Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Unraveling the distinctive gut microbiome of khulans (Equus hemionus hemionus) in comparison to their drinking water and closely related equids.

The microbial composition of host-associated microbiomes is influenced by co-evolutionary interactions, host genetics, domestication, and the environment. This study investigates the contribution of environmental microbiota from freshwater bodies to the gastrointestinal microbiomes of wild khulans (Equus hemionus hemionus, n = 21) and compares them with those of captive khulans (n = 12) and other equids-Przewalski's horse (n = 82) and domestic horse (n = 26). Using PacBio technology and the LotuS pipeline for 16S rRNA gene sequencing, we analyze microbial diversity and conduct differential abundance, alpha, and beta diversity analyses.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Targeting MYCN upregulates L1CAM tumor antigen in MYCN-dysregulated neuroblastoma to increase CAR T cell efficacy.

Current treatment protocols have limited success against MYCN-amplified neuroblastoma. Adoptive T cell therapy presents an innovative strategy to improve cure rates. However, L1CAM-targeting CAR T cells achieved only limited response against refractory/relapsed neuroblastoma so far.

Phosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential.

The Renin-Angiotensin System (RAS) is a complex neuroendocrine system consisting of a single precursor protein, angiotensinogen (AGT), which is processed into various peptide hormones, including the angiotensins [Ang I, Ang II, Ang III, Ang IV, Ang-(1-9), Ang-(1-7), Ang-(1-5), etc] and Alamandine-related peptides [Ang A, Alamandine, Ala-(1-5)], through intricate enzymatic pathways. Functionally, the RAS is divided into two axes with opposing effects: the classical axis, primarily consisting of Ang II acting through the AT receptor (ATR), and in contrast the protective axis, which includes the receptors Mas, ATR and MrgD and their respective ligands. A key area of RAS research is to gain a better understanding how signaling cascades elicited by these receptors lead to either "classical" or "protective" effects, as imbalances between the two axes can contribute to disease.

Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.

Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.

Sleep and circadian rhythms in delayed sleep-wake phase disorder: Phenotypic differences between patients with and without comorbid depression.

Delayed sleep-wake phase disorder involves chronic difficulty going to bed and waking up at conventional times and often co-occurs with depression. This study compared sleep and circadian rhythms between patients with delayed sleep-wake phase disorder with depression (DSWPD-D) and without (DSWPD-ND) comorbid depression. Clinical records of 162 patients with delayed sleep-wake phase disorder (70 DSWPD-D, 92 DSWPD-ND) were analysed, including a subset of 76 patients with circadian phase determined by the dim light melatonin onset.

Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder - recommendations from ECTRIMS and the EBMT.

Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing-remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD).

Herpesviruses mimic zygotic genome activation to promote viral replication.

Zygotic genome activation (ZGA) is crucial for maternal to zygotic transition at the 2-8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In humans, ZGA is induced by DUX4, a pioneer factor that drives expression of downstream germline-specific genes and retroelements. Here we show that herpesviruses from all subfamilies, papillomaviruses and Merkel cell polyomavirus actively induce DUX4 expression to promote viral transcription and replication.

hnRNPA2B1 drives colorectal cancer progression via the circCDYL/EIF4A3/PHF8 axis.

The RNA-binding protein hnRNPA2B1 acts as an m6A reader and plays a role in tumor development. This study investigates the potential mechanism of hnRNPA2B1 in colorectal cancer (CRC) progression. The expression profiles of hnRNPA2B1, circCDYL, and PHF8 in CRC cell lines were analyzed.

Intestinal interstitial fluid isolation provides novel insight into the human host-microbiome interface.

Aims: The gastrointestinal (GI) tract is composed of distinct sub-regions, which exhibit segment-specific differences in microbial colonization and (patho)physiological characteristics. Gut microbes can be collectively considered as an active endocrine organ. Microbes produce metabolites, which can be taken up by the host and can actively communicate with the immune cells in the gut lamina propria with consequences for cardiovascular health.

Gonadal sex and temperature independently influence germ cell differentiation and meiotic progression in .

In species with genetic sex determination (GSD), the sex identity of the soma determines germ cell fate. For example, in mice, XY germ cells that enter an ovary differentiate as oogonia, whereas XX germ cells that enter a testis initiate differentiation as spermatogonia. However, numerous species lack a GSD system and instead display temperature-dependent sex determination (TSD).

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.

Hyperreflective retinal foci are associated with retinal degeneration after optic neuritis in neuromyelitis optica spectrum disorders and multiple sclerosis.

Background: Hyperreflective retinal foci (HRF) visualized by optical coherence tomography (OCT) potentially represent clusters of microglia. We compared HRF frequencies and their association with retinal neurodegeneration between people with clinically isolated syndrome (pwCIS), multiple sclerosis (pwMS), aquaporin 4-IgG positive neuromyelitis optica spectrum disorder (pwNMOSD), and healthy controls (HC)-as well as between eyes with (ONeyes) and without a history of optic neuritis (ONeyes).

Methods: Cross-sectional data of pwCIS, pwMS, and pwNMOSD with previous ON and HC were acquired at Charité-Universitätsmedizin Berlin.

Sex hormone-dependent host-microbiome interactions and cardiovascular risk (XCVD): design of a longitudinal multi-omics cohort study.

Introduction: Cardiovascular diseases (CVDs) present differently in women and men, influenced by host-microbiome interactions. The roles of sex hormones in CVD outcomes and gut microbiome in modifying these effects are poorly understood. The XCVD study examines gut microbiome mediation of sex hormone effects on CVD risk markers by observing transgender participants undergoing gender-affirming hormone therapy (GAHT), with findings expected to extrapolate to cisgender populations.

Everolimus with or without mycophenolate mofetil for GVHD prophylaxis after allogeneic HSCT in children with acute kidney injury - a single-center retrospective analysis.

Background: Hematopoietic stem cell transplantation (HSCT) serves as a therapeutic intervention for various pediatric diseases. Acute and chronic graft-versus-host disease (GVHD) are decisive determinants for allogeneic HSCT success. The immunosuppressive agent, ciclosporin A, is most often used to prevent GVHD in pediatric patients, but is known to be nephrotoxic.

Toward a functional future for the cognitive neuroscience of human aging.

The cognitive neuroscience of human aging seeks to identify neural mechanisms behind the commonalities and individual differences in age-related behavioral changes. This goal has been pursued predominantly through structural or "task-free" resting-state functional neuroimaging. The former has elucidated the material foundations of behavioral decline, and the latter has provided key insight into how functional brain networks change with age.

Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing.

Single-cell genomics technologies have accelerated our understanding of cell-state heterogeneity in diverse contexts. Although single-cell RNA sequencing identifies rare populations that express specific marker transcript combinations, traditional flow sorting requires cell surface markers with high-fidelity antibodies, limiting our ability to interrogate these populations. In addition, many single-cell studies require the isolation of nuclei from tissue, eliminating the ability to enrich learned rare cell states based on extranuclear protein markers.

Aryl Hydrocarbon Receptor Activation Promotes Effector CD4+ T Cell Homeostasis and Restrains Salt-sensitive Hypertension.

Excess dietary salt and salt-sensitivity contribute to cardiovascular disease. Distinct T cell phenotypic responses to high salt and hypertension as well as influences from environmental cues are not well understood. The aryl hydrocarbon receptor (AhR) is activated by dietary ligands, promoting T cell and systemic homeostasis.

Prognostic value of CD163 macrophages in solid tumor malignancies: A scoping review.

Tumor-associated macrophages (TAMs) play crucial roles in development and progression of malignant diseases. Notably, CD163 TAMs likely perform specific pro-tumorigenic functions, suggesting that this subset may serve as both prognostic biomarkers and targets for future anti-cancer therapy. We conducted a scoping review to map the current knowledge on the prognostic role of CD163 TAMs in the five most lethal cancers worldwide: Lung, colorectal, gastric, liver, and breast cancer.

Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.

Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.