This article describes a preliminary OMERACT psoriatic arthritis magnetic resonance image scoring system (PsAMRIS) for evaluation of inflammatory and destructive changes in PsA hands, which was ...developed by the international OMERACT MRI in inflammatory arthritis group. MRI definitions of important pathologies in peripheral PsA and suggestions concerning appropriate MRI sequences for use in PsA hands are also provided.
Voltage-gated sodium (Na ᵥ) channels play a fundamental role in the generation and propagation of electrical impulses in excitable cells. Here we describe two unique structurally related nanomolar ...potent small molecule Na ᵥ channel inhibitors that exhibit up to 1,000-fold selectivity for human Na ᵥ1.3/Na ᵥ1.1 (ICA-121431, IC ₅₀, 19 nM) or Na ᵥ1.7 (PF-04856264, IC ₅₀, 28 nM) vs. other TTX-sensitive or resistant (i.e., Na ᵥ1.5) sodium channels. Using both chimeras and single point mutations, we demonstrate that this unique class of sodium channel inhibitor interacts with the S1–S4 voltage sensor segment of homologous Domain 4. Amino acid residues in the “extracellular” facing regions of the S2 and S3 transmembrane segments of Na ᵥ1.3 and Na ᵥ1.7 seem to be major determinants of Na ᵥ subtype selectivity and to confer differences in species sensitivity to these inhibitors. The unique interaction region on the Domain 4 voltage sensor segment is distinct from the structural domains forming the channel pore, as well as previously characterized interaction sites for other small molecule inhibitors, including local anesthetics and TTX. However, this interaction region does include at least one amino acid residue E1559 (Na ᵥ1.3)/D1586 (Na ᵥ1.7) that is important for Site 3 α-scorpion and anemone polypeptide toxin modulators of Na ᵥ channel inactivation. The present study provides a potential framework for identifying subtype selective small molecule sodium channel inhibitors targeting interaction sites away from the pore region.
The endocrine-disrupting chemical bisphenol A (BPA) is widely used in food and beverage packaging. Higher urinary BPA concentrations were cross-sectionally associated with heart disease in National ...Health and Nutrition Examination Survey (NHANES) 2003-2004 and NHANES 2005-2006, independent of traditional risk factors.
We included 758 incident coronary artery disease (CAD) cases and 861 controls followed for 10.8 years from the European Prospective Investigation of Cancer-Norfolk UK. Respondents aged 40 to 74 years and free of CAD, stroke, or diabetes mellitus provided baseline spot urine samples. Urinary BPA concentrations (median value, 1.3 ng/mL) were low. Per-SD (4.56 ng/mL) increases in urinary BPA concentration were associated with incident CAD in age-, sex-, and urinary creatinine-adjusted models (n=1919; odds ratio=1.13; 95% confidence interval, 1.02-1.24; P=0.017). With CAD risk factor adjustment (including education, occupational social class, body mass index category, systolic blood pressure, lipid concentrations, and exercise), the estimate was similar but narrowly missed 2-sided significance (n=1744; odds ratio=1.11; 95% confidence interval, 1.00-1.23; P=0.058). Sensitivity analyses with the fully adjusted model, excluding those with early CAD (<3-year follow-up), body mass index >30, or abnormal renal function or with additional adjustment for vitamin C, C-reactive protein, or alcohol consumption, all produced similar estimates, and all showed associations at P≤0.05.
Associations between higher BPA exposure (reflected in higher urinary concentrations) and incident CAD during >10 years of follow-up showed trends similar to previously reported cross-sectional findings in the more highly exposed NHANES respondents. Further work is needed to accurately estimate the prospective exposure-response curve and to establish the underlying mechanisms.
In this paper, we present a Bayesian classification approach for automatic text categorization using class-specific features. Unlike conventional text categorization approaches, our proposed method ...selects a specific feature subset for each class. To apply these class-specific features for classification, we follow Baggenstoss's PDF Projection Theorem (PPT) to reconstruct the PDFs in raw data space from the class-specific PDFs in low-dimensional feature subspace, and build a Bayesian classification rule. One noticeable significance of our approach is that most feature selection criteria, such as Information Gain (IG) and Maximum Discrimination (MD), can be easily incorporated into our approach. We evaluate our method's classification performance on several real-world benchmarks, compared with the state-of-the-art feature selection approaches. The superior results demonstrate the effectiveness of the proposed approach and further indicate its wide potential applications in data mining.
Despite their fundamental biological and clinical importance, the molecular mechanisms that regulate the first cell fate decisions in the human embryo are not well understood. Here we use ...CRISPR-Cas9-mediated genome editing to investigate the function of the pluripotency transcription factor OCT4 during human embryogenesis. We identified an efficient OCT4-targeting guide RNA using an inducible human embryonic stem cell-based system and microinjection of mouse zygotes. Using these refined methods, we efficiently and specifically targeted the gene encoding OCT4 (POU5F1) in diploid human zygotes and found that blastocyst development was compromised. Transcriptomics analysis revealed that, in POU5F1-null cells, gene expression was downregulated not only for extra-embryonic trophectoderm genes, such as CDX2, but also for regulators of the pluripotent epiblast, including NANOG. By contrast, Pou5f1-null mouse embryos maintained the expression of orthologous genes, and blastocyst development was established, but maintenance was compromised. We conclude that CRISPR-Cas9-mediated genome editing is a powerful method for investigating gene function in the context of human development.
Climate change is expected to modify rainfall, temperature and catchment hydrological responses across the world, and adapting to these water-related changes is a pressing challenge. This paper ...reviews the impact of anthropogenic climate change on water in the UK and looks at projections of future change. The natural variability of the UK climate makes change hard to detect; only historical increases in air temperature can be attributed to anthropogenic climate forcing, but over the last 50 years more winter rainfall has been falling in intense events. Future changes in rainfall and evapotranspiration could lead to changed flow regimes and impacts on water quality, aquatic ecosystems and water availability. Summer flows may decrease on average, but floods may become larger and more frequent. River and lake water quality may decline as a result of higher water temperatures, lower river flows and increased algal blooms in summer, and because of higher flows in the winter. In communicating this important work, researchers should pay particular attention to explaining confidence and uncertainty clearly. Much of the relevant research is either global or highly localized: decision-makers would benefit from more studies that address water and climate change at a spatial and temporal scale appropriate for the decisions they make.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Twelve polar and non-polar solvents were utilized for extraction of coffee lipids.•A correlation was observed between increasing solvent boiling point and oil yield.•High temperature trials were ...successful at limited duration and solvent consumption.•Extraction temperature increase is more beneficial for polar solvents like ethanol.•Solvent selection and process temperature impact on oil lipid and FFA composition.
Spent coffee grounds (SCG) are a potentially sustainable source of C16-C18 triglycerides. This study investigates known solvent extraction technologies with a wide range of solvents for lipid extraction from SCGs, and determines the effect of solvent selection and process temperature on the extraction efficiency and composition of the obtained oil. A correlation between increasing solvent boiling point, and therefore process temperature, and improved oil extraction efficiency was observed in Soxhlet extractions with a wide range of solvents. Experiments at elevated temperatures (up to 200 °C) were performed through Accelerated Solvent Extraction (ASE) and temperature increase initially improved the oil extraction efficiency when non-polar solvents were used, before decreasing it at higher temperatures. Utilization of ethanol resulted in the highest oil extraction ratio by ASE (at 165 °C), suggesting that temperature increase is more beneficial to the extraction efficiency of polar solvents. In addition, analysis of the oils was carried out to evaluate the composition of the oils extracted from SCGs using different solvents and extraction parameters. The Nuclear Magnetic Resonance (NMR) results were in agreement with the values obtained from the titrimetric determination of the free fatty acid content (FFA) of the oils in terms of the comparative trends, and also tentatively suggest that some differences in the composition of the extracted oils might be related to the type of extraction solvent used.
Phytoplankton evolved in the Archaean oceans more than 2.8 billion years ago and are of crucial importance in regulating aquatic food webs, biogeochemical cycles and the Earth's climate. Until ...recently, phytoplankton were considered immortal unless killed or eaten by predators. However, over the past decade, it has become clear that these organisms can either be infected by viruses or undergo programmed cell death (PCD) in response to environmental stress, resulting in mortality. Here, we discuss exogenous and endogenous mechanisms of phytoplankton death, specifically examining the experimental evidence for PCD in phytoplankton and exploring its evolutionary development and ecological impact. We consider phytoplankton PCD as an autocatalytic cell-suicide mechanism in which an endogenous biochemical pathway leads to cellular demise with apoptotic morphological changes. Phytoplankton have a core set of proteins that are orthologues of metazoan caspases. It seems that PCD in prokaryotic phytoplankton, and in independently evolving eukaryotic lineages, has deeply rooted origins that were appropriated and transferred to multicellular plants and animals in the past 700 million years of the Earth's history.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Comprehensive genome annotation is essential to understand the impact of clinically relevant variants. However, the absence of a standard for clinical reporting and browser display complicates the ...process of consistent interpretation and reporting. To address these challenges, Ensembl/GENCODE
and RefSeq
launched a joint initiative, the Matched Annotation from NCBI and EMBL-EBI (MANE) collaboration, to converge on human gene and transcript annotation and to jointly define a high-value set of transcripts and corresponding proteins. Here, we describe the MANE transcript sets for use as universal standards for variant reporting and browser display. The MANE Select set identifies a representative transcript for each human protein-coding gene, whereas the MANE Plus Clinical set provides additional transcripts at loci where the Select transcripts alone are not sufficient to report all currently known clinical variants. Each MANE transcript represents an exact match between the exonic sequences of an Ensembl/GENCODE transcript and its counterpart in RefSeq such that the identifiers can be used synonymously. We have now released MANE Select transcripts for 97% of human protein-coding genes, including all American College of Medical Genetics and Genomics Secondary Findings list v3.0 (ref.
) genes. MANE transcripts are accessible from major genome browsers and key resources. Widespread adoption of these transcript sets will increase the consistency of reporting, facilitate the exchange of data regardless of the annotation source and help to streamline clinical interpretation.
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