PRDX6 dictates ferroptosis sensitivity by directing cellular selenium utilization.

Selenium-dependent glutathione peroxidase 4 (GPX4) is the guardian of ferroptosis, preventing unrestrained (phospho)lipid peroxidation by reducing phospholipid hydroperoxides (PLOOH). However, the contribution of other phospholipid peroxidases in ferroptosis protection remains unclear. We show that cells lacking GPX4 still exhibit substantial PLOOH-reducing capacity, suggesting a contribution of alternative PLOOH peroxidases.

Tooth segmentation by low-dose CBCT for orthodontic treatment planning : Explorative ex vivo validation.

Purpose: Three-dimensional imaging has become an increasingly important component of orthodontics. Associated with this, however, is a higher radiation exposure for patients. New cone-beam computed tomography (CBCT) devices have been developed that can provide low-dose CBCT (LD-CBCT).

Dual nematode infection in Brassica nigra affects shoot metabolome and aphid survival in distinct contrast to single-species infection.

Previous studies showed that aphid performance was compromised on Brassica nigra infected by root-lesion nematodes (Pratylenchus penetrans, Pp), but less, or positively influenced by root-knot nematode (Meloidogyne spp.) infection. These experiments were on single-species nematode infections, but roots can be infected naturally with several nematode species simultaneously.

Single Acetylation-mimetic Mutation in TDP-43 Nuclear Localization Signal Disrupts Importin α1/β Signaling.

Cytoplasmic aggregation of the TAR-DNA binding protein of 43 kDa (TDP-43) is the hallmark of sporadic amyotrophic lateral sclerosis (ALS). Most ALS patients with TDP-43 aggregates in neurons and glia do not have mutations in the TDP-43 gene but contain aberrantly post-translationally modified TDP-43. Here, we found that a single acetylation-mimetic mutation (K82Q) near the TDP-43 minor Nuclear Localization Signal (NLS) box, which mimics a post-translational modification identified in an ALS patient, can lead to TDP-43 mislocalization to the cytoplasm and irreversible aggregation.

Do concentrations of non-esterified fatty acids change during gestation and lactation in healthy bitches?

During the gestation and lactation period, the energy demand in pregnant and lactating bitches is elevated. Non-esterified fatty acids (NEFAs) are utilized either directly from the fed diet or from body fat storage. High NEFA concentration in the blood plasma leads to an increased risk for diseases.

Proteomic Characterization of Undifferentiated Small Round Cell Sarcomas With EWSR1 and CIC::DUX4 Translocations Reveals Diverging Tumor Biology and Distinct Diagnostic Markers.

Undifferentiated small round cell sarcomas (USRS) of bone and soft tissue are a group of tumors with heterogenic genomic alterations sharing similar morphology. In the present study, we performed a comparative large-scale proteomic analysis of USRS (n = 42) with diverse genomic translocations including classic Ewing sarcomas with EWSR1::FLI1 fusions (n = 24) or EWSR1::ERG fusions (n = 4), sarcomas with an EWSR1 rearrangement (n = 2), CIC::DUX4 fusion (n = 8), as well as tumors classified as USRS with no genetic data available (n = 4). Proteins extracted from formalin-fixed, paraffin-embedded pretherapeutic biopsies were analyzed qualitatively and quantitatively using shotgun mass spectrometry (MS).

PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends.

DNA double-strand breaks (DSBs) are repaired at DSB sites. How DSB sites assemble and how broken DNA is prevented from separating is not understood. Here we uncover that the synapsis of broken DNA is mediated by the DSB sensor protein poly(ADP-ribose) (PAR) polymerase 1 (PARP1).

Integrated chemical and genetic screens unveil FSP1 mechanisms of ferroptosis regulation.

Ferroptosis, marked by iron-dependent lipid peroxidation, may present an Achilles heel for the treatment of cancers. Ferroptosis suppressor protein-1 (FSP1), as the second ferroptosis mainstay, efficiently prevents lipid peroxidation via NAD(P)H-dependent reduction of quinones. Because its molecular mechanisms have remained obscure, we studied numerous FSP1 mutations present in cancer or identified by untargeted random mutagenesis.

Triage of Critically Ill Patients: Characteristics and Outcomes of Patients Refused as Too Well for Intensive Care.

Background: The appropriate selection of patients for the intensive care unit (ICU) is a concern in acute care settings. However, the description of patients deemed too well for the ICU has been rarely reported.

Methods: We conducted a single-centre retrospective observational study of all patients either deemed "too well" for or admitted to the ICU during one year.

Investigating the Structure of the French WISC-V (WISC-V) for Five Age Groups Using Psychometric Network Modeling.

Since the seminal work of Spearman, exploratory and confirmatory factor analysis represents the standard method of examining the dimensionality of psychological instruments. Recently, within the network psychometrics approach, a new procedure was proposed to estimate the dimensionality of psychological instruments: exploratory graph analysis (EGA). This study investigated the structure of the French Wechsler Intelligence Scale for Children-Fifth Edition (WISC-V) with five standardization sample age groups (6-7, 8-9, 10-11, 12-13, and 14-16 years) using EGA.

Unloading, ablation, bridging and transplant: different indications and treatments using the Impella 5.5 as longer-term circulatory support in one patient-an interdisciplinary case report.

Background: In patients with cardiogenic shock the clinical treatment often involves temporary mechanical circulatory support for initial haemodynamic stabilization to enable further assessment of therapeutic strategies. The surgically implanted Impella 5.5 can be used for several indications like ventricular unloading, haemodynamic support during high-risk interventions, and as a bridge-to-transplant strategy.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe.

Distinct metabolite classes in root exudates are indicative for field- or hydroponically-grown cover crops.

Introduction: Plants release a large variety of metabolites via their roots to shape physico-chemical soil properties and biological processes in the rhizosphere. While hydroponic growth conditions facilitate accessibility of the root system and recovery of root exudates, the natural soil environment can alter root metabolism and exudate secretion, raising the question to what extent the quantity and composition of root exudates released in hydroponic growth systems reflect those recovered from soil-grown roots.

Methods: Using a root washing method, we sampled root exudates from four field-grown cover crop species with wide taxonomic distance, namely white mustard, lacy phacelia, bristle oat, and Egyptian clover.

Unravelling the Phytotoxic Effects of Glyphosate on Sensitive and Resistant Populations by GC-MS and LC-MS Metabolic Profiling.

Glyphosate, the most successful herbicide in history, specifically inhibits the activity of the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

Background & Aims: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs.

Preload and friction in an implant-abutment-screw complex including a carbon-coated titanium alloy abutment screw: an in vitro study.

Purpose: An experimental approach was designed to measure the preload force, the coefficient of friction and the component of the tightening torque that is needed to surmount the thread-friction in an implant-abutment-screw complex that includes a carbon-coated screw. With the determined preload values the coefficient of friction was calculated.

Methods: 25 unused complexes, containing an implant, an abutment and a carbon-coated titanium alloy abutment screw, were tested.

Transparent Exploration of Machine Learning for Biomarker Discovery from Proteomics and Omics Data.

Biomarkers are of central importance for assessing the health state and to guide medical interventions and their efficacy; still, they are lacking for most diseases. Mass spectrometry (MS)-based proteomics is a powerful technology for biomarker discovery but requires sophisticated bioinformatics to identify robust patterns. Machine learning (ML) has become a promising tool for this purpose.

Importin α/β and the tug of war to keep TDP-43 in solution: quo vadis?

The transactivation response-DNA binding protein of 43 kDa (TDP-43) is an aggregation-prone nucleic acid-binding protein linked to the etiology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). These conditions feature the accumulation of insoluble TDP-43 aggregates in the neuronal cytoplasm that lead to cell death. The dynamics between cytoplasmic and nuclear TDP-43 are altered in the disease state where TDP-43 mislocalizes to the cytoplasm, disrupting Nuclear Pore Complexes (NPCs), and ultimately forming large fibrils stabilized by the C-terminal prion-like domain.

Extended reality visualization of medical museum specimens: Online presentation of conjoined twins curated by Dr. Jacob Henle between 1844-1852.

Background: The purpose of this study is to characterize a full-term conjoined twins' cadaver curated by Dr. Jacob Henle sometime between 1844 and 1852 and demonstrate digital distribution of an old and rare medical museum specimen using an extended reality (XR) model workflow.

Methods: The cadaver (Preparation 296) is in the Department of Anatomy and Cell Biology at the University of Heidelberg.

Terminase Subunits from the Pseudomonas-Phage E217.

Pseudomonas phages are increasingly important biomedicines for phage therapy, but little is known about how these viruses package DNA. This paper explores the terminase subunits from the Myoviridae E217, a Pseudomonas-phage used in an experimental cocktail to eradicate P. aeruginosa in vitro and in animal models.

Determination of reference intervals for nonesterified fatty acids in the blood serum of healthy dogs.

Background: Nonesterified fatty acids (NEFAs) are an important energy substrate in mammals. Measurement of the NEFA concentration in blood serum is common practice and enables reliable detection of a negative energy balance in several species. This parameter can be used to detect subclinical metabolic diseases or to optimise feeding to prevent severe negative energy balance.

Homosalate boosts the release of tumour-derived extracellular vesicles with protection against anchorage-loss property.

Eukaryotic cells, including cancer cells, secrete highly heterogeneous populations of extracellular vesicles (EVs). EVs could have different subcellular origin, composition and functional properties, but tools to distinguish between EV subtypes are scarce. Here, we tagged CD63- or CD9-positive EVs secreted by triple negative breast cancer cells with Nanoluciferase enzyme, to set-up a miniaturized method to quantify secretion of these two EV subtypes directly in the supernatant of cells.