Two independent families with de novo whole APC gene deletion and intellectual disability: a case report.

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant colorectal tumour syndrome characterised by the formation of multiple adenomatous polyps throughout the colon. It is important to understand the extracolonic phenotype that characterizes FAP. Most previous case reports of patients with both FAP and intellectual disability (ID) have described deletions in all or part of chromosome 5q, including the APC locus.

Sexual dimorphism in lung transcriptomic adaptations in fetal alcohol spectrum disorders.

Current fetal alcohol spectrum disorders (FASD) studies primarily focus on alcohol's actions on the fetal brain although respiratory infections are a leading cause of morbidity/mortality in newborns. The limited studies examining the pulmonary adaptations in FASD demonstrate decreased surfactant protein A and alveolar macrophage phagocytosis, impaired differentiation, and increased risk of Group B streptococcal pneumonia with no study examining sexual dimorphism in adaptations. We hypothesized that developmental alcohol exposure in pregnancy will lead to sexually dimorphic fetal lung morphological and immune adaptations.

Exploring the role of splicing in TP53 variant pathogenicity through predictions and minigene assays.

Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.

Genetically engineered biomimetic ATP-responsive nanozyme for the treatment of cardiac fibrosis.

Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.

Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.

CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear.

Enhanced recovery after surgery protocol optimizes results and cost of laparoscopic radical nephroureterectomy.

Purpose: To evaluate the efficacy of an enhanced recovery after surgery (ERAS) strategy for upper tract urothelial carcinoma (UTUC) patients undergoing laparoscopic radical nephroureterectomy (LRNU).

Methods: 90 patients who received LRNU at Zhongnan Hospital of Wuhan University between January 2018 and July 2022 were retrospectively analyzed, including 43 in the ERAS group and 47 in the pre-ERAS group. The clinical features, postoperative complications, length of hospital stay (LOS), and hospital expenditures of the two groups were compared via t-test, Mann-Whitney test, and Chi-square test.

Inflammatory markers link triglyceride-glucose index and obesity indicators with adverse cardiovascular events in patients with hypertension: insights from three cohorts.

Background: Among hypertensive cohorts across different nations, the relationship between the triglyceride-glucose index (TyG) and its conjunction with obesity metrics in relation to cardiovascular disease (CVD) incidence and mortality remains to be elucidated.

Methods: This study enrolled 9,283, 164,357, and 5,334 hypertensives from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKBB), and Shanghai Pudong cohort. The related outcomes for CVD were defined by multivariate Cox proportional hazards models, Generalized Additive Models and Mendelian randomization analysis.

Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas.

Aim: The study was designed to evaluate molecular alterations, relevant to the prognosis and personalized therapy of salivary gland cancers (SGCs).

Materials And Methods: DNA was extracted from archival tissue of 40 patients with various SGCs subtypes. A targeted next-generation sequencing (NGS) panel was used for the identification of small-scale mutations, focal and chromosomal arm-level copy number changes.

Fertigation with alpha-tocopherol enhances morphological, physiological, and antioxidant responses in radish (Raphanus sativus L.) under drought stress.

Water scarcity is a foremost environmental concern and is expected to hasten in the forthcoming years due to severe fluctuations in weather patterns worldwide. The present work was designed to explore the potential role of alpha-tocopherol (α-Toc), a form of vitamin E, on the morphological, physio-biochemical, and cellular antioxidant responses of two radish genotypes grown under drought conditions (38 ± 3% of field capacity). The individual and combined applications of α-Toc (100 ppm) were used as T0- Control, T1- Control + TF (TF-alpha-tocopherol), T2- Drought (D), and T3- D + TF with three replications.

Network analysis combined with genome-wide association study helps identification of genes related to amino acid contents in soybean.

Background: Additional to total protein content, the amino acid (AA) profile is important to the nutritional value of soybean seed. The AA profile in soybean seed is a complex quantitative trait controlled by multiple interconnected genes and pathways controlling the accumulation of each AA. With a total of 621 soybean germplasm, we used three genome-wide association study (GWAS)-based approaches to investigate the genomic regions controlling the AA content and profile in soybean.

Role of T cell metabolism in brain tumor development: a genetic and metabolic approach.

Background: Malignant brain tumors are among the most lethal cancers. Recent studies emphasized the crucial involvement of the immune system, especially T cells, in driving tumor progression and influencing patient outcomes. The emerging field of immunometabolism has shown that metabolic pathways play a pivotal role in regulating immune responses within the tumor microenvironment.

Contribution of crossing over to genetic variance in maize and wheat populations.

Crossing over breaks linkages and leads to a wider array of allele combinations. My objective was to assess the contribution of crossing over to genetic variance (V) in maize (Zea mays L.) and wheat (Triticum aestivum L.

A phylogenetic approach to comparative genomics.

Comparative genomics, whereby the genomes of different species are compared, has the potential to address broad and fundamental questions at the intersection of genetics and evolution. However, species, genomes and genes cannot be considered as independent data points within statistical tests. Closely related species tend to be similar because they share genes by common descent, which must be accounted for in analyses.

Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.

Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.

Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.

A novel prognostic risk model for patients with refractory/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents.

Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.

Pancreatic organogenesis mapped through space and time.

The spatial organization of cells within a tissue is dictated throughout dynamic developmental processes. We sought to understand whether cells geometrically coordinate with one another throughout development to achieve their organization. The pancreas is a complex cellular organ with a particular spatial organization.

Migration of primordial germ cells and their relationship of PGCs with sex development in transgenic germline-specific fluorescent freshwater angelfish (Pterophyllum scalare).

Primordial germ cells (PGCs), the progenitors of gametes, are essential for teleost reproduction. While their formation is conserved across teleosts, the activation, migration routes, and localization periods vary among species. In this study, we developed a novel transgenic line, Tg(ddx4:TcCFP13-nanos3), based on the Nile tilapia genome, to label PGCs with clear fluorescent signals in the freshwater angelfish (Pterophyllum scalare).

Structural polymorphism and diversity of human segmental duplications.

Segmental duplications (SDs) contribute significantly to human disease, evolution and diversity but have been difficult to resolve at the sequence level. We present a population genetics survey of SDs by analyzing 170 human genome assemblies (from 85 samples representing 38 Africans and 47 non-Africans) in which the majority of autosomal SDs are fully resolved using long-read sequence assembly. Excluding the acrocentric short arms and sex chromosomes, we identify 173.

Triacylglycerol mobilization underpins mitochondrial stress recovery.

Mitochondria are central to myriad biochemical processes, and thus even their moderate impairment could have drastic cellular consequences if not rectified. Here, to explore cellular strategies for surmounting mitochondrial stress, we conducted a series of chemical and genetic perturbations to Saccharomyces cerevisiae and analysed the cellular responses using deep multiomic mass spectrometry profiling. We discovered that mobilization of lipid droplet triacylglycerol stores was necessary for strains to mount a successful recovery response.

Mapping the developmental trajectory of human astrocytes reveals divergence in glioblastoma.

Glioblastoma (GBM) is defined by heterogeneous and resilient cell populations that closely reflect neurodevelopmental cell types. Although it is clear that GBM echoes early and immature cell states, identifying the specific developmental programmes disrupted in these tumours has been hindered by a lack of high-resolution trajectories of glial and neuronal lineages. Here we delineate the course of human astrocyte maturation to uncover discrete developmental stages and attributes mirrored by GBM.

Transplantation of a genetically modified porcine heart into a live human.

Following our previous experience with cardiac xenotransplantation of a genetically modified porcine heart into a live human, we sought to achieve improved results by selecting a healthier recipient and through more sensitive donor screening for potential zoonotic pathogens. Here we transplanted a 10-gene-edited pig heart into a 58-year-old man with progressive, debilitating inotrope-dependent heart failure due to ischemic cardiomyopathy who was not a candidate for standard advanced heart failure therapies. He was maintained on a costimulation (anti-CD40L, Tegoprubart) blockade-based immunomodulatory regimen.

High-efficiency base editing in the retina in primates and human tissues.

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.

Inactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.

The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.

Maternal effects in the model system Daphnia: the ecological past meets the epigenetic future.

Maternal effects have been shown to play influential roles in many evolutionary and ecological processes. However, understanding how environmental stimuli induce within-generation responses that transverse across generations remains elusive, particularly when attempting to segregate confounding effects from offspring genotypes. This review synthesizes literature regarding resource- and predation-driven maternal effects in the model system Daphnia, detailing how the maternal generation responds to the environmental stimuli and the maternal effects seen in the offspring generation(s).

Longitudinal genomic profiling using liquid biopsies in metastatic nonsquamous NSCLC following first line immunotherapy.

Tumor genomic profiling is often limited to one or two timepoints due to the invasiveness of tissue biopsies, but longitudinal profiling may provide deeper clinical insights. Using ctDNA data from IMpower150 study, we examined genetic changes in metastatic non-squamous NSCLC post-first-line immunotherapy. Mutations were most frequently detected in TP53, KRAS, SPTA1, FAT3, and LRP1B at baseline and during treatment.