Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Bovine besnoitiosis: Assessment of the diagnostic accuracy of three different tests using a Bayesian latent class model approach and clinical characterization of the disease.

Bovine besnoitiosis, a disease caused by the tissue cyst-forming apicomplexan Besnoitia besnoiti, is re-emerging in Europe, leading to significant impairment of health and production, as well as economic losses. The early detection of the disease is of the utmost importance for the implementation of effective control measures, yet this is a challenge due to the lack of specific early clinical signs. The objectives of our study were 1) to estimate the diagnostic accuracy of three tests to detect B.

Identification of Ancylostoma caninum in Domestic Dogs from Ecuador via Various Techniques.

BACKGROUND Ancylostoma caninum is a soil-borne, soil-transmitted helminth with infective larvae and produces cutaneous larva migrans in humans. The objective of this study was to confirm the presence of A. caninum in domestic dogs from the urban-marginal and rural sectors of the Ecuadorian coast through morphometry, culture, and molecular techniques.

Prominent efficacy and good safety of sequential CD19 and CD22 CAR-T therapy in relapsed/refractory adult B-cell acute lymphoblastic leukemia.

Background: Sequential CD19 and CD22 chimeric antigen receptor (CAR)-T cell therapy offers a promising approach to antigen-loss relapse in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL); however, research in adults remains limited.

Methods: This study aimed to evaluate the efficacy and safety of sequential CD19 and CD22 CAR-T cell therapy in adult patients with R/R B-ALL between November 2020 and November 2023 (ChiCTR2100053871). Key endpoints included the adverse event incidence, overall survival (OS), and leukemia-free survival (LFS).

Deciphering the core shunt mechanism in Arabidopsis cuticular wax biosynthesis and its role in plant environmental adaptation.

Plant cuticular waxes serve as highly responsive adaptations to variable environments. Aliphatic waxes consist of very-long-chain (VLC) compounds produced from 1-alcohol- or alkane-forming pathways. The existing variation in 1-alcohols and alkanes across Arabidopsis accessions revealed that 1-alcohol amounts are negatively correlated with aridity factors, whereas alkanes display the opposite behaviour.

Variation in a single allele drives divergent yield responses to elevated CO between rice subspecies.

Rising atmospheric CO generally increases yield of indica rice, one of the two main Asian cultivated rice subspecies, more strongly than japonica rice, the other main subspecies. The molecular mechanisms driving this difference remain unclear, limiting the potential of future rice yield increases through breeding efforts. Here, we show that between-species variation in the DNR1 (DULL NITROGEN RESPONSE1) allele, a regulator of nitrate-use efficiency in rice plants, explains the divergent response to elevated atmospheric CO (eCO) conditions.

Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity.

Catalysis and specifically autocatalysis are the quintessential building blocks of life. Yet, although autocatalytic networks are necessary, they are not sufficient for the emergence of life-like properties, such as replication and adaptation. The ultimate and potentially fatal threat faced by molecular replicators is parasitism; if the polymerase error rate exceeds a critical threshold, even the fittest molecular species will disappear.

RNA-Based Next-Generation Sequencing in Non-Small Cell Lung Cancer patients: data from Campania, Italy.

Objective: ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations represent fundamental predictive biomarkers for advanced non-small cell lung cancer (NSCLC) patients to ensure the best treatment choice. In this scenario, RNA-based NGS approach has emerged as an extremely useful tool for detecting these alterations. In this study, we report our NGS molecular records on ALK, ROS1, NTRK, and RET gene fusions and MET exon 14 skipping alterations detected by using a narrow RNA-based NGS panel, namely SiRe fusion.

Baricitinib Treatment in RNU7-1-Associated Aicardi-Goutières Syndrome in a South African Child: A Case Report.

Aicardi-Goutières syndrome (AGS) is a rare monogenic type I interferonopathy. Janus kinase (JAK) inhibition has emerged as a potential treatment for AGS. RNU7-1 is one of the most recently discovered genes for AGS, and the clinical effects of JAK inhibition in these patients have not been reported.

High order expression dependencies finely resolve cryptic states and subtypes in single cell data.

Single cells are typically typed by clustering into discrete locations in reduced dimensional transcriptome space. Here we introduce Stator, a data-driven method that identifies cell (sub)types and states without relying on cells' local proximity in transcriptome space. Stator labels the same single cell multiply, not just by type and subtype, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order gene expression dependencies from a sparse gene-by-cell expression matrix.

Genome-scale evolution in local populations of wild chimpanzees.

Analysis of genome-scale evolution has been difficult in large, endangered animals because opportunities to collect high-quality genetic samples are limited. There is a need for novel field-friendly, cost-effective genetic techniques. This study conducted an exome-wide analysis of a total of 42 chimpanzees (Pan troglodytes) across six African regions, providing insights into population discrimination techniques.

Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank.

Bone marrow adipose tissue is a distinct adipose subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates of this tissue are unclear, and its genetic determinants remain unknown. Here, we use deep learning to measure bone marrow adiposity in the femoral head, total hip, femoral diaphysis, and spine from MRI scans of approximately 47,000 UK Biobank participants, including over 41,000 white and over 6300 non-white participants.

The transcription factor GABPA is a master regulator of naive pluripotency.

The establishment of naive pluripotency is a continuous process starting with the generation of inner cell mass (ICM) that then differentiates into epiblast (EPI). Recent studies have revealed key transcription factors (TFs) for ICM formation, but which TFs initiate EPI specification remains unknown. Here, using a targeted rapid protein degradation system, we show that GABPA is not only a regulator of major ZGA, but also a master EPI specifier required for naive pluripotency establishment by regulating 47% of EPI genes during E3.

Genome-wide characterization of 54 urinary metabolites reveals molecular impact of kidney function.

Dissecting the genetic mechanisms underlying urinary metabolite concentrations can provide molecular insights into kidney function and open possibilities for causal assessment of urinary metabolites with risk factors and disease outcomes. Proton nuclear magnetic resonance metabolomics provides a high-throughput means for urinary metabolite profiling, as widely applied for blood biomarker studies. Here we report a genome-wide association study meta-analysed for 3 European cohorts comprising 8,011 individuals, covering both people with type 1 diabetes and general population settings.

Centrophilic retrotransposon integration via CENH3 chromatin in Arabidopsis.

In organisms ranging from vertebrates to plants, major components of centromeres are rapidly evolving repeat sequences, such as tandem repeats (TRs) and transposable elements (TEs), which harbour centromere-specific histone H3 (CENH3). Complete centromere structures recently determined in human and Arabidopsis suggest frequent integration and purging of retrotransposons within the TR regions of centromeres. Despite the high impact of 'centrophilic' retrotransposons on the paradox of rapid centromere evolution, the mechanisms involved in centromere targeting remain poorly understood in any organism.

IFNγ and TNFα drive an inflammatory secretion profile in cancer-associated fibroblasts from human non-small cell lung cancer.

Cancer-associated fibroblasts (CAFs) are the dominant nonmalignant component of the tumour microenvironment (TME). CAFs demonstrate a high level of inter- and intra-tumour heterogeneity in solid tumours, though the drivers of CAF subpopulations are not fully understood. Here, we demonstrate that non-small cell lung cancer (NSCLC) patient-derived CAFs upregulate the secretion of inflammatory cytokines (IL6, LIF, IL33, GM-CSF, IL1ra) and chemokines (CCL2, CCL3, CCL4, CCL20, CXCL8, CXCL9, CXCL10, CXCL11) in response to in vitro co-culture with anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) via IFNγ and TNFα.

GPI transamidase complex is required for primordial germ cell migration and development in zebrafish.

Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of GPI transamidase in PGC migration and development in zebrafish embryos.

Prenatal gene-environment interactions mediate the impact of advanced maternal age on mouse offspring behavior.

Autism spectrum disorders encompass diverse neurodevelopmental conditions marked by alterations in social communication and repetitive behaviors. Advanced maternal age is associated with an increased risk of bearing children affected by autism but the etiological factors underlying this association are not well known. Here, we investigated the effects of advanced maternal age on offspring health and behavior in two genetically divergent mouse strains: the BTBR T Itpr3/J (BTBR) mouse model of idiopathic autism, and the C57BL/6 J (B6) control strain, as a model of genetic variability.

CHAMP1 premature termination codon mutations found in individuals with intellectual disability cause a homologous recombination defect through haploinsufficiency.

CHAMP1 (chromosome alignment-maintaining phosphoprotein 1) plays a role in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The CHAMP1 gene is one of the genes mutated in individuals with intellectual disability. The majority of the mutations are premature termination codon (PTC) mutations, while missense mutations have also been reported.

A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster.

Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein.