatal hypoxemia or sequelae of an emergent tracheostomy.
Related JoVE Video
Vibrational spectral signature of the proton defect in the three-dimensional H?(H?O)?? cluster.
Science
PUBLISHED: 05-31-2014
Show Abstract
Hide Abstract
The way in which a three-dimensional network of water molecules accommodates an excess proton is hard to discern from the broad vibrational spectra of dilute acids. The sharper bands displayed by cold gas-phase clusters, H(+)(H2O)n, are therefore useful because they encode the network-dependent speciation of the proton defect and yet are small enough to be accurately treated with electronic structure theory. We identified the previously elusive spectral signature of the proton defect in the three-dimensional cage structure adopted by the particularly stable H(+)(H2O)21 cluster. Cryogenically cooling the ion and tagging it with loosely bound deuterium (D2) enabled detection of its vibrational spectrum over the 600 to 4000 cm(-1) range. The excess charge is consistent with a tricoordinated H3O(+) moiety embedded on the surface of a clathrate-like cage.
Related JoVE Video
Bacterial actin MreB forms antiparallel double filaments.
Elife
PUBLISHED: 05-21-2014
Show Abstract
Hide Abstract
Filaments of all actin-like proteins known to date are assembled from pairs of protofilaments that are arranged in a parallel fashion, generating polarity. In this study, we show that the prokaryotic actin homologue MreB forms pairs of protofilaments that adopt an antiparallel arrangement in vitro and in vivo. We provide an atomic view of antiparallel protofilaments of Caulobacter MreB as apparent from crystal structures. We show that a protofilament doublet is essential for MreB's function in cell shape maintenance and demonstrate by in vivo site-specific cross-linking the antiparallel orientation of MreB protofilaments in E. coli. 3D cryo-EM shows that pairs of protofilaments of Caulobacter MreB tightly bind to membranes. Crystal structures of different nucleotide and polymerisation states of Caulobacter MreB reveal conserved conformational changes accompanying antiparallel filament formation. Finally, the antimicrobial agents A22/MP265 are shown to bind close to the bound nucleotide of MreB, presumably preventing nucleotide hydrolysis and destabilising double protofilaments.DOI: http://dx.doi.org/10.7554/eLife.02634.001.
Related JoVE Video
An ecological regime shift resulting from disrupted predator-prey interactions in Holocene Australia.
Ecology
PUBLISHED: 05-09-2014
Show Abstract
Hide Abstract
The mass extinction events during human prehistory are striking examples of ecological regime shifts, the causes of which are still hotly debated. In Australia, human arrival approximately 50 thousand years ago was associated with the continental-scale extinction of numerous marsupial megafauna species and a permanent change in vegetation structure. An alternative stable state persisted until a second regime shift occurred during the late Holocene, when the largest two remaining marsupial carnivores, the thylacine and devil, disappeared from mainland Australia. These extinctions have been widely attributed to the human-assisted invasion of a competing predator, the dingo. In this unusual case, the simultaneous effects of human "intensification" (population growth and technological advances) and climate change (particularly increased ENSO variability) have been largely overlooked. We developed a dynamic model system capable of simulating the complex interactions between the main predators (humans, thylacines, devils, dingoes) and their marsupial prey (macropods), which we coupled with reconstructions of human population growth and climate change for late-Holocene Australia. Because the strength of important interspecific interactions cannot be estimated directly, we used detailed scenario testing and sensitivity analysis to identify robust model outcomes and investigate competing explanations for the Holocene regime shift. This approach identified human intensification as the most probable cause, while also demonstrating the potential importance of synergies with the effects of climate change. Our models indicate that the prehistoric impact of humans on Australian mammals was not limited to the late Pleistocene (i.e., the megafaunal extinctions) but extended into the late Holocene.
Related JoVE Video
Effect of ?2-adrenergic receptor polymorphisms on epinephrine and exercise-stimulated lipolysis in humans.
Physiol Rep
PUBLISHED: 05-01-2014
Show Abstract
Hide Abstract
The ?2-adrenergic system is an important regulator of human adipose tissue lipolysis. Polymorphisms that result in amino acid substitutions in the ?2-adrenergic receptor have been reported to alter lipolysis. We hypothesized that variations in the amino acid at position 16 of the ?2-adrenergic receptor would result in different lipolytic responses to intravenous epinephrine and exercise. 17 volunteers homozygous for glycine at position 16 (Gly/Gly, nine female) and 16 volunteers homozygous for arginine at position 16 (Arg/Arg, eight female) of the ?2-adrenergic receptor participated in this study. On one study day participants received infusions of epinephrine at submaximal (5 ng kg(-1) min(-1)) and maximal (40 ng kg(-1) min(-1)) lipolytic doses. The other study day volunteers bicycled for 90 min at 50-60% of maximum oxygen consumption (VO2max). [9,10-(3)H] Palmitate was infused both days to measure free fatty acid - palmitate kinetics. Oxygen consumption was measured using indirect calorimetry. Palmitate release rates in response to epinephrine and exercise were not different in the Gly/Gly and Arg/Arg participants. The only statistically significant difference we observed was a lesser ?VO2 in Arg/Arg volunteers in response to the submaximal epinephrine infusion. The polymorphisms resulting in Arg/Arg and Gly/Gly at position 16 of the ?2-adrenergic receptor do not result in clinically meaningful differences in lipolysis responses to epinephrine or submaximal exercise.
Related JoVE Video
Pleomorphic Rhabdomyosarcoma Presenting as a Hypopharyngeal Mass.
Head Neck
PUBLISHED: 04-30-2014
Show Abstract
Hide Abstract
Background: Rhabdomyosarcoma is a rare malignancy derived from skeletal muscle with approximately 40% of cases involving the head and neck. The pleomorphic variant, however, most commonly occurs in the extremities and has never, to our knowledge, been described in the pharynx. Methods: A 46-year-old male with no significant medical history presented to the emergency department complaining of hemoptysis. A CT scan of the head and neck revealed a hypopharyngeal mass originally favored to be a benign process. Results: Operative endoscopy revealed a previously unseen mucosal ulceration, and subsequent biopsy resulted in the final diagnosis of pleomorphic rhabdomyosarcoma. Conclusions: Although quite rare, rhabdomyosarcoma should be considered in the differential diagnosis of a hypopharyngeal mass. Head Neck, 2014.
Related JoVE Video
Association between seven single nucleotide polymorphisms involved in inflammation and proteolysis and abdominal aortic aneurysm.
J. Vasc. Surg.
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
Abdominal aortic aneurysm (AAA) formation involves an inflammatory and proteolytic process. Previous studies suggest that AAA is a multifactorial disease with a strong genetic background. This study evaluated the role of seven important functional single nucleotide polymorphisms (SNPs) in AAA.
Related JoVE Video
Structure of the SAS-6 cartwheel hub from Leishmania major.
Elife
PUBLISHED: 03-06-2014
Show Abstract
Hide Abstract
Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella. They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6, but whether SAS-6 self-assembly can dictate cartwheel and thereby centriole symmetry is unclear. Here we show that Leishmania major SAS-6 crystallizes as a 9-fold symmetric cartwheel and provide the X-ray structure of this assembly at a resolution of 3.5 Å. We furthermore demonstrate that oligomerization of Leishmania SAS-6 can be inhibited by a small molecule in vitro and provide indications for its binding site. Our results firmly establish that SAS-6 can impose cartwheel symmetry on its own and indicate how this process might occur mechanistically in vivo. Importantly, our data also provide a proof-of-principle that inhibition of SAS-6 oligomerization by small molecules is feasible. DOI: http://dx.doi.org/10.7554/eLife.01812.001.
Related JoVE Video
Toll-like receptor-5 agonist Entolimod broadens the therapeutic window of 5-fluorouracil by reducing its toxicity to normal tissues in mice.
Oncotarget
PUBLISHED: 03-04-2014
Show Abstract
Hide Abstract
Myelosuppression and gastrointestinal damage are common side effects of cancer treatment limiting efficacy of DNA-damaging chemotherapeutic drugs. The Toll-like receptor 5 (TLR5) agonist Entolimod has demonstrated efficacy in mitigating damage to hematopoietic and gastrointestinal tissues caused by radiation. Here, using 5-Fluorouracil (5-FU) treated mice as a model of chemotherapy-induced side effects, we demonstrated significant reduction in the severity of 5-FU-induced morbidity and increased survival accompanied by the improved integrity of intestinal tissue and stimulated the restoration of hematopoiesis. Entolimod-stimulated IL-6 production was essential for Entolimod's ability to rescue mice from death caused by doses of 5-FU associated with hematopoietic failure. In contrast, IL-6 induction was not necessary for protection and restoration of drug-damaged gastrointestinal tissue by Entolimod. In a syngeneic mouse CT26 colon adenocarcinoma model, Entolimod reduced the systemic toxicity of 5-FU, but did not reduce its antitumor efficacy indicating that the protective effect of Entolimod was selective for normal, non-tumor, tissues. These results suggest that Entolimod has clinical potential to broaden the therapeutic window of genotoxic anticancer drugs by reducing their associated hematopoietic and gastrointestinal toxicities.
Related JoVE Video
Preliminary Investigation of the Treatment of Equine Medial Femoral Condylar Subchondral Cystic Lesions With a Transcondylar Screw.
Vet Surg
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
To determine if medial femoral condylar (MFC) subchondral cystic lesions (SCL) causing lameness will demonstrate radiographic evidence of healing and lameness reduction after placement of a transcondylar screw in lag fashion.
Related JoVE Video
Divergent regulation of ryanodine receptor 2 calcium release channels by arrhythmogenic human calmodulin missense mutants.
Circ. Res.
PUBLISHED: 02-21-2014
Show Abstract
Hide Abstract
Calmodulin (CaM) mutations are associated with an autosomal dominant syndrome of ventricular arrhythmia and sudden death that can present with divergent clinical features of catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome (LQTS). CaM binds to and inhibits ryanodine receptor (RyR2) Ca release channels in the heart, but whether arrhythmogenic CaM mutants alter RyR2 function is not known.
Related JoVE Video
Identification of a conserved branched RNA structure that functions as a factor-independent terminator.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-18-2014
Show Abstract
Hide Abstract
Anti-Q is a small RNA encoded on pCF10, an antibiotic resistance plasmid of Enterococcus faecalis, which negatively regulates conjugation of the plasmid. In this study we sought to understand how Anti-Q is generated relative to larger transcripts of the same operon. We found that Anti-Q folds into a branched structure that functions as a factor-independent terminator. In vitro and in vivo, termination is dependent on the integrity of this structure as well as the presence of a 3' polyuridine tract, but is not dependent on other downstream sequences. In vitro, terminated transcripts are released from RNA polymerase after synthesis. In vivo, a mutant with reduced termination efficiency demonstrated loss of tight control of conjugation function. A search of bacterial genomes revealed the presence of sequences that encode Anti-Q-like RNA structures. In vitro and in vivo experiments demonstrated that one of these functions as a terminator. This work reveals a previously unappreciated flexibility in the structure of factor-independent terminators and identifies a mechanism for generation of functional small RNAs; it should also inform annotation of bacterial sequence features, such as terminators, functional sRNAs, and operons.
Related JoVE Video
Experiments in no-impact control of dingoes: comment on Allen et al. 2013.
Front. Zool.
PUBLISHED: 02-13-2014
Show Abstract
Hide Abstract
There has been much recent debate in Australia over whether lethal control of dingoes incurs environmental costs, particularly by allowing increase of populations of mesopredators such as red foxes and feral cats. Allen et al. (2013) claim to show in their recent study that suppression of dingo activity by poison baiting does not lead to mesopredator release, because mesopredators are also suppressed by poisoning. We show that this claim is not supported by the data and analysis reported in Allen et al.'s paper.
Related JoVE Video
Comparative safety of periablation anticoagulation strategies for atrial fibrillation: data from a large multicenter study.
Pacing Clin Electrophysiol
PUBLISHED: 02-09-2014
Show Abstract
Hide Abstract
There are a variety of periprocedural anticoagulation strategies for atrial fibrillation (AF) ablation, including the use of dabigatran. It is unclear which strategy is superior.
Related JoVE Video
Differing impact of a major biogeographic barrier on genetic structure in two large kangaroos from the monsoon tropics of Northern Australia.
Ecol Evol
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Tropical savannas cover 20-30% of the world's land surface and exhibit high levels of regional endemism, but the evolutionary histories of their biota remain poorly studied. The most extensive and unmodified tropical savannas occur in Northern Australia, and recent studies suggest this region supports high levels of previously undetected genetic diversity. To examine the importance of barriers to gene flow and the environmental history of Northern Australia in influencing patterns of diversity, we investigated the phylogeography of two closely related, large, vagile macropodid marsupials, the antilopine wallaroo (Macropus antilopinus; n?=?78), and the common wallaroo (Macropus robustus; n?=?21). Both species are widespread across the tropical savannas of Australia except across the Carpentarian Barrier (CB) where there is a break in the distribution of M.?antilopinus. We determined sequence variation in the hypervariable Domain I of the mitochondrial DNA control region and genotyped individuals at 12 polymorphic microsatellite loci to assess the historical and contemporary influence of the CB on these species. Surprisingly, we detected only limited differentiation between the disjunct Northern Territory and QueenslandM.?antilopinus populations. In contrast, the continuously distributedM.?robustus was highly divergent across the CB. Although unexpected, these contrasting responses appear related to minor differences in species biology. Our results suggest that vicariance may not explain well the phylogeographic patterns in Australia's dynamic monsoonal environments. This is because Quaternary environmental changes in this region have been complex, and diverse individual species' biologies have resulted in less predictable and idiosyncratic responses.
Related JoVE Video
The relationship between area poverty rate and site-specific cancer incidence in the United States.
Cancer
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
The relationship between socioeconomic status and cancer incidence in the United States has not traditionally been a focus of population-based cancer surveillance systems.
Related JoVE Video
Mouse SLX4 is a tumor suppressor that stimulates the activity of the nuclease XPF-ERCC1 in DNA crosslink repair.
Mol. Cell
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
SLX4 binds to three nucleases (XPF-ERCC1, MUS81-EME1, and SLX1), and its deficiency leads to genomic instability, sensitivity to DNA crosslinking agents, and Fanconi anemia. However, it is not understood how SLX4 and its associated nucleases act in DNA crosslink repair. Here, we uncover consequences of mouse Slx4 deficiency and reveal its function in DNA crosslink repair. Slx4-deficient mice develop epithelial cancers and have a contracted hematopoietic stem cell pool. The N-terminal domain of SLX4 (mini-SLX4) that only binds to XPF-ERCC1 is sufficient to confer resistance to DNA crosslinking agents. Recombinant mini-SLX4 enhances XPF-ERCC1 nuclease activity up to 100-fold, directing specificity toward DNA forks. Mini-SLX4-XPF-ERCC1 also vigorously stimulates dual incisions around a DNA crosslink embedded in a synthetic replication fork, an essential step in the repair of this lesion. These observations define vertebrate SLX4 as a tumor suppressor, which activates XPF-ERCC1 nuclease specificity in DNA crosslink repair.
Related JoVE Video
Prevention counseling practices of HIV care providers with patients new to HIV medical care: medical monitoring project provider survey, 2009.
J Int Assoc Provid AIDS Care
PUBLISHED: 01-15-2014
Show Abstract
Hide Abstract
To determine the prevalence of prevention counseling discussions between HIV care providers and their patients who are newly linked to care and to assess factors that facilitate such discussions.
Related JoVE Video
Comparative genome-wide transcriptional analysis of human left and right internal mammary arteries.
Genomics
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
In coronary artery bypass grafting (CABG), the combined use of left and right internal mammary arteries (LIMA and RIMA) - collectively known as bilateral IMAs (BIMAs) provides a survival advantage over the use of LIMA alone. However, gene expression in RIMA has never been compared to that in LIMA. Here we report a genome-wide transcriptional analysis of BIMA to investigate the expression profiles of these conduits in patients undergoing CABG. As expected, in comparing the BIMAs to the aorta, we found differences in pathways and processes associated with atherosclerosis, inflammation, and cell signaling - pathways which provide biological support for the observation that BIMA grafts deliver long-term benefits to the patients and protect against continued atherosclerosis. These data support the widespread use of BIMAs as the preferred conduits in CABG.
Related JoVE Video
Outcomes of mandible fracture treatment at an academic tertiary hospital: a 5-year analysis.
J. Oral Maxillofac. Surg.
PUBLISHED: 01-07-2014
Show Abstract
Hide Abstract
To analyze the outcomes of mandible fractures treated using open reduction and internal fixation.
Related JoVE Video
Detection of glutamate, glutamine, and glutathione by radiofrequency suppression and echo time optimization at 7 tesla.
Magn Reson Med
PUBLISHED: 01-06-2014
Show Abstract
Hide Abstract
To achieve detection of glutamate (Glu), glutamine (Gln), and glutathione (GSH) by minimizing the N-acetyl-aspartate (NAA) multiplet signals at 2.49 ppm using a echo time (TE) -optimized PRESS pulse sequence and a novel J-suppression radiofrequency pulse.
Related JoVE Video
Male-Biased Predation and Its Effect on Paternity Skew and Life History in a Population of Common Brushtail Possums (Trichosurus vulpecula).
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Differences in predation risk may exert strong selective pressures on life history strategies of populations. We investigated the potential for predation to shape male mating strategies in an arboreal folivore, the common brushtail possum (Trichosurus vulpecula Kerr). We predicted that possums in a tropical population exposed to high natural levels of predation would grow faster and reproduce earlier compared to those in temperate populations with lower predation. We trapped a population of possums in eucalypt woodland in northern Australia each month to measure life history traits and used microsatellites to genotype all individuals and assign paternity to all offspring. We observed very high levels of male-biased predation, with almost 60% of marked male possums being eaten by pythons, presumably as a result of their greater mobility due to mate-searching. Male reproductive success was also highly skewed, with younger, larger males fathering significantly more offspring. This result contrasts with previous studies of temperate populations experiencing low levels of predation, where older males were larger and the most reproductively successful. Our results suggest that in populations exposed to high levels of predation, male possums invest in increased growth earlier in life, in order to maximise their mating potential. This strategy is feasible because predation limits competition from older males and means that delaying reproduction carries a risk of failing to reproduce at all. Our results show that life histories are variable traits that can match regional predation environments in mammal species with widespread distributions.
Related JoVE Video
Landscape management of fire and grazing regimes alters the fine-scale habitat utilisation by feral cats.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Intensification of fires and grazing by large herbivores has caused population declines in small vertebrates in many ecosystems worldwide. Impacts are rarely direct, and usually appear driven via indirect pathways, such as changes to predator-prey dynamics. Fire events and grazing may improve habitat and/or hunting success for the predators of small mammals, however, such impacts have not been documented. To test for such an interaction, we investigated fine-scale habitat selection by feral cats in relation to fire, grazing and small-mammal abundance. Our study was conducted in north-western Australia, where small mammal populations are sensitive to changes in fire and grazing management. We deployed GPS collars on 32 cats in landscapes with contrasting fire and grazing treatments. Fine-scale habitat selection was determined using discrete choice modelling of cat movements. We found that cats selected areas with open grass cover, including heavily-grazed areas. They strongly selected for areas recently burnt by intense fires, but only in habitats that typically support high abundance of small mammals. Intense fires and grazing by introduced herbivores created conditions that are favoured by cats, probably because their hunting success is improved. This mechanism could explain why, in northern Australia, impacts of feral cats on small mammals might have increased. Our results suggest the impact of feral cats could be reduced in most ecosystems by maximising grass cover, minimising the incidence of intense fires, and reducing grazing by large herbivores.
Related JoVE Video
Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported.
Related JoVE Video
Estimating the number of persons who inject drugs in the united states by meta-analysis to calculate national rates of HIV and hepatitis C virus infections.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Injection drug use provides an efficient mechanism for transmitting bloodborne viruses, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Effective targeting of resources for prevention of HIV and HCV infection among persons who inject drugs (PWID) is based on knowledge of the population size and disparity in disease burden among PWID. This study estimated the number of PWID in the United States to calculate rates of HIV and HCV infection.
Related JoVE Video
Epicardial Surgical Ligation of the Left Atrial Appendage Is Safe, Reproducible, and Effective by Transesophageal Echocardiographic Follow-up.
Innovations (Phila)
PUBLISHED: 12-19-2013
Show Abstract
Hide Abstract
The left atrial appendage (LAA) is the source of 90% of thrombi in patients with atrial fibrillation. Our double LAA ligation (LLAA) technique was shown to be 96% successful in a small study. However, the outcomes of these patients have yet to be compared with a set of nonligated patients.
Related JoVE Video
Ionic liquids from the bottom up: Local assembly motifs in [EMIM][BF4] through cryogenic ion spectroscopy.
J Chem Phys
PUBLISHED: 12-17-2013
Show Abstract
Hide Abstract
To clarify the intramolecular distortions exhibited by the complementary ions in the archetypal ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate [EMIM][BF4], we report the vibrational spectra of the isolated ionic constituents and small aggregates cooled to about 10 K. Deuteration of bare EMIM(+) at the C(2) position, the putative hydrogen bond donating group, establishes that the observed bulk red shift is too small (<10 cm(-1)) for hydrogen bonding to be a dominant structural feature. We then analyze how the vibrational patterns evolve with increasing size to identify the spectral signatures of well-defined structural motifs in the growing assembly. Surprisingly, the main features of the bulk spectrum are already developed in the cluster with a single BF4 (-) anion sandwiched between just two EMIM(+) cations. We suggest that this local motif, while not strongly hydrogen bonded, nonetheless induces considerable intensity in the C(2)H stretches and is a robust feature in the local molecular structure of the liquid.
Related JoVE Video
The Implications of Physical Injury on Otovestibular and Cognitive Symptomatology following Blast Exposure.
Otolaryngol Head Neck Surg
PUBLISHED: 12-16-2013
Show Abstract
Hide Abstract
ObjectiveIdentify a potential difference in the spectrum of otovestibular and cognitive symptoms in blast-exposed patients comparing individuals with or without significant extremity injuries.Study DesignCase series with chart review.SettingA military tertiary care medical center.Subjects and MethodsAll new patient referrals for otovestibular evaluation after a blast injury or exposure were identified in the electronic medical record. One hundred consecutive patients meeting these criteria were studied. Data including presence of severe extremity injuries, diagnosis of mild traumatic brain injury, symptoms of imbalance, vertigo, headache, tympanic membrane perforation, hearing loss, and tinnitus were collected and analyzed.ResultsOf 100 patients included, 38 suffered severe extremity injuries. Those patients with severe extremity injuries were more likely to suffer from tympanic membrane perforations (58% vs 23%, P < .001, odds ratio [OR], 4.71, 95% confidence interval [CI], 1.96-11.33) and hearing loss (53% vs 23%, P = .002, OR, 3.81, 95% CI, 1.59-9.11). However, those without severe extremity injuries were more likely to suffer from imbalance (79% vs 32%, P < .001, OR, 8.17, 95% CI, 3.26-20.44) and vertigo (47% vs 2%, P < .001, OR, 32.52, 95% CI, 4.19-252.07) and more likely to have been diagnosed with a mild traumatic brain injury following blast exposure (66% vs 26%, P < .001, OR, 5.47, 95% CI, 2.24-13.36).ConclusionBlast-exposed individuals who sustained severe extremity injuries reported significantly fewer cognitive and vestibular symptoms. In the aftermath of a blast, those who can walk away may have still sustained a significant injury. Specifically, they may suffer more long-term cognitive and vestibular symptoms than those with severe physical injuries.
Related JoVE Video
Investigating autonomic control of the cardiovascular system: a battery of simple tests.
Adv Physiol Educ
PUBLISHED: 12-03-2013
Show Abstract
Hide Abstract
Sympathetic and parasympathetic divisions of the autonomic nervous system constantly control the heart (sympathetic and parasympathetic divisions) and blood vessels (predominantly the sympathetic division) to maintain appropriate blood pressure and organ blood flow over sometimes widely varying conditions. This can be adversely affected by pathological conditions that can damage one or both branches of autonomic control. The set of teaching laboratory activities outlined here uses various interventions, namely, 1) the heart rate response to deep breathing, 2) the heart rate response to a Valsalva maneuver, 3) the heart rate response to standing, and 4) the blood pressure response to standing, that cause fairly predictable disturbances in cardiovascular parameters in normal circumstances, which serve to demonstrate the dynamic control of the cardiovascular system by autonomic nerves. These tests are also used clinically to help investigate potential damage to this control.
Related JoVE Video
Modes of Activation of Organometallic Iridium Complexes for Catalytic Water and C-H Oxidation.
Inorg Chem
PUBLISHED: 11-14-2013
Show Abstract
Hide Abstract
Sodium periodate (NaIO4) is added to Cp*Ir(III) (Cp* = C5Me5(-)) or (cod)Ir(I) (cod = cyclooctadiene) complexes, which are water and C-H oxidation catalyst precursors, and the resulting aqueous reaction is investigated from milliseconds to seconds using desorption electrospray ionization, electrosonic spray ionization, and cryogenic ion vibrational predissociation spectroscopy. Extensive oxidation of the Cp* ligand is observed, likely beginning with electrophilic C-H hydroxylation of a Cp* methyl group followed by nonselective pathways of further oxidative degradation. Evidence is presented that the supporting chelate ligand in Cp*Ir(chelate) precursors influences the course of oxidation and is neither eliminated from the coordination sphere nor oxidatively transformed. Isomeric products of initial Cp* oxidation are identified and structurally characterized by vibrational spectroscopy in conjunction with density functional theory (DFT) modeling. Less extensive but more rapid oxidation of the cod ligand is also observed in the (cod)Ir(I) complexes. The observations are consistent with the proposed role of Cp* and cod as sacrificial placeholder ligands that are oxidatively removed from the precursor complexes under catalytic conditions.
Related JoVE Video
Structural and mutational analysis reveals that CTNNBL1 binds NLSs in a manner distinct from that of its closest armadillo-relative, karyopherin ?.
FEBS Lett.
PUBLISHED: 09-10-2013
Show Abstract
Hide Abstract
CTNNBL1 is a spliceosome-associated protein that binds nuclear localization signals (NLSs) in splice factors CDC5L and Prp31 as well as the antibody diversifying enzyme AID. Here, crystal structures of human CTNNBL1 reveal a distinct structure from its closest homologue karyopherin-?. CTNNBL1 comprises a HEAT-like domain (including a nuclear export signal), a central armadillo domain, and a coiled-coil C-terminal domain. Structure-guided mutations of the region homologous to the karyopherin-? NLS-binding site fail to disrupt CTNNBL1-NLS interactions. Our results identify CTNNBL1 as a unique selective NLS-binding protein with striking differences from karyopherin-?s.
Related JoVE Video
The N-terminal domains of spider silk proteins assemble ultrafast and protected from charge screening.
Nat Commun
PUBLISHED: 08-08-2013
Show Abstract
Hide Abstract
Web spiders assemble spidroin monomers into silk fibres of unrivalled tensile strength at remarkably high spinning speeds of up to 1 m s(-1). The spidroin N-terminal domain contains a charge-driven, pH-sensitive relay that controls self-association by an elusive mechanism. The underlying kinetics have not yet been reported. Here we engineer a fluorescence switch into the isolated N-terminal domain from spidroin 1 of the major ampullate gland of the nursery web spider E. australis that monitors dimerization. We observe ultrafast association that is surprisingly insensitive to salt, contrasting the classical screening effects in accelerated, charged protein interfaces. To gain deeper mechanistic insight, we mutate each of the protonatable residue side chains and probe their contributions. Two vicinal aspartic acids are critically involved in an unusual process of accelerated protein association that is protected from screening by electrolytes, potentially facilitating the rapid synthesis of silk fibres by web spiders.
Related JoVE Video
Vibrational spectra and fragmentation pathways of size-selected, d2-tagged ammonium/methylammonium bisulfate clusters.
J Phys Chem A
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
Particles consisting of ammonia and sulfuric acid are widely regarded as seeds for atmospheric aerosol nucleation, and incorporation of alkylamines has been suggested to substantially accelerate their growth. Despite significant efforts, little direct experimental evidence exists for the structures and chemical processes underlying multicomponent particle nucleation. Here we are concerned with the positively charged clusters of ammonia and sulfuric acid with compositions H(+)(NH3)m(H2SO4)n (2 ? m ? 5, 1 ? n ? 4), for which equilibrium geometry structures have been reported in recent computational searches. The computed harmonic vibrational spectra of such minimum energy structures can be directly compared with the experimental spectra of each cluster composition isolated in the laboratory using cryogenic ion chemistry methods. We present one-photon (i.e., linear) infrared action spectra of the isolated gas phase ions cryogenically cooled to 10 K, allowing us to resolve the characteristic vibrational signatures of these clusters. Because the available calculated spectra for different structural candidates have been obtained using different levels of theory, we reoptimized the previously reported structures with several common electronic structure methods and find excellent agreement can be achieved for the (m = 3, n = 2) cluster using CAM-B3LYP with only minor structural differences from the previously identified geometries. At the larger sizes, the experimental spectra strongly resemble that observed for 180 nm ammonium bisulfate particles. The characteristic ammonium- and bisulfate-localized bands are clearly evident at all sizes studied, indicating that the cluster structures are indeed ionic in nature. With the likely (3,2) structure in hand, we then explore the spectral and structural changes caused when methylamine is substituted for ammonia. This process is found to occur with minimal perturbation of the unsubstituted cluster. The thermal decomposition pathways were also evaluated using multiple-photon induced dissociation and are, in all cases, dominated (>100:1) by evaporation of a neutral ammonia molecule rather than methylamine. Spectra obtained for the product cluster ions resulting from this evaporation are consistent with the formation of a single hydrogen bond between two neighboring bisulfate ions, partially regenerating a sulfuric acid molecule. These results provide critical experimental benchmarks for ongoing theoretical efforts to understand the early stages of aerosol growth.
Related JoVE Video
Structural Interactions between Inhibitor and Substrate Docking Sites Give Insight into Mechanisms of Human PS1 Complexes.
Structure
PUBLISHED: 06-26-2013
Show Abstract
Hide Abstract
Presenilin-mediated endoproteolysis of transmembrane proteins plays a key role in physiological signaling and in the pathogenesis of Alzheimer disease and some cancers. Numerous inhibitors have been found via library screens, but their structural mechanisms remain unknown. We used several biophysical techniques to investigate the structure of human presenilin complexes and the effects of peptidomimetic ?-secretase inhibitors. The complexes are bilobed. The head contains nicastrin ectodomain. The membrane-embedded base has a central channel and a lateral cleft, which may represent the initial substrate docking site. Inhibitor binding induces widespread structural changes, including rotation of the head and closure of the lateral cleft. These changes block substrate access to the catalytic pocket and inhibit the enzyme. Intriguingly, peptide substrate docking has reciprocal effects on the inhibitor binding site. Similar reciprocal shifts may underlie the mechanisms of other inhibitors and of the "lateral gate" through which substrates access to the catalytic site.
Related JoVE Video
Intracardiac juvenile xanthogranuloma with presentation in adulthood.
Cardiovasc. Pathol.
PUBLISHED: 06-21-2013
Show Abstract
Hide Abstract
Juvenile xanthogranuloma is the most frequent type of non-Langerhans cell histiocytosis. It most commonly presents in infancy and early childhood; manifesting as cutaneous lesions on the head, neck, and trunk that suddenly appear and usually undergo spontaneous regression. Extracutaneous involvement, although rare, may occur along with the cutaneous form or in isolation. It most frequently involves the eye, deep subcutaneous tissues, lung, and liver. Involvement of the heart is exceptionally rare, with only seven reports found in the English literature, all affecting infants. We present the first report of an intracardiac juvenile xanthogranuloma in an adult.
Related JoVE Video
Bicaudal-D uses a parallel, homodimeric coiled coil with heterotypic registry to coordinate recruitment of cargos to dynein.
Genes Dev.
PUBLISHED: 05-30-2013
Show Abstract
Hide Abstract
Cytoplasmic dynein is the major minus end-directed microtubule motor in eukaryotes. However, there is little structural insight into how different cargos are recognized and linked to the motor complex. Here we describe the 2.2 Å resolution crystal structure of a cargo-binding region of the dynein adaptor Bicaudal-D (BicD), which reveals a parallel coiled-coil homodimer. We identify a shared binding site for two cargo-associated proteins-Rab6 and the RNA-binding protein Egalitarian (Egl)-within a region of the BicD structure with classical, homotypic core packing. Structure-based mutagenesis in Drosophila provides evidence that occupancy of this site drives association of BicD with dynein, thereby coupling motor recruitment to cargo availability. The structure also contains a region in which, remarkably, the same residues in the polypeptide sequence have different heptad registry in each chain. In vitro and in vivo analysis of a classical Drosophila dominant mutation reveals that this heterotypic region regulates the recruitment of dynein to BicD. Our results support a model in which the heterotypic segment is part of a molecular switch that promotes release of BicD autoinhibition following cargo binding to the neighboring, homotypic coiled-coil region. Overall, our data reveal a pivotal role of a highly asymmetric coiled-coil domain in coordinating the assembly of cargo-motor complexes.
Related JoVE Video
Challenges of managing snakebite envenomation in a deployed setting.
J R Army Med Corps
PUBLISHED: 05-29-2013
Show Abstract
Hide Abstract
Snake bite envenomation causes a significant health burden globally, especially in austere or resource poor settings. This case series describes envenomation in two adults and two children presenting to the Role 3 Medical Treatment Facility in Camp Bastion, Afghanistan. Each case has similarities with respect to the coagulopathy of envenomation but differs in terms of time delay to presentation and response to treatment, including reactions to antivenom. We discuss the challenges and ethical dilemmas in delayed-presentation snakebite, the diagnosis and treatment of coagulopathy and the role of antivenom and surgical debridement.
Related JoVE Video
In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies.
BMC Vet. Res.
PUBLISHED: 05-01-2013
Show Abstract
Hide Abstract
Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown.
Related JoVE Video
Performance and biocompatibility of extremely tough alginate/polyacrylamide hydrogels.
Biomaterials
PUBLISHED: 05-01-2013
Show Abstract
Hide Abstract
Although hydrogels now see widespread use in a host of applications, low fracture toughness and brittleness have limited their more broad use. As a recently described interpenetrating network (IPN) of alginate and polyacrylamide demonstrated a fracture toughness of ? 9000 J/m(2), we sought to explore the biocompatibility and maintenance of mechanical properties of these hydrogels in cell culture and in vivo conditions. These hydrogels can sustain a compressive strain of over 90% with minimal loss of Youngs Modulus as well as minimal swelling for up to 50 days of soaking in culture conditions. Mouse mesenchymal stem cells exposed to the IPN gel-conditioned media maintain high viability, and although cells exposed to conditioned media demonstrate slight reductions in proliferation and metabolic activity (WST assay), these effects are abrogated in a dose-dependent manner. Implantation of these IPN hydrogels into subcutaneous tissue of rats for 8 weeks led to mild fibrotic encapsulation and minimal inflammatory response. These results suggest the further exploration of extremely tough alginate/PAAM IPN hydrogels as biomaterials.
Related JoVE Video
Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
Vertebrate Toll-like receptor 5 (TLR5) recognizes bacterial flagellin proteins and activates innate immune responses to motile bacteria. In addition, activation of TLR5 signaling can inhibit growth of TLR5-expressing tumors and protect normal tissues from radiation and ischemia-reperfusion injuries. To understand the mechanisms behind these phenomena at the organismal level, we assessed nuclear factor kappa B (NF-?B) activation (indicative of TLR5 signaling) in tissues and cells of mice treated with CBLB502, a pharmacologically optimized flagellin derivative. This identified the liver and gastrointestinal tract as primary CBLB502 target organs. In particular, liver hepatocytes were the main cell type directly and specifically responding to systemic administration of CBLB502 but not to that of the TLR4 agonist LPS. To assess CBLB502 impact on other pathways, we created multireporter mice with hepatocytes transduced in vivo with reporters for 46 inducible transcription factor families and found that along with NF-?B, CBLB502 strongly activated STAT3-, phenobarbital-responsive enhancer module (PREM), and activator protein 1 (AP-1-) -driven pathways. Livers of CBLB502-treated mice displayed induction of numerous immunomodulatory factors and massive recruitment of various types of immune cells. This led to inhibition of growth of liver metastases of multiple tumors regardless of their TLR5 status. The changed liver microenvironment was not, however, hepatotoxic, because CBLB502 induced resistance to Fas-mediated apoptosis in normal liver cells. Temporary occlusion of liver blood circulation prevented CBLB502 from protecting hematopoietic progenitors in lethally irradiated mice, indicating involvement of a factor secreted by responding liver cells. These results define the liver as the key mediator of TLR5-dependent effects in vivo and suggest clinical applications for TLR5 agonists as hepatoprotective and antimetastatic agents.
Related JoVE Video
C-reactive protein polymorphism rs3091244 is associated with abdominal aortic aneurysm.
J. Vasc. Surg.
PUBLISHED: 04-25-2013
Show Abstract
Hide Abstract
Abdominal aortic aneurysm (AAA) formation involves an inflammatory process with a strong genetic background. C-reactive protein (CRP) regulates inflammation and is elevated in patients with AAA. The aim of this study was to investigate the association of the triallelic (C, A, and T alleles) rs3091244 functional CRP single nucleotide polymorphism (SNP) with AAA.
Related JoVE Video
Blood transfusion in cardiac surgery does increase the risk of 5-year mortality: results from a contemporary series of 1714 propensity-matched patients.
Transfusion
PUBLISHED: 04-16-2013
Show Abstract
Hide Abstract
Studies have found that cardiac surgery patients receiving blood transfusions are at risk for increased mortality during the first year after surgery, but risk appears to decrease after the first year. This study compared 5-year mortality in a propensity-matched cohort of cardiac surgery patients.
Related JoVE Video
Examining the challenges of family recruitment to behavioral intervention trials: factors associated with participation and enrollment in a multi-state colonoscopy intervention trial.
Trials
PUBLISHED: 04-02-2013
Show Abstract
Hide Abstract
Colonoscopy is one of the most effective methods of cancer prevention and detection, particularly for individuals with familial risk. Recruitment of family members to behavioral intervention trials remains uniquely challenging, owing to the intensive process required to identify and contact them. Recruiting at-risk family members involves contacting the original cancer cases and asking them to provide information about their at-risk relatives, who must then be contacted for study enrollment. Though this recruitment strategy is common in family trials, few studies have compared influences of patient and relative participation to nonparticipation. Furthermore, although use of cancer registries to identify initial cases has increased, to our knowledge no study has examined the relationship between registries and family recruitment outcomes.
Related JoVE Video
Balancing the benefits and risks of blood transfusions in patients undergoing cardiac surgery: a propensity-matched analysis.
Interact Cardiovasc Thorac Surg
PUBLISHED: 03-28-2013
Show Abstract
Hide Abstract
Prior studies have found that cardiac surgery patients receiving blood transfusions are at risk for increased mortality and morbidity following surgery. It is not clear whether this increased risk occurs across all haematocrit (HCT) levels. The goal of this study was to compare operative mortality in propensity-matched cardiac surgery patients based on stratification of the preoperative HCT levels.
Related JoVE Video
The effect of multiple primary rules on population-based cancer survival.
Cancer Causes Control
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
Different rules for registering multiple primary (MP) cancers are used by cancer registries throughout the world, making international data comparisons difficult. This study evaluates the effect of Surveillance, Epidemiology, and End Results (SEER) and International Association of Cancer Registries (IACR) MP rules on population-based cancer survival estimates.
Related JoVE Video
The zebrafish reference genome sequence and its relationship to the human genome.
Kerstin Howe, Matthew D Clark, Carlos F Torroja, James Torrance, Camille Berthelot, Matthieu Muffato, John E Collins, Sean Humphray, Karen McLaren, Lucy Matthews, Stuart McLaren, Ian Sealy, Mario Caccamo, Carol Churcher, Carol Scott, Jeffrey C Barrett, Romke Koch, Gerd-Jörg Rauch, Simon White, William Chow, Britt Kilian, Leonor T Quintais, José A Guerra-Assunção, Yi Zhou, Yong Gu, Jennifer Yen, Jan-Hinnerk Vogel, Tina Eyre, Seth Redmond, Ruby Banerjee, Jianxiang Chi, Beiyuan Fu, Elizabeth Langley, Sean F Maguire, Gavin K Laird, David Lloyd, Emma Kenyon, Sarah Donaldson, Harminder Sehra, Jeff Almeida-King, Jane Loveland, Stephen Trevanion, Matt Jones, Mike Quail, Dave Willey, Adrienne Hunt, John Burton, Sarah Sims, Kirsten McLay, Bob Plumb, Joy Davis, Chris Clee, Karen Oliver, Richard Clark, Clare Riddle, David Elliot, David Eliott, Glen Threadgold, Glenn Harden, Darren Ware, Sharmin Begum, Beverley Mortimore, Beverly Mortimer, Giselle Kerry, Paul Heath, Benjamin Phillimore, Alan Tracey, Nicole Corby, Matthew Dunn, Christopher Johnson, Jonathan Wood, Susan Clark, Sarah Pelan, Guy Griffiths, Michelle Smith, Rebecca Glithero, Philip Howden, Nicholas Barker, Christine Lloyd, Christopher Stevens, Joanna Harley, Karen Holt, Georgios Panagiotidis, Jamieson Lovell, Helen Beasley, Carl Henderson, Daria Gordon, Katherine Auger, Deborah Wright, Joanna Collins, Claire Raisen, Lauren Dyer, Kenric Leung, Lauren Robertson, Kirsty Ambridge, Daniel Leongamornlert, Sarah McGuire, Ruth Gilderthorp, Coline Griffiths, Deepa Manthravadi, Sarah Nichol, Gary Barker, Siobhan Whitehead, Michael Kay, Jacqueline Brown, Clare Murnane, Emma Gray, Matthew Humphries, Neil Sycamore, Darren Barker, David Saunders, Justene Wallis, Anne Babbage, Sian Hammond, Maryam Mashreghi-Mohammadi, Lucy Barr, Sancha Martin, Paul Wray, Andrew Ellington, Nicholas Matthews, Matthew Ellwood, Rebecca Woodmansey, Graham Clark, James D Cooper, James Cooper, Anthony Tromans, Darren Grafham, Carl Skuce, Richard Pandian, Robert Andrews, Elliot Harrison, Andrew Kimberley, Jane Garnett, Nigel Fosker, Rebekah Hall, Patrick Garner, Daniel Kelly, Christine Bird, Sophie Palmer, Ines Gehring, Andrea Berger, Christopher M Dooley, Zübeyde Ersan-Ürün, Cigdem Eser, Horst Geiger, Maria Geisler, Lena Karotki, Anette Kirn, Judith Konantz, Martina Konantz, Martina Oberländer, Silke Rudolph-Geiger, Mathias Teucke, Christa Lanz, Günter Raddatz, Kazutoyo Osoegawa, Baoli Zhu, Amanda Rapp, Sara Widaa, Cordelia Langford, Fengtang Yang, Stephan C Schuster, Nigel P Carter, Jennifer Harrow, Zemin Ning, Javier Herrero, Steve M J Searle, Anton Enright, Robert Geisler, Ronald H A Plasterk, Charles Lee, Monte Westerfield, Pieter J de Jong, Leonard I Zon, John H Postlethwait, Christiane Nüsslein-Volhard, Tim J P Hubbard, Hugues Roest Crollius, Jane Rogers, Derek L Stemple.
Nature
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
Zebrafish have become a popular organism for the study of vertebrate gene function. The virtually transparent embryos of this species, and the ability to accelerate genetic studies by gene knockdown or overexpression, have led to the widespread use of zebrafish in the detailed investigation of vertebrate gene function and increasingly, the study of human genetic disease. However, for effective modelling of human genetic disease it is important to understand the extent to which zebrafish genes and gene structures are related to orthologous human genes. To examine this, we generated a high-quality sequence assembly of the zebrafish genome, made up of an overlapping set of completely sequenced large-insert clones that were ordered and oriented using a high-resolution high-density meiotic map. Detailed automatic and manual annotation provides evidence of more than 26,000 protein-coding genes, the largest gene set of any vertebrate so far sequenced. Comparison to the human reference genome shows that approximately 70% of human genes have at least one obvious zebrafish orthologue. In addition, the high quality of this genome assembly provides a clearer understanding of key genomic features such as a unique repeat content, a scarcity of pseudogenes, an enrichment of zebrafish-specific genes on chromosome 4 and chromosomal regions that influence sex determination.
Related JoVE Video
Donor and recipient BKV-specific IgG antibody and posttransplantation BKV infection: a prospective single-center study.
Transplantation
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
The study evaluated the relationship of pretransplantation BK virus (BKV)-specific donor and recipient serostatus to posttransplantation BKV infection.
Related JoVE Video
Cerebrovascular reactivity is associated with maximal aerobic capacity in healthy older adults.
J. Appl. Physiol.
PUBLISHED: 03-07-2013
Show Abstract
Hide Abstract
Recently, several high-impact reviews suggest that regular aerobic exercise is beneficial for maintaining cognitive function in aging adults. Higher cerebral blood flow and/or cerebrovascular reactivity may explain the favorable effect of exercise on cognition. In addition, prostaglandin-mediated vasodilator responses may be influenced by regular exercise. Therefore, our purpose was to evaluate middle cerebral artery (MCA) vasodilator responses in healthy adults before and after cyclooxygenase inhibition. A total of 16 young (26 ± 6 yr; 8 males, 8 females) and 13 older (64 ± 6 yr; 7 males, 6 females) healthy adults participated in the study. Aerobic fitness was determined by maximal aerobic capacity (Vo2max) on a cycle ergometer. MCA velocity (MCAv) was measured at baseline and during stepped hypercapnia (2%, 4%, and 6% FiCO2) before and after cyclooxygenase inhibition using indomethacin. To account for differences in blood pressure, cerebrovascular conductance index (CVCi) was calculated as MCAv/mean arterial pressure. Cerebrovascular reactivity slopes were calculated from the correlation between either MCAv or CVCi and end-tidal CO2. Young adults demonstrated greater MCAv reactivity (1.61 ± 0.17 vs. 1.06 ± 0.15 cm·s(-1)·mmHg(-1); P < 0.05) and CVCi reactivity (0.015 ± 0.002 vs. 0.007 ± 0.002 cm·s(-1)·mmHg(-1); P < 0.05) compared with the older adults. There was no association between cerebrovascular reactivity and Vo2max in the combined group of subjects; however, in older adults MCAv reactivity was correlated with maximal aerobic fitness (r = 0.64; P < 0.05). Furthermore, the change in MCAv reactivity (between baseline and indomethacin trials) was also associated with Vo2max (r = 0.59; P < 0.05) in older adults. Cerebral vasodilator responses to hypercapnia were associated with maximal aerobic capacity in healthy older adults. These results may explain the physiological link between regular aerobic exercise and improved cognitive function in aging adults.
Related JoVE Video

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.