Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

Sleep difficulties related to psychopathology and neurocognition in people with 22q11.2 deletion syndrome.

The 22q11.2 Deletion Syndrome (22q11.2DS) is a multisystem genetic disorder with prominent sleep disturbances, neuropsychiatric conditions and neurocognitive challenges.

Year in Review: Novel Insights in the Pathogenesis of Spondyloarthritis - SPARTAN 2024 Annual Meeting Proceedings.

Purpose Of Review: The canonical pathogenesis of spondyloarthritis (SpA) involves inflammation driven by HLA-B27, type 3 immunity, and gut microbial dysregulation. This review based on information presented at the SPARTAN meeting highlights studies on the pathogenesis of SpA from the past year, focusing on emerging mechanisms such as the roles of microbe-derived metabolites, microRNAs (miRNAs) and cytokines in plasma exosomes, specific T cell subsets, and neutrophils.

Recent Findings: The induction of arthritis in a preclinical model through microbiota-driven alterations in tryptophan catabolism provides new insights as to how intestinal dysbiosis may activate disease via the gut-joint axis.

Arvimicrobium flavum gen. nov., sp. nov., A Novel Genus in the Family Phyllobacteriaceae Isolated From Forest Soil.

During the study of microbial diversity of forest soil in the Republic of Korea, a yellow pigment-producing, Gram-stain-negative, rod-shaped, motile bacterium was isolated and designated as strain 1W2. This strain grew at temperature of 10-37 °C, at pH of 5.0-9.

Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats; establishment of human leukemia xenograft models.

Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan.

Molecular profiles of blood from numerous species that differ in sensitivity to acute inflammation.

Vertebrates differ over 100,000-fold in responses to pro-inflammatory agonists such as bacterial lipopolysaccharide (LPS), complicating use of animal models to study human sepsis or inflammatory disorders. We compared transcriptomes of resting and LPS-exposed blood from six LPS-sensitive species (rabbit, pig, sheep, cow, chimpanzee, human) and four LPS-resilient species (mice, rats, baboon, rhesus), as well as plasma proteomes and lipidomes. Unexpectedly, at baseline, sensitive species already had enhanced expression of LPS-responsive genes relative to resilient species.

Rare variants in cardiomyopathy genes predispose to cardiac injury in severe COVID-19 patients of African or Hispanic ancestry.

In one of the earliest reports from China during COVID-19, it was noted that over 20% of patients hospitalized with the disease had significant elevations of troponin, a marker of myocardial tissue damage, that put them at a higher risk. In a hypothesis-independent whole exome sequencing (WES) study in hospitalized COVID-19 patients of diverse ancestry, we observed putative enrichment in pathogenic variants in genes known to be involved in the pathogenesis of cardiomyopathy. This observation led us to hypothesize that the observed high morbidity and mortality in these patients might be due to the presence of rare genetic factors that had previously been silent but became relevant as a consequence of the severe stress inflicted by an infection with SARS-CoV-2.

Genome-scale modeling identifies dynamic metabolic vulnerabilities during the epithelial to mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) is a conserved cellular process critical for embryogenesis, wound healing, and cancer metastasis. During EMT, cells undergo large-scale metabolic reprogramming that supports multiple functional phenotypes including migration, invasion, survival, chemo-resistance and stemness. However, the extent of metabolic network rewiring during EMT is unclear.

Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.

Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

SPRTN metalloprotease participates in repair of ROS-mediated DNA-protein crosslinks.

Exposure to reactive oxygen species (ROS) can induce DNA-protein crosslinks (DPCs), unusually bulky DNA lesions that block replication and transcription and play a role in aging, cancer, cardiovascular disease, and neurodegenerative disorders. Repair of DPCs depends on the coordinated efforts of proteases and DNA repair enzymes to cleave the protein component of the lesion to smaller DNA-peptide crosslinks which can be processed by tyrosyl-DNA phosphodiesterases 1 and 2, nucleotide excision and homologous recombination repair pathways. DNA-dependent metalloprotease SPRTN plays a role in DPC repair, and SPRTN-deficient mice exhibit an accelerated aging phenotype and develop liver cancer early in life.

PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons.

Lack of association between common polymorphisms associated with successful aging and longevity in the population of Sardinian Blue Zone.

More than two decades ago, in the central-eastern region of the Mediterranean island of Sardinia, a mountain area was identified where the population displays exceptional longevity, especially among men (the Longevity Blue Zone, LBZ). This community was thoroughly investigated to understand the underlying causes of the phenomenon. The present study analyzed 11 genetic markers previously associated with increased survival in several long-lived populations.

Development of high-performance inducible and secretory expression vector and host system for enhanced recombinant protein production.

The production of lipopolysaccharide (LPS)-free recombinant proteins from culture supernatants is of great interest to biomedical research and industry. Due to the LPS-free cell wall structure and the well-defined secretion factor B (SecB)-dependent secretion pathway, Gram-positive bacteria are a superior alternative to Escherichia coli expression systems. However, the lack of inducible expression systems for high yields has been a bottleneck.

Prediction of late-onset preeclampsia using plasma proteomics: a longitudinal multi-cohort study.

Preeclampsia is a pregnancy disorder with substantial perinatal and maternal morbidity and mortality. Pregnant women at risk of preeclampsia would benefit from early detection for follow-up, timely interventions and delivery. Several attempts have been made to identify protein biomarkers of preeclampsia, but findings vary with demographics, clinical characteristics, and time of sampling.

Combination of paclitaxel with rosiglitazone induces synergistic cytotoxic effects in ovarian cancer cells.

Ovarian cancer is known to be a challenging disease to detect at an early stage and is a major cause of death among women. The current treatment for ovarian cancer typically involves a combination of surgery and the use of drugs such as platinum-based cytotoxic agents, anti-angiogenic drugs, etc. However, current treatment methods are not always effective in preventing the recurrence of ovarian cancer.

Genomic analysis of DS-1-like human rotavirus A strains uncovers genetic relatedness of NSP4 gene with animal strains in Manhiça District, Southern Mozambique.

Post rotavirus vaccine introduction in Mozambique (September 2015), we documented a decline in rotavirus-associated diarrhoea and genotypes changes in our diarrhoeal surveillance spanning 2008-2021. This study aimed to perform whole-genome sequencing of rotavirus strains from 2009 to 2012 (pre-vaccine) and 2017-2018 (post-vaccine). Rotavirus strains previously detected by conventional PCR as G2P[4], G2P[6], G3P[4], G8P[4], G8P[6], and G9P[6] from children with moderate-to-severe and less-severe diarrhoea and without diarrhoea (healthy community controls) were sequenced using Illumina MiSeq platform and analysed using bioinformatics tools.

Pharmacogenomic landscape of the Thai population from genome sequencing of 949 individuals.

Inter-individual variability in drug responses is significantly influenced by genetic factors, underscoring the importance of population-specific pharmacogenomic studies to optimize clinical outcomes. In this study, we analyzed whole genome sequencing data from 949 unrelated Thai individuals and conducted an in-depth analysis of 3239 genes involved in drug pharmacokinetics, pharmacodynamics, or immune-mediated adverse drug reactions. We identified 43 single nucleotide polymorphisms (SNPs), 134 diplotypes, and 15 human leukocyte antigen (HLA) alleles, all with moderate to high clinical significance.

Whole genome analysis of 26 bacterial strains reveals aromatic and hydrocarbon degrading enzymes from diverse environmental soil samples.

Polycyclic aromatic compounds and petroleum hydrocarbons (PHs) are hazardous pollutants and seriously threaten the environment and human health. However, native microbial communities can adapt to these toxic pollutants, utilize these compounds as a carbon source, and eventually evolve to degrade these toxic contaminants. With this in mind, we isolated 26 bacterial strains from various environmental soil samples.

GPR37-enhanced ubiquitination of ATP1A1 inhibits tumor progression and radiation resistance in esophageal squamous cell carcinoma.

Radiotherapy resistance is one of the main reasons for the dismal clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). Therefore, clarifying the targets and molecular mechanisms of radiotherapy resistance in ESCC is of great theoretical and clinical significance to enhance the efficacy of radiotherapy. In this study, GPR37 was identified as a key factor facilitating ESCC radiosensitization.

Bulk and Single-Cell Transcriptome Analyses Unravel Gene Signatures of Mitochondria-Associated Programmed Cell Death in Diabetic Foot Ulcer.

Mitochondrial programmed cell death (PCD) plays a critical role in the pathogenesis of diabetic foot ulcers (DFU). In this study, we performed a comprehensive transcriptome analysis to identify potential hub genes and key cell types associated with PCD and mitochondria in DFU. Using intersection analysis of PCD- and mitochondria-related genes, we identified candidate hub genes through protein-protein interaction and random forest analysis.

Immunohistochemical Analysis of a1-Acid Glycoprotein and Tumor Associated Macrophages in Clear Cell Renal Cell Carcinoma.

Background/aim: α1-Acid glycoprotein (AGP), also known as orosomucoid, is an acute-phase protein that has been found increased in plasma of cancer patients. This study investigates the role of AGP expression in clear cell renal cell carcinoma (ccRCC) and its association with clinical outcomes.

Materials And Methods: We investigated the correlation between AGP levels and the prognosis of ccRCC through an analysis of The Cancer Genome Atlas (TCGA) database.

Contribution of Cyclin Dependent Kinase Inhibitor 1A Genotypes to Childhood Acute Lymphocytic Leukemia Risk in Taiwan.

Background/aim: The disruption of cell-cycle control can lead to an imbalance in cell proliferation, often accompanied by genomic instability, which in turn can facilitate carcinogenesis. This study aimed to examine the impact of CDKN1A rs1801270 and rs1059234 polymorphisms on the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan.

Materials And Methods: The genotypes of CDKN1A rs1801270 and rs1059234 in 266 childhood ALL cases and 266 controls were determined using PCR-RFLP techniques.

In vivo bioengineered tooth formation using decellularized tooth bud extracellular matrix scaffolds.

The use of dental implants to replace lost or damaged teeth has become increasingly widespread due to their reported high survival and success rates. In reality, the long-term survival of dental implants remains a health concern, based on their short-term predicted survival of ~15 years, significant potential for jawbone resorption, and risk of peri-implantitis. The ability to create functional bioengineered teeth, composed of living tissues with properties similar to those of natural teeth, would be a significant improvement over currently used synthetic titanium implants.

Impact of SCN10A Polymorphism on Abdominal Pain Perception and Visceral Hypoalgesia in Crohn's Disease and Ulcerative Colitis.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073 val/val ) related to Na v 1.8, a voltage-gated sodium channel preferentially expressed on nociceptors.