Streptococcus abundance and oral site tropism in humans and non-human primates reflects host and lifestyle differences.

The genus Streptococcus is highly diverse and a core member of the primate oral microbiome. Streptococcus species are grouped into at least eight phylogenetically-supported clades, five of which are found almost exclusively in the oral cavity. We explored the dominant Streptococcus phylogenetic clades in samples from multiple oral sites and from ancient and modern-day humans and non-human primates and found that clade dominance is conserved across human oral sites, with most Streptococcus reads assigned to species falling in the Sanguinis or Mitis clades.

MethylBERT enables read-level DNA methylation pattern identification and tumour deconvolution using a Transformer-based model.

DNA methylation (DNAm) is a key epigenetic mark that shows profound alterations in cancer. Read-level methylomes enable more in-depth analyses, due to their broad genomic coverage and preservation of rare cell-type signals, compared to summarized data such as 450K/EPIC microarrays. Here, we propose MethylBERT, a Transformer-based model for read-level methylation pattern classification.

Preference for and resistance to a toxic sulfur volatile opens up a unique niche in Drosophila busckii.

The ability to tolerate otherwise toxic compounds can open up unique niches in nature. Among drosophilid flies, few examples of such adaptations are known and those which are known are typically from highly host-specific species. Here we show that the human commensal species Drosophila busckii uses dimethyldisulfide (DMDS) as a key mediator in its host selection.

Programmed neurite degeneration in human central nervous system neurons driven by changes in NAD metabolism.

Neurite degeneration (ND) precedes cell death in many neurodegenerative diseases. However, it remains unclear how this compartmentalized cell death process is orchestrated in the central nervous system (CNS). The establishment of a CNS axotomy model (using modified 3D LUHMES cultures) allowed us to study metabolic control of ND in human midbrain-derived neurons without the use of toxicants or other direct disturbance of cellular metabolism.

Remote sensing-derived time series of transient glacier snowline altitudes for High Mountain Asia, 1985-2021.

This study presents a new dataset of remote sensing-derived Transient Snowline Altitude (TSLA) measurements for glaciers in High Mountain Asia. We use the Google Earth Engine to obtain TSLA data for approx. 2.

RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses.

The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization.

Linking altered neuronal and synaptic properties to nicotinic receptor Alpha5 subunit gene dysfunction: a translational investigation in rat mPFC and human cortical layer 6.

Genetic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit of mice results in behavioral deficits linked to the prefrontal cortex (PFC). rs16969968 is the primary Single Nucleotide Polymorphism (SNP) in CHRNA5 strongly associated with nicotine dependence and schizophrenia in humans. We performed single cell-electrophysiology combined with morphological reconstructions on layer 6 (L6) excitatory neurons in the medial PFC (mPFC) of wild type (WT) rats, rats carrying the human coding polymorphism rs16969968 in Chrna5 and α5 knockout (KO) rats.

Frequency-specific changes in prefrontal activity associated with maladaptive belief updating in volatile environments in euthymic bipolar disorder.

Bipolar disorder (BD) involves altered reward processing and decision-making, with inconsistencies across studies. Here, we integrated hierarchical Bayesian modelling with magnetoencephalography (MEG) to characterise maladaptive belief updating in this condition. First, we determined if previously reported increased learning rates in BD stem from a heightened expectation of environmental changes.

Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

Effect of Application Mode and Aging on Microtensile Bond Strength of Universal Adhesives to Enamel of Primary Teeth.

Background: Limited reports are available regarding bonding of universal adhesives to primary teeth' enamel.

Aim: To evaluate the effect of application mode and aging on microtensile bond strength (μTBS) of universal adhesives to primary enamel.

Design: Ninety-six human primary molars were randomly assigned to three groups: SU: Scotchbond Universal (3M); CU: Clearfil Universal Bond Quick (Kuraray Noritake); iBU: iBond Universal (Heraeus Kulzer), then subdivided according to phosphoric acid etching time into three subgroups (SG): SG1: 0s; SG2: 15s; SG3: 30s.

A Global Relationship Between Genome Size and Encoded Carbon Metabolic Strategies of Soil Bacteria.

Microbial traits are critical for carbon sequestration and degradation in terrestrial ecosystems. Yet, our understanding of the relationship between carbon metabolic strategies and genomic traits like genome size remains limited. To address this knowledge gap, we conducted a global-scale meta-analysis of 2650 genomes, integrated whole-genome sequencing data, and performed a continental-scale metagenomic field study.

Silver N-heterocyclic biscarbene complexes: Potent inhibitors of thioredoxin reductase with anticancer activity in vitro and in vivo.

Silver N-heterocyclic carbene (NHC) complexes are known to form biscarbene species from monocarbene analogs in protic polar solvents. However, the effect of the respective species of silver NHC complexes on their biological activity against bacteria or cancer cells has not been systematically explored, either in vitro or in vivo. The direct and simple conversion of monocarbene silver N-heterocyclic carbene (NHC) halide complexes (NHC)AgX, (X= Cl, Br) 1a/b - 5a/b to their biscarbene analogues (NHC)2AgX 1c/d - 5c/d is reported.

Additive Effects of Multiple Global Change Factors on Plant Invasions Are Common.

Quantifying how co-acting global change factors (GCFs) influence plant invasion is crucial for predicting future invasion dynamics. We did a meta-analysis to assess pairwise effects of five GCFs (elevated CO, drought, eutrophication, increased rainfall and warming) on native and alien plants. We found that alien plants, compared to native plants, suffered less or benefited more for four of the eight pairwise GCF combinations, and that all GCFs acted additively.

Topographic Axes of Wiring Space Converge to Genetic Topography in Shaping Human Cortical Layout.

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles, revealing the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across cortex.

HO Mediated Photoreduction of Nitrates to Ammonia by Iron Filings under Ambient Conditions.

Herein, a simple ambient conditioned sunlight promoted photochemical reduction reaction is demonstrated for the of nitrate (NO) conversion to ammonia (NH) with the maximum conversion yield of ∼16 mM using iron filings (f-Fe) in the presence of HO. Based on a radical scavenging study of reactive species and the characterization of catalyst f-Fe before and after the reaction, a plausible mechanism has been proposed for the ambient conditioned synthesis of NH. The results associated with the NH synthesis have been verified using the N isotopic labeled nitrate (NO), which supports the simpler viability of the reported procedure.

The effect of a general practitioner's perception of a patient request for antibiotics on antibiotic prescribing for respiratory tract infections: secondary analysis of a point prevalence audit survey in 18 European countries.

Background: Illness severity, comorbidity, fever, age and symptom duration influence antibiotic prescribing for respiratory tract infections (RTI). Non-medical determinants, such as patient expectations, also impact prescribing.

Aim: To quantify the effect of general practitioners' (GPs') perception of a patient request for antibiotics on antibiotic prescribing for RTI and investigate effect modification by medical determinants and country.

Cerebral blood volume index in the era of thrombectomy-treated large and medium vessel ischemic strokes.

The cerebral blood volume index (CBV index) is a perfusion-based marker of collateral status. Several real-world data analyses from observational stroke cohorts have established relationships between this parameter and a range of favorable and unfavorable stroke outcomes. In this review, an overview is provided of the CBV index, within the context of thrombectomy-treated large vessel and medium vessel occlusion ischemic strokes.

Specific selection of stimulation-responsive γδ T-cells utilizing a short-term activation assay.

T cells expressing the γδ T-cell receptor (TCR) represent a numerically small proportion of total T cells. Unlike αβ T cells they are activated by non-peptide antigens independently of MHC-presentation. γδ T cells have been recognized as a favorable prognostic marker across different tumor entities.

Retrovirus-based manufacturing of chimeric antigen receptor-modified T cells for cancer therapy research.

Treatment with autologous chimeric antigen receptor (CAR)-modified T cells can achieve outstanding clinical response rates in heavily pretreated patients with B and plasma cell malignancies. However, relapses occur, and they limit the efficacy of this promising treatment approach. The complex GMP-compliant production and high treatment costs cause that CAR T cells cannot yet be used in a broad population.

Deciphering neutrophil heterogeneity in human blood and tumors: Methods for isolating neutrophils and assessing their effect on T-cell proliferation.

Neutrophils were historically considered a homogenous population of cells with functions limited to innate immunity against external threats. However, with the rise of immunotherapy, recent works have shown that neutrophils are also important actors in immuno-oncology. In this context, neutrophils appear as a more heterogenous population of cells.