A5033735039- RNA Research and Splicing
- Developmental Biology and Gene Regulation
- RNA and protein synthesis mechanisms
- Molecular Biology Techniques and Applications
- RNA Interference and Gene Delivery
- TGF-β signaling in diseases
- Dermatology and Skin Diseases
- Advanced biosensing and bioanalysis techniques
- Receptor Mechanisms and Signaling
- Climate Change and Health Impacts
- Gene expression and cancer classification
- Epigenetics and DNA Methylation
- Immune Response and Inflammation
- Ocular Diseases and Behçet’s Syndrome
- Genomics and Chromatin Dynamics
- IL-33, ST2, and ILC Pathways
- Cellular Mechanics and Interactions
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Renal cell carcinoma treatment
- Synthesis and Biological Evaluation
- Hippo pathway signaling and YAP/TAZ
- MicroRNA in disease regulation
- Zebrafish Biomedical Research Applications
- Wnt/β-catenin signaling in development and cancer
GlaxoSmithKline (Netherlands)
2015-2022
GlaxoSmithKline (India)
2021
GlaxoSmithKline (United Kingdom)
2006-2018
Age UK
2007-2016
GlaxoSmithKline (Sweden)
2013
University of Bristol
2011
Stanford University
2007
University of Montana
2004-2005
Cornell University
2001-2002
Rockefeller University
1995-1997
Research into environmental factors associated with suicide has historically focused on meteorological variables. Recently, a heightened risk of related to short-term exposure airborne particulate matter was reported. Here, we examined the associations between nitrogen dioxide, matter, and sulfur dioxide completed in Salt Lake County, Utah (n = 1,546) from 2000 2010. We used time-stratified case-crossover design estimate adjusted odds ratios for relationship air pollutants day during days...
ABSTRACT Morphogens are thought to establish pattern in early embryos by specifying several cell fates along a gradient of concentration; well-studied example is the Drosophila protein decapentaplegic (DPP) acting wing disc. Recent work has established that bone morphogenetic 4 (BMP4), vertebrate homologue DPP, controls fundamental choice between neural and epidermal ectoderm, under control antagonists secreted organizer region mesoderm. We now show BMP4 can act as morphogen, evoking...
Several publications have described biological roles for human patatin-like phospholipases (PNPLAs) in the regulation of adipocyte differentiation. Here, we report on characterization and expression profiling 10 PNPLAs. A variety bioinformatics approaches were used to identify characterize all PNPLAs encoded by genome. The genes represent a divergent family, most with highly conserved ortholog several mammalian species. In silico predicts that two function as integral membrane proteins are...
Following fertilization, the zygotic genome in many organisms is quiescent until midblastula transition (MBT), when large-scale transcription begins. In Xenopus embryos, for example, believed to be repressed twelfth cell division. Thus, although dorsal-ventral patterning begins during first cycle, little attention has been given transcriptional regulation pre-MBT development. We present evidence that regulated early cleavage stages and beta-catenin-Tcf complex required of nodal genes Xnr5...
With many safety and technical limitations partly mitigated through chemical modifications, antisense oligonucleotides (ASOs) are gaining recognition as therapeutic entities. The increase in potency realized by 'third generation chemistries' may, however, simultaneously affinity to unintended targets with partial sequence complementarity. However, putative hybridization-dependent off-target effects (OTEs), a risk historically regarded low, not being adequately investigated. Here we show an...
ABSTRACT We have analyzed cell behavior in the organizer region of Xenopus laevis gastrula by making high resolution time-lapse recordings cultured expiants. The dorsal marginal zone, comprising among other tissues prospective notochord and somitic mesoderm, was cut from early gastrulae a way that permits microscopy deep mesodermal cells, whose organized intercalation produces dramatic movements convergent extension. At first, expiants extend without much convergence. This initial expansion...
Abstract Morphometric data from scanning electron micrographs (SEM) of cells in intact embryos and high‐resolution time‐lapse recordings cell behavior cultured explants were used to analyze the cellular events underlying morphogenesis notochord during gastrulation neurulation Xenopus laevis . The becomes longer, narrower, thicker as it changes its shape arrangement more are added at posterior end. development fall into three phases. In first phase, occurring late gastrula, become distinct...
ABSTRACT Activins and other ligands in the TGFb superfamily signal through a heteromeric complex of receptors. Disruption signaling by truncated type II activin receptor, XActRIIB (previously called XAR1), blocks mesoderm induction promotes neuralization Xenopus embryos. We report cloning characterization I XALK4. Like XActRIIB, mutant (tXALK4) formation both vitro vivo; moreover, an active form receptor induces ligand-independent manner. Unlike however, tXALK4 does not induce neural tissue....
Abstract We make use of a novel system explant culture and high resolution video-film recording to analyse for the first time cell behaviour underlying convergent extension segmentation in somitic mesoderm Xenopus. find that sequence activities sweeps through from anterior posterior during gastrulation neurulation, beginning with radial intercalation or thinning, continuing mediolateral elongation, culminating somite rotation. Radial at tip lengthens tissue, while farther converges it toward...
Atopic eczema (AE) is characterized by skin barrier and immune dysfunction. Null mutations in filaggrin (FLG), a key epidermal protein, strongly predispose to AE; however, the precise role of FLG deficiency AE pathogenesis remains incompletely understood.We sought identify global proteomic changes downstream human living skin-equivalent (LSE) models validate findings patients with AE.Differentially expressed proteins from paired control (nontargeting short hairpin RNA [shNT]) knockdown (FLG...
RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by mechanism closely mirroring micro (miRNA) To better understand these effects, we investigated correlation between features within various subsections of strands, and its corresponding target sequences, with activities. Our results confirm previous reports that strength base-pairing in seed region...
Background/aims To compare two non‐invasive techniques of assessing wound healing, photography and high resolution ultrasound (HRUS) scanning, in experimentally induced full‐thickness human skin wounds. Methods Punch biopsy wounds, 4 mm diameter, were made aseptically through locally anaesthetised on the anterior (volar) surface non‐dominant forearm, 3 cm below base cubital fossa, 20 participants. The wounds treated with a topical antibiotic covered for days Mepore sterile dressings. Wound...
Mapping the physical location of nodes within a wireless sensor network (WSN) is critical in many applications such as tracking and environmental sampling. Passive RFID tags pose an interesting solution to localizing because outside reader, rather than tag, supplies power tag. Thus, utilizing passive technology allows localization scheme not be limited objects that have communication capability technique only requires object carries This paper illustrates method which can localized without...
Antisense oligonucleotide (ASO) gapmers downregulate gene expression by inducing enzyme-dependent degradation of targeted RNA and represent a promising therapeutic platform for addressing previously undruggable genes. Unfortunately, their application, particularly that the more potent chemistries (e.g., locked-nucleic-acid-containing gapmers), has been hampered frequent hepatoxicity, which could be driven hybridization-mediated interactions. An early de-risking this liability is crucial...
Abstract Chronic kidney disease and associated comorbidities (diabetes, cardiovascular diseases) manifest with an accelerated ageing phenotype, leading ultimately to organ failure renal replacement therapy. This process can be modulated by epigenetic environmental factors which promote loss of physiological function resilience stress earlier, linking biological age adverse outcomes post‐transplantation including delayed graft (DGF). The molecular features underpinning this have yet fully...
Lung pathology in cystic fibrosis is linked to dehydration of the airways epithelial surface which part results from inappropriately raised sodium reabsorption through channel (ENaC). To identify a small-interfering RNA (siRNA) selectively inhibits ENaC expression, chemically modified 21-mer siRNAs targeting human ENaCα were designed and screened. GSK2225745, was identified as potent inhibitor mRNA (EC(50) (half maximal effective concentration) = 0.4 nmol/l, maximum knockdown 85%) protein...
Despite good evidence of impaired innate antiviral responses in asthma, trials inhaled interferon-β given during exacerbations showed only modest benefits moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust vivo induction bronchial epithelial interferon response genes 4 days after virus inoculation 25 subjects with asthma but not 11 control subjects. This signature correlated loads and lower respiratory symptoms. Our data indicate that the is dysregulated...
Abstract Purpose: VEGF receptor (VEGFR) kinases are important drug targets in oncology that affect function of systemic endothelial cells. To discover genetic markers VEGFR inhibitor pharmacodynamics, we performed a genome-wide association study serum soluble vascular VEGFR2 concentrations [sVEGFR2], pharmacodynamic biomarker for inhibitors. Experimental Design: We conducted (GWAS) [sVEGFR2] 736 healthy Old Order Amish volunteers. Gene variants identified from the GWAS were genotyped...