NONCODE v2.0: decoding the non-coding

The NONCODE database is an integrated knowledge database designed for the analysis of non-coding RNAs (ncRNAs). Since NONCODE was first released 3 years ago, the number of known ncRNAs has grown rapidly, and there is growing recognition that ncRNAs play important regulatory roles in most organisms. In the updated version of NONCODE (NONCODE v2.0), the number of collected ncRNAs has reached 206 226, including a wide range of microRNAs, Piwi-interacting RNAs and mRNA-like ncRNAs. The improvements brought to the database include not only new and updated ncRNA data sets, but also an incorporation of BLAST alignment search service and access through our custom UCSC Genome Browser. NONCODE can be found under http://www.noncode.org or http://noncode.bioinfo.org.cn

On-Chip Contactless Four-Electrode Conductivity Detection for Capillary Electrophoresis Devices

In this contribution, a capillary electrophoresis microdevice with an integrated on-chip contactless fourelectrode conductivity detector is presented. A 6-cm-long, 70-µm-wide, and 20-µm-deep channel was etched in a glass substrate that was bonded to a second glass substrate in order to form a sealed channel. Four contactless electrodes (metal electrodes covered by 30-nm silicon carbide) were deposited and patterned on the second glass substrate for on-chip conductivity detection. Contactless conductivity detection was performed in either a two-or a four-electrode configuration. Experimental results confirmed the improved characteristics of the fourelectrode configuration over the classical two-electrode detection setup. The four-electrode configuration allows for sensitive detection for varying carrier-electrolyte background conductivity without the need for adjustment of the measurement frequency. Reproducible electrophoretic separations of three inorganic cations (K + , Na + , Li + ) and six organic acids are presented. Detection as low as 5 µM for potassium was demonstrated. In the development and optimization of miniaturized analytical systems, a delicate combination of science and technology originating from microelectronic device fabrication, electrical engineering, and analytical chemistry is essential. In this multidisciplinary field, microtechnology experts combine the demands from analytical chemistry and electronic instrumentation in the design and fabrication of novel analytical devices. 1,2 Chemical analysis systems, such as high-performance liquid chromatography (HPLC) or capillary electrophoresis (CE), always consist of the combination of a separation and a detection system. For separation, CE or CE-based separation techniques are highly suitable for implementation on the microchip format. Electrokinetic control of fluid transport eliminates the need for external components such as pumps and valves. The separation efficiency is relatively independent of the separation path length and is, therefore, more compatible with miniaturization than, for instance, chromatographic techniques. As far as detection is concerned, laser-induced fluorescence (LIF) is, at present, the most widely used detection technique in miniaturized analysis systems because of its high sensitivity. The drawbacks of LIF are its limited compatibility with miniaturization and on-chip integration and the requirement for labeling of most (bio) chemically relevant compounds. External devices such as the relatively large laser and the photodetector system strongly prohibit further miniaturization. The development of alternative detection methods compatible with miniaturization and full onchip integration is highly desirable. Since electrode deposition is a well-established process in microfabrication, the implementation of detection techniques utilizing integrated electrodes has become an attractive approach. Successful coupling of conventional CE with potentiometry, 3 amperometry, 4,5 and conductometry 6-10 has been reported in the literature. In addition, both amperometric and potentiometric detection were also implemented in chip-based CE systems. [11][12][13] The primary advantage of amperometric and potentiometric detection over conductivity detection is the high selectivity induced by the electrochemical reactions that take place at the electrode surface. Only electrochemically active compounds * Corresponding author: (tel) +31 (0) 15 278 6518; (fax) +31 (0) 15 278 5755

Tracking Marsupial Evolution Using Archaic Genomic Retroposon Insertions

Genome-wide comparisons of shared retroposon insertion patterns resolve the phylogeny of marsupials, clearly distinguishing South American and Australian species and lending support to Didelphimorphia as the basal split

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