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121.
This is a short summary of a meeting entitled "The Frontiers in Glycomics; Bioinformatics and Biomarkers in Disease" which was jointly organized by the NIH Consortium for Functional Glycomics (CFG), Human Disease Glycomics/Proteome Initiative (HGPI), National Cancer Institute, National Institute of General Medical Sciences, Japan Society for the Promotion of Science and National Center for Research Resources held at the NIH Campus, Bethesda, MD, Natcher Conference Center in September 11-13, 2006. 相似文献
122.
《Saudi Journal of Biological Sciences》2022,29(6):103283
ObjectiveInfluenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy.MethodsThe present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database.ResultsComputational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination.ConclusionsWe propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen–antibody reaction between mutant strains in the annual design of the influenza vaccine. 相似文献
123.
《Saudi Journal of Biological Sciences》2022,29(7):103329
To understand the effectual role of COVID-19 vaccination, we must analyze its effectiveness in dampening the disease severity and death outcome in patients who acquire infection and require hospitalization. The goal of this study was to see if there was an association between disease progression in admitted COVID-19 patients and their prior vaccination exposure. A prospective cohort study based on 1640 admitted COVID-19 patients were carried between June 2021 and October 2021. Depending on vaccination exposure they were divided into vaccinated (exposed) and unvaccinated (unexposed) groups, excluding partially vaccinated patients. Disease severity was assessed at admission on severity index scale. Disease progression to mortality or need of mechanical ventilation and survival were taken as outcome. Absolute difference with 95%CI and Risk Ratio were calculated using cross tabulation, Chi square test and multivariable logistic regression analysis. Among 1514 total analyzed cohort (median age, 53 years [IQR, 17,106]; 43.7% from 46 to 65 years of age group, 56.2% males,33.4% with no comorbid factor for disease progression) 369(24.4%) were vaccinated breakthrough cases and 1145(75.6%) were unvaccinated controls. 556(36.7%) progressed to death or mechanical ventilation, 958(63.3%) patients survived and were discharged home. Disease progression to death or mechanical ventilation was significantly associated with decreased likelihood of vaccination (24.9% among vaccinated breakthrough vs 40.5% unvaccinated controls, [Absolute difference ?15.6% 95%CI (?10.2% to ?20.6%); RR 0.615 95%CI (0.509, 0.744); p <.001]). This association was stronger for old age population and for increase time span between second dose of vaccine and onset of symptoms. There was no statistically significant difference among different types of vaccination and occurrence of outcome when compared to unvaccinated controls (RR 0.607(0.482, 0.763); 0.673(0.339, 1.33) and 0.623(0.441, 0.881) for Inactivated virus vaccine, mRNA and Adenovirus vector-based vaccine respectively. The patients who were fully vaccinated against SARS-COV-2 die or shift to mechanical ventilation less frequently than unvaccinated COVID-19 admitted patients. 相似文献
124.
125.
Parkinson's disease (PD) is a neurodegenerative disorder involving progressive deterioration of dopaminergic neurons. Although few genetic markers for familial PD are known, the etiology of sporadic PD remains poorly understood. Microarray data was analysed for induced pluripotent stem cells (iPSCs) derived from PD patients and mature neuronal cells (mDA) differentiated from these iPSCs. Combining expression and semantic similarity, a highly-correlated PD interactome was constructed that included interactions of established Parkinson's disease marker genes. A novel three-way comparative approach was employed, delineating topologically and functionally important genes. These genes showed involvement in pathways like Parkin-ubiquitin proteosomal system (UPS), immune associated biological processes and apoptosis. Of interest are three genes, eEF1A1, CASK, and PSMD6 that are linked to PARK2 activity in the cell and thereby form attractive candidate genes for understanding PD. Network biology approach delineated in this study can be applied to other neurodegenerative disorders for identification of important genetic regulators. 相似文献
126.
127.
Taylor Richards Kavindiya Modarage Charlotte Dean Aidan McCarthy-Boxer Helen Hilton Chris Esapa Jill Norman Patricia Wilson Paraskevi Goggolidou 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):378-390
Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a genetic disorder with an incidence of ~1:20,000 that manifests in a wide range of renal and liver disease severity in human patients and can lead to perinatal mortality. ARPKD is caused by mutations in PKHD1, which encodes the large membrane protein, Fibrocystin, required for normal branching morphogenesis of the ureteric bud during embryonic renal development. The variation in ARPKD phenotype suggests that in addition to PKHD1 mutations, other genes may play a role, acting as modifiers of disease severity. One such pathway involves non-canonical Wnt/Planar Cell Polarity (PCP) signalling that has been associated with other cystic kidney diseases, but has not been investigated in ARPKD. Analysis of the AtminGpg6 mouse showed kidney, liver and lung abnormalities, suggesting it as a novel mouse tool for the study of ARPKD. Further, modulation of Atmin affected Pkhd1 mRNA levels, altered non-canonical Wnt/PCP signalling and impacted cellular proliferation and adhesion, although Atmin does not bind directly to the C-terminus of Fibrocystin. Differences in ATMIN and VANGL2 expression were observed between normal human paediatric kidneys and age-matched ARPKD kidneys. Significant increases in ATMIN, WNT5A, VANGL2 and SCRIBBLE were seen in human ARPKD versus normal kidneys; no substantial differences were seen in DAAM2 or NPHP2. A striking increase in E-cadherin was also detected in ARPKD kidneys. This work indicates a novel role for non-canonical Wnt/PCP signalling in ARPKD and suggests ATMIN as a modulator of PKHD1. 相似文献
128.
Defective Glucose Transport Across Brain Tissue Barriers: A Newly Recognized Neurological Syndrome 总被引:6,自引:0,他引:6
Klepper J Wang D Fischbarg J Vera JC Jarjour IT O'Driscoll KR De Vivo DC 《Neurochemical research》1999,24(4):587-594
Impaired glucose transport across brain tissue barriers causes infantile seizures, developmental delay and acquired microcephaly. Since the first report in 1991 (De Vivo et al, NEJM, 1991) 17 patients have been identified with the glucose transporter protein syndrome (GTPS). The diagnostic feature of the syndrome is an unexplained hypoglycorrhachia in the clinical setting of an infantile epileptic encephalopathy. We review our clinical experience by highlighting one illustrative case: a 6-year old girl who presented at age 2 months with infantile seizures and hypoglycorrhachia. The CSF/blood glucose ratio was 0.33. DNA sequencing identified a missense mutation in exon 7 (C1108T). Erythrocyte GLUT1 immunoreactivity was normal. The time course of 3-0-methyl-glucose (3OMG) uptake by erythrocytes of the patient was 46% that of mother and father. The apparent Km was similar in all cases (2–4 mmol/L), but the apparent Vmax in the patient was only 28% that of the parents (500 versus 1,766 fmol/s/106RBC; p < 0.004). In addition, a 3-month trial of oral thioctic acid also benefited the patient and increased the Vmax to 935 fmol/s/106 RBC (p < 3 × 10–7). Uptake of dehydroascorbic acid by erythrocytes of the patient was impaired to the same degree as that of 3OMG (Vmax was 38% of that of the mother's), which supports previous observations of GLUT1 being multifunctional. These studies confirm the molecular basis of the GTPS and the multifunctional role of GLUT1. The need for more effective treatment is compelling. 相似文献
129.
Stockton JC Howson JM Awomoyi AA McAdam KP Blackwell JM Newport MJ 《FEMS immunology and medical microbiology》2004,41(2):157-160
The nucleotide oligomerization binding domain 2 gene (NOD2) encodes an intracellular receptor for bacterial components, which is expressed in monocytes and is associated with Crohn's Disease (CD). This finding, along with epidemiological evidence, supports a role for infection in the pathogenesis of CD. Speculation that mycobacteria are involved in CD led us to investigate NOD2 in susceptibility to tuberculosis (TB), a global public health problem caused by Mycobacterium tuberculosis. CD-associated NOD2 variants were absent in a case-control study of 640 Gambians, where CD is rare. Novel NOD2 promoter polymorphisms were identified but showed no association with TB in this African population sample. 相似文献
130.
Summary. The identification of increased polyamine concentrations in a variety of diseases from cancer and psoriasis to parasitic infections has led to the hypothesis that manipulation of polyamine metabolism is a realistic target for therapeutic or preventative intervention in the treatment of certain diseases.The early development of polyamine biosynthetic single enzyme inhibitors such as -difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) showed some interesting early promise as anticancer drugs, but ultimately failed in vivo. Despite this, DFMO is currently in use as an effective anti-parasitic agent and has recently also been shown to have further potential as a chemopreventative agent in colorectal cancer.The initial promise in vitro led to the development and testing of other potential inhibitors of the pathway namely the polyamine analogues. The analogues have met with greater success than the single enzyme inhibitors possibly due to their multiple targets. These include down regulation of polyamine biosynthesis through inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase and decreased polyamine uptake. This coupled with increased activity of the catabolic enzymes, polyamine oxidase and spermidine/spermine N1-acetyltransferase, and increased polyamine export has made the analogues more effective in depleting polyamine pools. Recently, the identification of a new oxidase (PAO-h1/SMO) in polyamine catabolism and evidence of induction of both PAO and PAO-h1/SMO in response to polyamine analogue treatment, suggests the analogues may become an important part of future chemotherapeutic and/or chemopreventative regimens. 相似文献