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Find video protocols related to scientific articles indexed in Pubmed.
Chaperoning of the A1-adenosine Receptor by Endogenous Adenosine - An Extension of the Retaliatory Metabolite Concept.
Mol. Pharmacol.
PUBLISHED: 10-29-2014
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Cell-permeable orthosteric ligands can assist folding of G protein coupled receptors in the endoplasmic reticulum (ER); this pharmacochaperoning translates into increased cell surface levels of receptors. Here we used a folding-defective mutant of human A1-adenosine receptor as a sensor to explore, if endogenously produced adenosine can exert a chaperoning effect. This A1-receptor-Y(288)A was retained in the ER of stably transfected HEK293 cells but rapidly reached the plasma membrane in cells incubated with an A1-antagonist. This was phenocopied by raising intracellular adenosine levels with a combination of inhibitors of adenosine kinase, adenosine deaminase and the equilibrative nucleoside transporter: mature receptors with complex glycosylation accumulated at the cell surface and bound an A1-selective antagonist with an affinity indistinguishable form the wild-type A1-receptor. The effect of the inhibitor combination was specific, because it did not result in enhanced surface levels of two folding-defective human V2--vasopressin receptor mutants, which were susceptible to pharmacochaperoning by their cognate antagonist. Raising cellular adenosine levels by subjecting cells to hypoxia (5% O2) reproduced chaperoning by the inhibitor combination and enhanced surface expression A1-receptor-Y(288)A within 1 h. These findings were recapitulated for the wild-type A1 receptor. Taken together, our observations document that endogenously formed adenosine can chaperone its cognate A1-receptor. This results in a positive feedback loop that has implications for the retaliatory metabolite concept of adenosine action: if chaperoning by intracellular adenosine results in elevated cell surface levels of A1-receptors, these cells will be more susceptible to extracellular adenosine and thus more likely to cope with metabolic distress.
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[Involvement of miR-200a in chemosensitivity regulation of ovarian cancer].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-21-2014
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To explore the role of miR-200a in chemosensitivity regulation of ovarian cancer.
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Ribavirin enhances myeloid-derived suppressor cell differentiation through CXCL9/10 downregulation.
Immunopharmacol Immunotoxicol
PUBLISHED: 09-25-2014
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Abstract Elevation of myeloid-derived suppressor cells (MDSCs) was observed in some viral infectious diseases. In this study, we studied whether ribavirin, a widely used clinical antiviral drug, could impact the differentiation of human MDSCs in vitro. Flow cytometric analysis showed that ribavirin treatment (5-20?µg/ml) significantly enhanced the differentiation of monocytic MDSCs in a dose-dependent manner. The ribavirin-generated MDSCs were immune-suppressive toward autologous T cells. The mRNA expression of some cytokines was further examined by quantitative reverse transcription polymerase chain reaction. We observed a significant down-regulation of chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10 mRNA in ribavirin-generated MDSCs, when compared with control. Peripheral blood mononuclear cells from clinical chronic hepatitis C patients subjected to ribavirin therapy also displayed a similar suppression in CXCL9/10 mRNA expression. Administration of recombinant CXCL9/10 proteins clearly counteracted the effect of ribavirin on MDSCs. In summary, this study showed that ribavirin enhanced human MDSCs differentiation in vitro, which may be attribute to the down-regulation of CXCL9/10 expression.
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Identification of a microspordium isolated from Megacopta cribraria (Hemiptera: Plataspidae) and characterization of its pathogenicity in silkworms.
Antonie Van Leeuwenhoek
PUBLISHED: 08-31-2014
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A new microsporidium isolated from Megacopta cribraria was characterized by both biological characteristics and phylogenetic analysis. Moreover, its pathogenicity to silkworms was also studied. The spores are oval in shape and measured 3.64 ± 0.2 × 2.20 ± 0.2 ?m in size. Its ultrastructure is characteristic of the genus Nosema: a diplokaryon, 13-14 polar filament coils and posterior vacuole. Its life cycle includes meronts, sporonts, sporoblasts and mature spores, with a typical diplokaryon in each stage and propagation in a binary fission. A phylogenetic tree based on SSU rRNA and rRNA ITS gene sequence analysis further indicated that the parasite is closely related to Nosema bombycis and should be placed in the genus Nosema and sub-group 'true' Nosema. Furthermore, the microsporidium heavily infects lepidopteran silkworm insect and can be transmitted per os (horizontally) and transovarially (vertically). Our findings showed that the microsporidium belongs to the 'true' Nosema group within the genus Nosema and heavily infects silkworms. Based on the information obtained during this study, we named this new microsporidium isolated from M. cribraria as Nosema sp. MC.
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Catechol-O-methyltransferase Val158Met polymorphism: modulation of wearing-off susceptibility in a Chinese cohort of Parkinson's disease.
Parkinsonism Relat. Disord.
PUBLISHED: 07-27-2014
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Catechol-O-methyltransferase (COMT) is one of the cardinal enzymes that metabolize dopamine and other catecholamine neurotransmitters in the central and peripheral nervous system. Recent studies have shown that the impact of COMT haplotypes on the development of wearing-off phenomenon is in dispute, while the relationship between COMT haplotypes and wearing-off phenomenon in ethnic Chinese population is lacking. The purpose of this study was to characterize the correlation between the Val158Met polymorphism in the COMT gene and the motor complication "wearing-off" in Chinese PD patients. We have sequenced the COMT gene in 259 PD patients and 257 healthy controls. Our results demonstrated that Met/Met homozygosity of the COMT Val158Met polymorphism was related to a decreased risk of developing wearing-off. This finding suggests that COMT Val158Met may affect susceptibility to wearing-off in PD.
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Efficacy of taxane-based regimens in a first-line setting for recurrent and/or metastatic Chinese patients with esophageal cancer.
Asian Pac. J. Cancer Prev.
PUBLISHED: 07-22-2014
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To compare the efficacy of taxane-based regimens in the first line setting retrospectively in Chinese patients with recurrent and/or metastatic esophageal cancer.
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COX-1-derived thromboxane A2 plays an essential role in early B-cell development via regulation of JAK/STAT5 signaling in mouse.
Blood
PUBLISHED: 07-16-2014
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Cyclooxygenases (COXs) and their prostanoid products play important roles in a diverse range of physiological processes, including in the immune system. Here, we provide evidence that COX-1 is an essential regulator in early stages of B-cell development. COX-1-deficient mice displayed systematic reduction in total B cells, which was attributed to the arrest of early B-cell development from pro-B to pre-B stage. We further demonstrated that this defect was mediated through downregulation of the Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling and its target genes, including Pax5, in COX-1(-/-) mice. Mechanistic studies revealed that COX-1-derived thromboxane A2 (TxA2) could regulate JAK3/STAT5 signaling through the cyclic adenosine monophosphate-protein kinase A pathway, via binding with its receptor thromboxane A2 receptor (TP). Administration of the TP agonist could rescue the defective B-cell development and JAK/STAT5 signaling activity in COX-1-deficient mice. Moreover, administration of low-dose aspirin caused a significant reduction in total B cells in peripheral blood of healthy human volunteers, coincidentally with reduced TxA2 production and downregulation of JAK/STAT5 signaling. Taken together, our results demonstrate that COX-1-derived TxA2 plays a critical role in the stage transition of early B-cell development through regulation of JAK/STAT5 signaling and indicate a potential immune-suppressive effect of low-dose aspirin in humans.
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[Expression and clinical significance of 6-phosphofructo-1-kinase in nasopharyngeal carcinoma].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 06-26-2014
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The aim of this study is to investigate the expression and clinical significance of 6-phosphofructo-1-kinase in nasopharyngeal carcinoma biopsy samples.
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D?galactose?induced mitochondrial DNA oxidative damage in the auditory cortex of rats.
Mol Med Rep
PUBLISHED: 06-02-2014
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Chronic administration of D?galactose (D?gal) is a useful method for establishing a model of natural aging in the auditory system. Previous studies have demonstrated that NADPH oxidases (NOXs) may be an important source of reactive oxygen species (ROS) in the peripheral auditory system (PAS) and cause an increase in mitochondrial DNA (mtDNA) common deletion (CD) levels in the PAS and central auditory system (CAS) of rats with D?gal?induced aging. However, the source of the ROS in the CAS and the mechanisms of age?related hearing loss (ARHL) have yet to be elucidated. In the present study, male Sprague Dawley rats were administered a daily injection of D?gal (150, 300 and 500 mg/kg, respectively) for eight weeks. All three doses of D?gal caused a significant increase in the expression of NOX2, 8?hydroxy?2?deoxyguanosine, a biomarker of DNA oxidative damage, and uncoupling protein 2, together with a decrease in the mitochondrial total antioxidant capabilities in the auditory cortex, as compared with the control rats (injected daily with the same volume of 0.9% saline for eight weeks). The levels of the mtDNA CD were also increased in the auditory cortex of the D?gal?induced aging rats. These findings suggest that both NOX? and mitochondria?associated ROS generation may contribute to mtDNA oxidative damage in the auditory cortex of the CAS of D?gal?induced aging rats. This study may provide novel insight into the development of ARHL.
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Sequencing of LRP2 Reveals Multiple Rare Variants Associated with Urinary Trefoil Factor-3.
J. Am. Soc. Nephrol.
PUBLISHED: 05-31-2014
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Novel biomarkers are being investigated to identify patients with kidney disease. We measured a panel of 13 urinary biomarkers in participants from the Offspring Cohort of the Framingham Heart Study. Using an Affymetrix chip with imputation to 2.5 M single-nucleotide polymorphisms (SNPs), we conducted a GWAS of these biomarkers (n=2640) followed by exonic sequencing and genotyping. Functional studies in zebrafish were used to investigate histologic correlation with renal function. Across all 13 biomarkers, there were 97 significant SNPs at three loci. Lead SNPs at each locus were rs6555820 (P=6.7×10(-49); minor allele frequency [MAF]=0.49) in HAVCR1 (associated with kidney injury molecule-1), rs7565788 (P=2.15×10(-16); MAF=0.22) in LRP2 (associated with trefoil factor 3 [TFF3]), and rs11048230 (P=4.77×10(-8); MAF=0.10) in an intergenic region near RASSF8 (associated with vascular endothelial growth factor). Validation in the CKDGen Consortium (n=67,093) showed that only rs7565788 at LRP2, which encodes megalin, was associated with eGFR (P=0.003). Sequencing of exons 16-72 of LRP2 in 200 unrelated individuals at extremes of urinary TFF3 levels identified 197 variants (152 rare; MAF<0.05), 31 of which (27 rare) were nonsynonymous. In aggregate testing, rare variants were associated with urinary TFF3 levels (P=0.003), and the lead GWAS signal was not explained by these variants. Knockdown of LRP2 in zebrafish did not alter the renal phenotype in static or kidney injury models. In conclusion, this study revealed common variants associated with urinary levels of TFF3, kidney injury molecule-1, and vascular endothelial growth factor and identified a cluster of rare variants independently associated with TFF3.
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[Comparison between albendazole and triclabendazole against Fasciola gigantica in human].
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi
PUBLISHED: 05-08-2014
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To compare the anthelmintic effect of albendazole with that of triclabendazole against Fasciola gigantica.
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Long-term differences in annual litter production between alien (Sonneratia apetala) and native (Kandelia obovata) mangrove species in Futian, Shenzhen, China.
Mar. Pollut. Bull.
PUBLISHED: 04-23-2014
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Annual litter production in alien (Sonneratia apetala) and native (Kandelia obovata) mangrove forests in Shenzhen, China were compared from 1999 to 2010. S. apetala had significantly higher litter production than K. obovata, with mean annual total litter of 18.1 t ha(-1) yr(-1) and 15.2 t ha(-1) yr(-1), respectively. The higher litter production in S. apetala forest indicates higher productivity and consequently more nutrient supply to the estuarine ecosystems but may be more invasive due to positive plant-soil feedbacks and nutrient availability to this alien species. Two peaks were recorded in S. apetala (May and October), while only one peak was observed in K. obovata, in early spring (March and April). Leaf and reproductive materials were the main contributors to litter production (>80%) in both forests. These results suggest that the ecological function of S. apetala and its invasive potential can be better understood based on a long-term litter fall analysis.
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Analysis of midgut gene expression profiles from different silkworm varieties after exposure to high temperature.
Gene
PUBLISHED: 04-21-2014
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The silkworm is a poikilothermic animal, whose growth and development is significantly influenced by environmental temperature. To identify genes and metabolic pathways involved in the heat-stress response, digital gene expression analysis was performed on the midgut of the thermotolerant silkworm variety '932' and thermosensitive variety 'HY' after exposure to high temperature (932T and HYT). Deep sequencing yielded 6,211,484, 5,898,028, 5,870,395 and 6,088,303 reads for the 932, 932T, HY and HYT samples, respectively. The annotated genes associated with these tags numbered 4357, 4378, 4296 and 4658 for the 932, 932T, HY and HYT samples, respectively. In the HY-vs-932, 932-vs-932T, and HY-vs-HYT comparisons, 561, 316 and 281 differentially expressed genes were identified, which could be assigned to 179, 140 and 123 biological pathways, respectively. It was found that some of the biological pathways, which included oxidative phosphorylation, related to glucose and lipid metabolism, are greatly affected by high temperature and may lead to a decrease in the ingestion of fresh mulberry. When subjected to an early period of continuous heat stress, HSP genes, such as HSP19.9, HSP23.7, HSP40-3, HSP70, HSP90 and HSP70 binding protein, are up-regulated but then reduced after 24h and the thermotolerant '932' strain has higher levels of mRNA of some HSPs, except HSP70, than the thermosensitive variety during continuous high temperature treatment. It is suggested that HSPs and the levels of their expression may play important roles in the resistance to high temperature stress among silkworm varieties. This study has generated important reference tools that can be used to further analyze the mechanisms that underlie thermotolerance differences among silkworm varieties.
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Copy number polymorphisms near SLC2A9 are associated with serum uric acid concentrations.
BMC Genet.
PUBLISHED: 03-31-2014
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Hyperuricemia is associated with multiple diseases, including gout, cardiovascular disease, and renal disease. Serum urate is highly heritable, yet association studies of single nucleotide polymorphisms (SNPs) and serum uric acid explain a small fraction of the heritability. Whether copy number polymorphisms (CNPs) contribute to uric acid levels is unknown.
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Renalase gene polymorphism in patients with hypertension and concomitant coronary heart disease.
Kidney Blood Press. Res.
PUBLISHED: 03-28-2014
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This study aimed to investigate renalase gene polymorphism in patients with hypertension and concomitant coronary heart disease (CHD) and to evaluate the risk for CHD in hypertensive patients from the view of genetics.
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COMPARING THE INCIDENCE OF CATHETER-RELATED COMPLICATIONS WITH STRAIGHT AND COILED TENCKHOFF CATHETERS IN PERITONEAL DIALYSIS PATIENTS--A SINGLE-CENTER PROSPECTIVE RANDOMIZED TRIAL.
Perit Dial Int
PUBLISHED: 03-04-2014
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We aimed to prospectively compare the incidence of catheter-related complications and catheter survival for straight (SCs) and coiled (CCs) Tenckhoff catheters in peritoneal dialysis (PD) patients. ? METHODS: This open prospective randomized trial recruited 189 PD patients with end-stage renal disease from the department of nephrology, The First Affiliated Hospital of Sun Yat-sen University from 6 November 2007 to 27 August 2008. The patients were randomized to a SC (n = 99) or a CC (n= 90) and were then followed for 2 years. All catheter placements were performed by two designated experienced nephrologists who used a standardized institutional placement protocol. The primary study outcomes were catheter-related complications and catheter survival at 1 and 2 years. ? RESULTS: We observed no significant differences in clinical and demographic characteristics between the groups at baseline. The overall incidence of catheter dysfunction was higher in the CC group than in the SC group (17.8% vs 7.1%, p = 0.03), and most of the events occurred 4 weeks or more after the catheters were implanted. Catheter tip migration and omental wrapping were the most common causes of catheter dysfunction. Surgical catheter rescue was more common in patients with CCs than in patients with SCs (9vs 3 patients respectively, p= 0.05). No significant differences were observed in other catheter-related complications, including dialysate leaks, hernias, and PD-related infections (peritonitis, exit-site, and tunnel infections). Catheter survival rates in the SC and CC groups were similar at 1 year (96.7% ± 1.9% vs 96.5% ± 2.0%, p= 0.98) and at 2 years (95.3%± 2.3% vs 92.4% ± 3.6%, p= 0.76). ? CONCLUSIONS: The incidence of PD catheter-related complications is probably higher with CCs than with SCs. The results of our study suggest that a SC is the better option to reduce subsequent catheter complications.
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Genome-wide meta-analysis of homocysteine and methionine metabolism identifies five one carbon metabolism loci and a novel association of ALDH1L1 with ischemic stroke.
PLoS Genet.
PUBLISHED: 03-01-2014
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Circulating homocysteine levels (tHcy), a product of the folate one carbon metabolism pathway (FOCM) through the demethylation of methionine, are heritable and are associated with an increased risk of common diseases such as stroke, cardiovascular disease (CVD), cancer and dementia. The FOCM is the sole source of de novo methyl group synthesis, impacting many biological and epigenetic pathways. However, the genetic determinants of elevated tHcy (hyperhomocysteinemia), dysregulation of methionine metabolism and the underlying biological processes remain unclear. We conducted independent genome-wide association studies and a meta-analysis of methionine metabolism, characterized by post-methionine load test tHcy, in 2,710 participants from the Framingham Heart Study (FHS) and 2,100 participants from the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, and then examined the association of the identified loci with incident stroke in FHS. Five genes in the FOCM pathway (GNMT [p = 1.60 × 10(-63)], CBS [p = 3.15 × 10(-26)], CPS1 [p = 9.10 × 10(-13)], ALDH1L1 [p = 7.3 × 10(-13)] and PSPH [p = 1.17 × 10(-16)]) were strongly associated with the difference between pre- and post-methionine load test tHcy levels (?POST). Of these, one variant in the ALDH1L1 locus, rs2364368, was associated with incident ischemic stroke. Promoter analyses reveal genetic and epigenetic differences that may explain a direct effect on GNMT transcription and a downstream affect on methionine metabolism. Additionally, a genetic-score consisting of the five significant loci explains 13% of the variance of ?POST in FHS and 6% of the variance in VISP. Association between variants in FOCM genes with ?POST suggest novel mechanisms that lead to differences in methionine metabolism, and possibly the epigenome, impacting disease risk. These data emphasize the importance of a concerted effort to understand regulators of one carbon metabolism as potential therapeutic targets.
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microRNA-21 protects against ischemia-reperfusion and hypoxia-reperfusion-induced cardiocyte apoptosis via the phosphatase and tensin homolog/Akt-dependent mechanism.
Mol Med Rep
PUBLISHED: 02-27-2014
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Myocardial tissue injury caused by ischemia and hypoxia is a major cause of fatal diseases, including coronary atherosclerosis resulting from myocardial infarction and stroke. A number of microRNAs have been demonstrated to function as protectors against ischemia-reperfusion (I/R) and/or hypoxia-reperfusion (H/R)-induced myocardial injury, including microRNA-21 (miR-21). However, the protective mechanism of miR-21 has not been fully elucidated. The present study demonstrated that miR-21 had an anti-apoptotic role in I/R-induced myocardial damage in vivo and in H/R-induced H9C2 cell death in vitro. Of note, the present study indicates that a common molecular mechanism is likely to exist in I/R- and H/R-induced cardiocyte apoptosis. During I/R and H/R, forced expression of miR-21 upregulated the Akt signaling activity via suppressing the expression of phosphatase and tensin homolog (PTEN) and the increased activity of Akt signaling further inhibited apoptosis partially by increasing the ratio of B-cell lymphoma 2(Bcl-2)/Bcl-2-associated X protein, which further suppressed the expression of caspase-3. In conclusion, to the best of our knowledge, it was shown for the first time that miR-21 had a protective role in I/R- and H/R-induced cardiocyte apoptosis via the PTEN/Akt-dependent mechanism. The present study indicates that miR-21 may be a promising agent for the treatment of I/R and H/R-induced myocardial injury.
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Genome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.
Jie Huang, Jennifer E Huffman, Munekazu Yamakuchi, Munekazu Yamkauchi, Stella Trompet, Folkert W Asselbergs, Maria Sabater-Lleal, David-Alexandre Trégouët, Wei-Min Chen, Nicholas L Smith, Marcus E Kleber, So-Youn Shin, Diane M Becker, Weihong Tang, Abbas Dehghan, Andrew D Johnson, Vinh Truong, Lasse Folkersen, Qiong Yang, Tiphaine Oudot-Mellkah, Brendan M Buckley, Jason H Moore, Frances M K Williams, Harry Campbell, Günther Silbernagel, Veronique Vitart, Igor Rudan, Geoffrey H Tofler, Gerjan J Navis, Anita DeStefano, Alan F Wright, Ming-Huei Chen, Anton J M de Craen, Bradford B Worrall, Alicja R Rudnicka, Ann Rumley, Ebony B Bookman, Bruce M Psaty, Fang Chen, Keith L Keene, Oscar H Franco, Bernhard O Böhm, André G Uitterlinden, Angela M Carter, J Wouter Jukema, Naveed Sattar, Joshua C Bis, Mohammad A Ikram, , Michèle M Sale, Barbara McKnight, Myriam Fornage, Ian Ford, Kent Taylor, P Eline Slagboom, Wendy L McArdle, Fang-Chi Hsu, Anders Franco-Cereceda, Alison H Goodall, Lisa R Yanek, Karen L Furie, Mary Cushman, Albert Hofman, Jacqueline C M Witteman, Aaron R Folsom, Saonli Basu, Nena Matijevic, Wiek H van Gilst, James F Wilson, Rudi G J Westendorp, Sekar Kathiresan, Muredach P Reilly, Russell P Tracy, Ozren Polašek, Bernhard R Winkelmann, Peter J Grant, Hans L Hillege, Francois Cambien, David J Stott, Gordon D Lowe, Timothy D Spector, James B Meigs, Winfried März, Per Eriksson, Lewis C Becker, Pierre-Emmanuel Morange, Nicole Soranzo, Scott M Williams, Caroline Hayward, Pim van der Harst, Anders Hamsten, Charles J Lowenstein, David P Strachan, Christopher J O'Donnell.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 02-27-2014
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Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for endogenous fibrinolysis. In some populations, elevated plasma levels of tPA have been associated with myocardial infarction and other cardiovascular diseases. We conducted a meta-analysis of genome-wide association studies to identify novel correlates of circulating levels of tPA.
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Efficacy of adding bevacizumab in the first-line chemotherapy of metastatic colorectal cancer: evidence from seven randomized clinical trials.
Gastroenterol Res Pract
PUBLISHED: 02-14-2014
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Background. Efficacy of adding bevacizumab in first-line chemotherapy of metastatic colorectal cancer (mCRC) has been controversial. The aim of this study is to gather current data to analyze efficacy of adding bevacizumab to the most used combination first-line chemotherapy in mCRC, based on the 2012 meta-analysis reported by Macedo et al.??Methods. Medline, EMBASE and Cochrane library, meeting presentations and abstracts were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated first-line chemotherapy with or without bevacizumab in mCRC. The extracting data were included and examined in the meta-analysis according to the type of chemotherapy regimen. Results. Seven trials, totaling 3436 patients, were analyzed. Compared with first-line chemothery alone, the adding of bevacizumab did not show clinical benefit for OS both in first-line therapy and the most used combination chemotherapy (HR = 0.89; 95% CI = 0.78-1.02; P = 0.08; HR = 0.93; 95% CI = 0.83-1.05; P = 0.24). In contrast with OS, the addition of bevacizumab resulted in significant improvement for PFS (HR?=?0.68; 95% CI?=?0.59-0.78; P < 0.00001). Moreover, it also demonstrated statistical benefit for PFS in the most used combination first-line chemotherapy (HR?=?0.84; 95% CI?=?0.75-0.94; P = 0.002). And the subgroup analysis indicated only capacitabine-based regimens were beneficial. Conclusions. This meta-analysis shows that the addition of bevacizumab to FOLFOX/FOLFIRI/XELOX regimens might not be beneficial in terms of OS. Benefit has been seen when PFS has been taken into account. In subgroup analysis, benefit adding bevacizumab has been seen when capecitabine-based regimens are used. Further studies are warranted to explore the combination with bevacizumab.
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Feasibility of diagnosis of postcardiotomy tamponade by miniaturized transesophageal echocardiography.
J. Surg. Res.
PUBLISHED: 02-11-2014
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Pericardial tamponade after cardiac surgery is a critical diagnosis that can be difficult to diagnose using conventional cardiac monitoring. Transesophageal echocardiography can provide comprehensive information to make the diagnosis but is not always available, whereas transthoracic echocardiography has its utility limited because of the body habitus or other surgical effects. New monitoring devices, miniaturized hemodynamic transesophageal echocardiography (hTEE), which allows point of care assessment of cardiac filling and functions, may aid in diagnosis of postcardiotomy tamponade.
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A genetic association study of D-dimer levels with 50K SNPs from a candidate gene chip in four ethnic groups.
Thromb. Res.
PUBLISHED: 01-17-2014
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D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.
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Systemic lymphoma arising from hydroa vacciniforme-like lymphoma: report of two cases with review of literature.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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Hydroa vacciniforme-like lymphoma (HVLL) is an extremely rare lymphoma described in children that occurs mainly in Asia and Latin American countries. It is an Epstein-Barr virus (EBV)-positive lymphoproliferative disease (LPD) characterized by a monoclonal proliferation of T or NK cells. In this study, we report the clinical and pathological features of two Chinese patients with HVLL showed T-cell phenotype expressing CD4. The two patients generally presented with similar clinical histories of waxing and waning ulcerative blistering lesions for ten years or more until progression to systemic lymphoma. One patient died two months after progression and another is alive with disease. In the two cases, persistence infection of EBV may be attributed to the disease progression, and systemic lymphoma arising from HVLL behaves in an aggressive fashion and is predisposing to chemotherapeutic agent resistance.
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Determination of albendazole and metabolites in silkworm Bombyx mori hemolymph by ultrafast liquid chromatography tandem triple quadrupole mass spectrometry.
PLoS ONE
PUBLISHED: 01-01-2014
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Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905-0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%-103.83% for ABZ, 66.51%-108.51% for ABZSO, 96.85%-105.6% for ABZSO2 and 96.46%-106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time.
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Salivary DJ-1 could be an indicator of Parkinson's disease progression.
Front Aging Neurosci
PUBLISHED: 01-01-2014
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The goal of the current investigation was to explore whether salivary DJ-1 could be a potential biomarker for monitoring disease progression in Parkinson's disease (PD) by evaluating the association between salivary DJ-1 concentrations and nigrostriatal dopaminergic function.
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Identification of a new Sprouty protein responsible for the inhibition of the Bombyx mori nucleopolyhedrovirus reproduction.
PLoS ONE
PUBLISHED: 01-01-2014
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The rat sarcoma-extracellular signal regulated kinase mitogen-activated protein kinases pathway, one of the most ancient signaling pathways, is crucial for the defense against Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Sprouty (Spry) proteins can inhibit the activity of this pathway by receptor tyrosine kinases. We cloned and identified a new B. mori gene with a Spry domain similar to the Spry proteins of other organisms, such as fruitfly, mouse, human, chicken, Xenopus and zebrafish, and named it BmSpry. The gene expression analysis showed that BmSpry was transcribed in all of the examined tissues and in all developmental stages from embryo to adult. BmSpry also induced expression of BmNPV in the cells. Our results indicated: (1) the knock-down of BmSpry led to increased BmNPV replication and silkworm larvae mortality; (2) over-expression of BmSpry led to reduced BmNPV replication; and (3) BmSpry regulated the activation of ERK and inhibited BmNPV replication. These results showed that BmSpry plays a crucial role in the antiviral defense of the silkworm both in vitro and in vivo.
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Using gastrocnemius sEMG and plasma ?-synuclein for the prediction of freezing of gait in Parkinson's disease patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Freezing of gait (FOG) is a complicated gait disturbance in Parkinson's disease (PD) and a relevant subclinical predictor algorithm is lacking. The main purpose of this study is to explore the potential value of surface electromyograph (sEMG) and plasma ?-synuclein levels as predictors of the FOG seen in PD. 21 PD patients and 15 normal controls were recruited. Motor function was evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Freezing of gait questionnaire (FOG-Q). Simultaneously, gait analysis was also performed using VICON capture system in PD patients and sEMG data was recorded as well. Total plasma ?-synuclein was quantitatively assessed by Luminex assay in all participants. Recruited PD patients were classified into two groups: PD patients with FOG (PD+FOG) and without FOG (PD-FOG), based on clinical manifestation, the results of the FOG-Q and VICON capture system. PD+FOG patients displayed higher FOG-Q scores, decreased walking speed, smaller step length, smaller stride length and prolonged double support time compared to the PD-FOG in the gait trial. sEMG data indicated that gastrocnemius activity in PD+FOG patients was significantly reduced compared to PD-FOG patients. In addition, plasma ?-synuclein levels were significantly decreased in the PD+FOG group compared to control group; however, no significant difference was found between the PD+FOG and PD-FOG groups. Our study revealed that gastrocnemius sEMG could be used to evaluate freezing gait in PD patients, while plasma ?-synuclein might discriminate freezing of gait in PD patients from normal control, though no difference was found between the PD+FOG and PD-FOG groups.
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Structural and diffusion property alterations in unaffected siblings of patients with obsessive-compulsive disorder.
PLoS ONE
PUBLISHED: 01-01-2014
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Disrupted white matter integrity and abnormal cortical thickness are widely reported in the pathophysiology of obsessive-compulsive disorder (OCD). However, the relationship between alterations in white matter connectivity and cortical thickness in OCD is unclear. In addition, the heritability of this relationship is poorly understood. To investigate the relationship of white matter microstructure with cortical thickness, we measure fractional anisotropy (FA) of white matter in 30 OCD patients, 19 unaffected siblings and 30 matched healthy controls. Then, we take those regions of significantly altered FA in OCD patients compared with healthy controls to perform fiber tracking. Next, we calculate the fiber quantity in the same tracts. Lastly, we compare cortical thickness in the target regions of those tracts. Patients with OCD exhibited decreased FA in cingulum, arcuate fibers near the superior parietal lobule, inferior longitudinal fasciculus near the right superior temporal gyrus and uncinate fasciculus. Siblings showed reduced FA in arcuate fibers near the superior parietal lobule and anterior limb of internal capsule. Significant reductions in both fiber quantities and cortical thickness in OCD patients and their unaffected siblings were also observed in the projected brain areas when using the arcuate fibers near the left superior parietal lobule as the starting points. Reduced FA in the left superior parietal lobule was observed not only in patients with OCD but also in their unaffected siblings. Originated from the superior parietal lobule, the number of fibers was also found to be decreased and the corresponding cortical regions were thinner relative to controls. The linkage between disrupted white matter integrity and the abnormal cortical thickness may be a vulnerability marker for OCD.
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[Characteristics of prospective memory impairments in patients with severe traumatic brain injury during recovery stage].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 10-16-2013
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To explore the characteristics of time-based prospective memory (TBPM) and event-based prospective memory (EBPM) in patients with severe traumatic brain injury (TBI) during recovery stage.
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Common variants in mendelian kidney disease genes and their association with renal function.
Afshin Parsa, Christian Fuchsberger, Anna Köttgen, Conall M O'Seaghdha, Cristian Pattaro, Mariza de Andrade, Daniel I Chasman, Alexander Teumer, Karlhans Endlich, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Young J Kim, Daniel Taliun, Man Li, Mary Feitosa, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Nicole Glazer, Aaron Isaacs, Madhumathi Rao, Albert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Asa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Couraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tonu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Tamara B Harris, Lenore J Launer, Thor Aspelund, Gudny Eiriksdottir, Braxton D Mitchell, Eric Boerwinkle, Helena Schmidt, Edith Hofer, Frank Hu, Ayse Demirkan, Ben A Oostra, Stephen T Turner, Jingzhong Ding, Jeanette S Andrews, Barry I Freedman, Franco Giulianini, Wolfgang Koenig, Thomas Illig, Angela Döring, H-Erich Wichmann, Lina Zgaga, Tatijana Zemunik, Mladen Boban, Cosetta Minelli, Heather E Wheeler, Wilmar Igl, Ghazal Zaboli, Sarah H Wild, Alan F Wright, Harry Campbell, David Ellinghaus, Ute Nöthlings, Gunnar Jacobs, Reiner Biffar, Florian Ernst, Georg Homuth, Heyo K Kroemer, Matthias Nauck, Sylvia Stracke, Uwe Völker, Henry Völzke, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Yurii S Aulchenko, Ozren Polašek, Nick Hastie, Veronique Vitart, Catherine Helmer, Jie Jin Wang, Bénédicte Stengel, Daniela Ruggiero, Sven Bergmann, Mika Kähönen, Jorma Viikari, Tiit Nikopensius, Michael Province, Helen Colhoun, Alex Doney, Antonietta Robino, Bernhard K Krämer, Laura Portas, Ian Ford, Brendan M Buckley, Martin Adam, Gian-Andri Thun, Bernhard Paulweber, Margot Haun, Cinzia Sala, Paul Mitchell, Marina Ciullo, Peter Vollenweider, Olli Raitakari, Andres Metspalu, Colin Palmer, Paolo Gasparini, Mario Pirastu, J Wouter Jukema, Nicole M Probst-Hensch, Florian Kronenberg, Daniela Toniolo, Vilmundur Gudnason, Alan R Shuldiner, Josef Coresh, Reinhold Schmidt, Luigi Ferrucci, Cornelia M van Duijn, Ingrid Borecki, Sharon L R Kardia, Yongmei Liu, Gary C Curhan, Igor Rudan, Ulf Gyllensten, James F Wilson, Andre Franke, Peter P Pramstaller, Rainer Rettig, Inga Prokopenko, Jacqueline Witteman, Caroline Hayward, Paul M Ridker, Murielle Bochud, Iris M Heid, David S Siscovick, Caroline S Fox, W Linda Kao, Carsten A Böger.
J. Am. Soc. Nephrol.
PUBLISHED: 09-12-2013
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Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
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Meta-analysis of genome-wide association studies identifies six new Loci for serum calcium concentrations.
Conall M O'Seaghdha, Hongsheng Wu, Qiong Yang, Karen Kapur, Idris Guessous, Annie Mercier Zuber, Anna Köttgen, Candice Stoudmann, Alexander Teumer, Zoltan Kutalik, Massimo Mangino, Abbas Dehghan, Weihua Zhang, Gudny Eiriksdottir, Guo Li, Toshiko Tanaka, Laura Portas, Lorna M Lopez, Caroline Hayward, Kurt Lohman, Koichi Matsuda, Sandosh Padmanabhan, Dmitri Firsov, Rossella Sorice, Sheila Ulivi, A Catharina Brockhaus, Marcus E Kleber, Anubha Mahajan, Florian D Ernst, Vilmundur Gudnason, Lenore J Launer, Aurelien Macé, Eric Boerwinckle, Dan E Arking, Chizu Tanikawa, Yusuke Nakamura, Morris J Brown, Jean-Michel Gaspoz, Jean-Marc Theler, David S Siscovick, Bruce M Psaty, Sven Bergmann, Peter Vollenweider, Veronique Vitart, Alan F Wright, Tatijana Zemunik, Mladen Boban, Ivana Kolčić, Pau Navarro, Edward M Brown, Karol Estrada, Jingzhong Ding, Tamara B Harris, Stefania Bandinelli, Dena Hernandez, Andrew B Singleton, Giorgia Girotto, Daniela Ruggiero, Adamo Pio D'adamo, Antonietta Robino, Thomas Meitinger, Christa Meisinger, Gail Davies, John M Starr, John C Chambers, Bernhard O Boehm, Bernhard R Winkelmann, Jie Huang, Federico Murgia, Sarah H Wild, Harry Campbell, Andrew P Morris, Oscar H Franco, Albert Hofman, André G Uitterlinden, Fernando Rivadeneira, Uwe Völker, Anke Hannemann, Reiner Biffar, Wolfgang Hoffmann, So-Youn Shin, Pierre Lescuyer, Hughes Henry, Claudia Schurmann, , Patricia B Munroe, Paolo Gasparini, Nicola Pirastu, Marina Ciullo, Christian Gieger, Winfried März, Lars Lind, Tim D Spector, Albert V Smith, Igor Rudan, James F Wilson, Ozren Polašek, Ian J Deary, Mario Pirastu, Luigi Ferrucci, Yongmei Liu, Bryan Kestenbaum, Jaspal S Kooner, Jacqueline C M Witteman, Matthias Nauck, W H Linda Kao, Henri Wallaschofski, Olivier Bonny, Caroline S Fox, Murielle Bochud.
PLoS Genet.
PUBLISHED: 09-01-2013
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Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ? 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.
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Epitope imprinted polymer coating CdTe quantum dots for specific recognition and direct fluorescent quantification of the target protein bovine serum albumin.
Biosens Bioelectron
PUBLISHED: 08-13-2013
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A novel epitope molecularly imprinted polymer (EMIP) for specific recognition and direct fluorescent quantification of the target protein bovine serum albumin (BSA) was demonstrated where polymerization was performed on the surface of silica nanospheres embedded CdTe quantum dots (QDs). The synthetic peptide derived from the surface-exposed C-terminus of bovine serum albumin (BSA, residues 599-607) was selected as the template molecule. The resulting EMIP film was able to selectively capture the template peptide and the corresponding target protein BSA via the recognition cavities. Based on the fluorescence quenching, the EMIP-coated QDs (molecular imprinted polymer coating CdTe QDs using epitope as the template) nanospheres were successfully applied to the direct fluorescence quantification of BSA. Compared with BMIP-coated QDs (molecular imprinted polymer coating CdTe QDs using BSA as the template), the imprinting factor and adsorption capacity of EMIP-coated QDs were greatly increased. The prepared EMIP-coated QDs can also discriminate even one mismatched sequences from the original sequences of the epitope of the BSA. The practical analytical performance of the EMIP-coated QDs was examined by evaluating the detection of BSA in the bovine calf serum sample with satisfactory results. In addition, the resulting EMIP-coated QDs nanospheres were also successfully applied to separating BSA from the bovine blood sample.
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Indirect Comparison Showed Survival Benefit from Adjuvant Chemoradiotherapy in Completely Resected Gastric Cancer with D2 Lymphadenectomy.
Gastroenterol Res Pract
PUBLISHED: 08-02-2013
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Background. Little data on directly comparing chemoradiotherapy with observation has yet been published in the setting of adjuvant therapy for resected gastric cancer who underwent D2 lymphadenectomy. The present indirect comparison aims to provide more evidence on comparing the two approaches. Methods. We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed indirect comparison to obtain the relative hazards of adjuvant chemoradiotherapy to observation on overall and disease-free survival. Results. seven randomized controlled trials were identified. Three trials compared adjuvant chemoradiotherapy with adjuvant chemotherapy, and 4 trials compared adjuvant chemotherapy with observation. Using indirect comparison, the relative hazards of adjuvant chemoradiotherapy to observation were 0.43 (95% CI: 0.33-0.55) in disease-free survival and 0.52 (95% CI: 0.38-0.71) in overall survival for completely resected gastric cancer with D2 lymphadenectomy. Conclusions. Postoperative chemoradiotherapy can prolong survival and decrease recurrence in patients with resected gastric cancer who underwent D2 gastrectomy. Molecular biomarker might be a promising direction in the prediction of clinical outcome to postoperative chemoradiotherapy, which warranted further study.
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[Morphological observation of human gastric cancer cell SGC-7901 clones and identification of gastric cancer stem cells].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 07-25-2013
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To dynamically investigate the morphology of human gastric cancer SGC-7901 cell clones, and then compare the tumorigenic ability of different clones in order to identify the tumor stem cell clones.
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[Indirect comparison of different adjuvant chemotherapies for stage II(-III( gastric cancer after D2 gastrectomy in Asian patients].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 06-27-2013
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To compare efficacy of different adjuvant chemotherapy regimens for stage II(-III( gastric cancer after D2 gastrectomy in Asian patients.
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[Anti-apoptosis and expression of microRNA-21 in rat myocardium during early ischemia-reperfusion injury].
Zhong Nan Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 05-31-2013
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To observe the expression and anti-apoptosis of microRNA-21(miR-21) in rat myocardium during early ischemia-reperfusion injury (I/R).
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A combined epidemiologic and metabolomic approach improves CKD prediction.
J. Am. Soc. Nephrol.
PUBLISHED: 05-16-2013
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Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry-based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of <60 ml/min per 1.73 m(2). Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P?0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non-GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77-0.83, P<0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P<0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.
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[Clinical research of early intervention of modified shuyu pill in vascular cognitive impairment no dementia].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 04-20-2013
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To observe early intervention effects of Modified Shuyu Pill (MSP) on vascular cognitive impairment no dementia (VCIND).
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Genome analysis and signature discovery for diving and sensory properties of the endangered Chinese alligator.
Cell Res.
PUBLISHED: 04-15-2013
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Crocodilians are diving reptiles that can hold their breath under water for long periods of time and are crepuscular animals with excellent sensory abilities. They comprise a sister lineage of birds and have no sex chromosome. Here we report the genome sequence of the endangered Chinese alligator (Alligator sinensis) and describe its unique features. The next-generation sequencing generated 314 Gb of raw sequence, yielding a genome size of 2.3 Gb. A total of 22 200 genes were predicted in Alligator sinensis using a de novo, homology- and RNA-based combined model. The genetic basis of long-diving behavior includes duplication of the bicarbonate-binding hemoglobin gene, co-functioning of routine phosphate-binding and special bicarbonate-binding oxygen transport, and positively selected energy metabolism, ammonium bicarbonate excretion and cardiac muscle contraction. Further, we elucidated the robust Alligator sinensis sensory system, including a significantly expanded olfactory receptor repertoire, rapidly evolving nerve-related cellular components and visual perception, and positive selection of the night vision-related opsin and sound detection-associated otopetrin. We also discovered a well-developed immune system with a considerable number of lineage-specific antigen-presentation genes for adaptive immunity as well as expansion of the tripartite motif-containing C-type lectin and butyrophilin genes for innate immunity and expression of antibacterial peptides. Multifluorescence in situ hybridization showed that alligator chromosome 3, which encodes DMRT1, exhibits significant synteny with chicken chromosome Z. Finally, population history analysis indicated population admixture 0.60-1.05 million years ago, when the Qinghai-Tibetan Plateau was uplifted.
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Analysis of genome-wide association study-linked loci in Parkinsons disease of Mainland China.
Mov. Disord.
PUBLISHED: 04-10-2013
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Genome-wide association studies (GWAS) have identified numerous single-nucleotide polymorphisms (SNPs) that can modulate the risk of developing Parkinsons disease (PD).
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The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch.
Nat. Cell Biol.
PUBLISHED: 03-18-2013
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Despite the complexity and variety of biological oscillators, their core design invariably includes an essential negative feedback loop. In the Xenopus laevis embryonic cell cycle oscillator, this loop consists of the kinase cyclin B-Cdk1 and the ubiquitin ligase APC/C(Cdc20); active Cdk1 activates APC/C(Cdc20), which then brings about cyclin B degradation and inactivates Cdk1. Here we ask how this negative feedback loop functions quantitatively, with the aim of understanding what mechanisms keep the Cdk1-APC/C(Cdc20) system from settling into a stable steady state with intermediate levels of Cdk1 and APC/C(Cdc20) activity. We found that the system operates as a time-delayed, digital switch, with a time lag of ? 15?min between Cdk1 and APC/C(Cdc20) activation and a tremendously high degree of ultrasensitivity (n(H)?17). Computational modelling shows how these attributes contribute to the generation of robust, clock-like oscillations. Principles uncovered here may also apply to other activator-repressor oscillators and help in designing robust synthetic clocks.
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Weaning of extracorporeal membrane oxygenation using continuous hemodynamic transesophageal echocardiography.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 03-05-2013
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Venoarterial extracorporeal membrane oxygenation (VA ECMO) has been used for profound cardiogenic shock to bridge to decision, ventricular assist device(s) (VADs), or transplant. To assess ventricular function and volume status along with hemodynamics during ECMO weaning, we developed a standardized weaning protocol, guided by a miniaturized transesophageal echocardiography probe designed for continuous hemodynamic monitoring (hemodynamic transesophageal echocardiography [hTEE]). We reviewed our experience with this weaning protocol with hTEE guidance to assess if we could predict patient outcomes.
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Association of a Cystatin C Gene Variant With Cystatin C Levels, CKD, and Risk of Incident Cardiovascular Disease and Mortality.
Am. J. Kidney Dis.
PUBLISHED: 02-20-2013
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Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality.
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Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients.
J. Clin. Immunol.
PUBLISHED: 01-26-2013
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Myeloid-derived suppressor cells (MDSCs) are known to accumulate under some pathologic conditions and suppress immune system in a variety of ways. This study aims to evaluate the significance of MDSCs in chronic Hepatitis C (CHC) patients.
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Transcriptome analysis of Pacific white shrimp (Litopenaeus vannamei) hepatopancreas in response to Taura syndrome Virus (TSV) experimental infection.
PLoS ONE
PUBLISHED: 01-22-2013
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The Pacific white shrimp, Litopenaeus vannamei, is a worldwide cultured crustacean species with important commercial value. Over the last two decades, Taura syndrome virus (TSV) has seriously threatened the shrimp aquaculture industry in the Western Hemisphere. To better understand the interaction between shrimp immune and TSV, we performed a transcriptome analysis in the hepatopancreas of L. vannamei challenged with TSV, using the 454 pyrosequencing (Roche) technology.
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Intraspecific polymorphism of rDNA among five Nosema bombycis isolates from different geographic regions in China.
J. Invertebr. Pathol.
PUBLISHED: 01-19-2013
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The microsporidian Nosema bombycis is the causative agent of pébrine, a highly infectious disease of the silkworm Bombyx mori. Three regions of the multicopy rDNA gene were examined in order to investigate the relationships among five Nosema isolates from various regions of China. Ribosomal DNA alleles are present on each of the 18 chromosomes of N. bombycis and show a high degree of variation. In this study the small subunit (SSU) rDNA, internal transcribed spacer (ITS) and intergenic spacer (IGS) regions for up to 10 different rDNA copies from each N. bombycis isolate were cloned and sequenced. As expected we see greater polymorphism in the ITS region (88 variable sites in 179 nucleotides) and IGS (200 variable sites in 279 nucleotides) than in the SSU rDNA (24 variable sites in 1232 nucleotides). Phylogenetic analysis shows greater differences between alleles within an isolate than between the same alleles from different isolates. The data reveal two very different groups, one from the Sichuan province and the other with a broad distribution including four provinces in southeast China and Japan. The Sichuan isolate does not have any rDNA alleles with sequences identical to those in the other isolates, implying that it is a separate, non-intermixing, population or perhaps a separate species from the other isolates. In light of the polymorphic nature of the rDNA alleles in N. bombycis and their presence on every chromosome, the rDNA gene may be useful for understanding the movement and ultimately the source of pébrine infections.
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Preparation and optical property of new fluorescent nanoparticles.
Macromol Rapid Commun
PUBLISHED: 01-18-2013
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A new fluorescent nanoparticle (PIOT-HA) is synthesized with cationic polyester (PIOT) and anionic hyaluronic acid (HA) by electrostatic interactions in an aqueous solution. The nanoparticles (NPs) are degradable upon treatments with alkali or hyaluronidase, which exhibits better biological safety and potential application in vitro and in vivo. Through specific interactions between the HA locating on the surfaces of PIOT-HA NPs and the CD44 protein over-expressed on the MDA-MB-231 cancer cell line, PIOT-HA NPs could selectively image the cancer cells. Upon white light irradiation, the PIOT-HA NPs can sensitize oxygen to generate reactive oxygen species (ROS) that inactivate the neighboring CD44 protein, which inhibits the migration of MDA-MB-231 cancer cells.
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Inhibition of Elongation Factor-2 Kinase Augments the Antitumor Activity of Temozolomide against Glioma.
PLoS ONE
PUBLISHED: 01-01-2013
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Glioblastoma multiforme (GBM), the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ) is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ.
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Transcriptome analysis of Litopenaeus vannamei in response to white spot syndrome virus infection.
PLoS ONE
PUBLISHED: 01-01-2013
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Pacific white shrimp (Litopenaeus vannamei) is the most extensively farmed crustacean species in the world. White spot syndrome virus (WSSV) is one of the major pathogens in the cultured shrimp. However, the molecular mechanisms of the host-virus interaction remain largely unknown. In this study, the impact of WSSV infection on host gene expression in the hepatopancreas of L. vannamei was investigated through the use of 454 pyrosequencing-based RNA-Seq of cDNA libraries developed from WSSV-challenged shrimp or normal controls. By comparing the two cDNA libraries, we show that 767 host genes are significantly up-regulated and 729 genes are significantly down-regulated by WSSV infection. KEGG analysis of the differentially expressed genes indicated that the distribution of gene pathways between the up- and down-regulated genes is quite different. Among the differentially expressed genes, several are found to be involved in various processes of animal defense against pathogens such as apoptosis, mitogen-activated protein kinase (MAPK) signaling, toll-like receptor (TLR) signaling, Wnt signaling and antigen processing and presentation pathways. The present study provides valuable information on differential expression of L. vannamei genes following WSSV infection and improves our current understanding of this host-virus interaction. In addition, the large number of transcripts obtained in this study provides a strong basis for future genomic research on shrimp.
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Postoperative chemoradiotherapy versus postoperative chemotherapy for completely resected gastric cancer with D2 Lymphadenectomy: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Both chemoradiotherapy and chemotherapy are used in postoperative adjuvant therapy for resected gastric cancer. However, it is controversial whether chemoradiotherapy or chemotherapy is the optimal strategy for patients with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to provide more evidence on the relative benefits of adjuvant therapies in this setting.
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Conjugated polymer nanoparticles for light-activated anticancer and antibacterial activity with imaging capability.
Langmuir
PUBLISHED: 11-17-2011
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A new water-soluble conjugated polymer containing fluorene and boron-dipyrromethene repeat units in the backbones (PBF) that exhibits red emission was synthesized and characterized. Cationic PBF forms uniform nanoparticles with negatively charged disodium salt 3,3-dithiodipropionic acid (SDPA) in aqueous solution through electrostatic interactions. The nanoparticles display absorption maximum at 550 nm and emission maximum at 590 nm. Upon photoexcitation with white light (400-800 nm) with 90 and 45 mW·cm(-2) for bacteria and cancer cells killing respectively, PBF nanoparticles can sensitize the oxygen molecule to readily produce reactive oxygen species (ROS) for rapidly killing neighboring bacteria and cancer cells. Furthermore, PBF nanoparticles concurrently provide optical imaging capability. PBF nanoparticles are therefore a promising multifunctional material for treating cancers and bacteria infections, while concurrently providing optical monitoring capabilities.
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Simple and sensitive method for detecting point mutations of epidermal growth factor receptor using cationic conjugated polymers.
ACS Appl Mater Interfaces
PUBLISHED: 11-04-2011
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The L858R mutation of epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer is associated with the increased sensitivity to EGFR tyrosine kinase inhibitors. In this paper, a simple and sensitive method for identification of L858R mutation in cell lines and tumor tissues was developed using cationic conjugated polymer-based fluorescence resonance energy transfer technology (CCP-based FRET). The new detection system can detect even as low as 4-8% mutation of the total DNA. Through the detection results for 48 DNA samples from tumor tissues, a sensitivity of 95.24% (20/21) and a specificity of 96.30% (26/27) were demonstrated. Further, the application of this method in clinical molecular diagnosis was validated by detecting T790 M in EGFR of 35 patients. In comparison with DNA sequencing and real-time PCR methods, our new protocol simplifies procedures by eliminating the need for primer labeling, cumbersome workups and sophisticated instruments and improves sensitivity by amplifying fluorescence signals. Our CCP-based FRET technology is particularly attractive because of its higher sensitivity, cost-effective, and simple characteristics. Particularly, this new method could confirm the suspected positive samples arisen by DNA sequencing and real-time PCR methods. Thus, the CCP-based FRET technology opens up an avenue for clinical therapy by guiding medication to lung cancer patients responsive to anti-EGFR therapy.
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Flexible semiparametric analysis of longitudinal genetic studies by reduced rank smoothing.
J R Stat Soc Ser C Appl Stat
PUBLISHED: 10-10-2011
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In family-based longitudinal genetic studies, investigators collect repeated measurements on a trait that changes with time along with genetic markers. Since repeated measurements are nested within subjects and subjects are nested within families, both the subject-level and measurement-level correlations must be taken into account in the statistical analysis to achieve more accurate estimation. In such studies, the primary interests include to test for quantitative trait locus (QTL) effect, and to estimate age-specific QTL effect and residual polygenic heritability function. We propose flexible semiparametric models along with their statistical estimation and hypothesis testing procedures for longitudinal genetic designs. We employ penalized splines to estimate nonparametric functions in the models. We find that misspecifying the baseline function or the genetic effect function in a parametric analysis may lead to substantially inflated or highly conservative type I error rate on testing and large mean squared error on estimation. We apply the proposed approaches to examine age-specific effects of genetic variants reported in a recent genome-wide association study of blood pressure collected in the Framingham Heart Study.
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[Vertical retraction syndrome caused by anomalous orbital structures].
Zhonghua Yan Ke Za Zhi
PUBLISHED: 09-03-2011
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To described the clinical feature and MRI imaging of six children with vertical retraction syndrome.
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Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs.
Bioorg. Med. Chem.
PUBLISHED: 08-22-2011
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A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 ?M and a selectivity index (SI) >7290. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated, which enriched the SAR of diarylpyrimidines (DAPYs).
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Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function allele.
Hum. Mol. Genet.
PUBLISHED: 07-18-2011
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Serum urate concentrations are highly heritable and elevated serum urate is a key risk factor for gout. Genome-wide association studies (GWAS) of serum urate in African American (AA) populations are lacking. We conducted a meta-analysis of GWAS of serum urate levels and gout among 5820 AA and a large candidate gene study among 6890 AA and 21 708 participants of European ancestry (EA) within the Candidate Gene Association Resource Consortium. Findings were tested for replication among 1996 independent AA individuals, and evaluated for their association among 28 283 EA participants of the CHARGE Consortium. Functional studies were conducted using (14)C-urate transport assays in mammalian Chinese hamster ovary cells. In the discovery GWAS of serum urate, three loci achieved genome-wide significance (P< 5.0 × 10(-8)): a novel locus near SGK1/SLC2A12 on chromosome 6 (rs9321453, P= 1.0 × 10(-9)), and two loci previously identified in EA participants, SLC2A9 (P= 3.8 × 10(-32)) and SLC22A12 (P= 2.1 × 10(-10)). A novel rare non-synonymous variant of large effect size in SLC22A12, rs12800450 (minor allele frequency 0.01, G65W), was identified and replicated (beta -1.19 mg/dl, P= 2.7 × 10(-16)). (14)C-urate transport assays showed reduced urate transport for the G65W URAT1 mutant. Finally, in analyses of 11 loci previously associated with serum urate in EA individuals, 10 of 11 lead single-nucleotide polymorphisms showed direction-consistent association with urate among AA. In summary, we identified and replicated one novel locus in association with serum urate levels and experimentally characterize the novel G65W variant in URAT1 as a functional allele. Our data support the importance of multi-ethnic GWAS in the identification of novel risk loci as well as functional variants.
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Assessment of genetic determinants of the association of ? fibrinogen in relation to cardiovascular disease.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 07-14-2011
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? fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of ? fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort.
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Synthesis and anti-HIV activity of aryl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazones as potent non-nucleoside reverse transcriptase inhibitors.
ChemMedChem
PUBLISHED: 07-07-2011
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A series of novel diarylpyrimidines (DAPYs) with a ketone hydrazone substituent on the methylene linker between the pyrimidine nucleus and the aryl moiety at the C-4 position were synthesized, and their antiviral activity against human immunodeficiency virus (HIV)-1 in MT-4 cells was evaluated. Most compounds of this class exhibited excellent activity against wild-type HIV-1, with EC(50) values in the range of 1.7-13.2 nM. Of these compounds, 2-bromophenyl-2-[(4-cyanophenyl)amino]-4-pyrimidinone hydrazone (9k) displayed the most potent anti-HIV-1 activity (EC(50) =1.7±0.6 nM), with excellent selectivity for infected over uninfected cells (SI=5762). In addition, the 4-methyl phenyl analogue 9d (EC(50) =2.4±0.2?nM, SI=18461) showed broad spectrum HIV inhibitory activity, with EC(50) values of 2.4±0.2 nM against wild-type HIV-1, 5.3±0.4 ?M against HIV-1 double-mutated strain RES056 (K103N+Y181C), and 5.5 ?M against HIV-2 ROD strain. Furthermore, structure-activity relationship (SAR) data and molecular modeling results for these compounds are also discussed.
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Differences in leaf construction cost between alien and native mangrove species in Futian, Shenzhen, China: implications for invasiveness of alien species.
Mar. Pollut. Bull.
PUBLISHED: 06-22-2011
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Construction cost (CC) is a quantifiable measure of energy demand for biomass production, and low CC is hypothesized to give an alien plant growth advantages and increase its potential to be an invader. Comparison of leaf CC and growth traits between alien and native mangroves in Shenzhen Futian Nature Reserve showed CC per unit mass (CC(mass)), carbon concentration and gross and ash-free caloric values of alien mangroves were significantly lower than those of native species, while the height and chest circumference were just the opposite. Alien species Sonneratia apetala had the lowest CC(mass) while Sonneratia caseolaris had the lowest CC(area), and were 8.99% and 32.17% lower than those of native species, respectively. Conversely, specific leaf area (SLA) of these two Sonneratia species was significantly higher than native species. Lower CC and higher SLA make the two Sonneratia species grow and spread faster than other mangroves and enhance their invasive potential.
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Genome-wide association studies of cerebral white matter lesion burden: the CHARGE consortium.
Ann. Neurol.
PUBLISHED: 06-18-2011
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White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified.
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Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs.
Bioorg. Med. Chem.
PUBLISHED: 06-17-2011
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A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC(50) value of 0.009 ?M, along with moderate activities against the double RT mutant (K103N+Y181C) HIV-1(III(B)) and HIV-2(ROD) with an EC(50) value of 6.2 and 6.0 ?M, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.
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Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 06-16-2011
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A series of (±)-benzhydrol derivatives featuring the essential sulfonamide group at the para position on the C-ring were synthesized and evaluated for the potential anti-HIV activity in C8166 cells. Most of these analogues demonstrated low concentration inhibitory activity with EC(50) values less than 1 ?M against the wild-type HIV-1. In particular, compound 7h was identified as the highest active inhibitor of wild-type HIV-1 with an EC(50) value of 0.12 ?M and selectivity index value of 312.73. Furthermore, some of them also exhibited moderate activity against the double mutant strain A(17) (K103N+Y181C) with EC(50) values lower than 5 ?M. In addition, the binding modes with RT and the preliminary structure-activity relationships of these derivatives were also explored for further chemical modifications.
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[Role of mitochondrial calcium uniporter in cardioprotection induced by ischemic postconditioning in isolated rat heart].
Zhejiang Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 06-15-2011
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To investigate the role of mitochondrial calcium uniporter in cardioprotection elicited by ischemic postconditioning (Postcond).
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A convenient preparation of multi-spectral microparticles by bacteria-mediated assemblies of conjugated polymer nanoparticles for cell imaging and barcoding.
Adv. Mater. Weinheim
PUBLISHED: 05-31-2011
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A novel technique was developed for preparing encoded multicolour microparticles based on the self-assembly of bacteria and conjugated polymer nanoparticles (CPNs) by a very simple and time-saving manner. These bacteria-CPNs microparticles show multicolor emissions by tuning FRET efficiencies among CPNs under single excitation wavelength and can be successfully applied for cell imaging and optical barcoding.
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Meta-analysis of genome-wide linkage scans for renal function traits.
Nephrol. Dial. Transplant.
PUBLISHED: 05-28-2011
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Several genome scans have explored the linkage of chronic kidney disease phenotypes to chromosomic regions with disparate results. Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance.
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Genome-wide comparison of African-ancestry populations from CARe and other cohorts reveals signals of natural selection.
Am. J. Hum. Genet.
PUBLISHED: 05-19-2011
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The study of recent natural selection in human populations has important applications to human history and medicine. Positive natural selection drives the increase in beneficial alleles and plays a role in explaining diversity across human populations. By discovering traits subject to positive selection, we can better understand the population level response to environmental pressures including infectious disease. Our study examines unusual population differentiation between three large data sets to detect natural selection. The populations examined, African Americans, Nigerians, and Gambians, are genetically close to one another (F(ST) < 0.01 for all pairs), allowing us to detect selection even with moderate changes in allele frequency. We also develop a tree-based method to pinpoint the population in which selection occurred, incorporating information across populations. Our genome-wide significant results corroborate loci previously reported to be under selection in Africans including HBB and CD36. At the HLA locus on chromosome 6, results suggest the existence of multiple, independent targets of population-specific selective pressure. In addition, we report a genome-wide significant (p = 1.36 × 10(-11)) signal of selection in the prostate stem cell antigen (PSCA) gene. The most significantly differentiated marker in our analysis, rs2920283, is highly differentiated in both Africa and East Asia and has prior genome-wide significant associations to bladder and gastric cancers.
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Synthesis and biological activity of naphthyl-substituted (B-ring) benzophenone derivatives as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
Bioorg. Med. Chem.
PUBLISHED: 05-09-2011
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A novel series of benzophenone derivatives with B-ring substituted by naphthyl ring has been synthesized and evaluated as non-nucleoside HIV-1 reverse transcriptase inhibitors. Most of these compounds showed good to moderate activity against wild-type HIV-1 and mutated viruses. In particular, the analogue 10i demonstrated the most potent activity against wild-type HIV-1 with an EC?? value of 4.8 nM, and with a high selectivity index up to 10347.9, it also proved to be active against the HIV-1 double mutant strain A?? (K103N+Y181C) with an EC?? value of 2.1 ?M. In addition, the molecular modeling study was used to explore the major interactions between the potent inhibitors with the HIV-1 RT. The investigation of the structure-activity relationships may serve as an important lead for the further optimization.
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Basic fibroblast growth factor affects the expression of angiogenin and cell proliferation in A375 human melanoma cells.
Tumori
PUBLISHED: 05-03-2011
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Human malignant melanoma is a very aggressive and highly angiogenesis-dependent tumor. Basic fibroblast growth factor and angiogenin are the potentially important angiogenic factors for melanoma progression and metastasis. Many studies have mainly focused on how they induce angiogenesis. In the present study, we investigated the effects of basic fibroblast growth factor on the expression of angiogenin and melanoma cell growth.
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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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