Host cell lectins ASGR1 and DC-SIGN jointly with TMEM106B confer ACE2 independence and imdevimab resistance to SARS-CoV-2 pseudovirus with spike mutation E484D.

The naturally occurring mutation E484D in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can render viral entry ACE2 independent and imdevimab resistant. Here, we investigated whether the cellular proteins ASGR1, DC-SIGN, and TMEM106B, which interact with the viral S protein, can contribute to these processes. Employing S protein-pseudotyped particles, we found that expression of ASGR1 or DC-SIGN jointly with TMEM106B allowed for robust entry of mutant E484D into otherwise non-susceptible cells, while this effect was not observed upon separate expression of the single proteins and upon infection with SARS-CoV-2 wild type (WT).

A Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

Epistatic hotspots organize antibody fitness landscape and boost evolvability.

The course of evolution is strongly shaped by interaction between mutations. Such epistasis can yield rugged sequence-function maps and constrain the availability of adaptive paths. While theoretical intuition is often built on global statistics of large, homogeneous model landscapes, mutagenesis measurements necessarily probe a limited neighborhood of a reference genotype.

Olfaction with legs-Spiders use wall-pore sensilla for pheromone detection.

The sense of smell is a central sensory modality of most terrestrial species. However, our knowledge of olfaction is based on vertebrates and insects. In contrast, little is known about the chemosensory world of spiders and nothing about how they perform olfaction despite their important ecological role.

Affinity maturation endows potent activity onto class 6 SARS-CoV-2 broadly neutralizing antibodies.

The emergence of SARS-CoV-2 variants of concern (VOCs) has greatly diminished the neutralizing activity of previously FDA-approved monoclonal antibodies (mAbs), including that of antibody cocktails and of first-generation broadly neutralizing antibodies such as S309 (Sotrovimab). In contrast, antibodies targeting cryptic conformational epitopes of the receptor binding domain (RBD) have demonstrated broad activity against emerging variants, but exert only moderate neutralizing activity, which has so far hindered clinical development. Here, we utilize in vitro display technology to identify and affinity-mature antibodies targeting the cryptic class 6 epitope, accessible only in the "up" conformation of the SARS-CoV-2 spike trimer.

Mass Balance Recovery, Absorption, Metabolism, and Excretion of Elinzanetant in Healthy Human Volunteers and in vitro Biotransformation.

Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.

Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling.

Angiotensin receptor blockers modulate the lupus CD4+ T cell epigenome characterized by TNF family-linked signaling.

In systemic lupus erythematosus (lupus), environmental effects acting within a permissive genetic background lead to autoimmune dysregulation. Dysfunction of CD4+ T cells contributes to pathology by providing help to autoreactive B and T cells, and CD4+ T cell dysfunction coincides with altered DNA methylation and histone modifications of select gene loci. However, chromatin accessibility states of distinct T cell subsets and mechanisms driving heterogeneous chromatin states across patients remain poorly understood.

Influence of a Lordotic Cage Profile on Global and Segmental Lordosis in the Context of Lumbar TLIF Surgeries: A Retrospective Radiological Analysis.

Cage implantation decompresses neural elements, stabilizes segments, and promotes fusion, with sagittal balance influenced by cage size, geometry, and position. This retrospective study compared the effects of lumbar interbody cages with 10° and 15° lordotic angles on global and segmental lordosis in patients undergoing transforaminal lumbar interbody fusion (TLIF). Data from 215 patients who underwent 259 TLIF procedures between 2018 and 2022 were analyzed.

Synthesis and reactivity of a six-membered heterocyclic 1,3-diphosphaallene.

1,3-Diphosphaallenes are a new class of heavier heteroallenes and show a fascinating chemical behavior and reactivity. Herein we report on the room temperature transformation of gallaphosphene LGa(OCP)PGaL 1 (L = HC[C(Me)N(Ar)], Ar = 2,6-i-PrCH) to the six-membered metallaheterocycle LGa(PCP)OGaL 2 featuring a LGa-substituted 1,3-diphosphaallene unit. The possible mechanism of formation of 2 is supported by quantum chemical calculations, which revealed that the formation of 2 is energetically more favorable ( 2 kcal mol) than the formation of 1 at ambient temperature.

Cellular and molecular characterization of peripheral glia in the lung and other organs.

Peripheral glia are important regulators of diverse physiologic functions yet their molecular distinctions and locations in almost all visceral organs are not well-understood. We performed a systematic analysis of peripheral glia, focusing on the lung and leveraging single cell RNA sequencing (scRNA-seq) analysis to characterize their cellular and molecular features. Using in vivo lineage studies, we characterized the anatomic, cellular, and molecular features of the Sox10+ glial lineage of the mouse lung.

Batrachopolyenes: Volatile Norsteroids from Femoral Scent Glands of Frogs.

Steroid hormones are C-C-sterane derivatives, featuring the typical 6-6-6-5 ring system. Here we report on a novel C-steroid ring system named batrachane with a contracted A-ring resulting in a 5-6-6-5 ring arrangement. The isolation, structural elucidation, and total synthesis of three members of the novel batrachopolyene family occurring in the tropical frog genus Odontobatrachus is reported.

Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1.

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.

Severe Periodontitis is Associated With Recurrent Cardiovascular Events-A 10-Year Longitudinal Cohort Study.

Aim: The study aimed to elucidate a putative association between severe periodontitis and the incidence of recurrent cardiovascular events in patients with cardiovascular disease (CVD) within 10 years after their initial hospitalisation.

Methods: A cohort of 1002 stationary patients with angiographically proven CVD was included. They were examined regarding prevalence of severe periodontitis (≥ 30% of the teeth with proximal attachment loss of ≥ 5 mm), probing depth, clinical attachment loss, bleeding on probing, number of missing teeth and oral care habits.

Chemical quantification of N-acyl alanine methyl ester (NAME) production and impact on temporal gene expression patterns in Roseovarius tolerans EL-164.

Background: Previous studies have identified structurally diverse N-acyl amino acid methyl esters (NAMEs) in culture extracts of Roseovarius tolerans EL-164 (Roseobacteraceae). NAMEs are structural analogues of the common signaling compounds N-acyl homoserine lactones (AHLs), but do not participate in AHL-mediated signaling. NAMEs show minor antialgal and antimicrobial activity, but whether this activity serves as the primary ecological role remains unclear.

ACE2-independent sarbecovirus cell entry can be supported by TMPRSS2-related enzymes and can reduce sensitivity to antibody-mediated neutralization.

The COVID-19 pandemic, caused by SARS-CoV-2, demonstrated that zoonotic transmission of animal sarbecoviruses threatens human health but the determinants of transmission are incompletely understood. Here, we show that most spike (S) proteins of horseshoe bat and Malayan pangolin sarbecoviruses employ ACE2 for entry, with human and raccoon dog ACE2 exhibiting broad receptor activity. The insertion of a multibasic cleavage site into the S proteins increased entry into human lung cells driven by most S proteins tested, suggesting that acquisition of a multibasic cleavage site might increase infectivity of diverse animal sarbecoviruses for the human respiratory tract.

Small animals with unique chemistry - the natural product chemistry of Collembola.

Covering up to September 2024Collembola, commonly known as springtails, are abundant and important members of soil ecosystems. Due to their small size and hidden life, not much is known about their secondary metabolites. This chemistry is remarkably different from that of insects, with which they share a common ancestor, although they diverged already around 450 mya.

Ultrasound-Guided Intranodal Lipiodol Lymphangiography for the Assessment and Treatment of Chylous Leaks: A Retrospective Case Series from a Single Center in Switzerland and a Systematic Review of the Literature.

Lymphatic leaks are well-known complications of major thoracic or abdominal surgeries, which significantly heighten morbidity and mortality rates. While the existing literature provides insights into managing these post-operative leaks, with a step-up approach from conservative measures (CMs) to surgical intervention, there are no standardized treatment guidelines. The purpose of this paper is to offer a management algorithm of post-operative lymphatic leaks based on a systematic literature review (SLR) of the therapeutic effect of Lipiodol lymphangiography (LL), completed by a case series of five patients who underwent LL in our department.

Unsupervised SapBERT-based bi-encoders for medical concept annotation of clinical narratives with SNOMED CT.

Objective: Clinical narratives provide comprehensive patient information. Achieving interoperability involves mapping relevant details to standardized medical vocabularies. Typically, natural language processing divides this task into named entity recognition (NER) and medical concept normalization (MCN).

Professional development of medical students - piloting a longitudinal curriculum at Jena University Hospital (LongProf).

Background: Professionalism is an important prerequisite for the quality of medical care with specific competencies anchored in the National Competence-Based Learning Objectives Catalogue Medicine 2.0. To date, there are hardly any explicit teaching formats at German universities to achieve these.