Associations between inflammation and striatal dopamine D2-receptor availability in aging.

Background: Normal brain aging is associated with dopamine decline, which has been linked to age-related cognitive decline. Factors underlying individual differences in dopamine integrity at older ages remain, however, unclear. Here we aimed at investigating: (i) whether inflammation is associated with levels and 5-year changes of in vivo dopamine D2-receptor (DRD2) availability, (ii) if DRD2-inflammation associations differ between men and women, and (iii) whether inflammation and cerebral small-vessel disease (white-matter lesions) serve as two independent predictors of DRD2 availability.

Genetic diversity of the immunoglobulin heavy chain locus in cohorts of patients affected with SARS-CoV-2.

Background: The Immunoglobulin Heavy Chain (IGH) genomic region is responsible for the production of circulating antibodies and warrants careful investigation for its association with COVID-19 characteristics. Multiple allelic variants within and across different IGH gene segments form a limited set of haplotypes. Previous studies have shown associations between some of these haplotypes and clinical outcomes of COVID-19.

Participation of COX2/mPGES1/PGE2 in mouse and human endometrial stromal decidualization.

Background: Prostaglandin E2 (PGE2) is vital for embryo implantation and decidualization. Whether COX2/mPGES1/PGE2 pathway is essential for mouse and human decidualization remains unclear.

Results: This study showed that mPGES1 was highly expressed in the mouse uterus's subluminal stromal cells at the implantation site.

Uropygial gland microbiota of nearctic-neotropical migrants vary with season and migration distance.

Symbiotic microbiota are important drivers of host behaviour, health, and fitness. While most studies focus on humans, model organisms, and domestic or economically important species, research investigating the role of host microbiota in wild populations is rapidly accumulating. Most studies focus on the gut microbiota; however, skin and other glandular microbiota also play an important role in shaping traits that may impact host fitness.

Lewy body diseases and the gut.

Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.

Targeting PCSK9, through an innovative cVLP-based vaccine, enhanced the therapeutic activity of a cVLP-HER2 vaccine in a preclinical model of HER2-positive mammary carcinoma.

Background: HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance and incomplete response remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for the management of dyslipidemia by enhancing the clearance of low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 and cancer cells.

Multiomics unravels the complexity of male obesity: a prospective observational study.

Background: Obesity is associated with varying degrees of metabolic dysfunction. In this study, we aimed to discover markers of the severity of metabolic impairment in men with obesity via a multiomics approach.

Methods: Thirty-two morbidly men with obesity who were candidates for Roux-en-Y gastric bypass (RYGB) surgery were prospectively followed.

Global seroprevalence of Toxoplasma gondii in pregnant women: a systematic review and meta-analysis.

Background: Toxoplasmosis in pregnancy is associated with serious and irreversible maternal and fetal detrimental consequences. Also, different seroprevalence of Toxoplasma gondii in pregnancy is reported in many countries. The present systematic review and meta-analysis study aimed to determine the global seroprevalence of Toxoplasma gondii in pregnant women.

Comprehensive transcriptomic analysis reveals turnip mosaic virus infection and its aphid vector Myzus persicae cause large changes in gene regulatory networks and co-transcription of alternative spliced mRNAs in Arabidopsis thaliana.

Background: Virus infection and herbivory can alter the expression of stress-responsive genes in plants. This study employed high-throughput transcriptomic and alternative splicing analysis to understand the separate and combined impacts on host gene expression in Arabidopsis thaliana by Myzus persicae (green peach aphid), and turnip mosaic virus (TuMV).

Results: By investigating changes in transcript abundance, the data shows that aphids feeding on virus infected plants intensify the number of differentially expressed stress responsive genes compared to challenge by individual stressors.

Single cell RNA sequencing improves the next generation of approaches to AML treatment: challenges and perspectives.

Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment.

Distinct Circle of Willis anatomical configurations in healthy preterm born adults: a 3D time-of-flight magnetic resonance angiography study.

Background: Preterm birth (< 37 weeks' gestation) alters cerebrovascular development due to the premature transition from a foetal to postnatal circulatory system, with potential implications for future cerebrovascular health. This study aims to explore potential differences in the Circle of Willis (CoW), a key arterial ring that perfuses the brain, of healthy adults born preterm.

Methods: A total of 255 participants (108 preterm, 147 full-term) were included in the analysis.

Identifying Safeguards Disabled by Epstein-Barr Virus Infections in Genomes From Patients With Breast Cancer: Chromosomal Bioinformatics Analysis.

Background: The causes of breast cancer are poorly understood. A potential risk factor is Epstein-Barr virus (EBV), a lifelong infection nearly everyone acquires. EBV-transformed human mammary cells accelerate breast cancer when transplanted into immunosuppressed mice, but the virus can disappear as malignant cells reproduce.

Toward a biological definition of neuronal and glial synucleinopathies.

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms.

Quantitative analysis of amino acid excretion by Methanothermobacter marburgensis under N-fixing conditions.

Methanogenic archaea (methanogens) possess fascinating metabolic characteristics, such as the ability to fix molecular nitrogen (N). Methanogens are of biotechnological importance due to the ability to produce methane (CH) from molecular hydrogen (H) and carbon dioxide (CO) and to excrete proteinogenic amino acids. This study focuses on analyzing the link between biological methanogenesis and amino acid excretion under N-fixing conditions.

Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1.

Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV.

Synaptic vulnerability to amyloid-β and tau pathologies differentially disrupts emotional and memory neural circuits.

Alzheimer's disease (AD) is characterized by memory loss and neuropsychiatric symptoms associated with cerebral amyloid-β (Aβ) and tau pathologies, but whether and how these factors differentially disrupt neural circuits remains unclear. Here, we investigated the vulnerability of memory and emotional circuits to Aβ and tau pathologies in mice expressing mutant human amyloid precursor protein (APP), Tau or both APP/Tau in excitatory neurons. APP/Tau mice develop age- and sex-dependent Aβ and phosphorylated tau pathologies, the latter exacerbated at early stages, in vulnerable brain regions.

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib.