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Find video protocols related to scientific articles indexed in Pubmed.
Atomic connectomics signatures for characterization and differentiation of mild cognitive impairment.
Brain Imaging Behav
PUBLISHED: 10-31-2014
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In recent years, functional connectomics signatures have been shown to be a very valuable tool in characterizing and differentiating brain disorders from normal controls. However, if the functional connectivity alterations in a brain disease are localized within sub-networks of a connectome, then accurate identification of such disease-specific sub-networks is critical and this capability entails both fine-granularity definition of connectome nodes and effective clustering of connectome nodes into disease-specific and non-disease-specific sub-networks. In this work, we adopted the recently developed DICCCOL (dense individualized and common connectivity-based cortical landmarks) system as a fine-granularity high-resolution connectome construction method to deal with the first issue, and employed an effective variant of non-negative matrix factorization (NMF) method to pinpoint disease-specific sub-networks, which we called atomic connectomics signatures in this work. We have implemented and applied this novel framework to two mild cognitive impairment (MCI) datasets from two different research centers, and our experimental results demonstrated that the derived atomic connectomics signatures can effectively characterize and differentiate MCI patients from their normal controls. In general, our work contributed a novel computational framework for deriving descriptive and distinctive atomic connectomics signatures in brain disorders.
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Global Public Health Impact of Recovered Supplies from Operating Rooms: A Critical Analysis with National Implications.
World J Surg
PUBLISHED: 10-17-2014
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In modern operating rooms, clean and unused medical supplies are routinely discarded and can be effectively recovered and redistributed abroad to alleviate the environmental burden of donor hospitals and to generate substantial health benefits at resource-poor recipient institutions.
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Characterizing and Differentiating Brain State Dynamics via Hidden Markov Models.
Brain Topogr
PUBLISHED: 09-30-2014
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Functional connectivity measured from resting state fMRI (R-fMRI) data has been widely used to examine the brain's functional activities and has been recently used to characterize and differentiate brain conditions. However, the dynamical transition patterns of the brain's functional states have been less explored. In this work, we propose a novel computational framework to quantitatively characterize the brain state dynamics via hidden Markov models (HMMs) learned from the observations of temporally dynamic functional connectomics, denoted as functional connectome states. The framework has been applied to the R-fMRI dataset including 44 post-traumatic stress disorder (PTSD) patients and 51 normal control (NC) subjects. Experimental results show that both PTSD and NC brains were undergoing remarkable changes in resting state and mainly transiting amongst a few brain states. Interestingly, further prediction with the best-matched HMM demonstrates that PTSD would enter into, but could not disengage from, a negative mood state. Importantly, 84 % of PTSD patients and 86 % of NC subjects are successfully classified via multiple HMMs using majority voting.
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Differentiating biliary atresia from other causes of cholestatic jaundice.
Am Surg
PUBLISHED: 09-09-2014
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Diagnosis of biliary atresia (BA) in infants presenting with cholestatic jaundice (CJ) requires exploratory surgery with cholangiography. However, the lack of a standardized approach to preoperative evaluation of infants with CJ can lead to a high number of negative surgical explorations. We reviewed our experience with CJ and BA to determine preoperative variables that might reliably identify BA. Infants explored for possible BA over a 5-year period were retrospectively reviewed. Preoperative clinical indices and liver biopsy results were reviewed. Statistical analysis was conducted by Student's t test and Fisher's exact test (P < 0.05). Twenty patients were identified, 10 with BA and 10 without (50% negative exploration rate). Nuclear cholescintigraphy (HIDA) excretion into the gastrointestinal tract was absent in all BA and in 8 of 10 without BA. Hepatomegaly was more common in the BA group (OR = 9.3, P = 0.07). BA had higher mean (± standard error) serum gamma-glutamyl transpeptidase levels (542 ± 130 vs 139 ± 25.8 U/L in non-BA, P = 0.03). There were insignificant differences in sex, type of feeding, TPN exposure and sepsis between the two groups. Although our small sample size limits conclusions, we suggest screening infants with CJ by measuring GGT levels, absence of hepatomegaly, presence of cholic stools and/or excretion on HIDA scan to undergo pecutaneous liver biopsy given the lower likelihood of BA necessary.
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Echocardiographic assessment and guidance in minimally invasive surgical device closure of perimembranous ventricular septal defects.
Heart Surg Forum
PUBLISHED: 09-03-2014
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The primary aim of this study was to explore the safety and feasibility of minimally invasive surgical device closure of perimembranous ventricular septal defects (PMVSDs) in children using echocardiography for preoperative assessment and intraoperative guidance.
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A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs.
PLoS ONE
PUBLISHED: 08-26-2014
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A hypomagnetic field is an extremely weak magnetic field--it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-?B ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.
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Bridging Laboratory and Large Scale Production: Preparation and In Vitro-Evaluation of Photosensitizer-Loaded Nanocarrier Devices for Targeted Drug Delivery.
Pharm. Res.
PUBLISHED: 08-25-2014
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Industrial production of nanosized drug delivery devices is still an obstacle to the commercialization of nanomedicines. This study encompasses the development of nanoparticles for peroral application in photodynamic therapy, optimization according to the selected product specifications, and the translation into a continuous flow process.
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Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men.
Clin. Lab.
PUBLISHED: 08-20-2014
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The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men.
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Predicting Utility of Exercise Tests Based on History/Holter in Patients with Premature Ventricular Contractions.
Pediatr Cardiol
PUBLISHED: 08-19-2014
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Premature ventricular contractions (PVCs) are considered benign in patients with structurally normal hearts, particularly if they suppress with exercise. Catecholaminergic polymorphic ventricular tachycardia (CPVT) requires exercise testing to unmask the malignant phenotype. We studied risk factors and Holter monitor variables to help predict the necessity of exercise testing in patients with PVCs. We retrospectively reviewed 81 patients with PVCs that suppressed at peak exercise and structurally normal hearts referred to the exercise laboratory in 2011. We reviewed 11 patients from 2003 to 2012 whose PVCs were augmented at peak exercise (mean age 13 ± 4 years; 52 % male, 180 exercise studies). We recorded clinical risk factors and comorbidities (family history of arrhythmia or sudden unexpected death [SUD], presence of syncope) and Holter testing parameters. Family history of VT or SUD (P = 0.011) and presence of VT on Holter (P = 0.011) were significant in predicting failure of PVCs to suppress at peak heart rate on exercise testing. Syncope was not statistically significant in predicting suppression (P = 0.18); however, CPVT was diagnosed in four patients with syncope during exercise. Quantity of PVCs, Lown grade, couplets on Holter, monomorphism, and PVC elimination at peak heart rate on Holter were not predictors of PVC suppression on exercise testing. Patients with syncope during exercise, family history of arrhythmia or SUD, or a Holter monitor showing VT warrant exercise testing to assess for CPVT.
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The Combination Use of Platelet-Rich Fibrin and Treated Dentin Matrix for Tooth Root Regeneration by Cell Homing.
Tissue Eng Part A
PUBLISHED: 08-11-2014
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Endogenous regeneration through cell homing provides an alternative approach for tissue regeneration, except cell transplantation, especially considering clinical translation. However, tooth root regeneration through cell homing remains a provocative approach in need of intensive study. Both platelet-rich fibrin (PRF) and treated dentin matrix (TDM) are warehouses of various growth factors, which can promote cell homing. We hypothesized that endogenous stem cells are able to sense biological cues from PRF membrane and TDM, and contribute to the regeneration of tooth root, including soft and hard periodontal tissues. Therefore, the biological effects of canine PRF and TDM on periodontal ligament stem cells (PDLSCs) and bone marrow mesenchymal stem cells (BMSCs) were evaluated respectively in vitro. Beagle dogs were used as orthotopic transplantation model. It was found that PRF significantly recruited and stimulated the proliferation of PDLSCs and BMSCs in vitro. Together, PRF and TDM induced cell differentiation by upregulating the mineralization-related gene expression of bone sialoprotein (BSP) and osteopotin (OPN) after 7 days coculture. In vivo, transplantation of autologous PRF and allogeneic TDM into fresh tooth extraction socket achieved successful root regeneration 3 months postsurgery, characterized by the regeneration of cementum and periodontal ligament (PDL)-like tissues with orientated fibers, indicative of functional restoration. The results suggest that tooth root connected to the alveolar bone by cementum-PDL complex can be regenerated through the implantation of PRF and TDM in a tooth socket microenvironment, probably by homing of BMSCs and PDLSCs. Furthermore, bioactive cues and inductive microenvironment are key factors for endogenous regeneration. This approach provides a tangible pathway toward clinical translation.
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Correlates of self-reported dietary cruciferous vegetable intake and urinary isothiocyanate from two cohorts in China.
Public Health Nutr
PUBLISHED: 08-08-2014
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To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors.
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The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.
Cell Reprogram
PUBLISHED: 07-29-2014
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Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases.
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Characterization of homologous and heterologous interactions between viroplasm proteins P6 and P9-1 of the fijivirus southern rice black-streaked dwarf virus.
Arch. Virol.
PUBLISHED: 07-19-2014
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P6 of southern rice black-streaked dwarf virus (SRBSDV) is a multifunctional protein that is involved in the formation of viroplasms by interacting with P5-1. Here, we used yeast two-hybrid and bimolecular fluorescence complementation assays to show that there were homologous and heterologous interactions between SRBSDV P6 and P9-1 in yeast and plant cells. Mutational analysis showed that the N-terminal region (residues 1-93) of P6 was necessary for the interaction between P6 and P9-1. Self-interactions only occurred between the full-length P6 or P9-1. P9-1 was able to form viroplasm-like inclusion structures alone in the absence of other viral proteins.
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Tumours induced by a plant virus are derived from vascular tissue and have multiple intercellular gateways that facilitate virus movement.
J. Exp. Bot.
PUBLISHED: 07-01-2014
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Structural studies showed that tumours induced by Southern rice black-streaked dwarf virus (SRBSDV; genus Fijivirus, family Reoviridae) were highly organized, modified phloem, composed of sclerenchyma, vessels, hyperplastic phloem parenchyma and sieve elements (SEs). Only parenchyma and SEs were invaded by the virus. There was a special region that consisted exclusively of SEs without the usual companion cells and a new flexible type of intercellular gateway was observed on all SE-SE interfaces in this region. These flexible gateways significantly increased the intercellular contacts and thus enhanced potential symplastic transport in the tumour. Flexible gateways were structurally similar to compressed plasmodesmata but were able to accommodate complete SRBSDV virions (~80 nm diameter). Virions were also found in sieve-pore gateways, providing strong evidence for the movement of a virus with large virions within phloem tissue and suggesting that the unusual neovascularization of plant virus-induced tumours facilitated virus spread. A working model for the spread of tumour-inducing reoviruses in plants is presented.
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Positive association between IL-16 rs11556218 T/G polymorphism and cancer risk: a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-28-2014
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Interleukin-16 (IL-16) is a multifunctional cytokine which plays a key role in inflammatory and autoimmune diseases as well as in cancer. Genetic polymorphisms of IL-16 have been implicated in susceptibility to cancer. However, associations remain inconclusive. The present meta-analysis was therefore carried out to establish a more conclusive association of IL-16 polymorphisms with cancer risk.
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Novel human H7N9 influenza virus in China.
Integr Zool
PUBLISHED: 06-24-2014
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Outbreaks of H7N9 avian influenza in humans in 5 provinces and 2 municipalities of China have reawakened concern that avian influenza viruses may again cross species barriers to infect the human population and thereby initiate a new influenza pandemic. Evolutionary analysis shows that human H7N9 influenza viruses originated from the H9N2, H7N3 and H11N9 avian viruses, and that it is as a novel reassortment influenza virus. This article reviews current knowledge on 11 subtypes of influenza A virus from human which can cause human infections.
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Characterization of pediatric acute lymphoblastic leukemia survival patterns by age at diagnosis.
J Cancer Epidemiol
PUBLISHED: 06-19-2014
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Age at diagnosis is a key prognostic factor in pediatric acute lymphoblastic leukemia (ALL) survivorship. However, literature providing adequate assessment of the survival variability by age at diagnosis is scarce. The aim of this study is to assess the impact of this prognostic factor in pediatric ALL survival. We estimated incidence rate of mortality, 5-year survival rate, Kaplan-Meier survival function, and hazard ratio using the Surveillance Epidemiology and End Results (SEER) data during 1973-2009. There was significant variability in pediatric ALL survival by age at diagnosis. Survival peaked among children diagnosed at 1-4 years and steadily declined among those diagnosed at older ages. Infants (<1 year) had the lowest survivorship. In a multivariable Cox proportional hazard model stratified by year of diagnosis, those diagnosed in age groups 1-4, 5-9, 10-14, and 15-19 years were 82%, 75%, 57%, and 32% less likely to die compared to children diagnosed in infancy, respectively. Age at diagnosis remained to be a crucial determinant of the survival variability of pediatric ALL patients, after adjusting for sex, race, radiation therapy, primary tumor sites, immunophenotype, and year of diagnosis. Further research is warranted to disentangle the effects of age-dependent biological and environmental processes on this association.
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Lack of association between CYP1A1 polymorphisms and risk of bladder cancer: a meta-analysis.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-18-2014
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The effects of CYP1A1 gene polymorphisms on the risk of bladder cancer (BC) remain controversial. We carried out a meta-analysis to clarify the role of CYP1A1 gene polymorphisms in BC.
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Molecular analysis of single oocyst of Eimeria by whole genome amplification (WGA) based nested PCR.
Exp. Parasitol.
PUBLISHED: 06-16-2014
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PCR-based molecular tools are widely used for the identification and characterization of protozoa. Here we report the molecular analysis of Eimeria species using combined methods of whole genome amplification (WGA) and nested PCR. Single oocyst of Eimeria stiedai or Eimeriamedia was directly used for random amplification of the genomic DNA with either primer extension preamplification (PEP) or multiple displacement amplification (MDA), and then the WGA product was used as template in nested PCR with species-specific primers for ITS-1, 18S rDNA and 23S rDNA of E. stiedai and E. media. WGA-based PCR was successful for the amplification of these genes from single oocyst. For the species identification of single oocyst isolated from mixed E. stiedai or E. media, the results from WGA-based PCR were exactly in accordance with those from morphological identification, suggesting the availability of this method in molecular analysis of eimerian parasites at the single oocyst level. WGA-based PCR method can also be applied for the identification and genetic characterization of other protists.
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Lack of association between LUM rs3759223 polymorphism and high myopia.
Optom Vis Sci
PUBLISHED: 06-14-2014
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Previous evidence has indicated that the lumican (LUM) gene is a candidate susceptibility gene of high myopia; however, the association between LUM promoter regions rs3759223 polymorphism and high myopia remains controversial and ambiguous. This study performed a meta-analysis to clarify the association between the rs3759223 polymorphism and high myopia risk.
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Overactivated neddylation pathway as a therapeutic target in lung cancer.
J. Natl. Cancer Inst.
PUBLISHED: 06-01-2014
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A number of oncoproteins and tumor suppressors are known to be neddylated, but whether the neddylation pathway is entirely activated in human cancer remains unexplored.
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Nitrate reduction pathway in an anaerobic acidification reactor and its effect on acid fermentation.
J. Biosci. Bioeng.
PUBLISHED: 05-28-2014
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This study investigated the performance of a reactor in which denitrification was integrated into the anaerobic acidogenic process. Industrial wastewater cassava stillage was used as the carbon source, and the nitrate reduction pathway and its effects on acid fermentation were examined. Results from batch and semi-continuous tests showed that the presence of nitrate did not inhibit anaerobic acidification but altered the distribution of volatile fatty acid (VFA) species. Nitrate reduction was attributable to denitrification and to dissimilatory nitrate reduction to ammonia (DNRA). The ratio of DNRA to denitrification was proportional to the ratio of [Formula: see text] . After 130 days of semi-continuous operation, denitrification removal efficiency accounted for about 60% at a [Formula: see text] of 50. The proportional distribution of VFAs was acetate, followed by propionate and then butyrate. The polymerase chain reaction-denaturing gradient gel electrophoresis results confirmed the contributions of denitrification and DNRA in the nitrate-amended reactor and showed that the addition of nitrate enriched the structure of the bacterial community, but did not suppress the activity of acid-producing bacteria.
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The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis.
J. Neuroimmunol.
PUBLISHED: 05-27-2014
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We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation. AS101 blocked the activation of transcriptional factor NFAT, Stat3, and ROR?t, and increased activation of Erk1/2, suggesting a mechanism of action of AS101. We further demonstrated that AS101 was effective in amelioration of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Finally, by real-time PCR analysis we showed that AS101 reduces the IL-17, IFN-?, GM-CSF, and IL-6 mRNA expression in inflammatory cells of spinal cords. Additionally, flow cytometry analysis also indicated that the CD4+ T cells and IL-17 and GM-CSF-producing cells were reduced in the spinal cords of AS101 treated mice compared to those treated with PBS.
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pH-adjustment strategy for volatile fatty acid production from high-strength wastewater for biological nutrient removal.
Water Sci. Technol.
PUBLISHED: 05-22-2014
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Volatile fatty acid (VFA) production from three types of high-strength organic wastewater (cassava thin stillage, starch wastewater and yellow-wine processing wastewater) were compared. The results showed that cassava thin stillage was the most suitable substrate, based on its high specific VFA production (0.68 g chemical oxygen demand (COD)/g initial soluble chemical oxygen demand (SCOD)) and yield (0.72 g COD/g SCOD) as well as low nutrient content in the substrate and fermented liquid. The acid fermented cassava thin stillage was evaluated and compared with sodium acetate in a sequencing batch reactor system. Total nitrogen removal efficiency was higher with fermented cassava thin stillage than with the sodium acetate. The effects of pH and a pH-adjustment strategy on VFA production and composition were determined using cassava thin stillage. At an initial pH range of 7-11, a relatively high VFA concentration of about 9 g COD/L was obtained. The specific VFA production (g COD/g initial SCOD) increased from 0.27 to 0.47 to 0.67 at pH 8 and from 0.26 to 0.68 to 0.81 at pH 9 (initial pH, interval pH, and constant pH adjustment, respectively). The dominant VFA species changed significantly with the increasing frequency of the pH adjustment. Further studies will examine the metabolic pathways responsible for VFA composition.
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Unequal allocation of excitation energy between photosystem II and I reduces cyanolichen photosynthesis in blue light.
Plant Cell Physiol.
PUBLISHED: 05-19-2014
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Photosynthesis was compared in two cyanobacterial lichens (Lobaria hallii and Peltigera praetextata) and two green algal lichens (Lobaria pulmonaria and Peltigera leucophlebia) exposed to red, green or blue light. Cyanolichens had substantially lower photosynthetic CO(2) uptake and O(2) evolution than the green algal lichens in blue light, but slightly higher photosynthesis in red and green light. The effective quantum yield of photosystem (PS) II (?(PSII)) decreased with increasing red and green light for all species, but in blue light this response occurred in green algal lichens only. Cyanolichen ?(PSII) increased with increasing blue light at low irradiances, but decreased at stronger exposures. However, after adding red light the efficiency of blue light for photosynthetic O(2) evolution increased by 2.4 times. Because phycobilisomes associated with PSII have a low blue light absorption, our results are consistent with blue light absorption mainly by Chl in PSI. Thereby, unequal allocation of excitation energy between PSII and PSI results in low cyanolichen photosynthesis under blue light. This is new knowledge in the science of lichenology with important implications for e.g. the reliability of using Chl fluorometers with blue light for cyanolichens.
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Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis.
Ren Fail
PUBLISHED: 05-15-2014
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The relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the susceptibility of diabetes remains inclusive or controversial. For better understanding of the influence of MTHFR A1298C polymorphism on diabetes risk, we performed this meta-analysis.
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An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-13-2014
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Various studies have evaluated the relationship between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusions have been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whether XRCC1 Arg399Gln polymorphism confers susceptibility to HCC.
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Fabrication of polyHEMA grids by micromolding in capillaries for cell patterning and single-cell arrays.
J. Biomed. Mater. Res. Part B Appl. Biomater.
PUBLISHED: 05-10-2014
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Control of cell adhesion and growth by microfabrication technology and surface chemistry is important in an increasing number of applications in biotechnology and medicine. In this study, we developed a method to fabricate (2-hydroxyethyl methacrylate) (polyHEMA) grids on glass by micromolding in capillaries (MIMIC). As a non-fouling biomaterial, polyHEMA was used to inhibit the nonspecific bonding of cells, whereas the glass surface provided a cell adhesive background. The polyHEMA chemical barrier was directly obtained using MIMIC without surface modification, and the microchannel networks used for capillarity were easily achieved by reversibly bonding the polydimethylsiloxane (PDMS)mold and the glass. After fabrication of the polyHEMA micropattern, individual cytophilic microwells surrounded by cytophobic sidewalls were presented on the glass surface. The polyHEMA micropattern proved effective in controlling the shape and spreading of cells, and square-shaped mouse osteoblast MC3T3-E1 cells were obtained in microwell arrays after incubation for 3 days. Moreover, the widths of the microwells in this micropattern were optimized for use as single-cell arrays. The proposed method could be a convenient tool in the field of drug screening, stem cell research, and tissue engineering. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2014.
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Towards structural systems pharmacology to study complex diseases and personalized medicine.
PLoS Comput. Biol.
PUBLISHED: 05-01-2014
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Genome-Wide Association Studies (GWAS), whole genome sequencing, and high-throughput omics techniques have generated vast amounts of genotypic and molecular phenotypic data. However, these data have not yet been fully explored to improve the effectiveness and efficiency of drug discovery, which continues along a one-drug-one-target-one-disease paradigm. As a partial consequence, both the cost to launch a new drug and the attrition rate are increasing. Systems pharmacology and pharmacogenomics are emerging to exploit the available data and potentially reverse this trend, but, as we argue here, more is needed. To understand the impact of genetic, epigenetic, and environmental factors on drug action, we must study the structural energetics and dynamics of molecular interactions in the context of the whole human genome and interactome. Such an approach requires an integrative modeling framework for drug action that leverages advances in data-driven statistical modeling and mechanism-based multiscale modeling and transforms heterogeneous data from GWAS, high-throughput sequencing, structural genomics, functional genomics, and chemical genomics into unified knowledge. This is not a small task, but, as reviewed here, progress is being made towards the final goal of personalized medicines for the treatment of complex diseases.
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Regulation of Rad51 promoter.
Cell Cycle
PUBLISHED: 04-29-2014
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The DNA double-strand break repair and homologous recombination protein Rad51 is overexpressed in the majority of human cancers. This correlates with therapy resistance and decreased patient survival. We previously showed that constructs containing Rad51 promoter fused to a reporter gene are, on average, 850-fold more active in cancer cells than in normal cells. It is not well understood what factors and sequences regulate the Rad51 promoter and cause its high activity in cancerous cells. Here we characterized regulatory regions and examined genetic requirements for oncogenic stimulation of the Rad51 promoter. We identified specific regions responsible for up- and downregulation of the Rad51 promoter in cancerous cells. Furthermore, we show that Rad51 expression is positively regulated by EGR1 transcription factor. We then modeled the malignant transformation process by expressing a set of oncoproteins in normal human fibroblasts. Expression of different combinations of SV40 large T antigen, oncogenic Ras and SV40 small T antigen resulted in step-wise increase in Rad51 promoter activity, with all the 3 oncoproteins together leading to a 47-fold increase in expression. Cumulatively, these results suggest that Rad51 promoter is regulated by multiple factors, and that its expression is gradually activated as cells progress toward malignancy.
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Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide.
Antioxid. Redox Signal.
PUBLISHED: 04-29-2014
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Abstract Aims: Mitochondrion is considered as the major source of intracellular reactive oxygen species (ROS). H2S has been reported to be an antioxidant, but its mechanism remains largely elusive. P66Shc is an upstream activator of mitochondrial redox signaling. The aim of this study was to explore whether the antioxidant effect of H2S is mediated by p66Shc. Results: Application of exogenous H2S with its donor, NaHS, or overexpression of its generating enzyme, cystathionine ?-synthase, induced sulfhydration of p66Shc, but inhibited its phosphorylation caused by H2O2/D-galactose in SH-SY5Y cells or in the mice cortex. H2S also decreased mitochondrial ROS production and protected neuronal cells against stress-induced senescence. PKC?II and PP2A are the two key proteins to regulate p66Shc phosphorylation. Although H2S failed to affect the activities of these two proteins, it disrupted their association. Cysteine-59 resides in proximity to serine-36, the phosphorylation site of p66Shc. The C59S mutant attenuated the above-described biological function of H2S. Innovation: We revealed a novel mechanism for the antioxidant effect of H2S and its role in oxidative stress-related diseases. Conclusion: H2S inhibits mitochondrial ROS production via the sulfhydration of Cys-59 residue, which in turn, prevents the phosphorylation of p66Shc. Antioxid. Redox Signal. 00, 000-000.
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Viral mimicking ternary polyplexes: a reduction-controlled hierarchical unpacking vector for gene delivery.
Adv. Mater. Weinheim
PUBLISHED: 04-24-2014
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Reduction-controlled hierarchical unpacking is proposed for the development of virus-mimicking gene carriers. Disulfide-bond-modified hyaluronic acid (HA) is deposited onto the surface of diselenide-conjugated oligoethylenimine/DNA polyplexes to form DNA/OEI-SeSex/HA-SS-COOH (DOS) polyplexes. The cleavage of the disulfide and diselenide bonds is triggered by the gradient GSH level at the tumor site and inside the cells. The transfection efficiency of DOS show significant enhancement over DNA/poly(ethylene imine) (DP) in vitro and in vivo.
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[Effect of PFT-? on apoptosis of spermatogenic cells caused by enorchia].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 04-22-2014
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To determine the molecular mechanism of germ cell apoptosis via investigating the effect of PFT-? on the expression of p53 and bcl-2/bax during experimental cryptorchid cell apoptosis.
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An in vitro study of a titanium surface modified by simvastatin-loaded titania nanotubes-micelles.
J Biomed Nanotechnol
PUBLISHED: 04-18-2014
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To develop an optimized local delivery system of simvastatin (SV) with improved osseointegration of titanium (Ti) implants, SV-loaded poly(ethylene glycol)-poly(epsilon-caprolactone) (PECL) micelles (80 nm in diameter) were loaded in titania nanotube (TNT) arrays (80-100 nm in diameter and 400 nm in length) that were fabricated by anodizing Ti sheets. An in vitro release experiment was performed and revealed that TNTs and micelles can jointly provide a sustained release of SV, and that TNTs alone might function in drug release. The effect of the Ti surface with TNTs or TNTs-micelles on osteoblast-like MG-63 cells was determined by analyzing cell morphology, cytoskeletal arrangement, early adhesion, proliferation, alkaline phosphatase activity, and intracellular and extracellular osteocalcin content. The results indicate that the Ti surface with SV-loaded TNTs-micelles not only has better able to promote early adhesion, spreading and early differentiation of osteoblasts than the Ti surface with TNTs alone but it is able to promote calcification of osteoblasts. Therefore, a Ti surface with TNTs or TNTs-micelles is expected to promote contact osteogenesis of the Ti implant, thus contributing to early osseointegration of the implant, whereas the osteogenic effect of the Ti surface with TNTs-micelles is expected to be stronger. This local delivery system can bridge the gap between basic research and applied science for a wide range of titanium-based orthopedic implants in diverse bone-loss diseases, including osteoporosis.
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Whole-exome sequencing identifies Y1495X of SCN5A to be associated with familial conduction disease and sudden death.
Sci Rep
PUBLISHED: 04-17-2014
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SCN5A mutations have been reported to underlie a variety of inherited arrhythmias, while the complex overlapping phenotype, especially with congenital heart disease (CHD), is rarely reported. The 48-year-old proband underwent a recent syncope during rest. A CHD (tetralogy of Fallot) and conduction disease was revealed by echocardiogram and ultrasonic cardiogram examination. We combined whole-exome sequencing (WES) and bioinformatics strategies to identify the pathogenic gene for this autosomal-dominant cardiac conduction disease (CCD) in a multi-generation pedigree. We examined four members of this family, including three affected and one unaffected. A novel nonsense mutation (Y1495X) in SCN5A was identified in the affected family members. This mutation is predicted to generate a truncated SCN5A protein, which could result in the loss of sodium current, a defined mechanism of SCN5A related arrhythmias. Our study provides evidence that WES is a highly effective approach for genetic analyses of rare clinical phenotypes. Our study also offers accurate genetic testing information for those yet clinically negative relatives.
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Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
Diabetes Res. Clin. Pract.
PUBLISHED: 04-09-2014
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Recent epidemiological studies indicated that use of metformin might decrease the risk of various cancers among patients with type 2 diabetes mellitus (T2DM). However, its influence on pancreatic cancer was controversial. Therefore, we did a meta-analysis of currently available observational studies on the issue.
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[Application of multiplex PCR for the screening of genotyping system for the rare blood groups Fy(a-), s-,k-,Di(b-) and Js(b-)].
Zhonghua Yi Xue Yi Chuan Xue Za Zhi
PUBLISHED: 04-09-2014
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To screen rare blood groups Fy(a-), s-, k-, Di(b-) and Js(b-) in an ethnic Zhuang population.
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Meta-analysis of the association between CR1 polymorphisms and risk of late-onset Alzheimer's disease.
Neurosci. Lett.
PUBLISHED: 04-07-2014
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CR1 polymorphisms have been reported to be associated with late-onset Alzheimer's disease (LOAD) susceptibility. The findings of these studies, however, have been inconsistent. Therefore, we performed a meta-analysis to assess the association between CR1 variants and LOAD susceptibility. We retrieved all relevant studies of the associations between CR1 polymorphisms and the susceptibility to LOAD for the period up to March 30, 2014. The strength of the association between CR1 polymorphisms and LOAD risk was estimated by odds ratios (ORs) and their 95% confidence intervals (CIs). A total of 6 articles were eventually identified with 2752 LOAD cases and 2313 controls for the rs6656401 polymorphism, and 4 studies containing 2547 LOAD cases and 2338 controls were included for the rs3818361 polymorphism. Overall, the pooled data showed that the CR1 rs6656401 polymorphism was significantly associated with LOAD risk in the overall population (A vs. G: OR=1.32, 95%CI=1.17-1.50, P=0.000; AG+AA vs. GG: OR=1.39, 95%CI=1.20-1.61, P=0.000). With respect to the CR1 rs3818361 polymorphism, a statistically significant increased LOAD risk was observed in the overall population (T vs. C: OR=1.24, 95% CI=1.13-1.37, P=0.000; TT+TC vs. CC: OR=1.30, 95% CI=1.15-1.46, P=0.000; TT vs. TC+CC: OR=1.35, 95% CI=1.06-1.71, P=0.014). This meta-analysis demonstrated significant associations of both the CR1 rs6656401 and CR1 rs3818361 polymorphisms with LOAD susceptibility.
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Anti-EGFR MoAb treatment in colorectal cancer: limitations, controversies, and contradictories.
Cancer Chemother. Pharmacol.
PUBLISHED: 04-01-2014
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Anti-epidermal growth-factor receptor (EGFR) monoclonal antibody (MoAb) treatment for chemotherapy refractory or metastatic colorectal cancer has obtained great achievement. However, not every colorectal patient responds to such molecular-targeted agent well. Biomarkers associated with anti-EGFR resistance are not limited to KRAS mutation up to now. It was recently reported that cross-talking molecular effectors interacted with EGFR-related pathway were also negative predictor for anti-EGFR treatment. However, the limited data, controversial results, and contradictories between in vitro and clinical studies restrict the clinical application of these new biomarkers. Although the current theory of tumor microenvironment supported the application of multi-target treatment, the results from the clinical studies were less than expected. Moreover, WHO or RECIST guideline for response assessment in anti-EGFR MoAb treatment was also queried by recent AIO KRK-0306 trial. This review focuses on these controversies, contradictories, and limitations, in order to uncover the unmet needs in current status of anti-EGFR MoAb treatment in colorectal cancer.
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Kidney stones and cardiovascular risk: a meta-analysis of cohort studies.
Am. J. Kidney Dis.
PUBLISHED: 03-26-2014
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Recent epidemiologic evidence suggests an association between kidney stones and incident cardiovascular disease after adjusting for other cardiovascular risk factors, but results are inconsistent.
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Construction of leaky strains and extracellular production of exogenous proteins in recombinant Escherichia coli.
Microb Biotechnol
PUBLISHED: 03-26-2014
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In this study, a strategy of the construction of leaky strains for the extracellular production of target proteins was exploited, in which the genes mrcA, mrcB, pal and lpp (as a control) from Escherichia coli were knocked out by using single- and/or double-gene deletion methods. Then the recombinant strains for the expression of exogenous target proteins including Trx-hPTH (human parathyroid hormone 1-84 coupled with thioredoxin as a fusion partner) and reteplase were reconstructed to test the secretory efficiency of the leaky strains. Finally, the fermentation experiments of the target proteins from these recombinant leaky strains were carried out in basic media (Modified R media) and complex media (Terrific Broth media) in flasks or fermenters. The results demonstrated that the resultant leaky strains were genetically stable and had a similar growth profile in the complex media as compared with the original strain, and the secretory levels of target proteins into Modified R media from the strains with double-gene deletion (up to 88.9%/mrcA lpp-pth) are higher than the excretory levels from the strains with single-gene deletion (up to 71.1%/lpp-pth) and the host E.?coli?JM109 (DE3) (near zero). The highest level of extracellular production of Trx-hPTH in fermenters is up to 680?mg?l(-1).
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Association between Tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis.
Diagn Pathol
PUBLISHED: 03-23-2014
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Tumor necrosis factor-alpha (TNF-?) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-? gene, -308G/A and -238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis.
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Quantitative assessment of CYP2D6 polymorphisms and risk of Alzheimer's disease: a meta-analysis.
J. Neurol. Sci.
PUBLISHED: 03-19-2014
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CYP2D6 gene encoding CYP2D6 enzyme belonging to the cytochrome P450 system has aroused long attention being a candidate gene for Alzheimer's disease (AD), but the results remain inconsistent and underpowered.
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Epidemiologic characterization of 30 confirmed cases of human infection with avian influenza A(H7N9) virus in Hangzhou, China.
BMC Infect. Dis.
PUBLISHED: 03-13-2014
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We examined the clinical and epidemiological characteristics of 30 cases of human infection with avian influenza A(H7N9) virus in Hangzhou and investigated their external environments to provide evidence for contact tracing and disease prevention and control.
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Cryopreserved dentin matrix as a scaffold material for dentin-pulp tissue regeneration.
Biomaterials
PUBLISHED: 03-10-2014
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Cryopreservation has been identified as an efficient approach to preserve tissue engineered products for a long term. Our prior studies have suggested that the treated dentin matrix (TDM) could be an ideal bioactive scaffold for dental tissue regeneration. In this study, we hypothesize that the cryopreservation could effectively maintain the survival and viability of dentinogenesis-related proteins of TDM and the cryopreserved dentin matrix (CDM) would provide the suitable biological scaffold and inductive microenvironment for the regeneration of dentin-pulp like tissue. CDM-3 and CDM-6 were prepared by cryopreserving TDM in liquid nitrogen (-196 °C) with cryoprotectant for 3 months and 6 months, respectively. Various biological characteristics of CDM, including mechanical properties, cell proliferation, and odontogenesis ability, were investigated. To further evaluate the inductive capacity of CDM, human dental follicle cells were encapsulated within CDM, and implanted the scaffold into a mouse model for 8 weeks, and the grafts were harvested and assessed histologically. The CDM showed superior mechanical properties than TDM. Compared to TDM, CDM can release more dentinogenesis-related proteins due to the larger pore diameter. Cell proliferation with the addition of CDM extract liquid was similar to that of TDM in the first five days. Human dental follicle cells, under the effect of CDM extract liquid, highly expressed bone sialoprotein, collagen-1, alkaline phosphatase, indicating that CDM, regarded as the inductive microenvironment, plays an important role in odontogenesis. Most importantly, in vivo, CDM could induce dental follicle cells to regenerate new dentin-pulp like tissues, such as dentinal tubules, predentin, collagen fibers, nerves, and blood vessels which were positive for dentin sialophosphoprotein, dental matrix protein-1, Tubulin, and collagen-1. In conclusion, CDM is an ideal biological scaffold material for human dentin-pulp like tissue regeneration. These findings indicated that TDM could be preserved as the tissue engineering scaffold that is readily available for patient treatments. Furthermore, the success of cryopreservation of TDM may also provide an insight into preserving other bioactive scaffold materials of tissue engineering.
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PP2A inhibitors suppress migration and growth of PANC-1 pancreatic cancer cells through inhibition on the Wnt/?-catenin pathway by phosphorylation and degradation of ?-catenin.
Oncol. Rep.
PUBLISHED: 03-09-2014
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Cantharidin is an active constituent of mylabris, a traditional Chinese medicine, and presents strong anticancer activity in various cell lines. Cantharidin is a potent and selective inhibitor of serine/threonine protein phosphatase 2A (PP2A). Our previous studies revealed the prospect of application of cantharidin, as well as other PP2A inhibitors, in the treatment of pancreatic cancer. However, the mechanisms involved in the anticancer effect of PP2A inhibitors have not been fully explored. The Wnt/??catenin pathway is involved in cell migration and proliferation and participates in the progression of pancreatic cancer. If ??catenin is phosphorylated and degraded, the Wnt/??catenin pathway is blocked. PP2A dephosphorylates ??catenin and keeps the Wnt/??catenin pathway active. In the present study, we found that PP2A inhibitor treatment induced phosphorylation and degradation of ??catenin. The suppression on the migration and growth of PANC?1 pancreatic cancer cells could be attenuated by pretreatment with FH535, a ??catenin pathway inhibitor. Microarray showed that PP2A inhibitor treatment induced expression changes in 13 of 138 genes downstream of the ??catenin pathway. Real?time PCR further confirmed that FH535 attenuated the expression changes induced by PP2A inhibitors in 6 of these 13 candidate genes. These 6 genes, VEGFB, Dkk3, KRT8, NRP1, Cacnalg and WISP2, have been confirmed to participate in the migration and/or growth regulation in previous studies. Thus, the phosphorylation- and degradation-mediated suppression on ??catenin participates in the cytotoxicity of PP2A inhibitors. Our findings may provide insight into the treatment of pancreatic cancer using a targeting PP2A strategy.
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Atomic dynamic functional interaction patterns for characterization of ADHD.
Hum Brain Mapp
PUBLISHED: 03-07-2014
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Modeling abnormal temporal dynamics of functional interactions in psychiatric disorders has been of great interest in the neuroimaging field, and thus a variety of methods have been proposed so far. However, the temporal dynamics and disease-related abnormalities of functional interactions within specific data-driven discovered subnetworks have been rarely explored yet. In this work, we propose a novel computational framework composed of an effective Bayesian connectivity change point model for modeling functional brain interactions and their dynamics simultaneously and an effective variant of nonnegative matrix factorization for assessing the functional interaction abnormalities within subnetworks. This framework has been applied on the resting state fmagnetic resonance imaging (fMRI) datasets of 23 children with attention-deficit/hyperactivity disorder (ADHD) and 45 normal control (NC) children, and has revealed two atomic functional interaction patterns (AFIPs) discovered for ADHD and another two AFIPs derived for NC. Together, these four AFIPs could be grouped into two pairs, one common pair representing the common AFIPs in ADHD and NC, and the other abnormal pair representing the abnormal AFIPs in ADHD. Interestingly, by comparing the abnormal AFIP pair, two data-driven abnormal functional subnetworks are derived. Strikingly, by evaluating the approximation based on the four AFIPs, all of the ADHD children were successfully differentiated from NCs without any false positive.
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Lack of association of INS VNTR polymorphism with polycystic ovary syndrome: a meta-analysis.
J. Assist. Reprod. Genet.
PUBLISHED: 03-04-2014
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An association between the INS VNTR polymorphisms and polycystic ovary syndrome (PCOS) susceptibility has been reported in previous studies, but the results were inconsistent. This study was conducted to explore this association using meta-analysis.
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Gut bacterial translocation may aggravate microinflammation in hemodialysis patients.
Dig. Dis. Sci.
PUBLISHED: 03-02-2014
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Bacterial translocation (BT) promotes microinflammation in predialysis patients with end-stage renal disease (ESRD). However, the change in BT has not been reported in ESRD patients undergoing regular hemodialysis treatment. The present study investigated whether hemodialysis promotes gut BT and microinflammation.
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A phase II randomized study of subcutaneous ixekizumab, an anti-interleukin-17 monoclonal antibody, in rheumatoid arthritis patients who were naive to biologic agents or had an inadequate response to tumor necrosis factor inhibitors.
PUBLISHED: 02-27-2014
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To evaluate ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics-naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors.
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Coffee consumption and prostate cancer risk: an updated meta-analysis.
Cancer Causes Control
PUBLISHED: 02-19-2014
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Many epidemiological studies have been conducted to explore the association between coffee consumption and prostate cancer. However, the results remain inconsistent. We performed a large meta-analysis of relevant studies to derive a more precise estimation of this relationship.
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Regulation of Mcl-1 by constitutive activation of NF-?B contributes to cell viability in human esophageal squamous cell carcinoma cells.
BMC Cancer
PUBLISHED: 02-11-2014
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Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies with a 5-year survival rate less than 15%. Understanding of the molecular mechanisms involved in the pathogenesis of ESCC becomes critical to develop more effective treatments.
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Association between Fc-gamma receptor IIa (CD32) gene polymorphism and malaria susceptibility: a meta-analysis based on 6928 subjects.
Infect. Genet. Evol.
PUBLISHED: 02-10-2014
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Previous studies about the association between the -131R/H polymorphism in the Fc-gamma receptor IIa (Fc?RIIa) gene and malaria susceptibility have yielded conflicting results. The aim of this meta-analysis was to clarify more accurately the association of this polymorphism with malaria risk.
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Effect of superoxide dismutase?entrapped liposomes and protein transduction domain?superoxide dismutase on human umbilical vein endothelial cells.
Mol Med Rep
PUBLISHED: 02-05-2014
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Superoxide dismutases (SOD) are able to remove the superoxide anion free radicals produced by environmental stress and thereby protect cells from being injured by reactive oxygen species. However, SOD is unable to transduce automatically across cell membranes. Protein transduction domains (PTDs) are peptides able to mediate protein delivery into cells and were first observed in the HIV?1 Tat protein. In the present study, PTD (RKKRRQRRR) was fused to Dunaliella salina (Ds)MnSOD to form PTD?DsMnSOD. This was inserted into pET32a to construct the recombinant plasmid pET32a?PTD?DsMnSOD and transduced into E. coli BL21(DE3) to obtain purified PTD?DsMnSOD proteins. Liposome?encapsulated proteins are also able to cross cell membranes. In this study, DsMnSOD proteins were purified and encapsulated by liposomes. The obtained MnSOD, PTD?MnSOD and liposome MnSOD were used to protect human umbilical vein endothelial cells (HUVECs) from injury under oxygen pressure. A cell counting kit 8 was used to test the survival rate of HUVECs and results indicated that the protective effect of MnSOD was limited compared with that of PTD?MnSOD and liposome MnSOD. Thus, PTD and liposomes exhibited improved effects when MnSOD was present in cells.
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CDR3 analysis of TCR V? repertoire of CD8? T cells from chickens infected with Eimeria maxima.
Exp. Parasitol.
PUBLISHED: 02-04-2014
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CD8(+) T cells play a major role in the immune protection of host against the reinfection of Eimeria maxima, the most immunogenic species of eimerian parasites in chickens. To explore the dominant complementarity-determining regions 3 (CDR3) of CD8(+) T cell populations induced by the infection of this parasite, sequence analysis was performed in this study for CDR3 of CD8(+) T cells from E. maxima infected chickens. After 5 days post the third or forth infection, intraepithelial lymphocytes were isolated from the jejunum of bird. CD3(+)CD8(+) T cells were sorted and subjected to total RNA isolation and cDNA preparation. PCR amplification and cloning of the loci between V?1 and C? was conducted for the subsequent sequencing of CDR3 of T cell receptor (TCR). After the forth infection, 2 birds exhibited two same frequent TCR CDR3 sequences, i.e., AKQDWGTGGYSNMI and AGRVLNIQY; while the third bird showed two different frequent TCR CDR3 sequences, AKQGARGHTPLN and AKQDIEVRGPNTPLN. No frequent CDR3 sequence was detected from uninfected birds, though AGRVLNIQY was also found in two uninfected birds. Our result preliminarily demonstrates that frequent CDR3 sequences may exist in E. maxima immunized chickens, encouraging the mining of the immunodominant CD8(+) T cells against E. maxima infection.
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Effects of storage time on Cytomegalovirus DNA stability in plasma determined by quantitative real-time PCR.
J. Virol. Methods
PUBLISHED: 02-01-2014
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Quantitative real-time PCR (QRT-PCR) assays are faster, more precise, and more sensitive quantitative laboratory methods for monitoring serial CMV DNA viral load in patients undergoing organ or hematopoietic stem cell transplantation. Clinical laboratories often face practical concerns about the storage of specimens from these patients to ensure the accuracy and reproducibility of CMV viral load test results. Different studies that have assessed CMV DNA stability have shown mixed results. Therefore, we analyzed CMV DNA stability of 30 EDTA plasma samples in samples containing between 300 and 100,000copies/ml over a 21 day period. The concentration of CMV DNA in all samples stored at 4°C for 21 days did not differ significantly from the baseline viral load (t=0.242, p=0.810), and no trend was evident to indicate continued degradation over a 2 week period.
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Bacterial Motility Patterns Reveal Importance of Exploitation over Exploration in Marine Microhabitats. Part I: Theory.
Biophys. J.
PUBLISHED: 01-28-2014
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Bacteria use different motility patterns to navigate and explore natural habitats. However, how these motility patterns are selected, and what their benefits may be, are not understood. In this article, we analyze the effect of motility patterns on a cell's ability to migrate in a chemical gradient and to localize at the top of the gradient, the two most important characteristics of bacterial chemotaxis. We will focus on two motility patterns, run-tumble and run-reverse-flick, that are observed and characterized in enteric bacterium Escherichia coli and marine bacterium Vibrio alginolyticus, respectively. To make an objective comparison, master equations are developed on the basis of microscopic motions of the bacteria. An unexpected yet significant result is that by adopting the run-reverse-flick motility pattern, a bacterium can reduce its diffusivity without compromising its drift in the chemical gradient. This finding is biologically important as it suggests that the motility pattern can improve a microorganism's ability to sequester nutrients in a competitive environment.
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?/?-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion.
Cell Metab.
PUBLISHED: 01-24-2014
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Glucose metabolism in pancreatic ? cells stimulates insulin granule exocytosis, and this process requires generation of a lipid signal. However, the signals involved in lipid amplification of glucose-stimulated insulin secretion (GSIS) are unknown. Here we show that in ? cells, glucose stimulates production of lipolysis-derived long-chain saturated monoacylglycerols, which further increase upon inhibition of the membrane-bound monoacylglycerol lipase ?/?-Hydrolase Domain-6 (ABHD6). ABHD6 expression in ? cells is inversely proportional to GSIS. Exogenous monoacylglycerols stimulate ? cell insulin secretion and restore GSIS suppressed by the pan-lipase inhibitor orlistat. Whole-body and ?-cell-specific ABHD6-KO mice exhibit enhanced GSIS, and their islets show elevated monoacylglycerol production and insulin secretion in response to glucose. Inhibition of ABHD6 in diabetic mice restores GSIS and improves glucose tolerance. Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion.
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Effect of aspirin and other non-steroidal anti-inflammatory drugs on prostate cancer incidence and mortality: a systematic review and meta-analysis.
BMC Med
PUBLISHED: 01-24-2014
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It has been postulated that non-steroidal anti-inflammatory drugs (NSAIDs) use leads to decreased prostate cancer (PCa) risk. In recent years, NSAIDs' role in PCa development has been extensively studied; however, there is not yet a definitive answer. Moreover, the epidemiological results for NSAIDs' effect on PCa-specific mortality have been inconsistent. Therefore, we performed a meta-analysis to examine the controversy.
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Prospective cohort studies of association between family history of liver cancer and risk of liver cancer.
Int. J. Cancer
PUBLISHED: 01-24-2014
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Uncertainty remains on the relationship between a family history of liver cancer and liver cancer risk in prospective cohort studies in a general population. Thus, we examined this association in 133,014 participants in the Shanghai Women's and Men's Health Studies. Family history of liver cancer was categorized through dichotomous and proportional score approaches. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox proportional hazards models with adjustment for potential confounders. A meta-analysis of observational studies through December 2013 on liver cancer risk in relation to family history of liver cancer was also performed. Study-specific risk estimates were combined using fixed or random effects models depending on whether significant heterogeneity was detected. For the Shanghai Women's and Men's Health Studies, 299 liver cancer cases were identified during follow-up through 2010. Family history of liver cancer was associated with liver cancer risk using both binary indicator (HR = 2.60, 95% CI: 1.77-3.80) and proportional score (high-risk vs. minimal-risk category: HR = 3.03, 95% CI: 1.73-5.31), with increasing HRs for increasing score categories. The meta-analysis also showed an increased risk for those with a family history of liver cancer (relative risk = 2.55, 95% CI: 2.05-3.16). Family history of liver cancer was related to increased risk of liver cancer in Chinese population. This risk is particularly high for those with an affected mother. The "dose-response" of risk with an increasing family history score of liver cancer might further facilitate future cancer prevention programs on identifying individuals with the highest potential liver cancer risk.
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Susceptibility to hepatocellular carcinoma in the Chinese population--associations with interleukin-6 receptor polymorphism.
Tumour Biol.
PUBLISHED: 01-15-2014
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Hepatocellular carcinoma (HCC) is one of the most deadly malignant diseases in the world. Genetic variations in cytokine genes may have an effect on the immune and inflammatory responses which are associated with HBV-HCC. The interleukin-6 (IL-6) receptor is known to be mainly expressed by hepatocytes, neutrophils, monocytes/macrophages, and some lymphocytes, which have been used as prognostic markers in a variety of inflammatory diseases such as rheumatoid arthritis, asthma, and Crohn's disease. To determine the association of IL-6 receptor (IL-6R) polymorphism with the risk of hepatocellular carcinoma (HCC) development in the Chinese population, a hospital based case-control study was designed consisting of 192 subjects with HCC and 192 healthy control subjects. Our results revealed no risk associations (p = 0.064) with rs6684439 CT genotypes. However, rs6684439 TT genotypes were associated with a significantly decreased risk of HBV-related HCC compared with the CC genotype (odds ratio (OR)?= 0.469, 95 % confidence interval (CI) 0.228-0.967, p = 0.040). The data also revealed that subjects with the T allele appeared to have a lower susceptibility to HBV-related HCC than those with the C allele (OR = 0.657, 95 % CI 0.476-0.907, p = 0.011). The present study supports the view that variants in the rs6684439 SNP of IL-6R is associated with a lower risk of HBV-related HCC, and this could provide valuable clues to understanding the mechanisms underlying susceptibility to this malignant disease. Replication and further functional studies should be carried out in the future using larger samples.
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Lack of association between vitamin D receptor gene ApaI, BsmI, and TaqI polymorphisms and primary biliary cirrhosis risk: a meta-analysis.
Tumour Biol.
PUBLISHED: 01-12-2014
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Previous studies have reported the association between vitamin D receptor (VDR) polymorphisms and the risk of primary biliary cirrhosis (PBC), although these results remain controversial. The aim of this meta-analysis was to evaluate the association of three polymorphisms in VDR with PBC risk. The relevant studies were identified through an electronic database search carried out in September 2013. The crude odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the association between VDR polymorphisms and PBC risk. Six eligible studies which met our selection criteria were included. Overall, the ApaI, BsmI, and TaqI polymorphisms in the VDR gene were not associated with PBC risk (ApaI A vs a OR?=?1.132, 95% CI?=?0.870-1.472, p?=?0.355; BsmI B vs b OR?=?1.148, 95% CI?=?0.697-1.891, p?=?0.589; TaqI t vs T OR?=?1.1432, 95% CI?=?0.709-1.841, p?=?0.584). Furthermore, in subgroup analysis by ethnicity for the ApaI, BsmI, and TaqI polymorphisms, there were no significant results in either Caucasians or Asians under the allele contrast and recessive and dominant models. This meta-analysis indicated that VDR polymorphisms were not a risk factor for PBC. Larger and more carefully designed studies are needed to verify our results.
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5-FU and ixabepilone modify the microRNA expression profiles in MDA-MB-453 triple-negative breast cancer cells.
Oncol Lett
PUBLISHED: 01-08-2014
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This study aimed to discover new potential mechanisms of chemotherapy with drugs used in the treatment of luminal androgen receptor (LAR)-type triple-negative breast cancer (TNBC). We examined the microRNA (miRNA) expression profiles of LAR-type TNBC in vitro, and explored the variation in miRNA expression profiles in cells when treated with the chemotherapy drugs capecitabine and ixabepilone. The present study revealed that the expression levels of the three antitumor miRNAs, miR-122a, miR-145 and miR-205, were significantly elevated in MDA-MB-453 LAR-type TNBC tumor cells treated with 5-fluorouracil together with ixabepilone. By contrast, carcinogenic miR-296 miRNA expression significantly declined, and levels of several other miRNAs such as miR-221, miR-210, miR-21 and miR-10b were also altered. The drugs may exert their effects through the regulation of miRNA expression levels, thereby providing a theoretical basis for clinical implementation of miRNA expression profiles as a diagnostic method for the early diagnosis, classification and prognosis of breast cancer.
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Phosphatidylinositol 4,5-biphosphate (PIP2) modulates syntaxin-1A binding to sulfonylurea receptor 2A to regulate cardiac ATP-sensitive potassium (KATP) channels.
J. Mol. Cell. Cardiol.
PUBLISHED: 01-06-2014
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Cardiac sarcolemmal syntaxin (Syn)-1A interacts with sulfonylurea receptor (SUR) 2A to inhibit ATP-sensitive potassium (KATP) channels. Phosphatidylinositol 4,5-bisphosphate (PIP2), a ubiquitous endogenous inositol phospholipid, known to bind Kir6.2 subunit to open KATP channels, has recently been shown to directly bind Syn-1A in plasma membrane to form Syn-1A clusters. Here, we sought to determine whether the interaction between Syn-1A and PIP2 interferes with the ability of Syn-1A to bind SUR2A and inhibit KATP channel activity. We found that PIP2 dose-dependently reduced SUR2A binding to GST-Syn-1A by in vitro pulldown assays. FRET studies in intact cells using TIRFM revealed that increasing endogenous PIP2 levels led to increased Syn-1A (-EGFP) cluster formation and a severe reduction in availability of Syn-1A molecules to interact with SUR2A (-mCherry) molecules outside the Syn-1A clusters. Correspondingly, electrophysiological studies employing SUR2A/Kir6.2-expressing HEK cells showed that increasing endogenous or exogenous PIP2 diminished the inhibitory effect of Syn-1A on KATP currents. The physiological relevance of these findings was confirmed by ability of exogenous PIP2 to block exogenous Syn-1A inhibition of cardiac KATP currents in inside-out patches of mouse ventricular myocytes. The effect of PIP2 on physical and functional interactions between Syn-1A and KATP channels is specific and not observed with physiologic concentrations of other phospholipids. To unequivocally demonstrate the specificity of PIP2 interaction with Syn-1A and its impact on KATP channel modulation by Syn-1A, we employed a PIP2-insensitive Syn-1A-5RK/A mutant. The Syn-1A-5RK/A mutant retains the ability to interact with SUR2A in both in vitro binding and in vivo FRET assays, although as expected the interaction is no longer disrupted by PIP2. Interestingly, at physiological PIP2 concentrations, Syn-1A-5RK/A inhibited KATP currents to a greater extent than Syn-1A-WT, indicating that the inhibitory effect of Syn-1A on KATP channels is not due to direct competition between Syn-1A and Kir6.2 for PIP2 binding. At high-dose PIP2, however, inhibition of KATP currents by Syn-1A-5RK/A was greatly reduced, likely overridden by the direct activating effect of PIP2 on KATP channels. Finally, depleting endogenous PIP2 with polyphosphoinositide phosphatase synaptojanin-1 known to disperse Syn-1A clusters, freed Syn-1A from Syn-1A clusters to bind SUR2A, causing optimal inhibition of KATP channels. These results taken together led us to conclude that PIP2 affects cardiac KATP channels not only by its actions on the channel directly but also by multi-modal effects of dynamically modulating Syn-1A mobility from Syn-1A clusters and thereby the availability of Syn-1A to inhibit KATP channels via interaction with SUR2A on the plasma membrane.
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LAPTM4B polymorphism increases susceptibility to multiple cancers in Chinese populations: a meta-analysis.
BMC Genet.
PUBLISHED: 01-05-2014
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Lysosome-associated protein transmembrane-4 beta (LAPTM4B) is a novel cancer-related gene. While recent studies have reported that the LAPTM4B polymorphism increased the susceptibility of several cancers, the results remain inconclusive. Therefore, we performed a meta-analysis to systematically summarize the possible association.
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The Association of HMGB1 Expression with Clinicopathological Significance and Prognosis in Hepatocellular Carcinoma: A Meta-Analysis and Literature Review.
PLoS ONE
PUBLISHED: 01-01-2014
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Hepatocellular carcinoma (HCC) is the fifth most common cancer, and it is the second most common cancer-related mortality globally. The prognostic value of high mobility group box 1 (HMGB1) remains controversial. The purpose of this study is to conduct a meta-analysis and literature review to evaluate the association of HMGB1 expression with the prognosis of patients with HCC.
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Risk of primary liver cancer associated with gallstones and cholecystectomy: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Recent epidemiological evidence points to an association between gallstones or cholecystectomy and the incidence risk of liver cancer, but the results are inconsistent. We present a meta-analysis of observational studies to explore this association.
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Rare de novo copy number variants in patients with congenital pulmonary atresia.
PLoS ONE
PUBLISHED: 01-01-2014
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Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA).
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Correlation between the methylation of SULF2 and WRN promoter and the irinotecan chemosensitivity in gastric cancer.
BMC Gastroenterol
PUBLISHED: 12-12-2013
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At present, no study has compared the correlation between SULF2, WRN promoter methylation and clinicopathological parameters of patients with gastric cancer and the sensitivity to irinotecan (CPT-11).
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What is Visualize?

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

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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.