The document reports on the discovery that human heat shock protein 90 (Hsp90) interacts with Neisseria meningitidis adhesin A (NadA) and interferes with NadA-mediated adhesion and invasion of human cells. Specifically, affinity chromatography revealed an interaction between recombinant soluble NadA and Hsp90. Further experiments using co-immunoprecipitation, dot blots, and far-Western blots confirmed the specific in vitro interaction between NadA and Hsp90, which required ADP but not ATP. Inhibition or modulation of Hsp90 in human cells through RNA interference, overexpression, addition of recombinant Hsp90, or use of the Hsp90 inhibitor 17-AAG
This study sequenced the genomes of 11 clinical Mycobacterium abscessus isolates from 8 US patients with pulmonary infections. Core genome analysis compared these isolates to 30 globally diverse strains to investigate population structure. Longitudinally sampled isolates showed very few genetic differences, suggesting homogenous infection populations. Genome content variation between isolates was 0.3-8.3% compared to the reference strain, indicating plasticity.
This document summarizes a study that analyzed DNA copy number aberrations in small-cell lung cancer (SCLC) tumors to identify activated molecular pathways. The key findings are:
1) Array comparative genomic hybridization identified 70 regions of copy number gain and 55 regions of copy number loss across 46 SCLC tumors.
2) Pathway analysis found these regions were enriched for 11 genes in the focal adhesion pathway and 8 genes in the neuroactive ligand-receptor interaction pathway.
3) Further analysis validated increased copy number and expression of focal adhesion kinase (FAK) in SCLC tumors and cell lines. Inhibition of FAK phosphorylation decreased adhesion of SCLC cells.
Karyotypic complexity and multiclonality: Two cytogenetic parameters to be co...Georgia Bardi
Karyotypic complexity and multiclonality (either cytogenetically unrelated clones or cytogenetically related clones) represent two parameters of prognostic significance in management of patients with Myelodysplastic syndromes.
Presented by Georgia Bardi, PhD at MDS workshop in Perugia 2008. Cytogenetic data produced by Eugenia Gourgouveli and Despina Iakovaki.
This article summarizes 9 research papers on gene and cell therapy approaches for treating cystic fibrosis. It provides brief summaries of the objectives, methods, and conclusions of each paper to give an overview of the current state of research on developing therapies for cystic fibrosis.
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
This document discusses how exome sequencing is revolutionizing the identification of genes that cause Mendelian diseases. It provides three main points:
1) Exome sequencing has identified over 30 new disease genes since 2009, improving clinical diagnosis, genotype-phenotype correlations, and understanding of rare genetic variation.
2) Our view of Mendelian diseases is changing as exome sequencing is less biased than previous methods and is identifying disease genes in cases where the genetic cause was unclear.
3) Exome sequencing is now the primary tool for studying Mendelian diseases as it can sequence hundreds of patient exomes per year more efficiently than whole genome sequencing.
This document provides a summary of research on Brucellosis, a bacterial infection. It discusses the epidemiology and transmission of Brucellosis, highlighting that it is one of the most common zoonotic diseases worldwide, with 500,000 cases annually. It then examines the pathogenic strategies that allow Brucella bacteria to evade the immune system, including modifications to its lipopolysaccharide that inhibit immune responses. Finally, it reviews the immunological response to Brucella, noting the importance of innate immune cells and Th1-type cytokines in both the initial response and long-term control of infection.
This study analyzed exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. It identified a mean exonic somatic mutation rate of 12.0 events/megabase and recurrent mutations in genes like U2AF1, RBM10 and ARID1A. Whole-genome analysis revealed frequent structural rearrangements including in-frame alterations in EGFR and SIK2 kinases. The candidate cancer genes identified may provide insights into lung adenocarcinoma pathogenesis and potential therapeutic targets.
This study sequenced the genomes of 11 clinical Mycobacterium abscessus isolates from 8 US patients with pulmonary infections. Core genome analysis compared these isolates to 30 globally diverse strains to investigate population structure. Longitudinally sampled isolates showed very few genetic differences, suggesting homogenous infection populations. Genome content variation between isolates was 0.3-8.3% compared to the reference strain, indicating plasticity.
This document summarizes a study that analyzed DNA copy number aberrations in small-cell lung cancer (SCLC) tumors to identify activated molecular pathways. The key findings are:
1) Array comparative genomic hybridization identified 70 regions of copy number gain and 55 regions of copy number loss across 46 SCLC tumors.
2) Pathway analysis found these regions were enriched for 11 genes in the focal adhesion pathway and 8 genes in the neuroactive ligand-receptor interaction pathway.
3) Further analysis validated increased copy number and expression of focal adhesion kinase (FAK) in SCLC tumors and cell lines. Inhibition of FAK phosphorylation decreased adhesion of SCLC cells.
Karyotypic complexity and multiclonality: Two cytogenetic parameters to be co...Georgia Bardi
Karyotypic complexity and multiclonality (either cytogenetically unrelated clones or cytogenetically related clones) represent two parameters of prognostic significance in management of patients with Myelodysplastic syndromes.
Presented by Georgia Bardi, PhD at MDS workshop in Perugia 2008. Cytogenetic data produced by Eugenia Gourgouveli and Despina Iakovaki.
This article summarizes 9 research papers on gene and cell therapy approaches for treating cystic fibrosis. It provides brief summaries of the objectives, methods, and conclusions of each paper to give an overview of the current state of research on developing therapies for cystic fibrosis.
Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that ...Enrique Moreno Gonzalez
Sox2, an embryonic stem cell marker, is aberrantly expressed in a subset of breast cancer (BC). While the aberrant expression of Sox2 has been shown to significantly correlate with a number of clinicopathologic parameters in BC, its biological significance in BC is incompletely understood.
This document discusses how exome sequencing is revolutionizing the identification of genes that cause Mendelian diseases. It provides three main points:
1) Exome sequencing has identified over 30 new disease genes since 2009, improving clinical diagnosis, genotype-phenotype correlations, and understanding of rare genetic variation.
2) Our view of Mendelian diseases is changing as exome sequencing is less biased than previous methods and is identifying disease genes in cases where the genetic cause was unclear.
3) Exome sequencing is now the primary tool for studying Mendelian diseases as it can sequence hundreds of patient exomes per year more efficiently than whole genome sequencing.
This document provides a summary of research on Brucellosis, a bacterial infection. It discusses the epidemiology and transmission of Brucellosis, highlighting that it is one of the most common zoonotic diseases worldwide, with 500,000 cases annually. It then examines the pathogenic strategies that allow Brucella bacteria to evade the immune system, including modifications to its lipopolysaccharide that inhibit immune responses. Finally, it reviews the immunological response to Brucella, noting the importance of innate immune cells and Th1-type cytokines in both the initial response and long-term control of infection.
This study analyzed exome and genome sequences of 183 lung adenocarcinoma tumor/normal DNA pairs. It identified a mean exonic somatic mutation rate of 12.0 events/megabase and recurrent mutations in genes like U2AF1, RBM10 and ARID1A. Whole-genome analysis revealed frequent structural rearrangements including in-frame alterations in EGFR and SIK2 kinases. The candidate cancer genes identified may provide insights into lung adenocarcinoma pathogenesis and potential therapeutic targets.
Surveying the small-spotted catshark (Scyliorhinus canicula) tumour necrosis ...Fiona Bakke
This honours research project report summarizes an investigation of the tumour necrosis factor superfamily (TNFSF) genes in the small-spotted catshark (Scyliorhinus canicula). Bioinformatic analysis of the S. canicula transcriptome identified potential TNFSF orthologs. A phylogenetic tree including TNFSF sequences from various vertebrates provided insight into the evolutionary relationships between these genes. Several S. canicula TNFSF sequences were amplified and sequenced to confirm their presence. The analysis suggests S. canicula possesses orthologs of most mammalian TNFSF genes, though is missing a few, and also expresses a TNFSF gene only found previously in cart
This document describes the development of a multiplex PCR assay targeting the cgcA gene, which encodes a diguanylate cyclase, to differentiate between species within the genus Cronobacter. Analysis of 12 Cronobacter genomes identified 7 conserved diguanylate cyclase-encoding genes, one of which, cgcA, showed species-specific divergence that matched known phylogenetic relationships between Cronobacter species. Primers were designed for this gene and tested in a multiplex PCR assay on 305 Cronobacter isolates representing 6 species. The assay correctly identified the species of all isolates tested and did not identify any of 20 non-Cronobacter species, demonstrating high specificity and sensitivity for rapid identification of Cronobacter.
Variable transcriptional adaptation between the laboratory (H37Rv) and clinic...Santhi Devasundaram
The remarkable success of M. tuberculosis as a pathogen is largely due to its ability to
persist within the host for long periods. To develop the effective intervention strategies, understanding the biology
of persistence is highly required. Accumulating evidences showed oxygen deprivation (hypoxia) as a potential
stimulus for triggering the transition of M. tuberculosis to a non-replicating persistent state analogous to
latency in vivo. To date, in vitro hypoxia experimental models used the laboratory adapted isolate H37Rv and
very little is known about the behavior of clinical isolates that are involved during disease outbreaks. Hence,
we compared the transcription profiles of H37Rv and two south Indian clinical isolates (S7 and S10) under hypoxia
to find differences in gene expression pattern.
This document discusses the FOXP3 gene as a promising candidate gene in susceptibility to generalized vitiligo. It summarizes that FOXP3 is the master transcription factor that regulates regulatory T cells, which play an important role in preventing autoimmunity. Studies have found associations between polymorphisms in the FOXP3 gene and an increased risk of vitiligo. The document argues that further investigation of FOXP3 genetic variants and their effects on regulatory T cell development and function could provide insights into vitiligo pathogenesis and potential new therapeutic approaches targeting the FOXP3 gene/regulatory T cell network.
Three key points:
1) The study identified a group of myeloma patients with an "ultra-high risk" of early relapse and poor survival outcomes based on having both high-risk genetic lesions and a high-risk gene expression profile.
2) In two large clinical trials, these ultra-high risk patients had a median progression-free survival of 13.4 months and median overall survival of 26.1 months, significantly worse than other patient groups.
3) Validation in an independent patient group confirmed ultra-high risk patients defined by both genetic and gene expression risk factors experienced particularly poor outcomes, with all progressing within 2 years and no survivors beyond 4 years.
This study examines the effects of galectins, VEGF-B, and stress conditions on human endothelial cell growth, survival, and migration. Various assays show that galectins and VEGF-B enhance cell growth under normal and stressed conditions, though the intended stressor did not work properly. Cell counts varied due to growth, not death. Galectins decreased phosphorylation of ERK and phospho-ERK under both conditions. The results suggest galectins and VEGF-B may have synergistic effects on angiogenesis, though more study is needed under effective stress.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Ong et al._Translational utility of next-generation sequencing_2013_GenomicsFrank Ong, MD, CPI
Next-generation sequencing (NGS) has made DNA sequencing rapid, cost-effective and highly accurate. NGS has translational utility in several areas: 1) It can detect genetic variations associated with disease risk and treatment response; 2) It enables non-invasive prenatal testing for fetal abnormalities; 3) Cancer genome sequencing can improve diagnosis, prognosis and treatment by deciphering a cancer's genetic makeup. NGS also has utility in rare genetic disease diagnosis and in precision medicine by matching patients to targeted therapies.
ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that ...Rubin Baskir, Ph.D.
This document reports on a study investigating a novel pericyte subpopulation in the lung called ABCG2pos mesenchymal stem cells (MSC). The study found:
1) ABCG2pos lung MSC numbers were decreased in human pulmonary fibrosis (PF) and interstitial lung disease samples compared to controls.
2) In a mouse model of bleomycin-induced lung injury, GFP-labeled lung MSC-derived cells increased in number and localized to fibrotic and microvessel remodeling areas after 14 days.
3) Lung MSC responded to in vivo bleomycin injury with a profibrotic gene expression profile that was not replicated with in vitro bleomycin treatment, but
This research article examines the role of sphingosine-1-phosphate (S1P) in regulating the proliferative and stem-like properties of glioblastoma stem cells (GSCs). The results showed that GSCs rapidly consume ceramide and export S1P into the extracellular environment. Extracellular S1P levels reached nanomolar concentrations in response to increased sphingosine. S1P was also found to act as an autocrine factor that promotes GSC proliferation and maintains their stem-like phenotype. This suggests that microenvironmental S1P critically modulates the GSC population by acting as an autocrine signal to support stemness and favor proliferation, survival, and therapeutic resistance of GSCs.
This document discusses genomic oncology and personalized medicine, using lung cancers as a model. It summarizes several key technologies that enable genomic oncology like cDNA microarrays, array CGH, and next generation sequencing. It provides examples of how these technologies have been used to classify cancers like diffuse large B-cell lymphoma and myelodysplastic syndrome, and identify genetic mutations that can guide targeted therapies for cancers like EGFR-mutated lung cancer.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
The document describes the design of a customized genome-wide genotyping array ("TxArray") for transplantation studies. It includes approximately 782,000 markers focused on loci related to HLA, KIR, pharmacogenomics, and metabolism that are important for transplantation. Testing on 85 HapMap samples showed high concordance (0.996) and low error rates, and genotype imputation was highly accurate (over 0.962). The array was designed to improve coverage of regions like KIR compared to other platforms and enable large-scale genetic studies in transplant cohorts.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
Objective: To analyze the sonographic features of different histopathological subtypes of borderline ovarian tumors (BOTs) confirmed by pathology, and to study the ultrasound performances of various types in borderline ovarian tumors.
Study Design: Retrospective analysis was performed on the pathological results and ultrasound projection findings of 129 patients diagnosed as BOTs by ultrasound department of our hospital from January 2012 to November 2019. All patients were confirmed by surgical pathology and scanned consecutively by the investigators using transabdominal or transvaginal ultrasound examination.
Results: Serous borderline tumors (SBOTs) were observed, and the prevalence rate (53%) was significantly higher than that of other subtypes, and the probability of bilateral lesions was higher (40%). The sonogram often showed ultrasound features of papillary neoplasm in the lesion and good internal echo (p<0.05). Mucinous borderline ovarian tumors (MBOTs) were mostly unilateral lesions (86%). The prevalence was second only to SBOTs. Histomorphological examinations were divided into gastrointestinal-type and endocervical-type. Among them, the gastrointestinal type of MBOTs were mostly unilateral, and their incidence was higher than that of endocervical-type of MBOTs. Compared with other pathological subtypes, the gastrointestinal type is more likely to show the sonographic characteristics of huge space occupying in the pelvic and abdominal cavity (mean diameter >10 cm), polycystic, multiple septums, and poor internal echo (p<0.05). The ultrasonographic features of the endocervical-type of MBOTs were similar to those of SBOTs. Compared with gastrointestinal type, the sonographic images showed smaller lesion diameter, less septal or cyst, and more papillary excrescences in the tumor (p<0.05). The borderline clear cell tumor is the intermediate transition between the clear cell adenofibroma and the clear cell carcinoma. The clinical manifestations are diverse and lack specificity. The histology of sonography was mainly solid, and the multiple microcapsules were honeycomb-like. It can also be shown as cystic. Among the 169 patients with BOTs, 20 cases of SBOTs, 17 cases of MBOTs, and 10 cases of other rare subtypes were complicated with other diseases or multiple subtypes. This study did not find significant ultrasonic characteristics were used for distinguish them from other subtypes.
Conclusion: BOTs is a common disease in women during the reproductive period. It is characterized by the development of malignant tumors. Its clinical and pathological subtypes are complex and diverse. It leads many doctors to use the terms “large pelvic mass” and “solid ovarian mass” for diagnosis because of their lack of experience and understanding.
Keywords: adenocarcinoma, mucinous; adenocarcinoma, serous; borderline ovarian tumors; diagnostic imaging; ovarian neoplasms; papillary neoplasms; prognosis; transvaginal ultrasound, ultrasonography
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
The document describes a study that used high-resolution microarray analysis to identify copy number variations (CNVs) in 15 patients with nonsyndromic cleft lip and palate (NSCLP) from Brazil. The analysis identified 11 exonic CNVs affecting candidate genes for NSCLP, including MSX1, TERT, MIR4457, CLPTM1L, and PHF8. The identification of CNVs overlapping genes implicated in NSCLP provides preliminary evidence that small exonic CNVs may contribute to susceptibility. Considering the importance of the affected genes to NSCLP pathogenesis, some of the identified CNVs, such as microdeletions of MSX1 and micro
Smith TC, Male MJ, Harper AL, Kroeger J, Tinkler G, Moritz-Korolev E, Herwaldt L, Diekema D. High prevalence of MRSA found in Midwestern US Swine and Swine workers. PLoS ONE, 4(1):e4258, 2009.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
Surveying the small-spotted catshark (Scyliorhinus canicula) tumour necrosis ...Fiona Bakke
This honours research project report summarizes an investigation of the tumour necrosis factor superfamily (TNFSF) genes in the small-spotted catshark (Scyliorhinus canicula). Bioinformatic analysis of the S. canicula transcriptome identified potential TNFSF orthologs. A phylogenetic tree including TNFSF sequences from various vertebrates provided insight into the evolutionary relationships between these genes. Several S. canicula TNFSF sequences were amplified and sequenced to confirm their presence. The analysis suggests S. canicula possesses orthologs of most mammalian TNFSF genes, though is missing a few, and also expresses a TNFSF gene only found previously in cart
This document describes the development of a multiplex PCR assay targeting the cgcA gene, which encodes a diguanylate cyclase, to differentiate between species within the genus Cronobacter. Analysis of 12 Cronobacter genomes identified 7 conserved diguanylate cyclase-encoding genes, one of which, cgcA, showed species-specific divergence that matched known phylogenetic relationships between Cronobacter species. Primers were designed for this gene and tested in a multiplex PCR assay on 305 Cronobacter isolates representing 6 species. The assay correctly identified the species of all isolates tested and did not identify any of 20 non-Cronobacter species, demonstrating high specificity and sensitivity for rapid identification of Cronobacter.
Variable transcriptional adaptation between the laboratory (H37Rv) and clinic...Santhi Devasundaram
The remarkable success of M. tuberculosis as a pathogen is largely due to its ability to
persist within the host for long periods. To develop the effective intervention strategies, understanding the biology
of persistence is highly required. Accumulating evidences showed oxygen deprivation (hypoxia) as a potential
stimulus for triggering the transition of M. tuberculosis to a non-replicating persistent state analogous to
latency in vivo. To date, in vitro hypoxia experimental models used the laboratory adapted isolate H37Rv and
very little is known about the behavior of clinical isolates that are involved during disease outbreaks. Hence,
we compared the transcription profiles of H37Rv and two south Indian clinical isolates (S7 and S10) under hypoxia
to find differences in gene expression pattern.
This document discusses the FOXP3 gene as a promising candidate gene in susceptibility to generalized vitiligo. It summarizes that FOXP3 is the master transcription factor that regulates regulatory T cells, which play an important role in preventing autoimmunity. Studies have found associations between polymorphisms in the FOXP3 gene and an increased risk of vitiligo. The document argues that further investigation of FOXP3 genetic variants and their effects on regulatory T cell development and function could provide insights into vitiligo pathogenesis and potential new therapeutic approaches targeting the FOXP3 gene/regulatory T cell network.
Three key points:
1) The study identified a group of myeloma patients with an "ultra-high risk" of early relapse and poor survival outcomes based on having both high-risk genetic lesions and a high-risk gene expression profile.
2) In two large clinical trials, these ultra-high risk patients had a median progression-free survival of 13.4 months and median overall survival of 26.1 months, significantly worse than other patient groups.
3) Validation in an independent patient group confirmed ultra-high risk patients defined by both genetic and gene expression risk factors experienced particularly poor outcomes, with all progressing within 2 years and no survivors beyond 4 years.
This study examines the effects of galectins, VEGF-B, and stress conditions on human endothelial cell growth, survival, and migration. Various assays show that galectins and VEGF-B enhance cell growth under normal and stressed conditions, though the intended stressor did not work properly. Cell counts varied due to growth, not death. Galectins decreased phosphorylation of ERK and phospho-ERK under both conditions. The results suggest galectins and VEGF-B may have synergistic effects on angiogenesis, though more study is needed under effective stress.
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Ong et al._Translational utility of next-generation sequencing_2013_GenomicsFrank Ong, MD, CPI
Next-generation sequencing (NGS) has made DNA sequencing rapid, cost-effective and highly accurate. NGS has translational utility in several areas: 1) It can detect genetic variations associated with disease risk and treatment response; 2) It enables non-invasive prenatal testing for fetal abnormalities; 3) Cancer genome sequencing can improve diagnosis, prognosis and treatment by deciphering a cancer's genetic makeup. NGS also has utility in rare genetic disease diagnosis and in precision medicine by matching patients to targeted therapies.
ABCG2pos lung mesenchymal stem cells are a novel pericyte subpopulation that ...Rubin Baskir, Ph.D.
This document reports on a study investigating a novel pericyte subpopulation in the lung called ABCG2pos mesenchymal stem cells (MSC). The study found:
1) ABCG2pos lung MSC numbers were decreased in human pulmonary fibrosis (PF) and interstitial lung disease samples compared to controls.
2) In a mouse model of bleomycin-induced lung injury, GFP-labeled lung MSC-derived cells increased in number and localized to fibrotic and microvessel remodeling areas after 14 days.
3) Lung MSC responded to in vivo bleomycin injury with a profibrotic gene expression profile that was not replicated with in vitro bleomycin treatment, but
This research article examines the role of sphingosine-1-phosphate (S1P) in regulating the proliferative and stem-like properties of glioblastoma stem cells (GSCs). The results showed that GSCs rapidly consume ceramide and export S1P into the extracellular environment. Extracellular S1P levels reached nanomolar concentrations in response to increased sphingosine. S1P was also found to act as an autocrine factor that promotes GSC proliferation and maintains their stem-like phenotype. This suggests that microenvironmental S1P critically modulates the GSC population by acting as an autocrine signal to support stemness and favor proliferation, survival, and therapeutic resistance of GSCs.
This document discusses genomic oncology and personalized medicine, using lung cancers as a model. It summarizes several key technologies that enable genomic oncology like cDNA microarrays, array CGH, and next generation sequencing. It provides examples of how these technologies have been used to classify cancers like diffuse large B-cell lymphoma and myelodysplastic syndrome, and identify genetic mutations that can guide targeted therapies for cancers like EGFR-mutated lung cancer.
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neu...Gul Muneer
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils. Lung tumors disrupt bone homeostasis and increase osteoblast activity and bone formation. Osteoblasts amplify tumor-associated SiglecFhigh neutrophils that promote tumor growth through angiogenesis, immunosuppression and other mechanisms. Serum from tumor-bearing mice increases osteoblast activity through elevated sRAGE, which stimulates neutrophil maturation. SiglecFhigh neutrophils correlate with poor survival in lung cancer patients. Therefore, lung tumors communicate with bone through factors like sRAGE to modulate osteoblasts and promote neutrophil-driven tumor progression.
The document describes the design of a customized genome-wide genotyping array ("TxArray") for transplantation studies. It includes approximately 782,000 markers focused on loci related to HLA, KIR, pharmacogenomics, and metabolism that are important for transplantation. Testing on 85 HapMap samples showed high concordance (0.996) and low error rates, and genotype imputation was highly accurate (over 0.962). The array was designed to improve coverage of regions like KIR compared to other platforms and enable large-scale genetic studies in transplant cohorts.
The document describes malaria immunology and epidemiology studies conducted in Papua New Guinea between 2004-2017. It involved several cohort and intervention studies with observational cohorts of approximately 500-2000 individuals. The studies aimed to understand immunity targets and mechanisms to malaria in order to rationalize vaccine development. They examined both antibody and cellular immune responses. Key findings included that γδ T cells are a major source of IFNγ response and certain NK cell receptors are associated with risk of high density infections.
Objective: To analyze the sonographic features of different histopathological subtypes of borderline ovarian tumors (BOTs) confirmed by pathology, and to study the ultrasound performances of various types in borderline ovarian tumors.
Study Design: Retrospective analysis was performed on the pathological results and ultrasound projection findings of 129 patients diagnosed as BOTs by ultrasound department of our hospital from January 2012 to November 2019. All patients were confirmed by surgical pathology and scanned consecutively by the investigators using transabdominal or transvaginal ultrasound examination.
Results: Serous borderline tumors (SBOTs) were observed, and the prevalence rate (53%) was significantly higher than that of other subtypes, and the probability of bilateral lesions was higher (40%). The sonogram often showed ultrasound features of papillary neoplasm in the lesion and good internal echo (p<0.05). Mucinous borderline ovarian tumors (MBOTs) were mostly unilateral lesions (86%). The prevalence was second only to SBOTs. Histomorphological examinations were divided into gastrointestinal-type and endocervical-type. Among them, the gastrointestinal type of MBOTs were mostly unilateral, and their incidence was higher than that of endocervical-type of MBOTs. Compared with other pathological subtypes, the gastrointestinal type is more likely to show the sonographic characteristics of huge space occupying in the pelvic and abdominal cavity (mean diameter >10 cm), polycystic, multiple septums, and poor internal echo (p<0.05). The ultrasonographic features of the endocervical-type of MBOTs were similar to those of SBOTs. Compared with gastrointestinal type, the sonographic images showed smaller lesion diameter, less septal or cyst, and more papillary excrescences in the tumor (p<0.05). The borderline clear cell tumor is the intermediate transition between the clear cell adenofibroma and the clear cell carcinoma. The clinical manifestations are diverse and lack specificity. The histology of sonography was mainly solid, and the multiple microcapsules were honeycomb-like. It can also be shown as cystic. Among the 169 patients with BOTs, 20 cases of SBOTs, 17 cases of MBOTs, and 10 cases of other rare subtypes were complicated with other diseases or multiple subtypes. This study did not find significant ultrasonic characteristics were used for distinguish them from other subtypes.
Conclusion: BOTs is a common disease in women during the reproductive period. It is characterized by the development of malignant tumors. Its clinical and pathological subtypes are complex and diverse. It leads many doctors to use the terms “large pelvic mass” and “solid ovarian mass” for diagnosis because of their lack of experience and understanding.
Keywords: adenocarcinoma, mucinous; adenocarcinoma, serous; borderline ovarian tumors; diagnostic imaging; ovarian neoplasms; papillary neoplasms; prognosis; transvaginal ultrasound, ultrasonography
Low expression of N-myc downstream-regulated gene 2 in oesophageal squamous c...Enrique Moreno Gonzalez
It is currently unclear whether a correlation exists between N-myc downstream-regulated gene 2 (NDRG2) expression and oesophageal squamous cell carcinoma (ESCC). The aim of this study was to examine the underlying clinical significance of NDRG2 expression in ESCC patients and to investigate the effects of NDRG2 up-regulation on ESCC cell growth in vitro and in vivo.
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
The document describes a study that used high-resolution microarray analysis to identify copy number variations (CNVs) in 15 patients with nonsyndromic cleft lip and palate (NSCLP) from Brazil. The analysis identified 11 exonic CNVs affecting candidate genes for NSCLP, including MSX1, TERT, MIR4457, CLPTM1L, and PHF8. The identification of CNVs overlapping genes implicated in NSCLP provides preliminary evidence that small exonic CNVs may contribute to susceptibility. Considering the importance of the affected genes to NSCLP pathogenesis, some of the identified CNVs, such as microdeletions of MSX1 and micro
Smith TC, Male MJ, Harper AL, Kroeger J, Tinkler G, Moritz-Korolev E, Herwaldt L, Diekema D. High prevalence of MRSA found in Midwestern US Swine and Swine workers. PLoS ONE, 4(1):e4258, 2009.
This study aimed to differentiate between invasive squamous cell carcinoma (SCC) and carcinoma-in-situ (CIS) of the uterine cervix using immunohistochemical markers. Tissue samples from 37 patients were stained for CD3, CD4, CD8, CD20, and CD138. Scoring showed decreased expression of CD8, CD20, and CD138 in invasive SCC compared to CIS, indicating differences in immune cell infiltration between invasive and non-invasive lesions. The results provide potential markers for differentiating invasive SCC from CIS of the cervix.
Jaspal Singh Abrol has over 12 years of experience in business development, sales, marketing, customer relationship management, and team management in the services sector. He is seeking a leadership role where he can utilize his expertise in developing strategies for business growth, managing key client relationships, and leading high-performing teams. He has a track record of consistently achieving sales targets and has experienced success developing both new and existing streams of revenue.
Promotes hair growth and reduces hair loss. A natural formula with essential nutrients supports healthy hair follicles and scalp. Regular use may help prevent thinning hair and promote thicker, fuller looking hair over time.
Christina A. Snell is seeking an entry-level paralegal position. She has over 5 years of experience in administrative roles providing customer service, file management, correspondence, and research. Her resume details employment history at the Texas Department of State Health Services, Texas Workforce Commission, and Round Rock Police Department in roles such as Administrative Assistant and Animal Control Officer. She also lists education including an Associate of Applied Science in Criminal Justice from Austin Community College and ongoing studies in Criminal Justice at Texas State University.
This document provides an overview of web content management. It defines key terms like content, data, information and discusses the differences between content management and web content management. It explains what a content management system and web content management system are and how they help manage the life cycle of web content. Some advantages and disadvantages of using a WCMS are also highlighted. Popular open source WCMS like WordPress, Joomla and Drupal are also mentioned.
Este documento resume y analiza el Real Decreto-Ley 4/2013 sobre medidas de apoyo al emprendimiento y estímulo del empleo en España. El RDL incluye medidas laborales, de financiación empresarial, contra la morosidad, en el sector ferroviario y de hidrocarburos. El autor critica que el RDL actúa como una ley de acompañamiento encubierta y que algunas medidas pueden precarizar el empleo juvenil. También señala aciertos potenciales como medidas para el autoempleo, pero cuestiona la
This document introduces Flume and Flive. It summarizes that Flume is a distributed data collection system that can easily extend to new data formats and scales linearly as new nodes are added. It discusses Flume's core concepts of events, flows, nodes, and reliability features. It then introduces Flive, an enhanced version of Flume developed by Hanborq that provides improved performance, functionality, manageability, and integration with Hugetable.
This document lists the top 10 digital marketing coaching institutes in Bangalore, providing their addresses and contact numbers. It includes coaching schools like Digital Marketing Paathshala, Internet Academy, Cheerons, Edu Pristine, Inventateq, Bizsmart Solutions India Pvt Ltd, Web Marketing Academy, Disciples India Educational Resources Pvt Ltd, TechRel Technologies pvt.ltd., and Varnaaz Technologies.
Promotes hair growth and reduces hair loss. A natural formula with ingredients like saw palmetto, biotin, and folic acid nourish hair follicles and support a healthy scalp. Regular use may help prevent further hair thinning and loss while encouraging new hair growth.
This document describes a microarray study that analyzed gene expression changes in Nicotiana benthamiana in response to infection by South African cassava mosaic virus (SACMV). The microarray identified over 600 genes whose expression was altered at 21 days post infection, including genes involved in transcription, defense responses, and hormone signaling. Notable changes were seen in genes related to sucrose and starch metabolism, as well as genes associated with intracellular movement and the cytoskeleton. The results provide insight into the complex molecular interactions between SACMV and its host plant during the infection process.
This study analyzed aneuploidy rates, apoptotic markers, and DNA fragmentation in sperm samples from normozoospermic men with unexplained infertility. Samples underwent density gradient centrifugation and then magnetic activated cell sorting (MACS). MACS significantly reduced the percentage of aneuploid, apoptotic, and DNA-damaged sperm. A positive correlation was found between reduced aneuploidy and lower DNA damage after MACS, but no correlation with apoptotic markers. The interactions between apoptotic markers, DNA integrity, and aneuploidy, as well as the effects of MACS on these parameters, require further investigation.
This PhD report aims to develop diagnostic tools to distinguish between protozoan parasites that infect ruminants, including Toxoplasma gondii, Neospora caninum, and Sarcocystis species. The report will identify genus-specific antigens for each parasite and develop antibodies and PCR tests that can detect the parasites individually. Recombinant antigens will be produced and used to generate genus-specific antibodies for diagnosis via immunohistochemistry. Genus-specific DNA targets and primers will also be identified to enable PCR-based detection of the protozoan parasites in tissue samples. Both diagnostic methods will be supported by a tissue bank of samples infected with the parasites.
The document reviews protocols for generating induced pluripotent stem cells (iPSCs) including choice of reprogramming factors, delivery methods, and target cell types. The core reprogramming factors are Oct4, Sox2, Klf4, and c-Myc, though variations exist. Initial methods used integrating viruses but newer approaches aim to be non-integrating. Fibroblasts are commonly used as starting cells but iPSCs have been made from other cell types. Standardization of parameters can improve comparisons between experiments.
Viral apoptotic mimicry is when viruses expose phosphatidylserine (PS) on their surface to mimic apoptotic cells and hijack the host cell's apoptotic clearance machinery. PS exposure allows viruses to bind to PS receptors on host cells and be endocytosed. Many viruses use classic apoptotic mimicry by directly exposing PS. Others use non-classic mimicry by mimicking PS receptors like Gas6. Targeting PS is a potential antiviral strategy, as antibodies against PS can opsonize viruses and induce immune clearance. However, more research is needed to fully understand the mechanisms and in vivo relevance of viral apoptotic mimicry.
This document discusses the use of viral metagenomics and structural studies to understand coronaviruses like SARS-CoV and MERS-CoV. It describes how viral metagenomics was used to trace the zoonotic origins of these viruses to bats and expand knowledge of coronavirus diversity. Structural studies of the spike protein provided insights into host transition and informed therapeutic development. Recent advances in cryo-EM have enabled visualization of the spike protein trimer. Reverse genetic systems have also been important for characterizing coronavirus infection and pathogenesis.
Use the Harvard Business Case, West Jet Airlines Information Tec.docxjessiehampson
Use the Harvard Business Case, “West Jet Airlines: Information Technology Governance and Corporate Strategy," as the basis for answering the following questions:
What was West Jet’s strategic plan?
What were the main problems faced by the West Jet IT organization?
Discuss how West Jet transformed their IT organizational structure. How was the structure itself realigned? What methods and processes were introduced or removed?
Discuss IT governance models that were considered to enable IT to function more efficiently at West Jet.
How does IT affect a company’s corporate strategy and the overall strategic impact?
Business School, Cespedes, Frank & Kindley, James
Minimum 2 scholarly Articles References.
Minimum of 500 Words, APA Format
Your paper will be submitted to Turnitin software, No plagiarism.
Contents lists available at ScienceDirect
Infection, Genetics and Evolution
journal homepage: www.elsevier.com/locate/meegid
Short communication
Genetic diversity and evolution of SARS-CoV-2
Tung Phan⁎
Division of Clinical Microbiology, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, PA, USA
A R T I C L E I N F O
Keywords:
Coronavirus
SARS-CoV-2
Mutations
Genomic diversity
A B S T R A C T
COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health
Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic
analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and
deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and
rapid evolution of this novel coronavirus.
1. The study
A new coronavirus SARS-CoV-2 is spreading cross the world (Phan,
2020). Since the virus emerged at the seafood wholesale market at the
end of last year (Zhu et al., 2019), the number of infected cases has
been rising dramatically (Velavan and Meyer, 2020). Human-to-human
transmission of SARS-CoV-2 has been confirmed (Nishiura et al., 2020).
The virus has been detected in bronchoalveolar-lavage (Zhu et al.,
2019), sputum (Lin et al., 2020), saliva (K.K. To et al., 2020), throat
(Bastola et al., 2020) and nasopharyngeal swabs (To et al., 2020).
Nucleotide substitution has been proposed to be one of the most
important mechanisms of viral evolution in nature (Lauring and
Andino, 2010). The rapid spread of SARS-CoV-2 raises intriguing
questions such as whether its evolution is driven by mutations. To as-
sess the genetic variation, eighty-six complete or near-complete gen-
omes of SARS-CoV-2 were collected from GISAID [https://www.gisaid.
org/]. These SARS-CoV-2 strains were detected in infected patients
from China (50), USA (11), Australia (5), Japan (5), France (4), Sin-
gapore (3), England (2), Taiwan (2), South Korea (1), Belgium (1),
Germany (1), and Vietnam (1). The pair-wise nucleotide sequence
alignment was performed by ClustalX2 (Saitou and Nei, ...
Prevalence and Antimicrobial Susceptibility of Methicillin Resistant StaphJoshua Owolabi
This document summarizes a study on the prevalence and antimicrobial susceptibility of methicillin resistant Staphylococcus aureus (MRSA) and coagulase-negative Staphylococci (CoNS) isolated from healthy university students in Nigeria. Swabs were collected from the noses and necks of 100 students. A total of 39 Staphylococcus species were identified, including MRSA and MRCoNS. The MRSA strains showed high resistance to methicillin and several other antibiotics. CoNS also demonstrated moderate to high resistance to several antibiotics tested. This highlights the need for surveillance of antibiotic resistance in the community and policies to prevent the spread of resistant infections.
This research article examines the ability of 5 nitric oxide donor compounds to disperse biofilms formed by Salmonella enterica and Escherichia coli O157:H7 on surfaces. The study found that all 5 nitric oxide donors were able to significantly disperse both pathogen biofilms, ranging from 35-80% dispersal. However, the degree of dispersal and optimal conditions varied between compounds and bacterial strains. In particular, molsidomine was effective at dispersing up to 50% of pre-formed Salmonella biofilm even at 4°C, suggesting potential use under refrigerated conditions. The study also identified a Salmonella genomic region that appears to be involved in the bacteria's response to nitric oxide signaling.
importance of pathogenomics in plant pathologyvinay ju
The document provides an outline for a seminar on pathogenomics for diagnosis and management of plant diseases. It includes sections on pathogenomics in plant pathology, diagnostic tools using next-generation sequencing technologies, host-microbe interaction and genes involved in virulence and resistance. The outline also lists various bioinformatics databases and molecular techniques used for pathogen detection, including PCR-based methods and microarrays. It discusses several examples of pathogenicity genes and host proteins involved in plant-virus interactions.
This document summarizes a research paper that studied the effects of a betasatellite associated with radish leaf curl disease (RaLCB) on the chloroplasts and photosynthesis of Nicotiana benthamiana. The key findings were:
1) The βC1 protein of RaLCB localized to the chloroplasts and caused damage to chloroplast ultrastructure.
2) RaLCB lacking the βC1 protein did not affect chloroplast structure or cause symptoms.
3) Expression of βC1 alone was able to induce vein flecking symptoms associated with chloroplast damage.
4) RaLCB infection down-regulated genes involved in chlorophyll biosynthesis and chloroplast development, reducing photosynthetic efficiency
This document summarizes a study examining the role of the Wiskott-Aldrich syndrome protein (WASp) in regulating type-I interferon production in plasmacytoid dendritic cells (pDCs). The study finds that WAS patients have increased numbers of pDCs in the spleen and elevated expression of type-I interferon-inducible genes. Using WASp-deficient mice and acute silencing of WASp, the study shows that WASp controls actin dynamics and intracellular trafficking in pDCs, restraining excessive activation of the TLR9-IFN-α pathway. This dysregulated production of type-I interferon by pDCs may contribute to the autoimmune phenomena seen
British J Pharmacology - 2021 - Healy - The importance of Ras in drug resista...RajeshKumarRapolu
This document discusses drug resistance in cancer that is mediated by oncogenic Ras mutations. It covers several key points:
1) Ras mutations can cause intrinsic and acquired resistance to chemotherapy and targeted therapies by constitutively activating proliferative and survival pathways. This resistance occurs across many cancer types.
2) Ras mutations contribute to the survival of cancer stem cells through pathways like Wnt/β-catenin and MAPK that promote stem cell self-renewal. Cancer stem cells are intrinsically resistant to chemotherapy.
3) Examples of drug resistance caused by downstream Ras mutations include resistance to EGFR inhibitors in cancers where Ras operates downstream of EGFR. Combination therapies may help prevent resistance arising from minor tumor subclones
This document provides a summary of Sheng Jian Cai's professional experience and qualifications. It summarizes him as a highly motivated and innovative senior scientist with extensive experience in areas related to cardiovascular diseases, diabetes, and oncology. It lists his roles at Merck from 2002 to present as a senior research biologist and senior scientist, where he has led assay development efforts and provided biology support for various programs.
1. The study developed a new PCR/RFLP technique to identify the 3 genotypes of Plasmodium vivax circumsporozoite protein (VK210, VK247, and P. vivax-like) using DNA extracted from blood samples.
2. The technique uses PCR amplification of the central immunodominant region of the CSP gene followed by restriction enzyme digestion and fragment analysis to distinguish the genotypes.
3. Testing demonstrated the technique could accurately identify the genotypes using plasmid controls for each variant, and that it had high sensitivity detecting parasitemia levels as low as 0.0069 parasites per microliter.
This document summarizes HIV-1 pathogenesis with a focus on genetic forms. It discusses how HIV-1 enters cells through envelope protein binding and membrane fusion. The virus infects CD4+ T cells and dendritic cells, forming syncytia. It describes the structure and roles of the envelope glycoproteins GP120 and GP41 in fusion. The document also outlines the major genetic subtypes and recombinants of HIV-1 globally. It concludes that HIV-1's high genetic variability poses challenges for vaccine and drug development.
Proteomic Analysis of the Serum and Excretory-Secretary proteins of Trichinel...AmalDhivaharS
The nematodes of the genus Trichinella are known to cause the pressing foodborne parasitic disease Trichinellosis and these parasites are known to complete all stages of development in one host with the enteral and parenteral phases observed during infection. Proteomics, in general, pertains to the systematic identification and quantification of the totality of proteins, which is the proteome of a biological system, at a specific point in time. The available proteomic studies have paved the way to identify and characterize Trichinella stage-specific proteins reacting with infected host-specific antibodies. Yet, very few contributions provide any information about changes in the global proteomic serum profile of Trichinella-infested individuals. Studies demonstrate that various Trichinella species and their phases of the invasion produce a characteristic proteomic pattern in the serum of experimentally infected pigs. Recent investigations have found that T. spiralis infection induced strong regulatory T cell responses through parasite excretory-secretory (ES) products, characterized by an increase of some regulatory T cells and growth factors. T. spiralis has also been reported to induce the angiogenic molecule vascular endothelial cell growth factor (VEGF) during nurse cell formation towards the induction of angiogenesis for nutrient supply and waste disposal. Herein, the various analogs considered in these studies include the serum, excretory-secretory proteins, surface proteins, immune-reactive proteins from muscle larvae (ML) and so on. Intestinal cultures, striated muscle tissues, pigs, mice, beavers, contributions from patients are some of the major models exploited for this purpose. The current analysis focuses on recapitulating the recent findings driven on this area to create a common ground for further studies and to ease any difficulty in continuing the proteomic analysis of T. spiralis using in vitro and in vivo models.
This document discusses biosafety considerations for gene therapy including criteria for categorizing biological risk, the history of human gene therapy, and risk management when working with adeno-associated virus (AAV) vectors. It provides guidelines for ensuring appropriate containment procedures based on risk group classifications from organizations like the NIH and WHO. Gene therapy aims to treat disease by replacing or correcting defective genes, and AAV vectors are promising for gene transfer and expression due to their ability to infect cells and remain as episomes.
This document discusses biosafety considerations for gene therapy. It provides information on criteria used to categorize biological risk, the history of human gene therapy, and risk management procedures when working with adeno-associated virus vectors. It also discusses criteria used to ensure appropriate containment procedures are followed.
Gene therapy is a technique that modifies a person's genes to treat or cure disease. Gene therapies can work by several mechanisms: Replacing a disease-causing gene with a healthy copy of the gene. Inactivating a disease-causing gene that is not functioning properly. Genetic therapies hold promise to treat many diseases, but they are still new approaches to treatment and may have risks. Potential risks could include certain types of cancer, allergic reactions, or damage to organs or tissues if an injection is involved. Recent advances have made genetic therapies much safer. Gene therapy is on course to revolutionize medical care for several conditions. The hope is that gene therapy will be a one-time curative therapeutic intervention for diseases ranging from inherited hemoglobinopathies, such as sickle cell disease and thalassemia, to acquired diseases such as HIV.
Similar to Montanari et al_Cellular_Microbiology_2011 (20)