Nuclear and cytosolic fractions of SOX2 synergize as transcriptional and translational co-regulators of cell fate.

Stemness and pluripotency are mediated by transcriptional master regulators that promote self-renewal and repress cell differentiation, among which is the high-mobility group (HMG) box transcription factor SOX2. Dysregulated SOX2 expression, by contrast, leads to transcriptional aberrations relevant to oncogenic transformation, cancer progression, metastasis, therapy resistance, and relapse. Here, we report a post-transcriptional mechanism by which the cytosolic pool of SOX2 contributes to these events in an unsuspected manner.

Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and expansion.

Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionised blood cancer treatment. Parsing the genetic underpinnings of T cell quality and CAR-T efficacy is challenging. Transcriptomics inform CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasises effector and metabolism genes.

Epstein-Barr Virus Lytic Transcripts Correlate with the Degree of Myocardial Inflammation in Heart Failure Patients.

The Epstein-Barr virus (EBV) is frequently found in endomyocardial biopsies (EMBs) from patients with heart failure, but the detection of EBV-specific DNA has not been associated with progressive hemodynamic deterioration. In this paper, we investigate the use of targeted next-generation sequencing (NGS) to detect EBV transcripts and their correlation with myocardial inflammation in EBV-positive patients with heart failure with reduced ejection fraction (HFrEF). Forty-four HFrEF patients with positive EBV DNA detection and varying degrees of myocardial inflammation were selected.

Total Synthesis of (15R)- and (15S)-Prostaglandin A.

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) type A receptors (GABAR) are provided.

Stepped, evidence-based and integrated care service model vs. usual care for mental disorders: A randomized controlled trial (RECOVER).

Stepped, evidence-based and integrated care service models have the potential to be used as a reference for mental health services. RECOVER aimed to evaluate cost savings, effectiveness, and cost-effectiveness of such a model within a two arm, assessor- and data analysist-blinded RCT in Hamburg, Germany. Participants aged 16-79 years with mental disorders were randomly assigned either to RECOVER or treatment as usual (TAU).

Prevalence of Liver Steatosis in Tuberous Sclerosis Complex Patients: A Retrospective Cross-Sectional Study.

Tuberous sclerosis complex (TSC) is a genetic disease caused by pathogenetic variants in either the or genes. Consequently, the mechanistic target of the rapamycin complex 1 (mTORC1) pathway, a regulator of cell growth, metabolism, and survival, becomes inappropriately activated, leading to the development of benign tumors in multiple organs. The role of mTORC1 in lipid metabolism and liver steatosis in TSC patients has not been well-studied, and clinical data on liver involvement in this population are scarce.

SAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize mRNA.

Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here, we addressed how murine adult hippocampal NSC fate is regulated and described how scaffold attachment factor B (SAFB) blocks oligodendrocyte production to enable neuron generation.

Engineered human osteoarthritic cartilage organoids.

The availability of human cell-based models capturing molecular processes of cartilage degeneration can facilitate development of disease-modifying therapies for osteoarthritis [1], a currently unmet clinical need. Here, by imposing specific inflammatory challenges upon mesenchymal stromal cells at a defined stage of chondrogenesis, we engineered a human organotypic model which recapitulates main OA pathological traits such as chondrocyte hypertrophy, cartilage matrix mineralization, enhanced catabolism and mechanical stiffening. To exemplify the utility of the model, we exposed the engineered OA cartilage organoids to factors known to attenuate pathological features, including IL-1Ra, and carried out mass spectrometry-based proteomics.

Demonstration of a Transportable Fabry-Pérot Refractometer by a Ring-Type Comparison of Dead-Weight Pressure Balances at Four European National Metrology Institutes.

Fabry-Pérot-based refractometry has demonstrated the ability to assess gas pressure with high accuracy and has been prophesized to be able to realize the SI unit for pressure, the pascal, based on quantum calculations of the molar polarizabilities of gases. So far, the technology has mostly been limited to well-controlled laboratories. However, recently, an easy-to-use transportable refractometer has been constructed.

Phage Paride can kill dormant, antibiotic-tolerant cells of Pseudomonas aeruginosa by direct lytic replication.

Bacteriophages are ubiquitous viral predators that have primarily been studied using fast-growing laboratory cultures of their bacterial hosts. However, microbial life in nature is mostly in a slow- or non-growing, dormant state. Here, we show that diverse phages can infect deep-dormant bacteria and suspend their replication until the host resuscitates ("hibernation").

Microbiological profiling and knowledge of food preservation technology to support guidance on a neutropenic diet for immunocompromised patients.

The current society consists of an increasing number of people vulnerable to infections. For certain people with severe immunodeficiency, a neutropenic or low-microbial diet is being prescribed, which substitutes high-risk foods that are more likely to contain human (opportunistic) pathogens with lower-risk alternatives. These neutropenic dietary guidelines are typically set up from a clinical and nutritional perspective, rather than from a food processing and food preservation perspective.

Estimates of 10-year risk of cardiovascular death and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) increases the risk of cardiovascular disease (CVD) in both morbidity and mortality. We used the risk chart of Systemic Coronary Risk Evaluation (SCORE) from European Society of Cardiology (ESC) to determine the 10-year risk of cardiovascular death, and adherence to cardiovascular risk factor management in Danish patients investigated for obstructive sleep apnea.

Research Design And Methods: In a prospective cohort study, 303 patients with mild, moderate and severe OSA were investigated for cardiovascular risk factors before initiating CPAP therapy.

Ars2-containing bispecific, Fab- and IgG1-format BAR-bodies to target DLBCL cells.

Despite recent advances in the therapy of diffuse large B-cell lymphoma, not otherwise specified (DLBCL), around 30% of patients develop refractory disease or relapse after first-line treatment. Recently, Ars2 was reported as the auto-antigenic target of the B-cell receptor (BCR) in approximately 25% of activated B-cell DLBCL cases. Ars2 could be used to specifically target B cells expressing Ars2-reactive BCRs.

Organ Protection by Caloric Restriction Depends on Activation of the De Novo NAD+ Synthesis Pathway.

Significance Statement: AKI is a major clinical complication leading to high mortality, but intensive research over the past decades has not led to targeted preventive or therapeutic measures. In rodent models, caloric restriction (CR) and transient hypoxia significantly prevent AKI and a recent comparative transcriptome analysis of murine kidneys identified kynureninase (KYNU) as a shared downstream target. The present work shows that KYNU strongly contributes to CR-mediated protection as a key player in the de novo nicotinamide adenine dinucleotide biosynthesis pathway.

Prevalence of silent atrial fibrillation and cardiovascular disease in patients with obstructive sleep apnea.

Objective: Patients with silent and undiagnosed atrial fibrillation (AF) have increased risk of ischemic stroke. Patients with obstructive sleep apnea (OSA) have an increased risk of both AF and ischemic stroke. Our aim was to investigate the prevalence of silent AF and associated risk factors in patients investigated for OSA or with known OSA.

Stuck between medals and participation: an institutional theory perspective on why sport federations struggle to reach Sport-for-All goals.

Background: Sport-for-All emphasizes that every individual has the right to participate in sport. Despite all efforts to deliver Sport-for-All during the past decades, studies indicate that sport participation rates have been stagnating, whereas social inequalities in sport continue to exist. By applying an institutional theory lens, this study sheds light on how the dual mission of sport federations, i.

Study protocol of a randomized controlled trial evaluating home treatment with peer support for acute mental health crises (HoPe).

Background: Home treatment (HT) is a treatment modality for patients with severe mental illness (SMI) in acute mental crises. It is frequently considered equivalent to psychiatric inpatient treatment in terms of treatment outcome. Peer Support (PS) means that people with lived experience of a mental illness are trained to support others on their way towards recovery.

B-cell receptors of EBV-negative Burkitt lymphoma bind modified isoforms of autoantigens.

Burkitt lymphoma (BL) represents the most aggressive B-cell-lymphoma. Beside the hallmark of -translocation, surface B-cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra-nodal sites suggest antigenic triggers.