Atomic Mutagenesis of -Methyladenosine Reveals Distinct Recognition Modes by Human mA Reader and Eraser Proteins.

-methyladenosine (mA) is an important modified nucleoside in cellular RNA associated with multiple cellular processes and is implicated in diseases. The enzymes associated with the dynamic installation and removal of mA are heavily investigated targets for drug research, which requires detailed knowledge of the recognition modes of mA by proteins. Here, we use atomic mutagenesis of mA to systematically investigate the mechanisms of the two human mA demethylase enzymes FTO and ALKBH5 and the binding modes of YTH reader proteins YTHDF2/DC1/DC2.

A SAM analogue-utilizing ribozyme for site-specific RNA alkylation in living cells.

Post-transcriptional RNA modification methods are in high demand for site-specific RNA labelling and analysis of RNA functions. In vitro-selected ribozymes are attractive tools for RNA research and have the potential to overcome some of the limitations of chemoenzymatic approaches with repurposed methyltransferases. Here we report an alkyltransferase ribozyme that uses a synthetic, stabilized S-adenosylmethionine (SAM) analogue and catalyses the transfer of a propargyl group to a specific adenosine in the target RNA.

ICESat-2 river surface slope (IRIS): A global reach-scale water surface slope dataset.

The global reach-scale "ICESat-2 River Surface Slope" (IRIS) dataset comprises average and extreme water surface slopes (WSS) derived from ICESat-2 observations between October 2018 and August 2022 as a supplement to 121,583 reaches from the "SWOT Mission River Database" (SWORD). To gain full advantage of ICESat-2's unique measurement geometry with six parallel lidar beams, the WSS is determined across pairs of beams or along individual beams, depending on the intersection angle of spacecraft orbit and river centerline. Combining both approaches maximizes spatial and temporal coverage.

Testing three coping strategies for time pressure in categorizations and similarity judgments.

This article compares three psychological mechanisms to make multi-attribute inferences under time pressure in the domains of categorization and similarity judgments. Specifically, we test if people under time pressure attend to fewer object features (attention focus), if they respond less precisely (lower choice sensitivity), or if they simplify a psychological similarity function (simplified similarity). The simpler psychological similarity considers the number of matching features but ignores the actual feature value differences.

Global coastal attenuation of wind-waves observed with radar altimetry.

Coastal studies of wave climate and evaluations of wave energy resources are mainly regional and based on the use of computationally very expensive models or a network of in-situ data. Considering the significant wave height, satellite radar altimetry provides an established global and relatively long-term source, whose coastal data are nevertheless typically flagged as unreliable within 30 km of the coast. This study exploits the reprocessing of the radar altimetry signals with a dedicated fitting algorithm to retrieve several years of significant wave height records in the coastal zone.

Mechanism of SARS-CoV-2 polymerase stalling by remdesivir.

Remdesivir is the only FDA-approved drug for the treatment of COVID-19 patients. The active form of remdesivir acts as a nucleoside analog and inhibits the RNA-dependent RNA polymerase (RdRp) of coronaviruses including SARS-CoV-2. Remdesivir is incorporated by the RdRp into the growing RNA product and allows for addition of three more nucleotides before RNA synthesis stalls.

Frequency of blood pressure and estimated glomerular filtration rate monitoring in patients affected by hypertension: a retrospective study with 176 565 patients in Germany.

Objective: The aim of this study was to analyze the frequency of blood pressure (BP) and estimated glomerular filtration rate (eGFR) monitoring in hypertension patients followed in primary care practices in Germany.

Patients And Methods: This study included patients who had received at least two hypertension diagnoses (ICD-10: I10) in 2016. The primary outcome of this study was the frequency of BP and eGFR monitoring in patients with hypertension in the year 2016.

[Without Net and Double Floor: Comparison of Umbilical Hernia Repair by Spitzy in Children and Adults].

Unlabelled: Umbilical hernia occur in both adults and children. For over 100 years, umbilical hernia in children has been treated surgically by the Spitzy method. With adult patients, meshes are being increasingly used.

Intake of silica nanoparticles by giant lipid vesicles: influence of particle size and thermodynamic membrane state.

The uptake of nanoparticles into cells often involves their engulfment by the plasma membrane and a fission of the latter. Understanding the physical mechanisms underlying these uptake processes may be achieved by the investigation of simple model systems that can be compared to theoretical models. Here, we present experiments on a massive uptake of silica nanoparticles by giant unilamellar lipid vesicles (GUVs).

Intravenous immunoglobulin maintenance treatment in myasthenia gravis: a randomized, controlled trial sample size simulation.

Introduction: In cases of exacerbation or crisis, myasthenia gravis (MG) patients can be treated with intravenous immunoglobulin (IVIg), plasmapheresis, or immunoadsorption. However, IVIg efficacy data in maintenance treatment are sparse.

Methods: We prospectively observed 16 index patients with chronic and insufficiently controlled MG under standard immunosuppressant therapy and symptomatic treatment.

Fingolimod reduces recurrence of disease activity after natalizumab withdrawal in multiple sclerosis.

After discontinuation of natalizumab (NAT), multiple sclerosis (MS) disease activity often recurs. We assessed the recurrence of clinical disease activity during the first year after switching from NAT to fingolimod (FTY) in patients with relapsing-remitting MS. The number of relapses and the annualized relapse rate (ARR) before, during and after NAT discontinuation were determined and compared between 26 MS patients who switched to FTY within 24 weeks, and 10 MS patients who remained without disease modifying therapy (therapy free group = TFG).

Sibling disability risk at onset and during disease progression in familial multiple sclerosis.

Background: The objective of this study was to address the differences in onset and disease progression between familial and sporadic multiple sclerosis (MS) and the association within sibling pairs.

Methods: Ninety-eight siblings and their controls were included from a database of 763 sporadic MS-patients, randomly pair-matched for age, gender, clinical course, disease duration and treatment. Sixty-eight available siblings completed a prospective six-year follow-up.

Immunization as treatment for Parkinson's disease.

Parkinson's disease and other neurodegenerative disorders share a common pathologic pathway with aggregation and deposition of misfolded proteins causing a disruption of particular neuronal networks. Several mechanisms have been implicated in the downstream events following deposition of misfolded proteins including free radical formation and failure of cellular defences such as autophagy or protein-degradation by the ubiquitin-proteasome pathway among many others. Treatments, however, capable of arresting or at least effectively modifying the course of disease do not yet exist.