A Noncatalytic Cysteine Residue Modulates Cobalamin Reactivity in the Human B Processing Enzyme CblC.

Human CblC catalyzes the indispensable processing of dietary vitamin B by the removal of its β-axial ligand and an either one- or two-electron reduction of its cobalt center to yield cob(II)alamin and cob(I)alamin, respectively. Human CblC possesses five cysteine residues of an unknown function. We hypothesized that Cys149, conserved in mammals, tunes the CblC reactivity.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Reticulocyte hemoglobin content: a new frontier in iron deficiency diagnostics for major surgical patients.

Background: Iron deficiency (ID) is the most common nutritional deficiency among patients undergoing major surgery. Treatment of ID is straightforward, however implementing a comprehensive anemia management strategy within clinical routines is complex. Recently, reticulocyte hemoglobin content (Ret-He) has been evaluated as an early marker for ID diagnosis.

Safety outcome trials in four mainline medical journals 30 years apart: a narrative review and the need for the transparency of informed consents.

Background: It was our impression that safety outcome trials were getting more frequent, raising ethical issues mainly related to patient autonomy. We and others had also proposed this autonomy would be best served if wording of the informed consents would be in the public domain.

Methods: Initially two observers and an arbiter tabulated the main aims of randomized controlled trials (RCTs) published in 1990-1991 vs.

Extending from Adaptation to Resilience Pathways: Perspectives from the Conceptual Framework to Key Insights.

The extent and timescale of climate change impacts remain uncertain, including global temperature increase, sea level rise, and more frequent and intense extreme events. Uncertainties are compounded by cascading effects. Nevertheless, decision-makers must take action.

Arginine metabolism in myeloid cells in health and disease.

Metabolic flexibility is key for the function of myeloid cells. Arginine metabolism is integral to the regulation of myeloid cell responses. Nitric oxide (NO) production from arginine is vital for the antimicrobial and pro-inflammatory responses.

Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia.

Background: Arginine infusion stimulates copeptin secretion, a surrogate marker of arginine vasopressin (AVP), thereby serving as a diagnostic test in the differential diagnosis of suspected AVP deficiency (AVP-D). Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea.

Adding checkpoint inhibitors to first-line chemotherapy for NUT carcinoma patients.

Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers.

Extracellular vesicles from pancreatic cancer and its tumour microenvironment promote increased Schwann cell migration.

Background: Pancreatic ductal adenocarcinoma (PDAC) exhibits a high frequency of neural invasion (NI). Schwann cells (SCs) have been shown to be reprogrammed to facilitate cancer cell migration and invasion into nerves. Since extracellular vesicles (EVs) affect the tumour microenvironment and promote metastasis, the present study analysed the involvement of EVs from pancreatic cancer cells and their microenvironment in altering SC phenotype as part of the early events in the process of NI.

Exogenous dsRNA triggers sequence-specific RNAi and fungal stress responses to control Magnaporthe oryzae in Brachypodium distachyon.

In vertebrates and plants, dsRNA plays crucial roles as PAMP and as a mediator of RNAi. How higher fungi respond to dsRNA is not known. We demonstrate that Magnaporthe oryzae (Mo), a globally significant crop pathogen, internalizes dsRNA across a broad size range of 21 to about 3000 bp.

A safe haven for cancer cells: tumor plus stroma control by DYRK1B.

The development of resistance remains one of the biggest challenges in clinical cancer patient care and it comprises all treatment modalities from chemotherapy to targeted or immune therapy. In solid malignancies, drug resistance is the result of adaptive processes occurring in cancer cells or the surrounding tumor microenvironment (TME). Future therapy attempts will therefore benefit from targeting both, tumor and stroma compartments and drug targets which affect both sides will be highly appreciated.

Practice makes better? The influence of increased practice on task conflict in the Stroop task.

The Stroop task is widely used to study attentional control and cognitive flexibility. However, questions about its sensitivity to training and the impact of task conflict on attentional control remain open. We investigated the effects of practice and task conflict on attentional control in the Stroop task, with participants completing four sessions of a Stroop task over 3 weeks in low and high task-conflict conditions.

Identification of the conditions and minimum requirements necessary for the release of autologous fresh CAR T-cell products under hospital exemption: a position paper from the WP-bioproduction of the UNITC consortium.

The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption.

Comparison of the diagnostic performance of non-contrast MR angiography and planar V/Q scintigraphy for pulmonary embolism: a systematic review and meta-analysis.

Objectives: To conduct a meta-analysis of the diagnostic performance of non-contrast magnetic resonance pulmonary angiography (NC-MRPA) and ventilation-perfusion (V/Q) scintigraphy for the detection of acute pulmonary embolism (PE).

Materials And Methods: Systematic searches of electronic databases were conducted from 2000 to 2024. Primary outcomes were per-patient sensitivity and specificity of NC-MRPA and V/Q scintigraphy.

Temporal transcriptional profiling of host cells infected by a veterinary alphaherpesvirus using nanopore sequencing.

In our research, we performed temporal transcriptomic profiling of host cells infected with Equid alphaherpesvirus 1 (EHV-1) by utilizing direct cDNA sequencing based on nanopore MinION technology. The sequencing reads were harnessed for transcript quantification at various time points. Viral infection-induced differential gene expression was identified through the edgeR package.

Temperature dependence of liverwort diversification reveals a cool origin and hot hotspots.

The evolutionary history underlying gradients in species richness is still subject to discussions and understanding the past niche evolution might be crucial in estimating the potential of taxa to adapt to changing environmental conditions. In this study we intend to contribute to elucidation of the evolutionary history of liverwort species richness distributions along elevational gradients at a global scale. For this purpose, we linked a comprehensive data set of genus occurrences on mountains worldwide with a time-calibrated phylogeny of liverworts and estimated mean diversification rates (DivElev) and mean ages (AgeElev) of the respective genera per elevational band.

Enhanced optical properties of chitosan polymer doped with orange peel dye investigated via UV-Vis and FTIR analysis.

The current research aims to determine the impact of orange peel dye (OPD), an eco-friendly addition, on the optical properties of biodegradable polymers. This study investigates the enhancement of optical properties in solid electrolytes based on chitosan (CS) and glycerol, with varying OPD concentrations. UV-Vis-NIR spectroscopy revealed significantly enhanced UV-visible light absorption in the 200-500 nm region and effective UV light blocking.

Characterizing the omics landscape based on 10,000+ datasets.

The characteristics of data produced by omics technologies are pivotal, as they critically influence the feasibility and effectiveness of computational methods applied in downstream analyses, such as data harmonization and differential abundance analyses. Furthermore, variability in these data characteristics across datasets plays a crucial role, leading to diverging outcomes in benchmarking studies, which are essential for guiding the selection of appropriate analysis methods in all omics fields. Additionally, downstream analysis tools are often developed and applied within specific omics communities due to the presumed differences in data characteristics attributed to each omics technology.

A process inspired by fractals for embedding digital codes into additively manufactured components for supply chain security.

This study describes procedures for embedding digital information into additively manufactured components as well as procedures for readout and tensile testing. Embedded digital codes were printed inside ASTM E8/E8M dumbbells using Direct Metal Laser Melting (DMLS) with an EOS M290 printer. The codes were configured as either ellipsoids or prolate spheroids in patterns given by the Cantor dust fractal.

Biocompatibility of variable thicknesses of a novel directly printed aligner in orthodontics.

Direct printed aligners (DPAs) offer benefits like the ability to vary layer thickness within a single DPA and to 3D print custom-made removable orthodontic appliances. The biocompatibility of appliances made from Tera Harz TA-28 (Graphy Inc., Seoul, South Korea) depends on strict adherence to a standardized production and post-production protocol, including UV curing.

[Formula: see text]-roaming dynamics in the formation of [Formula: see text] following two-photon double ionization of ethanol and aminoethanol.

Roaming reactions involving a neutral fragment of a molecule that transiently wanders around another fragment before forming a new bond are intriguing and peculiar pathways for molecular rearrangement. Such reactions can occur for example upon double ionization of small organic molecules, and have recently sparked much scientific interest. We have studied the dynamics of the [Formula: see text]-roaming reaction leading to the formation of [Formula: see text] after two-photon double ionization of ethanol and 2-aminoethanol, using an XUV-UV pump-probe scheme.

DeepExtremeCubes: Earth system spatio-temporal data for assessing compound heatwave and drought impacts.

With climate extremes' rising frequency and intensity, robust analytical tools are crucial to predict their impacts on terrestrial ecosystems. Machine learning techniques show promise but require well-structured, high-quality, and curated analysis-ready datasets. Earth observation datasets comprehensively monitor ecosystem dynamics and responses to climatic extremes, yet the data complexity can challenge the effectiveness of machine learning models.

Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.

Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase.

Ferroptosis triggers mitochondrial fragmentation via Drp1 activation.

Constitutive mitochondrial dynamics ensure quality control and metabolic fitness of cells, and their dysregulation has been implicated in various human diseases. The large GTPase Dynamin-related protein 1 (Drp1) is intimately involved in mediating constitutive mitochondrial fission and has been implicated in mitochondrial cell death pathways. During ferroptosis, a recently identified type of regulated necrosis driven by excessive lipid peroxidation, mitochondrial fragmentation has been observed.

The α-globin super-enhancer acts in an orientation-dependent manner.

Individual enhancers are defined as short genomic regulatory elements, bound by transcription factors, and able to activate cell-specific gene expression at a distance, in an orientation-independent manner. Within mammalian genomes, enhancer-like elements may be found individually or within clusters referred to as locus control regions or super-enhancers (SEs). While these behave similarly to individual enhancers with respect to cell specificity, distribution and distance, their orientation-dependence has not been formally tested.