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.
Automated update, revision and quality control of the Zea mays genome annotations using MAKER-P improves the B73 RefGen_v3 gene models and identifies new genes.
Plant Physiol.
PUBLISHED: 11-12-2014
Show Abstract
Hide Abstract
The large size and relative complexity of many plant genomes makes creation, quality control, and dissemination of high quality gene-structure annotations challenging. In response we have developed MAKER-P, a fast and easy-to-use genome annotation engine for plants. Here we report the use of MAKER-P to update and revise the Zea mays B73 RefGen_v3 annotation build (5b+) in less than three hours using the iPlant Cyberinfrastructure. MAKER-P identified and annotated 4,466 additional, well-supported protein-coding genes not present in the 5b+ annotation build; added additional untranslated regions (UTR) to 1,393 5b+ gene models, identified 2,647 5b+ gene models that lack any supporting evidence (despite the use of a large and diverse evidence datasets), identified 102,370 pseudogene fragments, and created an additional 2,522 non-coding gene annotations. We also describe a method for de novo training of MAKER-P for annotation of novel grass genomes. Collectively these results lead to the 6a maize genome annotation and demonstrate the utility of MAKER-P for rapid annotation, management, and quality control of grasses and other difficult-to-annotate plant genomes.
Related JoVE Video
Nanocrystals: orientationally ordered colloidal co-dispersions of gold nanorods and cellulose nanocrystals (adv. Mater. 42/2014).
Adv. Mater. Weinheim
PUBLISHED: 11-11-2014
Show Abstract
Hide Abstract
Liquid-crystalline dispersions of cellulose nanocrystals mediate the self-assembly of plasmonic nanoparticles. By imposing nematic-like and helicoidal ordering on the spatial organization of anisotropic metal nanoparticles, mesostructured composites with novel properties such as polarization-dependent surface plasmon resonance are obtained by I. I. Smalyuk and co-workers on page 7178. Obtained using crossed polarizers and a retardation plate, the optical image depicts drops with gold nanorods mimicking order in the liquid-crystalline matrix of cellulose nanocrystals.
Related JoVE Video
Splitting, linking, knotting, and solitonic escape of topological defects in nematic drops with handles.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-04-2014
Show Abstract
Hide Abstract
Topologically nontrivial field excitations, including solitonic, linked, and knotted structures, play important roles in physical systems ranging from classical fluids and liquid crystals, to electromagnetism, classic, and quantum field theories. These excitations can appear spontaneously during symmetry-breaking phase transitions. For example, in cosmological theories, cosmic strings may have formed knotted configurations influencing the Early Universe development, whereas in liquid crystals transient tangled defect lines were observed during isotropic-nematic transitions, eventually relaxing to defect-free states. Knotted and solitonic fields and defects were also obtained using optical manipulation, complex-shaped colloids, and frustrated cholesterics. Here we use confinement of nematic liquid crystal by closed surfaces with varied genus and perpendicular boundary conditions for a robust control of appearance and stability of such field excitations. Theoretical modeling and experiments reveal structure of defect lines as a function of the surface topology and material and geometric parameters, establishing a robust means of controlling solitonic, knotted, linked, and other field excitations.
Related JoVE Video
Energy weighted x-ray dark-field imaging.
Opt Express
PUBLISHED: 10-17-2014
Show Abstract
Hide Abstract
The dark-field image obtained in grating-based x-ray phase-contrast imaging can provide information about the objects' microstructures on a scale smaller than the pixel size even with low geometric magnification. In this publication we demonstrate that the dark-field image quality can be enhanced with an energy-resolving pixel detector. Energy-resolved x-ray dark-field images were acquired with a 16-energy-channel photon-counting pixel detector with a 1 mm thick CdTe sensor in a Talbot-Lau x-ray interferometer. A method for contrast-noise-ratio (CNR) enhancement is proposed and validated experimentally. In measurements, a CNR improvement by a factor of 1.14 was obtained. This is equivalent to a possible radiation dose reduction of 23%.
Related JoVE Video
Psychiatrists With Substance Use Disorders: Positive Treatment Outcomes From Physician Health Programs.
Psychiatr Serv
PUBLISHED: 10-02-2014
Show Abstract
Hide Abstract
The objective of this study was to compare outcomes of psychiatrists and nonpsychiatrist physicians enrolled in state physician health programs for substance use disorders.
Related JoVE Video
How spectroscopic x-ray imaging benefits from inter-pixel communication.
Phys Med Biol
PUBLISHED: 09-26-2014
Show Abstract
Hide Abstract
Spectroscopic x-ray imaging based on pixellated semiconductor detectors can be sensitive to charge sharing and K-fluorescence, depending on the sensor material used, its thickness and the pixel pitch employed. As a consequence, spectroscopic resolution is partially lost. In this paper, we study a new detector ASIC, the Medipix3RX, that offers a novel feature called charge summing, which is established by making adjacent pixels communicate with each other. Consequently, single photon interactions resulting in multiple hits are almost completely avoided. We investigate this charge summing mode with respect to those of its imaging properties that are of interest in medical physics and benchmark them against the case without charge summing. In particular, we review its influence on spectroscopic resolution and find that the low energy bias normally present when recording energy spectra is dramatically reduced. Furthermore, we show that charge summing provides a modulation transfer function which is almost independent of the energy threshold setting, which is in contrast to approaches common so far. We demonstrate that this property is directly linked to the detective quantum efficiency, which is found to increase by a factor of three or more when the energy threshold approaches the photon energy and when using charge summing. As a consequence, the contrast-to-noise ratio is found to double at elevated threshold levels and the dynamic range increases for a given counter depth. All these effects are shown to lead to an improved ability to perform material discrimination in spectroscopic CT, using iodine and gadolinium contrast agents. Hence, when compared to conventional photon counting detectors, these benefits carry the potential of substantially reducing the imaging dose a patient is exposed to during diagnostic CT examinations.
Related JoVE Video
Ultrasound-guided methylene blue dye injection for parathyroid localization in the reoperative neck.
World J Surg
PUBLISHED: 09-06-2014
Show Abstract
Hide Abstract
The goal of this study was to review a single institution's experience using intraoperative ultrasound-guided (ioUSG) methylene blue dye injection for the localization and removal of enlarged parathyroid glands in patients with primary hyperparathyroidism and a history of previous neck surgery.
Related JoVE Video
The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial.
BMJ Open
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education.
Related JoVE Video
Global population-specific variation in miRNA associated with cancer risk and clinical biomarkers.
BMC Med Genomics
PUBLISHED: 08-28-2014
Show Abstract
Hide Abstract
MiRNA expression profiling is being actively investigated as a clinical biomarker and diagnostic tool to detect multiple cancer types and stages as well as other complex diseases. Initial investigations, however, have not comprehensively taken into account genetic variability affecting miRNA expression and/or function in populations of different ethnic backgrounds. Therefore, more complete surveys of miRNA genetic variability are needed to assess global patterns of miRNA variation within and between diverse human populations and their effect on clinically relevant miRNA genes.
Related JoVE Video
Orientationally ordered colloidal co-dispersions of gold nanorods and cellulose nanocrystals.
Adv. Mater. Weinheim
PUBLISHED: 08-28-2014
Show Abstract
Hide Abstract
Nematic-like and helicoidally orientational self-assemblies of gold nanorods co-dispersed with cellulose nanocrystals to form liquid crystalline phases are developed. Polarization-sensitive extinction spectra and two-photon luminescence imaging are used to characterize orientations and spatial distributions of gold nanorods. Cholesteric-isotropic phase coexistence and continuous domains of single-phase regions are observed and qualitatively discussed on the basis of entropic and electrostatic interactions in co-dispersions of rigid rods of different aspect ratios. Potential applications include biologically compatible plasmonic composite nanomaterials for solar biofuel production and polarization-sensitive plasmonic papers and fabrics.
Related JoVE Video
Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-18-2014
Show Abstract
Hide Abstract
Myeloid cells are key regulators of the tumor microenvironment, governing local immune responses. Here we report that tumor-infiltrating myeloid cells and circulating monocytes in patients with glioblastoma multiforme (GBM) express ligands for activating the Natural killer group 2, member D (NKG2D) receptor, which cause down-regulation of NKG2D on natural killer (NK) cells. Tumor-infiltrating NK cells isolated from GBM patients fail to lyse NKG2D ligand-expressing tumor cells. We demonstrate that lactate dehydrogenase (LDH) isoform 5 secreted by glioblastoma cells induces NKG2D ligands on monocytes isolated from healthy individuals. Furthermore, sera from GBM patients contain elevated amounts of LDH, which correlate with expression of NKG2D ligands on their autologous circulating monocytes. NKG2D ligands also are present on circulating monocytes isolated from patients with breast, prostate, and hepatitis C virus-induced hepatocellular carcinomas. Together, these findings reveal a previously unidentified immune evasion strategy whereby tumors produce soluble factors that induce NKG2D ligands on myeloid cells, subverting antitumor immune responses.
Related JoVE Video
Detection of non-classical space-time correlations with a novel type of single-photon camera.
Opt Express
PUBLISHED: 08-05-2014
Show Abstract
Hide Abstract
During the last decades, multi-pixel detectors have been developed capable of registering single photons. The newly developed hybrid photon detector camera has a remarkable property that it has not only spatial but also temporal resolution. In this work, we apply this device to the detection of non-classical light from spontaneous parametric down-conversion and use two-photon correlations for the absolute calibration of its quantum efficiency.
Related JoVE Video
Patterns of abstinence or continued drug use among methadone maintenance patients and their relation to treatment retention.
J Psychoactive Drugs
PUBLISHED: 07-24-2014
Show Abstract
Hide Abstract
The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes.
Related JoVE Video
Unanticipated Thyroid Cancer in Patients with Substernal Goiters: Are We Underestimating the Risk?
Ann. Surg. Oncol.
PUBLISHED: 07-20-2014
Show Abstract
Hide Abstract
The rate of unexpected thyroid cancers found at the time of thyroidectomy is thought to be similar in patients with cervical and substernal multinodular goiters (MNGs).
Related JoVE Video
Challenges of cluster randomized trials.
J Comp Eff Res
PUBLISHED: 06-28-2014
Show Abstract
Hide Abstract
Cluster randomized trials are trials that randomize clusters of people, rather than individuals. They are becoming increasingly common. A number of innovations have been developed recently, particularly in the calculation of the required size of a cluster trial, the handling of missing data, designs to minimize recruitment bias, the ethics of cluster randomized trials and the stepped wedge design. This article will highlight and illustrate these developments. It will also discuss issues with regards to the reporting of cluster randomized trials.
Related JoVE Video
Topological polymer dispersed liquid crystals with bulk nematic defect lines pinned to handlebody surfaces.
Phys. Rev. Lett.
PUBLISHED: 05-16-2014
Show Abstract
Hide Abstract
Polymer dispersed liquid crystals are a useful model system for studying the relationship between surface topology and defect structures. They are comprised of a polymer matrix with suspended spherical nematic drops and are topologically constrained to host defects of an elementary hedgehog charge per droplet, such as bulk or surface point defects or closed disclination loops. We control the genus of the closed surfaces confining such micrometer-sized nematic drops with tangential boundary conditions for molecular alignment imposed by the polymer matrix, allowing us to avoid defects or, on the contrary, to generate them in a controlled way. We show, both experimentally and through numerical modeling, that topological constraints in nematic microdrops can be satisfied by hosting topologically stable half-integer bulk defect lines anchored to opposite sides of handlebody surfaces. This enriches the interplay of topologies of closed surfaces and fields with nonpolar symmetry, yielding new unexpected configurations that cannot be realized in vector fields, having potential implications for topologically similar defects in cosmology and other fields.
Related JoVE Video
Prognosis for Emergency Physician with Substance Abuse Recovery: 5-year Outcome Study.
West J Emerg Med
PUBLISHED: 04-04-2014
Show Abstract
Hide Abstract
Emergency physicians (EPs) are reported to have a higher rate of substance use disorder (SUD) than most specialties, although little is known about their prognosis. We examined the outcomes of emergency physician compared to other physicians in the treatment of substance use disorders in Physician Health Programs (PHP).
Related JoVE Video
A reproducible ex vivo model for transanal minimally invasive surgery.
JSLS
PUBLISHED: 04-01-2014
Show Abstract
Hide Abstract
Rectal tumors can be excised through a number of minimally invasive transanal techniques including transanal excision, transanal endoscopic microsurgery, and transanal minimally invasive surgery (TAMIS). Specialty training is often required to master the nuances of these approaches. This study aimed to create a reproducible transanal excision training model that is suited for laparoendoscopic techniques.
Related JoVE Video
Gibbon genome and the fast karyotype evolution of small apes.
Lucia Carbone, R Alan Harris, Sante Gnerre, Krishna R Veeramah, Belen Lorente-Galdos, John Huddleston, Thomas J Meyer, Javier Herrero, Christian Roos, Bronwen Aken, Fabio Anaclerio, Nicoletta Archidiacono, Carl Baker, Daniel Barrell, Mark A Batzer, Kathryn Beal, Antoine Blancher, Craig L Bohrson, Markus Brameier, Michael S Campbell, Oronzo Capozzi, Claudio Casola, Giorgia Chiatante, Andrew Cree, Annette Damert, Pieter J de Jong, Laura Dumas, Marcos Fernandez-Callejo, Paul Flicek, Nina V Fuchs, Ivo Gut, Marta Gut, Matthew W Hahn, Jessica Hernandez-Rodriguez, LaDeana W Hillier, Robert Hubley, Bianca Ianc, Zsuzsanna Izsvák, Nina G Jablonski, Laurel M Johnstone, Anis Karimpour-Fard, Miriam K Konkel, Dennis Kostka, Nathan H Lazar, Sandra L Lee, Lora R Lewis, Yue Liu, Devin P Locke, Swapan Mallick, Fernando L Mendez, Matthieu Muffato, Lynne V Nazareth, Kimberly A Nevonen, Majesta O'Bleness, Cornelia Ochis, Duncan T Odom, Katherine S Pollard, Javier Quilez, David Reich, Mariano Rocchi, Gerald G Schumann, Stephen Searle, James M Sikela, Gabriella Skollar, Arian Smit, Kemal Sonmez, Boudewijn ten Hallers, Elizabeth Terhune, Gregg W C Thomas, Brygg Ullmer, Mario Ventura, Jerilyn A Walker, Jeffrey D Wall, Lutz Walter, Michelle C Ward, Sarah J Wheelan, Christopher W Whelan, Simon White, Larry J Wilhelm, August E Woerner, Mark Yandell, Baoli Zhu, Michael F Hammer, Tomas Marques-Bonet, Evan E Eichler, Lucinda Fulton, Catrina Fronick, Donna M Muzny, Wesley C Warren, Kim C Worley, Jeffrey Rogers, Richard K Wilson, Richard A Gibbs.
Nature
PUBLISHED: 03-23-2014
Show Abstract
Hide Abstract
Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ?5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.
Related JoVE Video
Outdoor air pollution, subtypes and severity of ischemic stroke--a small-area level ecological study.
Int J Health Geogr
PUBLISHED: 03-17-2014
Show Abstract
Hide Abstract
Evidence linking outdoor air pollution and incidence of ischemic stroke subtypes and severity is limited. We examined associations between outdoor PM10 and NO2 concentrations modeled at a fine spatial resolution and etiological and clinical ischemic stroke subtypes and severity of ischemic stroke.
Related JoVE Video
Late-stage formation of carbon-fluorine bonds.
Chem Rec
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
In this account, we review work from our lab on the development of methods for carbon-fluorine bond formation, with an emphasis on late-stage fluorination of functionalized small molecules and synthesis of (18) F-labeled molecules for potential use as tracers in positron emission tomography (PET). We attempt to highlight reactions that we feel are of particular practical relevance, as well as areas of research where there is still significant room for advancement.
Related JoVE Video
Support of academic synthetic chemistry using separation technologies from the pharmaceutical industry.
Org. Biomol. Chem.
PUBLISHED: 03-05-2014
Show Abstract
Hide Abstract
The use of state-of-the-art separation tools from the pharmaceutical industry for addressing intractable separation problems from academic synthetic chemistry is evaluated, showing fast and useful results for the resolution of complex mixtures, separation of closely related components, visualization of difficult to detect compounds and purification of synthetic intermediates. Some recommendations for potential near term deployment of separation tools within academia and the evolution of next generation separation technologies are discussed.
Related JoVE Video
A hazard ratio was estimated by a ratio of median survival times, but with considerable uncertainty.
J Clin Epidemiol
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
To evaluate the empirical concordance between the hazard ratio (HR) and the median ratio (MR) in survival cancer studies.
Related JoVE Video
Treatment of potato tubers with the synthetic cytokinin 1-(?-ethylbenzyl)-3-nitroguanidine results in rapid termination of endodormancy and induction of transcripts associated with cell proliferation and growth.
Funct. Integr. Genomics
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
Perennial plants undergo repression of meristematic activity in a process called dormancy. Dormancy is a complex metabolic process with implications for plant breeding and crop yield. Endodormancy, a specific subclass of dormancy, is characteristic of internal physiological mechanisms resulting in growth suppression. In this study, we examine transcriptional changes associated with the natural cessation of endodormancy in potato tuber meristems and in endodormant tubers treated with the cytokinin analog 1-(?-ethylbenzyl)-3-niroguanidine (NG), which terminates dormancy. RNA-sequencing was used to examine transcriptome changes between endodormant and non-dormant meristems from four different harvest years. A total of 35,091 transcripts were detected with 2132 differentially expressed between endodormant and non-dormant tuber meristems. Endodormant potato tubers were treated with the synthetic cytokinin NG and transcriptome changes analyzed using RNA-seq after 1, 4, and 7 days following NG exposure. A comparison of natural cessation of dormancy and NG-treated tubers demonstrated that by 4 days after NG exposure, potato meristems exhibited transcriptional profiles similar to the non-dormant state with elevated expression of multiple histones, a variety of cyclins, and other genes associated with proliferation and cellular replication. Three homologues encoding for CYCD3 exhibited elevated expression in both non-dormant and NG-treated potato tissues. These results suggest that NG terminates dormancy and induces expression cell cycle-associated transcripts within 4 days of treatment.
Related JoVE Video
Genetic origins of lactase persistence and the spread of pastoralism in Africa.
Am. J. Hum. Genet.
PUBLISHED: 02-14-2014
Show Abstract
Hide Abstract
In humans, the ability to digest lactose, the sugar in milk, declines after weaning because of decreasing levels of the enzyme lactase-phlorizin hydrolase, encoded by LCT. However, some individuals maintain high enzyme amounts and are able to digest lactose into adulthood (i.e., they have the lactase-persistence [LP] trait). It is thought that selection has played a major role in maintaining this genetically determined phenotypic trait in different human populations that practice pastoralism. To identify variants associated with the LP trait and to study its evolutionary history in Africa, we sequenced MCM6 introns 9 and 13 and ~2 kb of the LCT promoter region in 819 individuals from 63 African populations and in 154 non-Africans from nine populations. We also genotyped four microsatellites in an ~198 kb region in a subset of 252 individuals to reconstruct the origin and spread of LP-associated variants in Africa. Additionally, we examined the association between LP and genetic variability at candidate regulatory regions in 513 individuals from eastern Africa. Our analyses confirmed the association between the LP trait and three common variants in intron 13 (C-14010, G-13907, and G-13915). Furthermore, we identified two additional LP-associated SNPs in intron 13 and the promoter region (G-12962 and T-956, respectively). Using neutrality tests based on the allele frequency spectrum and long-range linkage disequilibrium, we detected strong signatures of recent positive selection in eastern African populations and the Fulani from central Africa. In addition, haplotype analysis supported an eastern African origin of the C-14010 LP-associated mutation in southern Africa.
Related JoVE Video
Promoting public health research in BRICS through a multinational public health prize fund.
Indian J Med Ethics
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
This article proposes the establishment of a prize fund to incentivise public health research within the BRICS association, which comprises the five major emerging world economies: Brazil, Russia, India, China and South Africa. This would stimulate cooperative healthcare research within the group and, on the proviso that the benefits of the research are made freely available within the association, would be rewarding for researchers. The results of the research stimulated by the prize would provide beneficial new healthcare technologies, targeting the most vulnerable and needy groups. The proposed fund is consistent with current international patent law and would not only avoid some of the problems associated with the "Health Impact Fund", but also create a new model for healthcare research.
Related JoVE Video
Adrenalectomy outcomes are superior with the participation of residents and fellows.
J. Am. Coll. Surg.
PUBLISHED: 02-10-2014
Show Abstract
Hide Abstract
Adrenalectomy is a complex procedure performed in many settings, with and without residents and fellows. Patients often ask, "Will trainees be participating in my operation?" and seek reassurance that their care will not be adversely affected. The purpose of this study was to determine the association between trainee participation and adrenalectomy perioperative outcomes.
Related JoVE Video
Intrauterine growth restriction increases TNF ? and activates the unfolded protein response in male rat pups.
J Obes
PUBLISHED: 02-04-2014
Show Abstract
Hide Abstract
Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNF ? ). TNF ? contributes to adipocyte inflammation and impaired insulin signaling. TNF ? has also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNF ? , TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2 ? , and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNF ? , (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNF ? increased and after UPR activation. We speculate that programmed dysregulation of TNF ? and UPR contributed to the development of glucose intolerance in male IUGR rats.
Related JoVE Video
Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.
J. Hum. Genet.
PUBLISHED: 01-28-2014
Show Abstract
Hide Abstract
Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.
Related JoVE Video
Anti-hypertensive drugs in children and adolescents.
World J Cardiol
PUBLISHED: 01-27-2014
Show Abstract
Hide Abstract
Worldwide the prevalence of essential hypertension in children and adolescents continues to increase. Traditionally providers have used "off-label" drugs to treat pediatric hypertension, meaning that rigorous clinical trials of these drugs have not been specifically performed in pediatric patient populations. Consequently providers have extrapolated dosing, safety and efficacy from trials in adults. This practice is sub-optimal as children demonstrate unique differences in drug metabolism and response. Use of unstudied or understudied drugs increases risk of adverse events and/or can lead to sub-optimal efficacy. Recognizing these concerns, regulatory agencies have created financial incentives for industry to conduct pediatric clinical trials. These incentives, coupled with the emerging pediatric hypertension epidemic, have spurred over 30 clinical trials of anti-hypertensive drugs over the past 15 years and have resulted in labeling of 10 new drugs by the United States Food and Drug Administration for treatment of hypertension in children and adolescents. Unfortunately the financial incentive structures focus on newer drugs and drug classes. Consequently there is now a relative dearth of trial data for older but sometimes commonly prescribed pediatric antihypertensive drugs. This article reviews recent pediatric antihypertensive drug trials with a focus on trial design and endpoints, drug dosing, safety, efficacy and specific drug indications. We also review the available data and experience for some of the more commonly prescribed, but less well studied "older" pediatric antihypertensive drugs.
Related JoVE Video
Pilot and feasibility studies: is there a difference from each other and from a randomised controlled trial?
Contemp Clin Trials
PUBLISHED: 01-27-2014
Show Abstract
Hide Abstract
A crucial part in the development of any intervention is the preliminary work carried out prior to a large-scale definitive trial. However, the definitions of these terms are not clear cut and many authors redefine them. Because of this, the terms feasibility and pilot are often misused.
Related JoVE Video
Maternal tobacco smoke increased visceral adiposity and serum corticosterone levels in adult male rat offspring.
Pediatr. Res.
PUBLISHED: 01-24-2014
Show Abstract
Hide Abstract
Maternal tobacco smoke (MTS) predisposes human and rat offspring to visceral obesity in early adulthood. Glucocorticoid excess also causes visceral obesity. We hypothesized that in utero MTS would increase visceral adiposity and alter the glucocorticoid pathway in young adult rats.
Related JoVE Video
Adjusting survival time estimates to account for treatment switching in randomized controlled trials--an economic evaluation context: methods, limitations, and recommendations.
Med Decis Making
PUBLISHED: 01-21-2014
Show Abstract
Hide Abstract
Treatment switching commonly occurs in clinical trials of novel interventions in the advanced or metastatic cancer setting. However, methods to adjust for switching have been used inconsistently and potentially inappropriately in health technology assessments (HTAs).
Related JoVE Video
Simplified silvestrol analogues with potent cytotoxic activity.
ChemMedChem
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
The complex natural products silvestrol (1) and episilvestrol (2) are inhibitors of translation initiation through binding to the DEAD-box helicase eukaryotic initiation factor?4A (eIF4A). Both compounds are potently cytotoxic to cancer cells in vitro, and 1 has demonstrated efficacy in vivo in several xenograft cancer models. Here we show that 2 has limited plasma membrane permeability and is metabolized in liver microsomes in a manner consistent with that reported for 1. In addition, we have prepared a series of analogues of these compounds where the complex pseudo-sugar at C6 has been replaced with chemically simpler moieties to improve drug-likeness. Selected compounds from this work possess excellent activity in biochemical and cellular translation assays with potent activity against leukemia cell lines.
Related JoVE Video
Development and characterization of an antibody-labeled super-paramagnetic iron oxide contrast agent targeting prostate cancer cells for magnetic resonance imaging.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
In this study we developed, characterized and validated in vitro a functional superparagmagnetic iron-oxide based magnetic resonance contrast agent by conjugating a commercially available iron oxide nanoparticle, Molday ION Rhodamine-B Carboxyl (MIRB), with a deimmunized mouse monoclonal antibody (muJ591) targeting prostate-specific membrane antigen (PSMA). This functional contrast agent is intended for the specific and non-invasive detection of prostate cancer cells that are PSMA positive, a marker implicated in prostate tumor progression and metastasis. The two-step carbodiimide reaction used to conjugate the antibody to the nanoparticle was efficient and we obtained an elemental iron content of 1958 ± 611 per antibody. Immunofluorescence microscopy and flow cytometry showed that the conjugated muJ591:MIRB complex specifically binds to PSMA-positive (LNCaP) cells. The muJ591:MIRB complex reduced cell adhesion and cell proliferation on LNCaP cells and caused apoptosis as tested by Annexin V assay, suggesting anti-tumorigenic characteristics. Measurements of the T2 relaxation time of the muJ591:MIRB complex using a 400 MHz Innova NMR and a multi-echo spin-echo sequence on a 3T MRI (Achieva, Philips) showed a significant T2 relaxation time reduction for the muJ591:MIRB complex, with a reduced T2 relaxation time as a function of the iron concentration. PSMA-positive cells treated with muJ591:MIRB showed a significantly shorter T2 relaxation time as obtained using a 3T MRI scanner. The reduction in T2 relaxation time for muJ591:MIRB, combined with its specificity against PSMA+LNCaP cells, suggest its potential as a biologically-specific MR contrast agent.
Related JoVE Video
MAKER-P: a tool-kit for the rapid creation, management, and quality control of plant genome annotations.
Plant Physiol.
PUBLISHED: 12-04-2013
Show Abstract
Hide Abstract
We have optimized and extended the widely used annotation-engine MAKER to in order to better support plant genome annotation efforts. New features include better parallelization for large repeat-rich plant genomes, ncRNA annotation capabilities, and support for pseudogene identification. We have benchmarked the resulting software toolkit, MAKER-P, using the A. thaliana and Z. mays genomes. Here we demonstrate the ability of the MAKER-P toolkit to automatically update, extend, and revise the A. thaliana annotations in light of newly available data; and to annotate pseudogenes and ncRNAs absent from the TAIR10 build. Our results demonstrate that MAKER-P can be used to manage and improve the annotations of even A. thaliana, perhaps the best-annotated plant genome. We have also installed and benchmarked MAKER-P on the Texas Advanced Computing Center (TACC). We show that this public resource can de novo annotate the entire Arabidopsis and Zea mays genomes in less than three hours, and produce annotations of comparable quality to those of the current TAIR10 and Z. mays V2 annotation builds.
Related JoVE Video
Two analogues of fenarimol show curative activity in an experimental model of chagas disease.
J. Med. Chem.
PUBLISHED: 12-04-2013
Show Abstract
Hide Abstract
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compounds, 6 and (S)-7, with PCR-confirmed curative activity in a mouse model of established T. cruzi infection after once daily oral dosing for 20 days at 20 mg/kg 6 and 10 mg/kg (S)-7. Compounds 6 and (S)-7 have potent in vitro activity, are noncytotoxic, show no adverse effects in vivo following repeat dosing, are prepared by a short synthetic route, and have druglike properties suitable for preclinical development.
Related JoVE Video
Prognostic Value of Cardiovascular Magnetic Resonance Imaging Measurements Corrected for Age and Gender in Idiopathic Pulmonary Arterial Hypertension.
Circ Cardiovasc Imaging
PUBLISHED: 11-25-2013
Show Abstract
Hide Abstract
-There is limited data on the prognostic value of cardiovascular magnetic resonance (CMR) measurements in idiopathic pulmonary arterial hypertension, with no studies investigating the impact of correction of CMR indices for age and gender on prognostic value.
Related JoVE Video
Grating-based x-ray phase-contrast imaging with a multi energy-channel photon-counting pixel detector.
Opt Express
PUBLISHED: 11-13-2013
Show Abstract
Hide Abstract
We have carried out grating-based x-ray differential phase-contrast measurements with a hybrid pixel detector in 16 energy channels simultaneously. A method for combining the energy resolved phase-contrast images based on energy weighting is presented. An improvement in contrast-to-noise ratio by 58.2% with respect to an emulated integrating detector could be observed in the final image. The same image quality could thus be achieved with this detector and with energy weighting at 60.0% reduced dose compared to an integrating detector. The benefit of the method depends on the object, spectrum, interferometer design and the detector efficiency.
Related JoVE Video
Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa.
Mol. Biol. Evol.
PUBLISHED: 10-30-2013
Show Abstract
Hide Abstract
Bitter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. To better understand the genetic architecture and patterns of phenotypic variability of bitter taste perception, we sequenced a 996 bp region, encompassing the coding exon of TAS2R16, a bitter taste receptor gene, in 595 individuals from 74 African populations and in 94 non-Africans from 11 populations. We also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from Central and East Africa. In addition, we characterized TAS2R16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. Here, we report striking signatures of positive selection, including significant Fay and Wus H statistics predominantly in East Africa, indicating strong local adaptation and greater genetic structure among African populations than expected under neutrality. Furthermore, we observed a "star-like" phylogeny for haplotypes with the derived allele at polymorphic site 516 associated with increased bitter taste perception that is consistent with a model of selection for "high-sensitivity" variation. In contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. We also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at TAS2R16 influences salicin recognition. Additionally, we detected geographic differences in levels of bitter taste perception in Africa not previously reported and infer an East African origin for high salicin sensitivity in human populations.
Related JoVE Video
Variation in centre-specific survival in patients starting renal replacement therapy in England is explained by enhanced comorbidity information from hospitalization data.
Nephrol. Dial. Transplant.
PUBLISHED: 09-19-2013
Show Abstract
Hide Abstract
Unadjusted survival on renal replacement therapy (RRT) varies widely from centre to centre in England. Until now, missing data on case mix have made it impossible to determine whether this variation reflects genuine differences in the quality of care. Data linkage has the capacity to reduce missing data.
Related JoVE Video
Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.
J. Am. Chem. Soc.
PUBLISHED: 09-16-2013
Show Abstract
Hide Abstract
A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic acid derivatives is presented. The reaction is operationally simple and amenable to multigram-scale synthesis. Evaluation of the reaction mechanism suggests a single-electron-transfer pathway, involving a Pd(III) intermediate that has been isolated and characterized.
Related JoVE Video
Abnormal Agitated Saline Study Results after Tetralogy of Fallot Repair.
Echocardiography
PUBLISHED: 09-15-2013
Show Abstract
Hide Abstract
Residual intracardiac or extracardiac shunting is frequently seen in patients with repaired congenital heart disease and can cause systemic hypoxemia. We present the case of an adult with tetralogy of Fallot who underwent two corrective surgical procedures as a child with subsequent pulmonary valve replacement due to residual pulmonary insufficiency. Further details of her operative history were otherwise unknown. After being lost to follow-up for many years, she presented with unexplained cyanosis and a markedly abnormal agitated saline study on transthoracic echocardiography in which only the left heart filled after contrast administration. We review the differential diagnosis for such a presentation and discuss the utility of cardiac magnetic resonance imaging (MRI) to define the etiology. Cardiac MRI, a frequently used imaging modality to longitudinally assess adult patients with congenital heart disease, provides excellent image quality of cardiac structures and the ability to perform angiography in a variety of imaging planes. These advantages render cardiac MRI, a useful modality to determine the etiology of unexplained cyanosis in these patients as both intracardiac and extracardiac shunts can be detected.
Related JoVE Video
One-dimensional palladium wires: influence of molecular changes on supramolecular structure.
Inorg Chem
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
Nanostructured materials based on one-dimensional (1D) metal wires are of potential utility; however, to date, there is a lack of synthetic methods that allow for variation of structure and therefore properties. Here we report the use of molecular control elements to alter the solid-state structures of 1D palladium wires, including Pd-Pd bond distances and the porosity of the supramolecular framework.
Related JoVE Video
Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis.
Traffic
PUBLISHED: 09-09-2013
Show Abstract
Hide Abstract
Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or into rings in the presence of SH3 domain proteins. Dynasore is a dynamin inhibitor of moderate potency (IC?? ~ 15??M in vitro). We show that dynasore binds stoichiometrically to detergents used for in vitro drug screening, drastically reducing its potency (IC?? = 479??M) and research tool utility. We synthesized a focused set of dihydroxyl and trihydroxyl dynasore analogs called the Dyngo™ compounds, five of which had improved potency, reduced detergent binding and reduced cytotoxicity, conferred by changes in the position and/or number of hydroxyl substituents. The Dyngo compound 4a was the most potent compound, exhibiting a 37-fold improvement in potency over dynasore for liposome-stimulated helical dynamin activity. In contrast, while dynasore about equally inhibited dynamin assembled in its helical or ring states, 4a and 6a exhibited >36-fold reduced activity against rings, suggesting that they can discriminate between helical or ring oligomerization states. 4a and 6a inhibited dynamin-dependent endocytosis of transferrin in multiple cell types (IC?? of 5.7 and 5.8??M, respectively), at least sixfold more potently than dynasore, but had no effect on dynamin-independent endocytosis of cholera toxin. 4a also reduced synaptic vesicle endocytosis and activity-dependent bulk endocytosis in cultured neurons and synaptosomes. Overall, 4a and 6a are improved and versatile helical dynamin and endocytosis inhibitors in terms of potency, non-specific binding and cytotoxicity. The data further suggest that the ring oligomerization state of dynamin is not required for clathrin-mediated endocytosis.
Related JoVE Video
ABR in newborns: effects of electrode configuration, stimulus rate, and EEG rejection levels on test efficiency.
Int J Audiol
PUBLISHED: 08-01-2013
Show Abstract
Hide Abstract
This study investigated the effect of electrode configuration, stimulus rate, and EEG rejection level on the efficiency of ABR testing in babies.
Related JoVE Video
Cellular Photo Digital Breathalyzer for Monitoring Alcohol Use: A Pilot Study.
Eur Addict Res
PUBLISHED: 07-09-2013
Show Abstract
Hide Abstract
Background: Monitoring alcohol use is important in numerous situations. Direct ethanol metabolites, such as ethyl glucuronide (EtG), have been shown to be useful tools in detecting alcohol use and documenting abstinence. For very frequent or continuous control of abstinence, they lack practicability. Therefore, devices measuring ethanol itself might be of interest. This pilot study aims at elucidating the usability and accuracy of the cellular photo digital breathalyzer (CPDB) compared to self-reports in a naturalistic setting. Method: 12 social drinkers were included. Subjects used a CPDB 4 times daily, kept diaries of alcohol use and submitted urine for EtG testing over a period of 5 weeks. Results: In total, the 12 subjects reported 84 drinking episodes. 1,609 breath tests were performed and 55 urine EtG tests were collected. Of 84 drinking episodes, CPDB detected 98.8%. The compliance rate for breath testing was 96%. Of the 55 EtG tests submitted, 1 (1.8%) was positive. Conclusions: The data suggest that the CPDB device holds promise in detecting high, moderate, and low alcohol intake. It seems to have advantages compared to biomarkers and other monitoring devices. The preference for CPDB by the participants might explain the high compliance. Further studies including comparison with biomarkers and transdermal devices are needed. © 2013 S. Karger AG, Basel.
Related JoVE Video
ImagePlane: an automated image analysis pipeline for high-throughput screens using the planarian Schmidtea mediterranea.
J. Comput. Biol.
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
ImagePlane is a modular pipeline for automated, high-throughput image analysis and information extraction. Designed to support planarian research, ImagePlane offers a self-parameterizing adaptive thresholding algorithm; an algorithm that can automatically segment animals into anterior-posterior/left-right quadrants for automated identification of region-specific differences in gene and protein expression; and a novel algorithm for quantification of morphology of animals, independent of their orientations and sizes. ImagePlane also provides methods for automatic report generation, and its outputs can be easily imported into third-party tools such as R and Excel. Here we demonstrate the pipelines utility for identification of genes involved in stem cell proliferation in the planarian Schmidtea mediterranea. Although designed to support planarian studies, ImagePlane will prove useful for cell-based studies as well.
Related JoVE Video
Treatment of refractory perianal fistulas with ligation of the intersphincteric fistula tract: preliminary results.
Am Surg
PUBLISHED: 07-03-2013
Show Abstract
Hide Abstract
Several surgical options exist for management of fistula in ano. The goal of treatment is to achieve closure of the fistula while maintaining continence. Sphincter-sparing operations to close perianal fistulas include advancement flap, anal fistula plug, fibrin glue, and fistulectomy. Variable success rates from 30 to 80 per cent have been reported. Ligation of intersphincteric fistula tract (LIFT), first described in 2007, has a reported success rate from 40 to 94 per cent. The objective of this study was to study our results of the LIFT procedure for refractory perianal fistulas. We conducted a retrospective 18-month review of consecutive patients with refractory perianal disease treated with the LIFT procedure at an academic, tertiary, colorectal practice. All patients undergoing a LIFT procedure for anal fistula from August 2010 to August 2012 were included in the study. The primary end points were success rates at 1 month and 3 months. Secondary end points were postoperative complications and maintenance of continence. Twenty patients underwent LIFT procedures of whom nine had previously failed treatments. Mean age was 45 years and included 12 male and eight female patients. Success rate at 1 month was 70 per cent (14 patients) and at 3 months was 80 per cent (16 patients). Success rates for patients with previously failed attempts were 67 per cent at 1 month and 89 per cent at 3 months. Continence was maintained in 100 per cent of patients. Our data support the use of the LIFT procedure for refractory perirectal fistulas.
Related JoVE Video
Robot-assisted rectopexy and colpopexy for rectal prolapse.
Int Urogynecol J
PUBLISHED: 06-27-2013
Show Abstract
Hide Abstract
This video demonstrates a technique for robot-assisted combined rectopexy with colpopexy, but without the use of mesh for rectal prolapse.
Related JoVE Video
Vandetanib and the management of advanced medullary thyroid cancer.
Curr Opin Oncol
PUBLISHED: 05-11-2013
Show Abstract
Hide Abstract
Vandetanib is a small molecule tyrosine kinase inhibitor that has been recently approved as an orphan drug for the treatment of patients with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC).
Related JoVE Video
Pilot study of a brief intervention based on the theory of planned behaviour and self-identity to increase chlamydia testing among young people living in deprived areas.
Br J Health Psychol
PUBLISHED: 04-30-2013
Show Abstract
Hide Abstract
This study sought to estimate the effects of a novel intervention, compared with usual chlamydia testing promotion, on chlamydia test uptake and intentions among young people living in deprived areas. The intervention was based on the theory of planned behaviour, augmented with self-identity, and targeted the significant predictors of chlamydia testing intentions identified in the previous research.
Related JoVE Video
Factors impacting echocardiographic imaging after the fontan procedure: a report from the pediatric heart network fontan cross-sectional study.
Echocardiography
PUBLISHED: 04-25-2013
Show Abstract
Hide Abstract
Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great arteries, systemic veins, and pulmonary veins were less likely to be adequately imaged than other cardiac structures. Quantitative analysis of ventricular volume was possible in 76% overall, but only 41% of those with mixed ventricular morphology. Factors independently associated with better quality included younger age, levocardia, acquisition of the echocardiogram at a longer time since the beginning of enrollment, absence of a pulmonary artery stent, and clinical site. Patient and center-specific factors are associated with echocardiographic quality after the Fontan procedure. Increased familiarity and experience with a standard imaging protocol is likely to result in improved quality.
Related JoVE Video
Estimated Albumin Excretion Rate Versus Urine Albumin-Creatinine Ratio for the Estimation of Measured Albumin Excretion Rate: Derivation and Validation of an Estimated Albumin Excretion Rate Equation.
Am. J. Kidney Dis.
PUBLISHED: 04-17-2013
Show Abstract
Hide Abstract
Glomerular filtration rate estimation equations use demographic variables to account for predicted differences in creatinine generation rate. In contrast, assessment of albuminuria from urine albumin-creatinine ratio (ACR) does not account for these demographic variables, potentially distorting albuminuria prevalence estimates and clinical decision making.
Related JoVE Video
Direct risk standardisation: a new method for comparing casemix adjusted event rates using complex models.
BMC Med Res Methodol
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
Comparison of outcomes between populations or centres may be confounded by any casemix differences and standardisation is carried out to avoid this. However, when the casemix adjustment models are large and complex, direct standardisation has been described as "practically impossible", and indirect standardisation may lead to unfair comparisons. We propose a new method of directly standardising for risk rather than standardising for casemix which overcomes these problems.
Related JoVE Video
Discovery and structure-activity relationships of pyrrolone antimalarials.
J. Med. Chem.
PUBLISHED: 03-21-2013
Show Abstract
Hide Abstract
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC(50) ~ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
Related JoVE Video
Transverse incisions for resection of ileocolic Crohns disease.
Am Surg
PUBLISHED: 03-07-2013
Show Abstract
Hide Abstract
Laparoscopic ileocecectomy is advocated as the ideal surgical approach for ileocecal Crohns disease. Our experience suggests that equivalent outcomes are accomplished through a small right lower quadrant (RLQ) transverse incision in this patient population. We conducted a retrospective chart review of 39 patients undergoing ileocectomy for Crohns disease using a RLQ transverse incision between 1991 and 2009. The mean operative time was 99 minutes with a mean length of hospital stay of 4.2 days and mean duration until return of bowel function of 2.9 days. There were no deaths or major complications. Long-term follow-up revealed four patients (13%) who required hospitalization for small bowel obstructions, one patient (3%) developed an incisional hernia, and no patients required an ileostomy. Ileocecectomy performed for Crohns disease using a RLQ transverse incision yielded similar hospital lengths of stay and time to return of bowel function as those published for laparoscopic resection. This approach may result in shorter operative times when compared with the inexperienced surgeon performing a laparoscopic resection. Long-term follow-up revealed the risk for future RLQ ileostomy is low and the development of hernias or bowel obstruction is unlikely.
Related JoVE Video
The African coelacanth genome provides insights into tetrapod evolution.
Chris T Amemiya, Jessica Alföldi, Alison P Lee, Shaohua Fan, Hervé Philippe, Iain MacCallum, Ingo Braasch, Tereza Manousaki, Igor Schneider, Nicolas Rohner, Chris Organ, Domitille Chalopin, Jeramiah J Smith, Mark Robinson, Rosemary A Dorrington, Marco Gerdol, Bronwen Aken, Maria Assunta Biscotti, Marco Barucca, Denis Baurain, Aaron M Berlin, Gregory L Blatch, Francesco Buonocore, Thorsten Burmester, Michael S Campbell, Adriana Canapa, John P Cannon, Alan Christoffels, Gianluca De Moro, Adrienne L Edkins, Lin Fan, Anna Maria Fausto, Nathalie Feiner, Mariko Forconi, Junaid Gamieldien, Sante Gnerre, Andreas Gnirke, Jared V Goldstone, Wilfried Haerty, Mark E Hahn, Uljana Hesse, Steve Hoffmann, Jeremy Johnson, Sibel I Karchner, Shigehiro Kuraku, Marcia Lara, Joshua Z Levin, Gary W Litman, Evan Mauceli, Tsutomu Miyake, M Gail Mueller, David R Nelson, Anne Nitsche, Ettore Olmo, Tatsuya Ota, Alberto Pallavicini, Sumir Panji, Barbara Picone, Chris P Ponting, Sonja J Prohaska, Dariusz Przybylski, Nil Ratan Saha, Vydianathan Ravi, Filipe J Ribeiro, Tatjana Sauka-Spengler, Giuseppe Scapigliati, Stephen M J Searle, Ted Sharpe, Oleg Simakov, Peter F Stadler, John J Stegeman, Kenta Sumiyama, Diana Tabbaa, Hakim Tafer, Jason Turner-Maier, Peter Van Heusden, Simon White, Louise Williams, Mark Yandell, Henner Brinkmann, Jean-Nicolas Volff, Clifford J Tabin, Neil Shubin, Manfred Schartl, David B Jaffe, John H Postlethwait, Byrappa Venkatesh, Federica Di Palma, Eric S Lander, Axel Meyer, Kerstin Lindblad-Toh.
Nature
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
The discovery of a living coelacanth specimen in 1938 was remarkable, as this lineage of lobe-finned fish was thought to have become extinct 70 million years ago. The modern coelacanth looks remarkably similar to many of its ancient relatives, and its evolutionary proximity to our own fish ancestors provides a glimpse of the fish that first walked on land. Here we report the genome sequence of the African coelacanth, Latimeria chalumnae. Through a phylogenomic analysis, we conclude that the lungfish, and not the coelacanth, is the closest living relative of tetrapods. Coelacanth protein-coding genes are significantly more slowly evolving than those of tetrapods, unlike other genomic features. Analyses of changes in genes and regulatory elements during the vertebrate adaptation to land highlight genes involved in immunity, nitrogen excretion and the development of fins, tail, ear, eye, brain and olfaction. Functional assays of enhancers involved in the fin-to-limb transition and in the emergence of extra-embryonic tissues show the importance of the coelacanth genome as a blueprint for understanding tetrapod evolution.
Related JoVE Video
3-(Oxazolo[4,5-b]pyridin-2-yl)anilides as a novel class of potent inhibitors for the kinetoplastid Trypanosoma brucei, the causative agent for human African trypanosomiasis.
Eur J Med Chem
PUBLISHED: 02-17-2013
Show Abstract
Hide Abstract
A whole organism high-throughput screen of approximately 87,000 compounds against Trypanosoma brucei brucei led to the recent discovery of several novel compound classes with low micromolar activity against this organism and without appreciable cytotoxicity to mammalian cells. Herein we report a structure-activity relationship (SAR) investigation around one of these hit classes, the 3-(oxazolo[4,5-b]pyridin-2-yl)anilides. Sharp SAR is revealed, with our most active compound (5) exhibiting an IC?? of 91 nM against the human pathogenic strain T.b. rhodesiense and being more than 700 times less toxic towards the L6 mammalian cell line. Physicochemical properties are attractive for many compounds in this series. For the most potent representatives, we show that solubility and metabolic stability are key parameters to target during future optimisation.
Related JoVE Video
Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.
J Obes
PUBLISHED: 02-01-2013
Show Abstract
Hide Abstract
Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- ? 2 (PPAR ? 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR ? increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR ? agonist, would normalize IUGR adipose deposition in association with increased PPAR ? , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR ? expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.
Related JoVE Video
Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution.
Nat. Genet.
PUBLISHED: 01-31-2013
Show Abstract
Hide Abstract
Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ?500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey whole-genome sequence and assembly. We note challenges faced owing to its high content of repetitive elements and GC bases, as well as the absence of broad-scale sequence information from closely related species. Analyses of the assembly indicate that two whole-genome duplications likely occurred before the divergence of ancestral lamprey and gnathostome lineages. Moreover, the results help define key evolutionary events within vertebrate lineages, including the origin of myelin-associated proteins and the development of appendages. The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms.
Related JoVE Video
Genomic diversity and evolution of the head crest in the rock pigeon.
Science
PUBLISHED: 01-31-2013
Show Abstract
Hide Abstract
The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.
Related JoVE Video
Did hospital mortality in England change from 2005 to 2010? A retrospective cohort analysis.
BMC Health Serv Res
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
BACKGROUND: There is some evidence that hospital performance in England measured by the Dr Foster Hospital Standardised Mortality Ratio (HSMR) has improved substantially over the last 10 years. This study explores mortality in-hospital and up to 30 days post-discharge over a five year period to determine whether there have been improvements in case-mix adjusted mortality, to examine if any changes are due to changes in case-mix adjustment variables such as age, sex, method of admission and comorbidity, and to compare changes between hospital trusts. METHODS: Using Hospital Episode Statistics linked to mortality data from the Office for National Statistics the Summary Hospital-Level Mortality Index (SHMI) was calculated for all patients who were discharged or died in general acute hospital trusts in England for the period 01/04/2005 to 30/09/2010. RESULTS: During this five year period the number of admissions rose by 8% but deaths fell by 5%. The SHMI fell by 24% from 112 to 85 over the period, partly due to fewer deaths but partly due to increasing numbers predicted by the SHMI model. Excluding comorbidities from the model the SHMI fell by 18% from 108 to 89 over this period. The reduction was similar in emergency and elective admissions and in all other sub-groups examined. The average quarterly change in SHMI varied considerably between trusts (range: -4.4 to -0.2). CONCLUSIONS: As measured by the SHMI there has been a 24% improvement in mortality in acute general trusts in England over a period of five and a half years. Part of this improvement is an artificial effect caused by changes in the depth of coding of comorbidities and other effects due to change in case-mix or non-constant risk.
Related JoVE Video
Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.).
Genome Biol.
PUBLISHED: 01-04-2013
Show Abstract
Hide Abstract
Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan.
Related JoVE Video
The prognostic implications of macrophages expressing proliferating cell nuclear antigen in breast cancer depend on immune context.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
TUMOR ASSOCIATED MACROPHAGES (TAMS) ARE RECRUITED FROM THE CIRCULATION TO THE TUMOR SITE, AND CAN UNDERGO A SPECTRUM OF PHENOTYPIC CHANGES, WITH TWO CONTRASTING ACTIVATION STATES DESCRIBED IN THE LITERATURE: the M1 and M2 phenotypes. We previously identified a population of TAMs that express proliferating cell nuclear antigen (PCNA) and are associated with high grade, hormone receptor negative breast cancers and poor outcomes. In the present exploratory study we again found that high PCNA(+) TAM counts in pre-treatment tumor biopsies (102 invasive breast cancer cases from the I-SPY 1 Trial, a prospective neoadjuvant trial with serial core biopsies and gene array data) were associated with high grade, hormone receptor negativity, and decreased recurrence free survival. We explored the association of these PCNA(+) TAMs with the expression of M1 and M2 related genes and, contrary to expectation, observed that high PCNA(+) TAM levels were associated with more M1- than M2-related genes. An immune gene signature, derived from cytotoxic T cell and MHC Class II genes (Tc/ClassII), was developed and we found that high PCNA(+) TAM counts, in the context of a low Tc/ClassII signature score, were associated with significantly worse recurrence free survival in all cases and in hormone receptor negative only cases. We observed similar results using a gene signature-proxy for PCNA(+) TAMs in a larger independent set of 425 neoadjuvant-treated breast cancer cases. The results of this exploratory study indicate that high numbers of PCNA(+) TAMs, in the absence of an anti-tumor immune microenvironment (as indicated by a low Tc/ClassII signature score), are associated with poor outcomes in breast cancer patients treated with neoadjuvant chemotherapy. This, along with the observation that PCNA(+) TAMs were associated predominantly with M1-related genes, may provide new insights into the role of the immune microenvironment in breast cancer.
Related JoVE Video
Parent perceptions to promote a healthier lifestyle for their obese child.
Soc Work Health Care
PUBLISHED: 12-06-2011
Show Abstract
Hide Abstract
Parents of children referred to a pediatric multidisciplinary weight-management clinic were queried regarding the importance of and their readiness to promote healthy lifestyle behaviors with their children and also regarding their confidence in their ability to adopt those changes. Among the 193 childrens parents who completed a questionnaire (93.7% response), greater than 75% of respondents recognized the importance of healthy eating and physical activity, and many indicated feeling both confident and ready to make changes. Surprisingly, even among those not confident, parents also indicated they were ready to change their childs eating (p < .001). This study explores the discrepancy between parents indicating a high level of importance and readiness to promote healthy lifestyle behaviors but having less confidence that they would actually be able to enact change.
Related JoVE Video
Evolution of functionally diverse alleles associated with PTC bitter taste sensitivity in Africa.
Mol. Biol. Evol.
PUBLISHED: 11-29-2011
Show Abstract
Hide Abstract
Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.
Related JoVE Video
Prognosis for the recovery of surgeons from chemical dependency: a 5-year outcome study.
Arch Surg
PUBLISHED: 11-23-2011
Show Abstract
Hide Abstract
Rates of relapse, monitoring contract completion, and return to medical practice may differ between surgeons and nonsurgeons being monitored for diagnosed substance use disorders.
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.