Neurobeachin regulates receptor downscaling at GABAergic inhibitory synapses in a protein kinase A-dependent manner.

GABAergic synapses critically modulate neuronal excitability, and plastic changes in inhibitory synaptic strength require reversible interactions between GABA receptors (GABARs) and their postsynaptic anchor gephyrin. Inhibitory long-term potentiation (LTP) depends on the postsynaptic recruitment of gephyrin and GABARs, whereas the neurotransmitter GABA can induce synaptic removal of GABARs. However, the mechanisms and players underlying plastic adaptation of synaptic strength are incompletely understood.

Does the posterior tibial slope in caliper-verified unrestricted kinematically aligned TKA using manual instruments match the slope in the contralateral healthy knee and improve function?

Purpose: Unrestricted kinematically aligned total knee arthroplasty (unKA TKA) strives to restore the pre-arthritic posterior tibial slope (PTS), however consistency of achieving this alignment target is unknown. The present study determined the proportion of subjects with differences in PTS less than 2° from the target and the improvement in patient-reported function after unKA TKA.

Methods: A review of 562 postoperative scanograms identified 99 patients (51 female) with a unKA TKA in one limb, a contralateral healthy limb, and a postoperative axial CT scan.

Anterior femoral offset is a flawed measurement of patellofemoral overstuffing.

Background: Patellofemoral joint (PFJ) issues after total knee arthroplasty (TKA) are becoming a topic of interest once again. Due to the complex three-dimensional shape of the trochlea, various two-dimensional proxy measurements on plain X-rays have been described. One of these measurements is the anterior femoral offset (AFO).

Weekday effect of surgery on in-hospital outcome in pancreatic surgery: a population-based study.

Importance: There is conflicting evidence regarding weekday dependent outcome in complex abdominal surgery, including pancreatic resections.

Objective: To clarify weekday-dependency of outcome after pancreatic resections in a comprehensive nationwide context.

Design: Retrospective cross-sectional study of anonymized nationwide hospital billing data (DRG data).

Predisposition footprints in the somatic genome of Wilms tumours.

Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis.

Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study.

Background: Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations.

Antibiotic resistance and molecular characterization of non-invasive clinical isolates in Germany 2019 and 2020.

Background: (Hi) is known as a cause of invasive and non-invasive diseases. Especially ear, nose and throat (ENT) infections are common reasons for antibiotic prescriptions in outpatient settings in Germany. Therefore, antibiotic resistance surveillance is important to provide the basis of recommendations for the empirical usage of antibiotic agents.

Microbial iCLIP2: enhanced mapping of RNA-protein interaction by promoting protein and RNA stability.

The entire RNA life cycle, spanning from transcription to decay, is intricately regulated by RNA-binding proteins (RBPs). To understand their precise functions, it is crucial to identify direct targets, pinpoint their exact binding sites, and unravel the underlying specificity in vivo. Individual-nucleotide resolution UV cross-linking and immunoprecipitation 2 (iCLIP2) is a state-of-the-art technique that enables the identification of RBP-binding sites at single-nucleotide resolution.

Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress.

Many eIF4F and poly(A)-binding protein (PABP) paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types/developmental stages. Each eIF4F complex has its own proteins, messenger RNAs (mRNAs) and, consequently, a distinct function.

Unveiling Usage Patterns and Explaining Usage of Symptom Checker Apps: Explorative Longitudinal Mixed Methods Study.

Background: Symptom checker apps (SCA) aim to enable individuals without medical training to classify perceived symptoms and receive guidance on appropriate actions, such as self-care or seeking professional medical attention. However, there is a lack of detailed understanding regarding the contexts in which individuals use SCA and their opinions on these tools.

Objective: This mixed methods study aims to explore the circumstances under which medical laypeople use SCA and to identify which aspects users find noteworthy after using SCA.

Cancer Cells Show Higher Sensitivity to Melatonin-Tamoxifen Drug Conjugates than to Combination of Melatonin and Tamoxifen.

Drug conjugates of tamoxifen and melatonin linked through the amide side chain of melatonin (,) were reported as promising agents for future treatment of breast cancer, possibly reversing the adverse effects of tamoxifen. Here, we report the synthesis and pharmacological evaluation of a novel series of anticancer drug conjugates linking melatonin with tamoxifen through polymethylene spacers through the ether oxygen of melatonin (-, -, ) and compare them to the previously reported amide-linked analogues and . All hybrid ligands are antagonists of estrogen receptor alpha and agonists of the melatonin MT receptor with variable potencies.

Prediction of Perceived Exertion Ratings in National Level Soccer Players Using Wearable Sensor Data and Machine Learning Techniques.

This study aimed to identify relationships between external and internal load parameters with subjective ratings of perceived exertion (RPE). Consecutively, these relationships shall be used to evaluate different machine learning models and design a deep learning architecture to predict RPE in highly trained/national level soccer players. From a dataset comprising 5402 training sessions and 732 match observations, we gathered data on 174 distinct parameters, encompassing heart rate, GPS, accelerometer data and RPE (Borg's 0-10 scale) of 26 professional male professional soccer players.

Intraspecific genetic diversity with unrestricted gene flow in the domoic acid-producing diatom Nitzschia navis-varingica (Bacillariophyceae) from the Western Pacific.

The benthic pennate diatom Nitzschia navis-varingica, known for producing domoic acid (DA) and its isomers, is widely distributed in the Western Pacific (WP) region. To investigate the genetic differentiation and gene flow patterns among the populations in the WP, the genetic diversity of 354 strains of N. navis-varingica was analysed using two nuclear-encoded rDNA loci: the large subunit rDNA (LSU rDNA) and the internal transcribed spacer 2 (ITS2).

Cataglyphis ants have a polarity-sensitive magnetic compass.

Spatial orientation based on the geomagnetic field (GMF) is a widespread phenomenon in the animal kingdom, predominantly observed in long-distance migrating birds, sea turtles, lobsters, and Lepidoptera. Although magnetoreception has been studied intensively, the mechanism remains elusive. A crucial question for a mechanistic understanding of magnetoreception is whether animals rely on inclination or polarity-based magnetic information.

Identification of suitable target/E3 ligase pairs for PROTAC development using a rapamycin-induced proximity assay (RiPA).

The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest.

Characterization of the chemical profiles and biological activities of Thesium bertramii Azn. Extracts using a combination of in vitro, in silico, and network pharmacology methods.

The genus Thesium, family Santalaceae, comprises about 350 species, and, although many of them are used as functional food and in traditional medicine, there are limited studies evaluating their pharmacological potential. The present study was designed to evaluate the chemical profile, antioxidant, and enzyme inhibition potential of aerial parts and roots of T. bertramii Azn.

Structure Elucidation of the Daptomycin Products Generated upon Heterologous Expression of the Daptomycin Resistance Gene Cluster .

Recently, a high-level daptomycin (DAP)-resistant strain (TS92) was identified, which mediates a 33% decline of DAP when incubated in Mueller-Hinton (MH) medium. The genetic background of the DAP resistance in TS92 is a newly discovered two-gene operon, named whose expression was reported to impair the structural integrity of DAP, eventually leading to its inactivation. Here, we set out to elucidate the chemical nature of -mediated DAP modification by applying a general unknown comparative screening (GUCS) approach in high-resolution mass spectrometry.