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Find video protocols related to scientific articles indexed in Pubmed.
Recent development in [1,4]benzodiazepines as potent anticancer agents: a review.
Mini Rev Med Chem
PUBLISHED: 10-15-2014
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The [1,4]benzodiazepine is an important class of heterocyclic compounds and clinically used for many ailments in humans. The [1,4]benzodiazepine has unique structure that mimics the peptide linkage. This interesting observation completely shifted the interest of medicinal chemist for [1,4]benzodiazepine from CNS acting drugs to anticancer agents. During last few decades, a large number of reports have appeared in the literature highlighting the anticancer activity of [1,4]benzodiazepines. Here, in this article, we have discussed the brief synthesis, origin of [1,4]benzodiazepines as anticancer agent, their mechanism of action and latest developments in this field. We have compiled the most important literature reports from last few decades till date.
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Metastatic squamous cell carcinoma of the lung masquerading as a soft tissue tumor.
J Cytol
PUBLISHED: 09-12-2014
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Carcinoma of lung can metastasize to any organ system; however, metastasis to skeletal muscles is extremely rare. A 63-year-old man, known case of pulmonary tuberculosis on treatment, presented with a painful swelling in his left leg. Examination revealed a 5.0 cm × 3.0 cm calf swelling, which on imaging was suggestive of a soft tissue tumor. Fine-needle aspiration cytology of the swelling revealed it to be squamous cell carcinoma. Further investigations revealed a mass in the left lower lobe of the lung. Biopsies from both the lung lesion and calf swelling confirmed the diagnosis of squamous cell carcinoma of lung with metastasis to the calf muscle. The case is being presented because of its unusual presentation and rarity.
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Genetic polymorphisms, Biochemical Factors, and Conventional Risk Factors in Young and Elderly North Indian Patients With Acute Myocardial Infarction.
Clin. Appl. Thromb. Hemost.
PUBLISHED: 08-25-2014
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This study compared genetic polymorphisms (factor V Leiden [FVL] 1691G/A, factor VII [FVII] 10976G/A, FVII HVR4, platelet membrane glycoproteins GP1BA 1018C/T, GP1BA VNTR, integrin ITGB3 1565T/C, ITGA2 807C/T and methylenetetrahydrofolate reductase [MTHFR] 677C/T), biochemical (fibrinogen and homocysteine), and conventional risk factors in 184 young and 166 elderly north Indian patients with acute myocardial infarction (AMI). Univariate analysis revealed higher prevalence of hypertension and obesity in elderly patients while smoking, alcohol intake, and low socioeconomic status in young patients (P < .001). Although mean fibrinogen predominated (P = .01) in elderly patients, mean homocysteine was higher (P < .001) among young patients. Prevalence of hyperhomocysteinemia was greater in young than in elderly patients (odds ratio: 2.8, 95% confidence interval: 1.8-4.4, P < .001); however, genetic polymorphisms were equally prevalent in young and elderly patients. Multiple logistic regression analysis showed smoking (P < .001), alcohol intake (P = .046), and hyperhomocysteinemia (P = .001) to be associated with AMI in the young patients while hypertension (P = .006) in elderly patients. To conclude, smoking, alcohol intake, and elevated homocysteine are the risk factors for AMI among young while hypertension among elderly patients.
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Pivotal role for a tail subunit of the RNA polymerase II mediator complex CgMed2 in azole tolerance and adherence in Candida glabrata.
Antimicrob. Agents Chemother.
PUBLISHED: 07-28-2014
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Antifungal therapy failure can be associated with increased resistance to the employed antifungal agents. Candida glabrata, the second most common cause of invasive candidiasis, is intrinsically less susceptible to the azole class of antifungals and accounts for 15% of all Candida bloodstream infections. Here, we show that C. glabrata MED2 (CgMED2), which codes for a tail subunit of the RNA polymerase II Mediator complex, is required for resistance to azole antifungal drugs in C. glabrata. An inability to transcriptionally activate genes encoding a zinc finger transcriptional factor, CgPdr1, and multidrug efflux pump, CgCdr1, primarily contributes to the elevated susceptibility of the Cgmed2? mutant toward azole antifungals. We also report for the first time that the Cgmed2? mutant exhibits sensitivity to caspofungin, a constitutively activated protein kinase C-mediated cell wall integrity pathway, and elevated adherence to epithelial cells. The increased adherence of the Cgmed2? mutant was attributed to the elevated expression of the EPA1 and EPA7 genes. Further, our data demonstrate that CgMED2 is required for intracellular proliferation in human macrophages and modulates survival in a murine model of disseminated candidiasis. Lastly, we show an essential requirement for CgMed2, along with the Mediator middle subunit CgNut1 and the Mediator cyclin-dependent kinase/cyclin subunit CgSrb8, for the high-level fluconazole resistance conferred by the hyperactive allele of CgPdr1. Together, our findings underscore a pivotal role for CgMed2 in basal tolerance and acquired resistance to azole antifungals.
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A systematic analysis reveals an essential role for high-affinity iron uptake system, haemolysin and CFEM domain-containing protein in iron homoeostasis and virulence in Candida glabrata.
Biochem. J.
PUBLISHED: 07-03-2014
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Iron is an essential nutrient for all living organisms and human pathogens employ a battery of factors to scavenge iron from the high-affinity iron-binding host proteins. In the present study, we have elucidated, via a candidate gene approach, major iron acquisition and homoeostatic mechanisms operational in an opportunistic human fungal pathogen Candida glabrata. Phenotypic, biochemical and molecular analysis of a set of 13 C. glabrata strains, deleted for proteins potentially implicated in iron metabolism, revealed that the high-affinity reductive iron uptake system is required for utilization of alternate carbon sources and for growth under both in vitro iron-limiting and in vivo conditions. Furthermore, we show for the first time that the cysteine-rich CFEM (common in fungal extracellular membranes) domain-containing cell wall structural protein, CgCcw14, and a putative haemolysin, CgMam3, are essential for maintenance of intracellular iron content, adherence to epithelial cells and virulence. Consistent with their roles in iron homoeostasis, mitochondrial aconitase activity was lower and higher in mutants disrupted for high-affinity iron transport, and haemolysin respectively. Additionally, we present evidence that the mitochondrial frataxin, CgYfh1, is pivotal to iron metabolism. Besides yielding insights into major in vitro and in vivo iron acquisition strategies, our findings establish high-affinity iron uptake mechanisms as critical virulence determinants in C. glabrata.
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Recent developments in tubulin polymerization inhibitors: An overview.
Eur J Med Chem
PUBLISHED: 06-04-2014
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Microtubules are protein biopolymers formed through polymerization of heterodimers of ?- and ?-tubulins. Disruption of microtubules can induce cell cycle arrest in G2-M phase and formation of abnormal mitotic spindles. Their importance in mitosis and cell division makes microtubules an attractive target for anticancer drug discovery. A number of naturally occurring compounds such as paclitaxel, epothilones, vinblastine, combretastatin, and colchicines exert their effect by changing dynamics of tubulin such as polymerization and depolymerization. During past few years, rapid development of the novel tubulin polymerization inhibitors has been witnessed. Diverse classes of chemical compounds from the natural as well as from the synthetic origin have been extensively studied. This review highlights the various classes of synthetically derived chemical compounds those have been reported in last few years as potential tubulin polymerization inhibitors. A brief synthetic methodology to access these compounds has been highlighted along with the brief SAR studies. We strongly believe that this review will provide a platform to the synthetic chemists and biologists to design and synthesize new and potent compounds to inhibit the tubulin polymerization.
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An essential role for phosphatidylinositol 3-kinase in the inhibition of phagosomal maturation, intracellular survival and virulence in Candida glabrata.
Cell. Microbiol.
PUBLISHED: 04-24-2014
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The yeast class III phosphoinositide 3-kinase (PI3K) that catalyses production of the lipid signalling molecule, phosphatidylinositol-3-phosphate, is primarily implicated in vesicle-mediated transport and autophagy. In this study, we identified, through a genetic screen, the Candida glabrata?CgVPS15 gene, an orthologue of the Saccharomyces cerevisiae?PI3K regulatory subunit-encoding open reading frame (ORF) to be required for impairment of phagosomal maturation in human macrophages. We also disrupted catalytic subunit of the C.?glabrata?PI3K complex, CgVps34, and found it to be pivotal to arrest mature phagolysosome biogenesis. Further, deletion of either CgVPS15 or CgVPS34 rendered C.?glabrata cells hyperadherent to epithelial cells and susceptible to the antimicrobial arsenal of primary murine and cultured human macrophages and diverse stresses. Despite no growth retardation at 37°C, Cgvps15? and Cgvps34? mutants were severely virulence attenuated in mice. We demonstrate that trafficking and/or processing of the vacuolar lumenal hydrolase, carboxypeptidase Y, and the major adhesin, Epa1, rely on PI3K regulatory mechanisms in C.?glabrata. By disrupting autophagy-related PI3K complex genes, we show that C.?glabrata?PI3K-impeded phagolysosomal acidification is primarily owing to its role in cellular trafficking events. Altogether, our findings underscore the essentiality of PI3K signalling in modulation of host immune response, intracellular survival and virulence in C.?glabrata.
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Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans.
Biochem. J.
PUBLISHED: 03-14-2014
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The QDR (quinidine drug resistance) family of genes encodes transporters belonging to the MFS (major facilitator superfamily) of proteins. We show that QDR transporters, which are localized to the plasma membrane, do not play a role in drug transport. Hence, null mutants of QDR1, QDR2 and QDR3 display no alterations in susceptibility to azoles, polyenes, echinocandins, polyamines or quinolines, or to cell wall inhibitors and many other stresses. However, the deletion of QDR genes, individually or collectively, led to defects in biofilm architecture and thickness. Interestingly, QDR-lacking strains also displayed attenuated virulence, but the strongest effect was observed with qdr2?, qdr3? and in qdr1/2/3? strains. Notably, the attenuated virulence and biofilm defects could be reversed upon reintegration of QDR genes. Transcripts profiling confirmed differential expression of many biofilm and virulence-related genes in the deletion strains as compared with wild-type Candida albicans cells. Furthermore, lipidomic analysis of QDR-deletion mutants suggests massive remodelling of lipids, which may affect cell signalling, leading to the defect in biofilm development and attenuation of virulence. In summary, the results of the present study show that QDR paralogues encoding MFS antiporters do not display conserved functional linkage as drug transporters and perform functions that significantly affect the virulence of C. albicans.
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Development and characterization of in situ oral gel of spiramycin.
Biomed Res Int
PUBLISHED: 02-28-2014
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The present investigation deals with the optimization, formulation, and characterization of oral in situ gel of spiramycin. Sodium alginate and hydroxypropyl methylcellulose were used as cross-linking and viscosifying agents, respectively. Sodium bicarbonate was used as a floating agent. In preformulation studies, the melting point, pH, and partition coefficient were found to be 133 °C, 9.5, and 0.193, respectively. The drug had retention time at around 2.65 minutes in high performance liquid chromatography (HPLC). During compatibility studies of drug with all polymers, we observed that there were no changes in the FTIR spectra of a mixture of drug and polymers. All the formulations showed good pourability. Floating time and total floating time were ~30 sec and >12 hours, respectively. During in vitro drug release studies, the drug was released from the formulation around 80-100% for 12-16 hrs. In TEM analysis, we found that the drug molecules were well entrapped in the polymer and the drug was released slowly for up to 12 hrs. In these studies, we found that the concentration of sodium alginate and HPMC had significant influence on floating lag time, gelling capacity, and cumulative percentage drug release. During antimicrobial studies, we found that the formulation containing spiramycin showed good zone of inhibition against different microbial strains (Staphylococcus aureus and Escherichia coli).
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Visibility of gingiva - An important determinant for an esthetic smile.
J Indian Soc Periodontol
PUBLISHED: 01-21-2014
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Need for having better esthetics is the new emerging trend seen in patients' demands and expectations. Various periodontal procedures including the mucogingival procedures have been designed to enhance the esthetics. The amount of gingival display of the patient is also an important parameter while considering the esthetics of the patient. Till date, very few studies have been done in which the amount of gingival visibility have been determined. So, the aim of this study was to evaluate the amount of visibility of gingiva during natural smile and forced smile in the patients visiting Himachal Dental College and Hospital.
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Yield-enhancing heterotic QTL transferred from wild species to cultivated rice Oryza sativa L.
PLoS ONE
PUBLISHED: 01-01-2014
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Utilization of "hidden genes" from wild species has emerged as a novel option for enrichment of genetic diversity for productivity traits. In rice we have generated more than 2000 lines having introgression from 'A' genome-donor wild species of rice in the genetic background of popular varieties PR114 and Pusa44 were developed. Out of these, based on agronomic acceptability, 318 lines were used for developing rice hybrids to assess the effect of introgressions in heterozygous state. These introgression lines and their recurrent parents, possessing fertility restoration ability for wild abortive (WA) cytoplasm, were crossed with cytoplasmic male sterile (CMS) line PMS17A to develop hybrids. Hybrids developed from recurrent parents were used as checks to compare the performance of 318 hybrids developed by hybridizing alien introgression lines with PMS17A. Seventeen hybrids expressed a significant increase in yield and its component traits over check hybrids. These 17 hybrids were re-evaluated in large-size replicated plots. Of these, four hybrids, viz., ILH299, ILH326, ILH867 and ILH901, having introgressions from O. rufipogon and two hybrids (ILH921 and ILH951) having introgressions from O. nivara showed significant heterosis over parental introgression line, recurrent parents and check hybrids for grain yield-related traits. Alien introgressions were detected in the lines taken as male parents for developing six superior hybrids, using a set of 100 polymorphic simple sequence repeat (SSR) markers. Percent introgression showed a range of 2.24 from in O. nivara to 7.66 from O. rufipogon. The introgressed regions and their putative association with yield components in hybrids is reported and discussed.
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Filarial abscess in the submandibular region.
J Oral Maxillofac Pathol
PUBLISHED: 11-20-2013
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Filariasis is a parasitic infectious disease caused by filarial nematode worms. These worms mainly dwell in subcutaneous tissues and lymphatics of the human host, with a predilection for lower limbs, retroperitoneal tissues, spermatic cord, and epididymis. Oral or perioral involvement of the filarial nematode is rare. This case report describes a filarial abscess in the right submandibular region. Fine needle aspiration cytology of the abscess revealed the presence of microfilaria of Wuchereria bancrofti species. The parasite was also present in the peripheral blood smear. Filarial infection presenting in this region is unusual and can cause diagnostic dilemma. The clinician can consider filariasis as one of the differential diagnosis while treating those abscesses in the orofacial region that are unresponsive to routine management, especially, patients hailing from endemic areas.
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Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages.
J Vis Exp
PUBLISHED: 10-17-2013
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A cell culture model system, if a close mimic of host environmental conditions, can serve as an inexpensive, reproducible and easily manipulatable alternative to animal model systems for the study of a specific step of microbial pathogen infection. A human monocytic cell line THP-1 which, upon phorbol ester treatment, is differentiated into macrophages, has previously been used to study virulence strategies of many intracellular pathogens including Mycobacterium tuberculosis. Here, we discuss a protocol to enact an in vitro cell culture model system using THP-1 macrophages to delineate the interaction of an opportunistic human yeast pathogen Candida glabrata with host phagocytic cells. This model system is simple, fast, amenable to high-throughput mutant screens, and requires no sophisticated equipment. A typical THP-1 macrophage infection experiment takes approximately 24 hr with an additional 24-48 hr to allow recovered intracellular yeast to grow on rich medium for colony forming unit-based viability analysis. Like other in vitro model systems, a possible limitation of this approach is difficulty in extrapolating the results obtained to a highly complex immune cell circuitry existing in the human host. However, despite this, the current protocol is very useful to elucidate the strategies that a fungal pathogen may employ to evade/counteract antimicrobial response and survive, adapt, and proliferate in the nutrient-poor environment of host immune cells.
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Anticonvulsant activity of ethanol extracts of Vetiveria zizanioides roots in experimental mice.
Pharm Biol
PUBLISHED: 07-18-2013
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Vetiveria zizanioides Linn. (Gramineae), an aromatic plant commonly known as vetiver, is traditionally used for various ailments. Ethanol and aqueous extract of this plant found extensive use in Indian folklore medicine and used in treatment of a wide range of disorders including seizure. However, the anticonvulsant activity of this plant has not been studied.
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Characterization of ?-casein gene in Indian riverine buffalo.
Gene
PUBLISHED: 05-09-2013
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The study aimed at characterization of buffalo ?-casein gene and its promoter by PCR-SSCP analysis. Complete ?-casein exon VII region analysis revealed two SSCP band patterns, with pattern-I representing predominant allele B (85%) present in homozygous (genotype BB) condition and pattern-II representing a rare allele A1 present in heterozygous condition (genotype A1B). Sequencing of two patterns revealed three nucleotide substitutions at codon 68, 151 and 193 of exon VII. The cDNA sequence of buffalo ?-casein gene indicated three further nucleotide substitutions between allele A1 and B at codon 10, 39, and 41. Analysis of ?-casein proximal promoter region (-350 upstream to +32) revealed four SSCP band patterns. These SSCP patterns corresponded to nucleotide substitutions at seven locations within 382 bp 5 UTR region of ?-casein gene. Haplotype analysis suggested pattern-I of exon VII (wild type) was associated with three types of promoters and pattern-II of exon VII (rare type) corresponded to one exclusive type of promoter. The study suggested two haplotypes of exon VII and four haplotypes of promoter for buffalo ?-casein.
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Comparison of protective and curative potential of Daucus carota root extract on renal ischemia reperfusion injury in rats.
Pharm Biol
PUBLISHED: 04-29-2013
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Daucus carota Linn (Apiaceae), a useful vegetable, is traditionally used in treating kidney and hepatic dysfunctions.
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Rehydration of Air-Dried Smears versus Wet Fixation: A Cross-Sectional Study.
Acta Cytol.
PUBLISHED: 04-12-2013
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The Papanicolaou (Pap) smear is an effective method for early detection of cervical cancer. The routine practice of staining is to immediately fix the cervical smear in 95% ethyl alcohol. An alternative method of rehydrating the air-dried cervical smears followed by fixation and conventional staining method can overcome most of the problems associated with short supply and storage of alcohol, wet fixing of slides and transporting them to the cytology centre if the Pap smears are prepared at a peripheral centre. There are only few studies regarding rehydration of cervical smears as a substitute for wet fixation.
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Recent development in [1,4]-Benzodiazepines as Potent Anticancer Agents: A Review.
Mini Rev Med Chem
PUBLISHED: 04-11-2013
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The [1,4]-benzodiazepine is an important class of heterocyclic compounds and clinically used for many ailments in humans. The [1,4]-benzodiazepine has unique structure that mimics the peptide linkage. This interesting observation completely shifted the interest of medicinal chemist for [1,4]-benzodiazepine from CNS acting drugs to anticancer agent. During last few decades, large number of reports has appeared in the literature highlighting the anticancer activity of [1,4]-benzodiazepines. Here, in this article, we have discussed the brief synthesis, origin of [1,4]-benzodiazepines as anticancer agent, its mechanism of action and latest developments in this field. We have compiled the most important literature reports from last few decades to till date.
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Adherence to hand hygiene in high-risk units of a tertiary care hospital in India.
Am J Infect Control
PUBLISHED: 04-09-2013
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To improve the compliance to hand hygiene in our health care workers, 3 hand hygiene awareness weeks have been conducted over the past one-and-a-half years in our hospital. This observational audit conducted from October 2011 to March 2012 was planned to assess the impact of the above awareness drives. Although overall compliance increased significantly in 7 intensive care units from 23.1% to 41.2% (P < .0001), several deficiencies were noticed both in technique used as well as during specific opportunities of hand hygiene.
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Central giant cell granuloma of the maxilla.
BMJ Case Rep
PUBLISHED: 03-12-2013
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Central giant cell granuloma (CGCG), formerly called giant cell reparative granuloma, is a non-neoplastic proliferative lesion of an unknown aetiology. It occurs most commonly in the mandible. The case reported here resembled a wide variety of conditions that led to a misdiagnosis both on clinical and radiographic examinations but was histopathologically diagnosed as CGCG. We managed this case by endoscopic excision and curettage via nasal route without producing external scar and avoiding damage to the un-erupted tooth.
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"Cannon balls or pus balls" in pap smears: a case report.
J Clin Diagn Res
PUBLISHED: 02-05-2013
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A 50-year old female presented with the chief complaint of a discharge per vaginum, which was there for the past 15 days. A routine PAP smear was received in the Department of Pathology, Government Medical College, Patiala, India. After its fixation and staining, it was examined under the microscope. It showed the Trichomonas vaginalis infection, with the neutrophils forming cannon balls at places. Neutrophils in the PAP smear are a nonspecific finding, particularly if they are low in numbers or if they are seen in the premenstrual and the menstrual phases. The neutrophils which are adherent to the squamous cells are called "cannon balls" or "pus balls", which are common in the Chlamydia infection. This case is being presented because of the presence of these rare morphological structures i.e. "cannon balls" or "pus balls".
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Draft Genome Sequence of the Wolbachia Endosymbiont of Drosophila suzukii.
Genome Announc
PUBLISHED: 01-14-2013
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Wolbachia is one of the most successful and abundant symbiotic bacteria in nature, infecting more than 40% of the terrestrial arthropod species. Here we report the draft genome sequence of a novel Wolbachia strain named "wSuzi" that was retrieved from the genome sequencing of its host, the invasive pest Drosophila suzukii.
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The Rho1 GTPase-activating protein CgBem2 is required for survival of azole stress in Candida glabrata.
J. Biol. Chem.
PUBLISHED: 08-08-2011
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Invasive fungal infections are common clinical complications of neonates, critically ill, and immunocompromised patients worldwide. Candida species are the leading cause of disseminated fungal infections, with Candida albicans being the most prevalent species. Candida glabrata, the second/third most common cause of candidemia, shows reduced susceptibility to a widely used antifungal drug fluconazole. Here, we present findings from a screen of 9134 C. glabrata Tn7 insertion mutants for altered survival profiles in the presence of fluconazole. We have identified two components of RNA polymerase II mediator complex, three players of Rho GTPase-mediated signaling cascade, and two proteins implicated in actin cytoskeleton biogenesis and ergosterol biosynthesis that are required to sustain viability during fluconazole stress. We show that exposure to fluconazole leads to activation of the protein kinase C (PKC)-mediated cell wall integrity pathway in C. glabrata. Our data demonstrate that disruption of a RhoGAP (GTPase activating protein) domain-containing protein, CgBem2, results in bud-emergence defects, azole susceptibility, and constitutive activation of CgRho1-regulated CgPkc1 signaling cascade and cell wall-related phenotypes. The viability loss of Cgbem2? mutant upon fluconazole treatment could be partially rescued by the PKC inhibitor staurosporine. Additionally, we present evidence that CgBEM2 is required for the transcriptional activation of genes encoding multidrug efflux pumps in response to fluconazole exposure. Last, we report that Hsp90 inhibitor geldanamycin renders fluconazole a fungicidal drug in C. glabrata.
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Social stratification in the Sikh population of Punjab (India) has a genetic basis: evidence from serological and biochemical markers.
Genet Test Mol Biomarkers
PUBLISHED: 03-31-2011
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The present study was planned to assess whether social stratification in the Sikh population inhabiting the northwest border Indian state of Punjab has any genetic basis.
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A novel role for a glycosylphosphatidylinositol-anchored aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata.
Mol. Microbiol.
PUBLISHED: 02-09-2011
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Proteases, key virulence factors of many bacterial and fungal pathogens, are pivotally important for nutrient acquisition, invasion and adherence to host cells and evasion/escape from host immune cells. In this study, we report a novel role for CgYps1, member of a family of 11 GPI-linked aspartyl proteases, in a human opportunistic fungal pathogen, Candida glabrata, in the regulation of pH homeostasis under acidic environmental conditions. We show that CgYps1 is required to survive low-external-pH environment and the inability of Cgyps1? mutant to maintain pH homeostasis results in intracellular acidification and increased reactive oxygen species (ROS) production. We also provide evidence that the reduced intracellular pH in Cgyps1? mutant under acidic conditions is, partly, owing to the diminished activity of a plasma membrane proton pump, CgPma1, an orthologue of a key component of pH homeostasis machinery in Saccharomyces cerevisiae, Pma1. In addition, we have examined C. glabratas response to low environmental pH via genome-wide expression analysis and several genes required for protein folding/modification and stress response pathways including seven of the CgYPS genes were found to be upregulated. Lastly, we show that C. glabrata responds to acidic environment by reducing total ?-glucan levels in the cell wall in a CgYps1-dependent manner.
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Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: essential in C. glabrata, and essential for virulence in C. albicans.
Microbiology (Reading, Engl.)
PUBLISHED: 10-21-2010
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Redox pathways play a key role in pathogenesis. Glutathione, a central molecule in redox homeostasis in yeasts, is an essential metabolite, but its requirements can be met either from endogenous biosynthesis or from the extracellular milieu. In this report we have examined the importance of glutathione biosynthesis in two major human opportunistic fungal pathogens, Candida albicans and Candida glabrata. As the genome sequence of C. glabrata had suggested the absence of glutathione transporters, we initially investigated exogenous glutathione utilization in C. glabrata by disruption of the MET15 gene, involved in methionine biosynthesis. We observed an organic sulphur auxotrophy in a C. glabrata met15? strain; however, unlike its Saccharomyces cerevisiae counterpart, the C. glabrata met15? strain was unable to grow on exogenous glutathione. This inability to grow on exogenous glutathione was demonstrated to be due to the lack of a functional glutathione transporter, despite the presence of a functional glutathione degradation machinery (the Dug pathway). In the absence of the ability to obtain glutathione from the extracellular medium, we examined and could demonstrate that ?-glutamyl cysteine synthase, the first enzyme of glutathione biosynthesis, was essential in C. glabrata. Further, although ?-glutamyl cysteine synthase has been reported to be non-essential in C. albicans, we report here for what is believed to be the first time that the enzyme is required for survival in human macrophages in vitro, as well as for virulence in a murine model of disseminated candidiasis. The essentiality of ?-glutamyl cysteine synthase in C. glabrata, and its essentiality for virulence in C. albicans, make the enzyme a strong candidate for antifungal development.
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Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques.
Acta Pharm
PUBLISHED: 10-13-2009
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Identification and characterization of different forms of methotrexate were carried out by crystallization from different solvents. Five different forms of the drug were obtained. Appearance of a desolvation endotherm in the DSC accompanied by mass loss in TGA for forms I, II, IV and V showed these forms to be acetonitrile solvate hydrate (form I), trihydrate (forms II and IV) and dimethylformamide solvate (form V), respectively. However, the desolvation peak was absent in form III (obtained from methanol) indicating the absence of any solvent of crystallization. This form was found to be partially crystalline by its XRPD pattern. Solution calorimetry was further used to differentiate between the forms as they differ in lattice energy, resulting in different enthalpies of solution. The dissolution and solubility profiles were correlated with the enthalpy of solution and subsequently with crystallinity of all the forms; the least endothermic form (form III) had the highest dissolution rate.
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Experience with Kangaroo mother care in a neonatal intensive care unit (NICU) in Chandigarh, India.
Indian J Pediatr
PUBLISHED: 04-18-2009
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To study the feasibility and acceptability of Kangaroo mother care (KMC) on the low birth weight infants (LBWI) in the neonatal intensive care unit (NICU) by the mothers, family members and health care workers (HCW) and to observe its effect on the vital parameters of the babies.
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Multiple eccrine hidrocystomas in a patient of sarcoidosis.
Indian J Dermatol
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A 45-year-old female patient known case of sarcoidosis presented in skin department with chief complaint of skin-colored papulonodular lesions over face with exacerbation in summer season since last 4 years. On examination lesions were multiple, firm and skin colored. Biopsy was done showing features of eccrine hidrocystoma. Patient was treated with electrocautery and showed improvement.
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Polypharmacy (herbal and synthetic drug combination): a novel approach in the treatment of type-2 diabetes and its complications in rats.
J Nat Med
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The aim of present study was to evaluate the effect of aqueous leaf extract of Annona squamosa with Glipizide in a high fat diet and streptozocin-induced type-2 diabetes. Nine groups (n = 6) of male Sprague-Dawley rats were used for the study, with. Basal blood glucose, urine volume, and body weights were measured and the rate were kept on a high fat diet. After 15 days, streptozocin in sub-diabetic dose (35 mg/kg) was administered to the animals to induce diabetes. With 1 week of consistent hyperglycemia, treatment was initiated. Aqueous extract of Annona squamosa was administered orally at 350 mg/kg body weight alone and in combination with reduced and reducing dose combinations of Glipizide. Blood glucose, body weight, urine volume were measured every 10th day. The elevated blood-glucose level in diabetic rats was controlled better with combination therapy compared with the synthetic drug alone or the herbal stand-alone drug. All the results were statistically significant (P < 0.001). A combination of Annona squamosa along with Glipizide may be helpful in dose reduction of Glipizide up to 50%, reducing the risk of the onset of insulin therapy.
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Disseminated cryptococcosis presenting with generalized lymphadenopathy.
J Cytol
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Cryptococcosis is a common opportunistic infection among immunocompromised individuals. Some of the commonly affected sites are respiratory and central nervous system. Lymph node is an unusual site of involvement which could mimic tuberculosis, as seen in our case. We report a 32-year-old male immunocompromised patient presenting with generalized lymphadenopathy who was clinically suspected to have tuberculous lymphadenitis. He was diagnosed to have disseminated cryptococcosis on fine needle aspiration cytology and fungal isolation on culture.
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Non-invasive ventilation in patients with acute lupus pneumonitis: A case report and review of literature.
Lung India
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Acute lupus pneumonitis is an uncommon but life threatening condition associated with systemic lupus erythematosus. We report the case of a young female who presented to us with acute hypoxemic respiratory failure secondary to acute lupus pneumonitis as initial presenting manifestation of lupus. She was managed with non-invasive ventilation and pulse steroids, with which she had dramatic improvement.
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Functional genomic analysis of Candida glabrata-macrophage interaction: role of chromatin remodeling in virulence.
PLoS Pathog.
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Fungal septicemia is an increasingly common complication of immunocompromised patients worldwide. Candida species are the leading cause of invasive mycoses with Candida glabrata being the second most frequently isolated Candida species from Intensive Care Unit patients. Despite its clinical importance, very little is known about the mechanisms that C. glabrata employs to survive the antimicrobial and immune response of the mammalian host. Here, to decipher the interaction of C. glabrata with the host immune cells, we have screened a library of 18,350 C. glabrata Tn7 insertion mutants for reduced survival in human THP-1 macrophages via signature-tagged mutagenesis approach. A total of 56 genes, belonging to diverse biological processes including chromatin organization and golgi vesicle transport, were identified which are required for survival and/or replication of C. glabrata in macrophages. We report for the first time that C. glabrata wild-type cells respond to the intracellular milieu of macrophage by modifying their chromatin structure and chromatin resistance to micrococcal nuclease digestion, altered epigenetic signature, decreased protein acetylation and increased cellular lysine deacetylase activity are the hall-marks of macrophage-internalized C. glabrata cells. Consistent with this, mutants defective in chromatin organization (Cgrsc3-a?, Cgrsc3-b?, Cgrsc3-a?b?, Cgrtt109?) and DNA damage repair (Cgrtt107?, Cgsgs1?) showed attenuated virulence in the murine model of disseminated candidiasis. Further, genome-wide transcriptional profiling analysis on THP-1 macrophage-internalized yeasts revealed deregulation of energy metabolism in Cgrsc3-a? and Cgrtt109? mutants. Collectively, our findings establish chromatin remodeling as a central regulator of survival strategies which facilitates a reprogramming of cellular energy metabolism in macrophage-internalized C. glabrata cells and provide protection against DNA damage.
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An updated review on the Oenothera genus.
Zhong Xi Yi Jie He Xue Bao
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Oenothera genus (Onagraceae) has been used as a folk remedy since ancient times for the treatment of asthma, gastrointestinal disorders, neuralgia, skin diseases, and hepatic and kidney diseases. Different chemical constituents like lipids, flavonoids, tannins, steroids and triterpenes have been isolated from this genus. The various notable pharmacological activities reported from the genus are antioxidant, cytotoxic, antibacterial, antiviral, anti-inflammatory, antihyperlipidaemic, thrombolytic and antidiarrhoeal. The present paper is to summarize the worldwide reported biological activities and phytoconstituents associated with this genus for about 50 years and highlight the medicinally important species belonging to this genus so that these species can be further explored and used as therapeutic agents for various diseases.
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The role of culture in substance abuse treatment programs for American Indian and Alaska Native communities.
Psychiatr Serv
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Culture figures prominently in discussions regarding the etiology of alcohol and substance abuse in American Indian and Alaska Native (AI/AN) communities, and a substantial body of literature suggests that it is critical to developing meaningful treatment interventions. However, no study has characterized how programs integrate culture into their services. Furthermore, reports regarding the associated challenges are limited.
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Prothrombotic gene polymorphisms and plasma factors in young North Indian survivors of acute myocardial infarction.
J. Thromb. Thrombolysis
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The aim of this study was to evaluate the association of prothrombotic gene polymorphisms [factor V Leiden (FVL) 1691GA, factor VII (FVII) 10976GA, FVII HVR4, platelet membrane glycoproteins GP1BA 1018CT, GP1BA VNTR, integrin ITGB3 1565TC, integrin ITGA2 807CT and methylenetetrahydrofolate reductase (MTHFR) 677C/T], plasma factors (fibrinogen and homocysteine) and traditional risk factors with acute myocardial infarction (AMI) in 184 patients ? 40 years of age and 350 controls (? 40 years) from north India. Multiple logistic-regression analysis showed that hypertension (OR 1.9, 95 % CI 1.1-3.8, p = 0.042), diabetes mellitus (OR 10.5, 95 % CI 2.0-56.7, p = 0.006), smoking (OR 7.1, 95 % CI 3.7-13.6, p < 0.001), low socio-economic status (OR 13.5, 95 % CI 2.3-78.4, p = 0.004), high waist-hip ratio (OR 35.6, 95 % CI 11.1-53.7, p < 0.001) and FVL 1691GA (OR 6.0, 95 % CI 1.2-13.4, p = 0.03) were independent risk predictors of AMI in young. Elevated plasma fibrinogen also showed association with increased AMI risk. ITGA2 807C/T polymorphism showed protection against AMI in univariate analysis only, while GP1BA VNTR-ac (OR 0.4, 95 % CI 0.2-0.9, p = 0.033) showed significant protection even after adjusting for age and sex. Multinominal logistic-regression analysis showed gene-gene (GP1BA 1018C/T with GP1BA VNTR and ITGA2 807C/T with ITGB3 1565T/C polymorphisms) and gene-environment interactions (gene polymorphisms with smoking) operating in the occurrence of AMI in young. In conclusion, the role of inherited predisposition to thrombosis in complex, polygenic and multifactorial disease like AMI is limited to certain genetic factors, in combination with environmental factor like smoking.
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Synergistic effect of angiotensin II type-1 receptor 1166A/C with angiotensin-converting enzyme polymorphism on risk of acute myocardial infarction in north Indians.
J Renin Angiotensin Aldosterone Syst
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This first study from north India investigated the synergistic effect of AT1R 1166A/C with the ACE I/D polymorphism on risk of acute myocardial infarction (AMI).
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Glycosylphosphatidylinositol (GPI)-linked aspartyl proteases regulate vacuole homeostasis in Candida glabrata.
Biochem. J.
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A family of eleven glycosylphosphatidylinositol (GPI)-linked, cell surface-associated aspartyl proteases (yapsins)in a human opportunistic fungal pathogen Candida glabrata is required for cell wall remodeling and pH homeostasis, survival in macrophages and virulence in a murine model of disseminated candidiasis. Here, we report new roles for yapsins in C. glabrata physiology and implicate them for the first time in the regulation of vacuole homeostasis. We show that a C. glabrata mutant lacking all eleven yapsins, Cgyps1-11?, possesses an enlarged vacuole and displays vma- (vacuolar membrane ATPase)-like phenotypes with elevated metal ion susceptibility in alkaline pH medium and diminished Vma activity. Our data also demonstrate a singular role for CgYps1 in the maintenance of ion homeostasis under normal and calcineurin-inhibited conditions. Elevated polyphosphate levels and diminished cellular CPY activity in Cgyps1-11? mutant highlight the yapsin requirement for a properly functioning vacuole. Lastly, a gross perturbation of cellular homeostasis in Cgyps1-11? mutant, even in the absence of external stressors, characterized by reduced levels of ATP and stress metabolites, elevated reactive oxygen species levels, cell surface abnormalities and constitutively activated protein kinase C signaling pathway, underscore diverse physiological functions of yapsins in C. glabrata.
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