An interkinetic envelope surrounds chromosomes between meiosis I and II in C. elegans oocytes.

At the end of cell division, the nuclear envelope reassembles around the decondensing chromosomes. Female meiosis culminates in two consecutive cell divisions of the oocyte, meiosis I and II, which are separated by a brief transition phase known as interkinesis. Due to the absence of chromosome decondensation and the suppression of genome replication during interkinesis, it has been widely assumed that the nuclear envelope does not reassemble between meiosis I and II.

The persistent pool of HIV-1-infected cells is formed episodically during untreated infection.

Previous studies have shown that the majority of long-lived cells harboring persistent HIV-1 proviral genomes originates from viruses circulating in the year prior to antiretroviral therapy (ART) initiation, but a smaller proportion originates from viruses circulating much earlier in untreated infection. These observations suggest that discrete biological factors influence the entry and persistence of viruses into the persistent proviral pool, and there may be periods earlier in untreated infection with increased seeding. Therefore, we examined the timing of formation of the long-lived pool of infected cells that persists during ART in seven women (after a median of 5.

Clinical Molecular Testing for Clonal Relatedness of Second Melanoma Tumors.

Context.—: Patients with melanoma can develop second tumors representing either metastases or new primary melanoma. This distinction has profound implications for management.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk.

Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes.

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Introduction: Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy.

Methods: This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery.

Functional genomics of primary congenital glaucoma by pathway analysis and functional characterization of CYP1B1 mutations.

CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention.

Urothelial carcinoma in situ with "early papillary formation" vs "lateral spread/shoulder lesion" of prior high-grade noninvasive papillary urothelial carcinoma: A survey of pathologist and urologist interpretations.

Objectives: Urothelial carcinoma in situ (CIS) with early papillary formation is terminology sometimes used to suggest incipient high-grade papillary urothelial carcinoma (PUC) but may lead to confusion between true CIS and lateral flat spread of PUC.

Methods: It remains unclear how pathologists and urologists interpret this scenario, so a survey was circulated to 68 pathologists (group 1 = 28 academic genitourinary pathologists; group 2 = 17 pathologists with a self-reported genitourinary focus; group 3 = 23 pathologists self-reported as not genitourinary specialists) and 32 urologists.

Results: Regarding atypical urothelial lesions that appear mainly flat but contain possible papillae, group 3 was more likely to label this as CIS compared with groups 1 and 2 (35% for group 3 vs 13% for groups 1 and 2), while groups 1 and 2 more often adopted another descriptive diagnosis, such as "CIS with early papillary features" (38% for groups 1 and 2 vs 13% for group 3).

3D chromatin hubs as regulatory units of identity and survival in human acute leukemia.

Cancer progression involves genetic and epigenetic changes that disrupt chromatin 3D organization, affecting enhancer-promoter interactions and promoting growth. Here, we provide an integrative approach, combining chromatin conformation, accessibility, and transcription analysis, validated by in silico and CRISPR-interference screens, to identify relevant 3D topologies in pediatric T cell leukemia (T-ALL and ETP-ALL). We characterize 3D hubs as regulatory centers for oncogenes and disease markers, linking them to biological processes like cell division, inflammation, and stress response.

An atlas of the shared genetic architecture between atopic and gastrointestinal diseases.

Comorbidity among atopic diseases (ADs) and gastrointestinal diseases (GIDs) has been repeatedly demonstrated by epidemiological studies, whereas the shared genetic liability remains largely unknown. Here we establish an atlas of the shared genetic architecture between 10 ADs or related traits and 11 GIDs, comprehensively investigating the comorbidity-associated genomic regions, cell types, genes and genetically predicted causality. Although distinct genetic correlations between AD-GID are observed, including 14 genome-wide and 28 regional correlations, genetic factors of Crohn's disease (CD), ulcerative colitis (UC), celiac disease and asthma subtypes are converged on CD4 T cells consistently across relevant tissues.

Hepatocellular carcinoma hosts cholinergic neural cells and tumoral hepatocytes harboring targetable muscarinic receptors.

Background & Aims: Owing to unexplained interpatient variation and treatment failure in hepatocellular carcinoma (HCC), novel therapeutic approaches remain an urgent clinical need. Hepatic neurons, belonging to the autonomic nervous system (ANS), mediate liver/whole body crosstalk. Pathological innervation of the ANS has been identified in cancer, nurturing tumor stroma and conferring stronger carcinogenic properties.

HMGA2 overexpression with specific chromosomal abnormalities predominate in CALR and ASXL1 mutated myelofibrosis.

Although multiple genetic events are thought to play a role in promoting progression of the myeloproliferative neoplasms (MPN), the individual events that are associated with the development of more aggressive disease phenotypes remain poorly defined. Here, we report that novel genomic deletions at chromosome 12q14.3, as detected by a high-resolution array comparative genomic hybridization plus single nucleotide polymorphisms platform, occur in 11% of MPN patients with myelofibrosis (MF) and MPN-accelerated/blast phase (AP/BP) but was not detected in patients with polycythemia vera or essential thrombocythemia.

is implicated in central nervous system, orofacial and maxillofacial anomalies.

Background: Previous studies in mouse, and zebrafish embryos show strong expression in progenitor cells of neuronal and neural crest tissues suggesting its involvement in neural crest specification. However, the role of human transcription factor activator protein 2 ( in human embryonic central nervous system (CNS), orofacial and maxillofacial development is unknown.

Methods: Through a collaborative work, exome survey was performed in families with congenital CNS, orofacial and maxillofacial anomalies.

An analysis of RNA quality metrics in human brain tissue.

Human brain tissue studies have used a range of metrics to assess RNA quality but there are few large-scale cross-comparisons of presequencing quality metrics with RNA-seq quality. We analyzed how postmortem interval (PMI) and RNA integrity number (RIN) before RNA-seq relate to RNA quality after sequencing (percent of counts in top 10 genes [PTT], 5' bias, and 3' bias), and with individual gene counts across the transcriptome. We analyzed 4 human cerebrocortical tissue sets (1 surgical, 3 autopsy), sequenced with varying protocols.

Long non-coding RNA fine-tunes bone homeostasis and repair by orchestrating cellular crosstalk and β-catenin-OPG/Jagged1 pathway.

The IncRNA was initially believed to be dispensable for physiology due to the lack of observable phenotypes in knockout (KO) mice. However, our study challenges this conclusion. We found that both KO and conditional KO mice in the osteoblast lineage exhibit significant osteoporosis.

The role of the Latin American Professional Society of Genetic Counseling (SPLAGen): Advancing genetic counseling in Latin America.

The increasing importance of genomics and its expanding clinical application underscore the significance of genetic counseling in disseminating this vital information. In many countries, including regions of Latin America and the Caribbean, there is a shortage of adequately trained genetics providers thus limiting access to these essential services. Moreover, providers practicing genetic counseling are scarce and experience a lack of professional support.

WebGWAS: A web server for instant GWAS on arbitrary phenotypes.

Complex disease genetics is a key area of research for reducing disease and improving human health. Genome-wide association studies (GWAS) help in this research by identifying regions of the genome that contribute to complex disease risk. However, GWAS are computationally intensive and require access to individual-level genetic and health information, which presents concerns about privacy and imposes costs on researchers seeking to study complex diseases.

Connectome-based symptom mapping and related gene expression in children with autism and/or attention-deficit/hyperactivity disorder.

Clinical, neuroimaging and genomics evidence have increasingly underscored a degree of overlap between autism and attention-deficit/hyperactivity disorder (ADHD). This study explores the specific contribution of their core symptoms to shared biology in a sample of N=166 verbal children (6-12 years) with rigorously-established primary diagnoses of either autism or ADHD (without autism). We investigated the associations between inter-individual differences in clinician-based dimensional measures of autism and ADHD symptoms and whole-brain low motion intrinsic functional connectivity (iFC).

Social and Polygenic Risk Factors for Time to Comorbid Diagnoses in Individuals with Substance Use Disorders: A Phenome-Wide Survival Analysis.

Importance: Persons with substance use disorders (SUD) often suffer from additional comorbidities, including psychiatric conditions and physical health problems. Researchers have explored this overlap in electronic health records (EHR) using phenome wide association studies (PheWAS) to characterize how different indicators are related to all conditions in an individual's EHR. However, analyses have been largely cross-sectional in nature.