Activiteit

Our study sets precedents for use of V2IDA in genetic diversity analysis and in silico stability investigation of attenuated viral vaccines, facilitating genetic surveillance during the vaccine production process.Dendritic cells (DCs) are the major specialized antigen-presenting cells, thereby connecting innate and adaptive immunity. Because of their role in establishing adaptive immunity, they constitute promising targets for immunotherapy. Monocytes can differentiate into DCs in vitro in the presence of colony-stimulating factor 2 (CSF2) and interleukin 4 (IL4), activating four signalling pathways (MAPK, JAK/STAT, NFKB and PI3K). However, the downstream transcriptional programme responsible for DC differentiation from monocytes (moDCs) remains unknown. By analysing the scientific literature on moDC differentiation, we established a preliminary logical model that helped us identify missing information regarding the activation of genes responsible for this differentiation, including missing targets for key transcription factors (TFs). Using ChIP-seq and RNA-seq data from the Blueprint consortium, we defined active and inactive promoters, together with differentially expressed genes in monocytes, moDCs and macrophages, which correspond to an alternative cell fate. We then used this functional genomic information to predict novel targets for previously identified TFs. By integrating this information, we refined our model and recapitulated the main established facts regarding moDC differentiation. Prospectively, the resulting model should be useful to develop novel immunotherapies targeting moDCs.Whole-genome doubling, tripling or replicating to a greater degree, due to fixation of polyploidization events, is attested in almost all lineages of the flowering plants, recurring in the ancestry of some plants two, three or more times in retracing their history to the earliest angiosperm. This major mechanism in plant genome evolution, which generally appears as instantaneous on the evolutionary time scale, sets in operation a compensatory process called fractionation, the loss of duplicate genes, initially rapid, but continuing at a diminishing rate over millions and tens of millions of years. We study this process by statistically comparing the distribution of duplicate gene pairs as a function of their time of creation through polyploidization, as measured by sequence similarity. The stochastic model that accounts for this distribution, though exceedingly simple, still has too many parameters to be estimated based only on the similarity distribution, while the computational procedures for compiling the distribution from annotated genomic data is heavily biased against earlier polyploidization events-syntenic ‘crumble’. Other parameters, such as the size of the initial gene complement and the ploidy of the various events giving rise to duplicate gene pairs, are even more inaccessible to estimation. Here, we show how the frequency of unpaired genes, identified via their embedding in stretches of duplicate pairs, together with previously established constraints among some parameters, adds enormously to the range of successive polyploidization events that can be analysed. This also allows us to estimate the initial gene complement and to correct for the bias due to crumble. We explore the applicability of our methodology to four flowering plant genomes covering a range of different polyploidization histories.The most common symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are fevers, fatigue and dry cough. However, growing data suggest gastrointestinal (GI) manifestations occur in the majority of patients. Small bowel obstruction remains a significant cause of surgical abdominal emergencies in the adult population, although most cases are secondary to adhesive disease. Taurine mw We present a case of ileocolonic intussusception in an adult with active COVID-19 infection. Our patient presented with small bowel obstruction 4 days after diagnosis of COVID-19 with typical respiratory symptoms. Imaging revealed ileocolonic intussusception and possible cecal mass for which a right hemicolectomy was performed. Recovery was unremarkable. Pathology suggested necrosis without an identifiable mass. To the best of our knowledge, this is the first documented case of small bowel obstruction secondary to ileocolonic intussusception in an adult related to GI manifestation of COVID-19.Bleeding from the appendix is a rare cause of lower gastrointestinal haemorrhage. Previous publications have noted diagnosis via colonoscopy or computed tomography angiogram and treatment via surgical or endoscopy. We report a case of large volume per rectal bleeding from the appendix, with diagnosis and treatment via angiography and coil insertion, which is the first of its kind reported in the literature.

Critical care populations experience demographic shifts in response to trends in population and healthcare, with increasing severity and/or complexity of illness a common observation worldwide. Inflammation in critical illness impacts glucose-insulin metabolism, and hyperglycaemia is associated with mortality and morbidity. This study examines longitudinal trends in insulin sensitivity across almost a decade of glycaemic control in a single unit.

A clinically validated model of glucose-insulin dynamics is used to assess hour-hour insulin sensitivity over the first 72 h of insulin therapy. Insulin sensitivity and its hour-hour percent variability are examined over 8 calendar years alongside severity scores and diagnostics.

Insulin sensitivity was found to decrease by 50-55% from 2011 to 2015, and remain low from 2015 to 2018, with no concomitant trends in age, severity scores or risk of death, or diagnostic category. Insulin sensitivity variability was found to remain largely unchanged year to year and wvariability) challenge to glycaemic control. Increasing insulin resistance may imply greater inflammation and severity of illness not captured by existing severity scores. Insulin resistance reduces glucose tolerance, and can cause greater incidence of insulin saturation and resultant hyperglycaemia. Overall, these results have significant clinical implications for glycaemic control and nutrition management.