Modeling the Effects of Passive Immunity in Birds for the Disease Dynamics of West Nile Virus

West Nile Virus (WNV) is a mosquito-borne virus that circulates among birds but also affects humans. Migrating birds carry these viruses from one place to another each year. WNV has spread rapidly across the continental United States resulting in numerous human infections and deaths. Several studies suggest that larval mosquito control measures should be taken as early as possible in a season to control the mosquito population size. Also, adult mosquito control measures are necessary to prevent the transmission of WNV from mosquitoes to birds and humans. To better understand the effective strategy for controlling affected larvae mosquito population, we have developed a mathematical model using a system of first order differential equations to investigate the transmission dynamics of WNV in a mosquito-bird-human community. We also incorporated vertical transmission in mosquitoes and passive immunity in birds to more accurately simulate the spread of the disease

Waste Coir Nanofiller Fused Gallus-Gallus Fibres Reinforced PMC

This research aims to increase the utility of globally and abundantly available waste natural fibres of Gallus-Gallus fibres coir waste from mattress and car seat manufacturing factories. The composite samples were prepared with a rally round of polyester resin of grade GP500 bio-epoxy by synthesizing specially treated Gallus-Gallus fibres selectively used for reinforcement and characterizing them through static and dynamic mechanical analyses to identify their wide range of applicability. The Gallus-Gallus fibres are preprocessed with sodium oxidative and a half per cent of potassium manganate (VII) chemical solution. The selective use includes 5 mm, 10 mm, 15 mm, and 20 mm length of the Gallus-Gallus fibre, and the quantity of reinforcement was 10%, 20%, and 30%. Five alternate layers of matrix and fibres, with vertical and horizontal orientation, are considered; 12 different samples of Gallus-Gallus fibres reinforced polyester polymer composites and a neat polyester composites were synthesized and characterized for moisture absorbability, tensile strength, tensile modulus, flexural strength, flexural modulus, wear resistance, and outperformed composites were included in microscopic examination and dynamic Mmchanical analysis. The interesting results are the preferred resin, supported for good surface finish, interface bonding, and totally in the enhancement of Composite properties. The composites are strong in tension (760.89 MPa) and sufficiently flexible (flexural modulus 5441.32 MPa), absorbed less moisture (5.8 g), high wear-resistant (least weight loss upon abrasion with a value of 0.1989 g), secured good results in dynamic analysis, and ensured homogeneous distribution of fibres in the matrix through a scanning electron microscopy image. The composites CPPC10, CPPC11, and CPPC12 performed well but composite CPPC12 outperformed

Multi centre study from Malaysia on student preparedness for clinical learning- Perspectives of lecturers and students from medicine, pharmacy and allied health sciences

Objectives: To determine the characteristics important in health profession students’ preparedness for clinical learning from the perspectives of lecturers and studentsMethods: A descriptive cross sectional study was conducted at International Medical University, Perdana University and Monash University in Malaysia. All lecturers involved in preparing students for clinical learning in medicine, dentistry, nursing, pharmacy, nutrition and dietetics, chiropractic and Chinese medicine and immediate preclinical students were invited. We explored views regarding student preparedness on knowledge and understanding, willingness to learn, professionalism, communication and interaction, personal attributes and interpersonal skills rated on a 7 point Likert scale in a questionnaire with 62 items.Results: A total of 187 lecturers and 317 students participated. Fifty percent of lecturers had 5-9year of experience. Neither the lecturers nor the students had differentiated or identified specific characteristics as more important over the others but rated all 62 items as important (score >5) for training. The mean score of the 6 themes for lecturers and students respectively were for knowledge and understanding (5.44,5.09), willingness (5.95,5.51), professionalism (5.89,5.49), communication and interaction (5.54,5.34), personal attributes (5.54,5.35) and interpersonal skills (5.54,5.38). Interesting suggestions such as promotion of inter-professional learning among student from different disciplines, case discussions as a team with other professional categories, self reflection for lecturers regarding their attitudes towards students and teaching methods had been stated by students.Conclusions: Both lecturers and students deem that the knowledge and understanding is not the most important characteristic that makes a student better prepared for clinical learning.

Effects of Cyclic Strain and Growth Factors on Vascular Smooth Muscle Cell Responses

Under physiological and pathological conditions, vascular smooth muscle cells (SMC) are exposed to different biochemical factors and biomechanical forces. Previous studies pertaining to SMC responses have not investigated the effects of both factors on SMCs. Thus, in our research we investigated the combined effects of growth factors like Bfgf (basic fibroblast growth factor), TGF-β (transforming growth factor β) and PDGF (platelet-derived growth factor) along with physiological cyclic strain on SMC responses. Physiological cyclic strain (10% strain) significantly reduced SMC proliferation compared to static controls while addition of growth factors bFGF, TGF-β or PDGF-AB had a positive influence on SMC growth compared to strain alone. Microarray analysis of SMCs exposed to these growth factors and cyclic strain showed that several bioactive genes (vascular endothelial growth factor, epidermal growth factor receptor, etc.) were altered upon exposure. Further work involving biochemical and pathological cyclic strain stimulation will help us better understand the role of cyclic strain and growth factors in vascular functions and development of vascular disorders

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

From cyanobacteria to plants: conservation of PII functions during plastid evolution

This article reviews the current state-of-the-art concerning the functions of the signal processing protein PII in cyanobacteria and plants, with a special focus on evolutionary aspects. We start out with a general introduction to PII proteins, their distribution, and their evolution. We also discuss PII-like proteins and domains, in particular, the similarity between ATP-phosphoribosyltransferase (ATP-PRT) and its PII-like domain and the complex between N-acetyl-L-glutamate kinase (NAGK) and its PII activator protein from oxygenic phototrophs. The structural basis of the function of PII as an ATP/ADP/2-oxoglutarate signal processor is described for Synechococcus elongatus PII. In both cyanobacteria and plants, a major target of PII regulation is NAGK, which catalyzes the committed step of arginine biosynthesis. The common principles of NAGK regulation by PII are outlined. Based on the observation that PII proteins from cyanobacteria and plants can functionally replace each other, the hypothesis that PII-dependent NAGK control was under selective pressure during the evolution of plastids of Chloroplastida and Rhodophyta is tested by bioinformatics approaches. It is noteworthy that two lineages of heterokont algae, diatoms and brown algae, also possess NAGK, albeit lacking PII; their NAGK however appears to have descended from an alphaproteobacterium and not from a cyanobacterium as in plants. We end this article by coming to the conclusion that during the evolution of plastids, PII lost its function in coordinating gene expression through the PipX-NtcA network but preserved its role in nitrogen (arginine) storage metabolism, and subsequently took over the fine-tuned regulation of carbon (fatty acid) storage metabolism, which is important in certain developmental stages of plants

From 2-Oxoglutarate sensing to enzyme control by the Synechococcus elongatus PII signal transduction protein

PII signal transduction proteins have key functions in coordination of central metabolism by integrating signals from carbon, nitrogen and energy status of the cell. In the cyanobacterium Synechococcus elongatus PCC7942 PII binds ATP and 2-oxoglutarate (2-OG) in a synergistic manner, with the ATP- binding sites also accepting ADP. Depending on its effector molecule binding status, P II from this cyanobacterium and other oxygenic phototrophs complexes regulates the key enzyme of the cyclic ornitine pathway, N- acetyl-L-glutamate kinase (NAGK), to control arginine biosynthesis. In wild type PII E85 forms a salt bridge with R233 of NAGK, and consequently E85-PII mutants loose the ability to interact with NAGK. We found PII variants (I86N and I86T) that are able to bind to a NAGK variant (R233A) that was previously shown to be unable to bind wild type PII protein. Analysis of interactions between these P II variants and wild type NAGK as well as the NAGK R233A variant suggested that the I86N variant in the presence of ATP was a superactive NAGK binder, also indicating that PII -E85/NAGK-R233 is not essential for the interaction of the two proteins. To reveal the structural basis of this property, the crystal structure of the PII I86N variant was solved at atomic resolution. Based on the data we propose a two-step model for the mechanism of P II -NAGK complex formation: in an initiating step, a contact between R233 of NAGK and E85 of PII initiates the bending of the extended T-loop of PII , followed by a second step, where a bended T-loop deeply inserts into the NAGK clefts to form the tight complex. Crystal structures identify the binding site of 2-OG located in the vicinity between the subunit clefts and the base of the T-loop showing a novel conformation and explaining the negative effect of 2-OG on PII-NAGK interaction. Trimers with one or two 2-OG molecules shed light on the inter- subunit signalling mechanism by which P II senses effectors in a wide range of concentrations