6 research outputs found
The complete genome, comparative and functional analysis of Stenotrophomonas maltophilia reveals an organism heavily shielded by drug resistance determinants
The complete Stenotrophomonas maltophilia genome sequence suggests that it can act as a reservoir of antibiotic resistance determinants
Identification of Neural Outgrowth Genes using Genome-Wide RNAi
While genetic screens have identified many genes essential for neurite outgrowth, they have been limited in their ability to identify neural genes that also have earlier critical roles in the gastrula, or neural genes for which maternally contributed RNA compensates for gene mutations in the zygote. To address this, we developed methods to screen the Drosophila genome using RNA-interference (RNAi) on primary neural cells and present the results of the first full-genome RNAi screen in neurons. We used live-cell imaging and quantitative image analysis to characterize the morphological phenotypes of fluorescently labelled primary neurons and glia in response to RNAi-mediated gene knockdown. From the full genome screen, we focused our analysis on 104 evolutionarily conserved genes that when downregulated by RNAi, have morphological defects such as reduced axon extension, excessive branching, loss of fasciculation, and blebbing. To assist in the phenotypic analysis of the large data sets, we generated image analysis algorithms that could assess the statistical significance of the mutant phenotypes. The algorithms were essential for the analysis of the thousands of images generated by the screening process and will become a valuable tool for future genome-wide screens in primary neurons. Our analysis revealed unexpected, essential roles in neurite outgrowth for genes representing a wide range of functional categories including signalling molecules, enzymes, channels, receptors, and cytoskeletal proteins. We also found that genes known to be involved in protein and vesicle trafficking showed similar RNAi phenotypes. We confirmed phenotypes of the protein trafficking genes Sec61alpha and Ran GTPase using Drosophila embryo and mouse embryonic cerebral cortical neurons, respectively. Collectively, our results showed that RNAi phenotypes in primary neural culture can parallel in vivo phenotypes, and the screening technique can be used to identify many new genes that have important functions in the nervous system
P482: The clinical utility of genome-wide sequencing for rare disease: A multidimensional map
Kontaminiert Werden Magazin #2
Kontamination, Verunreinigung, Vermischung. Urbane Natur/Kulturen und die Beziehungen zwischen Menschen und Pflanzen sind vielfältig. In Begegnung und Austausch finden gegenseitige Veränderungen statt. Ohne Kollaborationen wäre ein (Über)Leben nicht möglich. In diesen Momenten der Transformation fragen wir: Wie finden solche Prozesse in unserer Nähe statt? Was heißt es, kontaminiert zu werden? Und wer kontaminiert wen?
Ohne den Versuch eine klare Antwort finden zu wollen, spiegeln sich diese Fragen in den Beiträgen des ‘Kontaminiert Werden Magazin #2’ wider – etwa in Form von Essays, Prosa, Praxis- und Feldberichten.Contamination, pollution, mingling. Urban nature/cultures and the relationships between people and plants are diverse. In encounters and exchanges, mutual transformations take place and without collaborations living and surviving would not be possible. In these ongoing moments of transformation, we ask: How do such processes take place close to us? What does it mean to become contaminated? Who is contaminating whom?
Without trying to find a clear answer these questions are reflected in the contributions of 'Kontaminiert Werden Magazin #2, for example in form of essays, prose, practical reports and field notes
Progesterone and medroxyprogesterone acetate differentially regulate α4 subunit expression of GABAA receptors in the CA1 hippocampus of female rats
Empagliflozin in Patients with Chronic Kidney Disease
Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo