The classe of antibiotics, membrane-targeting drugs of last resort i.e. polymyxin and lipopeptide used to treat infections caused by multi-drug-resistant pathogens. Polymyxins treat infections caused by carbapenem-resistant species such as Escherichia coli , Acinetobacter baumannii and Pseudomonas aeruginosa  by targeting the membrane consist of lipopolysaccharide of most Gram negative species . By contrast, the lipopeptide daptomycin requires membrane phosphatidylglycerol for activity and is only used to treat infections … Continue reading Membrane targeting drugs polymyxin and lipopeptide.

In this multicenter, randomized, crossover trial, we recruited children 1 to 7 years of age with type 1 diabetes who were receiving insulin-pump therapy.  Participants received treatment in two 16-week periods, in random order, in which the closed-loop system was compared with sensor-augmented pump therapy. The primary end point was between-treatment difference in the percentage of time that the sensor glucose measurement was in the … Continue reading Trial of Closed-Loop therapy in Young Children with Type 1 Diabetes

India with a huge population and known for endogamous and consanguineous marriages — within the same community or family — it is necessary for every married couple to undergo genetic testing for thalassemia since there is a chance of one in 30 to pass on the gene to the off-spring, said scientists of the CSIR-Centre for Cellular and Molecular Biology (CCMB) on Thursday. CCMB has … Continue reading Genetic testing mandatory for every married couple, say CSIR-CCMB scientists

Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson’s disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component. We performed an hypothesis-free whole-exome sequencing (WES)-based screening of time-to-LID onset and attempted replication of previously published candidate gene studies. A WES … Continue reading Exome-wide association study of levodopa-induced dyskinesia

Tumor progression requires bidirectional cell-to-cell communication within a complex tumor microenvironment (TME). Extracellular vesicles (EVs) as carriers have the capacity to shuttle regulatory molecules, including nucleic acids, proteins, and lipids, between cancer cells and multiple stromal cells, inducing remarkable phenotypic alterations in the TME. Recently proposed the concept “immunogenic stress”, which means in some stressed microenvironment, cancer cells can release EVs containing specific immunoregulatory mediators, … Continue reading Extracellular vesicles and immunogenic stress in cancer

Mutations in SPOP E3 ligase gene are reportedly associated with genome-wide DNA hypermethylation in prostate cancer (PCa) although the underlying mechanisms remain elusive. Here, we demonstrate that SPOP binds and promotes polyubiquitination and degradation of histone methyltransferase and DNMT interactor GLP. SPOP mutation induces stabilization of GLP and its partner protein G9a and aberrant upregulation of global DNA hypermethylation in cultured PCa cells and primary PCa specimens. … Continue reading SPOP mutation induces DNA methylation

The determination of molecular features that mediate clinically aggressive phenotypes in prostate cancer remains a major biological and clinical challenge. Recent advances in interpretability of machine learning models as applied to biomedical problems may enable discovery and prediction in clinical cancer genomics. Here we developed P-NET—a biologically informed deep learning model—to stratify patients with prostate cancer by treatment-resistance state and evaluate molecular drivers of treatment resistance for … Continue reading Biologically informed deep neural network for prostate cancer

Glioblastoma is the most common malignant primary brain tumor. To date, clinically relevant biomarkers are restricted to isocitrate dehydrogenase (IDH) gene 1 or 2 mutations and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Long non-coding RNAs (lncRNAs) have been shown to contribute to glioblastoma pathogenesis and could potentially serve as novel biomarkers. The clinical significance of HOXA Transcript Antisense RNA, Myeloid-Specific 1 (HOTAIRM1) was determined by analyzing HOTAIRM1 in multiple … Continue reading The long non-coding RNA HOTAIRM1 promotes tumor aggressiveness

Increasing numbers of SARS-CoV-2-positive (SARS-CoV-2pos) subjects are detected at silent SARS-CoV-2 infection stage (SSIS). Yet, SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease. Here, we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-CoV-2pos subjects, 47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects, and interrogated them with … Continue reading Distinct immune signatures discriminate between asymptomatic and presymptomatic