Apigenin inhibits NLRP3 inflammasome activation in monocytes and macrophages independently of CD38.

Introduction: CD38, a regulator of intracellular calcium signalling, is highly expressed in immune cells. Mice lacking CD38 are very susceptible to acute bacterial infections, implicating CD38 in innate immune responses. The effects of CD38 inhibition on NLRP3 inflammasome activation in human primary monocytes and monocyte-derived macrophages have not been investigated.

Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.

While clozapine is the most effective antipsychotic drug, its use is limited due to hematological adverse effects involving the reduction of granulocyte counts with potential life-threatening agranulocytosis. It is not yet possible to predict or prevent the risk of agranulocytosis, and the mechanisms are unknown but likely related to clozapine metabolism. Genome-wide association studies (GWASs) of clozapine metabolism and clozapine-induced agranulocytosis have identified few genetic loci.

Effects of oxytocin administration on non-social executive functions in humans: a preregistered systematic review and meta-analysis.

Background: Oxytocin has received considerable research attention for its role in affiliative behaviors, particularly regarding its pro-social effects. More recent evidence has pointed to a broader role of oxytocin signaling, which includes non-social cognitive processes. However, meta-analytic data on oxytocin's effects on non-social cognition is currently limited.

Reduced lipid and glucose oxidation and reduced lipid synthesis in AMPKα2 myotubes.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from and mice. Myotubes from mice had lower basal oleic acid and glucose oxidation compared to myotubes from mice.

COA5 has an essential role in the early stage of mitochondrial complex IV assembly.

Pathogenic variants in cytochrome oxidase assembly factor 5 (COA5), a proposed complex IV (CIV) assembly factor, have been shown to cause clinical mitochondrial disease with two siblings affected by neonatal hypertrophic cardiomyopathy manifesting a rare, homozygous missense variant (NM_001008215.3: c.157G>C, p.

Cortisol and C-reactive protein (CRP) regulation in severe mental disorders.

Background: People with schizophrenia (SZ) and bipolar disorder (BD) show abnormalities in the biological stress system and low-grade inflammation. However, whether the hypothalamic-pituitary-adrenal (HPA) axis-immune regulation is disrupted in SZ and BD, is yet to be determined.

Methods: Cortisol and C-reactive protein (CRP) were measured in blood samples collected at or before 10 am in participants with SZ (N = 257), BD (N = 153), and healthy controls (N = 40).

Deriving Mendelian Randomization-based Causal Networks of Brain Imaging Phenotypes and Bipolar Disorder.

Neuroanatomical variation in individuals with bipolar disorder (BD) has been previously described in observational studies. However, the causal dynamics of these relationships remain unexplored. We performed Mendelian Randomization of 297 structural and functional neuroimaging phenotypes from the UK BioBank and BD using genome-wide association study summary statistics.

Reading the repertoire: Progress in adaptive immune receptor analysis using machine learning.

The adaptive immune system holds invaluable information on past and present immune responses in the form of B and T cell receptor sequences, but we are limited in our ability to decode this information. Machine learning approaches are under active investigation for a range of tasks relevant to understanding and manipulating the adaptive immune receptor repertoire, including matching receptors to the antigens they bind, generating antibodies or T cell receptors for use as therapeutics, and diagnosing disease based on patient repertoires. Progress on these tasks has the potential to substantially improve the development of vaccines, therapeutics, and diagnostics, as well as advance our understanding of fundamental immunological principles.

Sacubitril/valsartan preserves regional cardiac function following myocardial infarction in rats.

Aims: Sacubitril/valsartan (Sac/Val) is used for treatment of heart failure. The effect of Sac/Val on regional dysfunction following myocardial infarction (MI) remains uncertain. This study aimed at understanding the effects of Sac/Val on regional function after MI.

Sialylation inhibition improves macrophage mediated tumor cell phagocytosis of breast cancer cells triggered by therapeutic antibodies of different isotypes.

Tumor cell phagocytosis by macrophages is considered a relevant mechanism of action for many therapeutic IgG antibodies. However, tumor cells employ several mechanisms to evade immune recognition, including hypersialylation. Here, we describe how reduction of sialic acid exposure on tumor cells promotes antibody-dependent tumor cell phagocytosis (ADCP) by macrophages.

Copy-number dosage regulates telomere maintenance and disease-associated pathways in neuroblastoma.

Telomere maintenance in neuroblastoma is linked to poor outcome and caused by either telomerase reverse transcriptase (TERT) activation or through alternative lengthening of telomeres (ALT). In contrast to TERT activation, commonly caused by genomic rearrangements or MYCN amplification, ALT is less well understood. Alterations at the ATRX locus are key drivers of ALT but only present in ∼50% of ALT tumors.

Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development.

The observation that the risk of developing Alzheimer's disease is reduced in individuals with high premorbid cognitive functioning, higher educational attainment, and occupational status has led to the 'cognitive reserve' hypothesis. This hypothesis suggests that individuals with greater cognitive reserve can tolerate a more significant burden of neuropathological changes before the onset of cognitive decline. The underpinnings of cognitive reserve remain poorly understood, although a shared genetic basis between measures of cognitive reserve and Alzheimer's disease has been suggested.

Single-cell integration reveals metaplasia in inflammatory gut diseases.

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease. Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood.

Integrative pan-cancer analysis reveals a common architecture of dysregulated transcriptional networks characterized by loss of enhancer methylation.

Aberrant DNA methylation contributes to gene expression deregulation in cancer. However, these alterations' precise regulatory role and clinical implications are still not fully understood. In this study, we performed expression-methylation Quantitative Trait Loci (emQTL) analysis to identify deregulated cancer-driving transcriptional networks linked to CpG demethylation pan-cancer.

Foetal Microchimerism Correlates With Foetal-Maternal Histocompatibility Both During Pregnancy and Postpartum.

Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum.

Leveraging the Genetics of Psychiatric Disorders to Prioritize Potential Drug Targets and Compounds.

Background: Genetics has the potential to inform biologically relevant drug treatment and repurposing which may ultimately improve patient care. In this study, we combine methods which leverage the genetics of psychiatric disorders to prioritize potential drug targets and compounds.

Methods: We used the largest available genome-wide association studies, in European ancestry, of four psychiatric disorders [i.

Importance of environmental signals for cardiac morphological development in Atlantic salmon.

The hearts of salmonids display remarkable plasticity, adapting to various environmental factors that influence cardiac function and demand. For instance, in response to cold temperature, the salmonid heart undergoes growth and remodeling to counterbalance the reduced contractile function associated with dropping temperatures. Alongside heart size, the distinct pyramidal shape of the wild salmonid heart is essential for optimal cardiac performance, yet the environmental drivers behind this optimal cardiac morphology remain to be fully understood.

Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.

Methylation is a common biochemical reaction, and a number of methyltransferase (MTase) enzymes mediate the various methylation events occurring in living cells. Almost all MTases use the methyl donor S-adenosylmethionine (AdoMet), and, in humans, the largest group of AdoMet-dependent MTases are the so-called seven-β-strand (7BS) MTases. Collectively, the 7BS MTases target a wide range of biomolecules, i.

Aerobic adaptation and metabolic dynamics of DSM 20271: insights from comparative transcriptomics and surfaceome analysis.

Unlabelled: () DSM 20271 is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271 to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling.