microbiota model recapitulates and predicts individualised sensitivity to dietary emulsifier.

Background: Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

Objectives: This study aimed to establish an approach for predicting an individual's sensitivity to dietary emulsifiers via their baseline microbiota.

APOBEC-1 cofactors regulate APOBEC3-induced mutations in hepatitis B virus.

Unlabelled: APOBEC3 proteins (A3s) play an important role in host innate immunity against viruses and DNA mutations in cancer. A3s-induced mutations in both viral and human DNA genomes vary significantly from non-lethal mutations in viruses to localized hypermutations, such as kataegis in cancer. How A3s are regulated remains largely unknown.

The Use of Dansyl Chloride to Probe Protein Structure and Dynamics.

Dansyl labeling is a widely used approach for enhancing the detection of small molecules by UV spectroscopy and mass spectrometry. It has been successfully applied to identify and quantify a variety of biological and environmental specimens. Despite clear advantages, the dansylation reaction has found very few applications in the study of proteins.

Breeding Partners Have Dissimilar Foraging Strategies in a Long-Lived Arctic Seabird.

For long-lived species with biparental care, coordination and compatibility in the foraging behavior of breeding mates may be crucial to successfully raise offspring. While high foraging success is clearly important to reproductive success, it might be equally important that the mate has a complementary foraging strategy. We test whether breeding partners have similar or dissimilar foraging strategies in a species where both partners share breeding responsibilities and exhibit high mate fidelity (thick-billed murre; ).

Rat as a Predictive Model for Human Clearance and Bioavailability of Monoclonal Antibodies.

Background: The prediction of human clearance (CL) and subcutaneous (SC) bioavailability is a critical aspect of monoclonal antibody (mAb) selection for clinical development. While monkeys are a well-accepted model for predicting human CL, other preclinical species have been less-thoroughly explored. Unlike CL, predicting the bioavailability of SC administered mAbs in humans remains challenging as contributing factors are not well understood, and preclinical models have not been systematically evaluated.

Perceptions of sexual assault perpetrators, victims, and event depend on system justification beliefs and perpetrator atonement.

When accused of wrongdoing, a sexual assault perpetrator may express atonement, i.e., he may acknowledge harm done, take responsibility, and make amends.

Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing.

Distinct excitatory synaptic inputs to the locus coeruleus (LC) modulate behavioral flexibility. Here we identify a novel monosynaptic glutamatergic input to the LC from the ventral tegmental area (VTA). We show robust VTA axonal projections provide direct glutamatergic transmission to LC.

Draft genome sequences of six high pH adapted strains isolated from Mariana forearc serpentinite mud volcanoes.

Six marine bacterial isolates were obtained from fluid and sediments collected at alkaline serpentinite mud volcanoes of the Mariana forearc to examine life at high pH in a marine environment. Here, we present the draft genome sequences of these six isolates, classified as strains of the species .

Class B Scavenger Receptor CD36 as a Potential Therapeutic Target in Inflammation Induced by Danger-Associated Molecular Patterns.

The class B scavenger receptor CD36 is known to bind and mediate the transport of lipid-related ligands and it functions as a pattern recognition receptor (PRR) for a variety of pathogens, including bacteria and viruses. In this study, we assessed CD36's role as a PRR mediating pro-inflammatory effects of several known Danger-Associated Molecular Patterns (DAMPs) used either as a single preparation or as a combination of DAMPs in the form of total cell/skeletal muscle tissue lysates. Our data demonstrated that multiple DAMPs, including HMGB1, HSPs, histone H3, SAA, and oxPAPC, as well as cell/tissue lysate preparations, induced substantially higher (~7-10-fold) IL-8 cytokine responses in HEK293 cells overexpressing CD36 compared to control WT cells.

Molecular and Clinical Characterization of a Founder Mutation Causing G6PC3 Deficiency.

G6PC3 deficiency is a monogenic immunometabolic disorder that causes severe congenital neutropenia type 4. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Here, we investigated the origin and functional consequence of the G6PC3 c.

Discovery and Optimization of First-in-Class Molecular Glue Degraders of the WIZ Transcription Factor for Fetal Hemoglobin Induction to Treat Sickle Cell Disease.

Sickle cell disease (SCD) is a prevalent, life-threatening condition with few treatment options, attributed to a heritable mutation in β-hemoglobin. Therapeutic induction of fetal hemoglobin (HbF) with small molecules has been pursued as a treatment to ameliorate many disease complications but with limited success. Herein, we report the discovery of , a novel, potent, and selective molecular glue degrader of the transcription factor WIZ that robustly induces HbF expression as a potential treatment for SCD.

A Mixed-Pure Planar Heterojunction Structure of Active Layers for Efficient Sequential Blade-Coating Organic Solar Cells.

Precise modulating the vertical structure of active layers to boost charge transfer is an effective way to achieve high power conversion efficiencies (PCEs) in organic solar cells (OSCs). Herein, efficient OSCs with a well-controlled vertical structure are realized by a rapid film-forming method combining low boiling point solvent and the sequential blade-coating (SBC) technology. The results of grazing incident wide-angle X-ray scattering measurement show that the vertical component distribution is varied by changing the processing solvent.

The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.

A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity.

Diet can protect from autoimmune disease; however, whether diet acts via the host and/or microbiome remains unclear. Here, we use a ketogenic diet (KD) as a model to dissect these complex interactions. A KD rescued the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in a microbiota-dependent fashion.