A Molecular Characterization of the Allelic Expression of the Founder Δ9-12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer.

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in has increased across populations due to the effect of founder mutations.

Underlying Mechanisms of the Protective Effects of Lifestyle Factors On Age-Related Diseases.

The rise in life expectancy has significantly increased the occurrence of age-related chronic diseases, leading to escalating expenses for both society and individuals. Among the main factors influencing health and lifespan, lifestyle takes a forefront position. Specifically, nutrition, mental activity, and physical exercise influence the molecular and functional mechanisms that contribute to the prevention of major age-related diseases.

Destination Matters More: Relapse following Hospital-Based Treatment of Substance Use Disorders With and Without Co-Occurring Disorders.

Objectives: Addressing substance use in psychiatric care encounters significant barriers, but the emergence of specialized services offers an opportunity to advance and scale up the integration of addiction services within psychiatric settings. However, research gaps still exist in this field, particularly in understanding the substance relapse rates of people with co-occurring disorders after a psychiatric hospitalization. This study aimed to investigate and compare the relapse rates of patients under inpatient care with exclusively addiction-related issues and those with co-occurring disorders after a hospitalization in a psychiatric ward and gain insights into differences in outcomes for these two patient groups.

Association of and GLUR4 Ion Transporters with Neoadjuvant Chemoresistance in Luminal Locally Advanced Breast Cancer.

Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer.

Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity.

Modified parental histones are segregated symmetrically to daughter DNA strands during replication and can be inherited through mitosis. How this may sustain the epigenome and cell identity remains unknown. Here we show that transmission of histone-based information during DNA replication maintains epigenome fidelity and embryonic stem cell plasticity.

Recycling of modified H2A-H2B provides short-term memory of chromatin states.

Chromatin landscapes are disrupted during DNA replication and must be restored faithfully to maintain genome regulation and cell identity. The histone H3-H4 modification landscape is restored by parental histone recycling and modification of new histones. How DNA replication impacts on histone H2A-H2B is currently unknown.

Promoter sequence and architecture determine expression variability and confer robustness to genetic variants.

Genetic and environmental exposures cause variability in gene expression. Although most genes are affected in a population, their effect sizes vary greatly, indicating the existence of regulatory mechanisms that could amplify or attenuate expression variability. Here, we investigate the relationship between the sequence and transcription start site architectures of promoters and their expression variability across human individuals.

Genomic Profile in a Non-Seminoma Testicular Germ-Cell Tumor Cohort Reveals a Potential Biomarker of Sensitivity to Platinum-Based Therapy.

Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant.

Endogenous retroviruses co-opted as divergently transcribed regulatory elements shape the regulatory landscape of embryonic stem cells.

Transposable elements are an abundant source of transcription factor binding sites, and favorable genomic integration may lead to their recruitment by the host genome for gene regulatory functions. However, it is unclear how frequent co-option of transposable elements as regulatory elements is, to which regulatory programs they contribute and how they compare to regulatory elements devoid of transposable elements. Here, we report a transcription initiation-centric, in-depth characterization of the transposon-derived regulatory landscape of mouse embryonic stem cells.

The Evolutionary Landscape of SARS-CoV-2 Variant B.1.1.519 and Its Clinical Impact in Mexico City.

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We reported the emergence of SARS-CoV-2 variant B.1.

Proteasome inhibition alters mitotic progression through the upregulation of centromeric α-Satellite RNAs.

Cell cycle progression requires control of the abundance of several proteins and RNAs over space and time to properly transit from one phase to the next and to ensure faithful genomic inheritance in daughter cells. The proteasome, the main protein degradation system of the cell, facilitates the establishment of a proteome specific to each phase of the cell cycle. Its activity also strongly influences transcription.

Breaking Isolation: Social Work in Solidarity with Migrant Workers through and beyond COVID-19.

In the early months of COVID-19's proliferation through Canadian communities, the now largely documented uneven impacts and burdens of the illness were emerging. Among the early COVID-19 casualties were workers in Alberta's meatpacking plants, with infection rates so high that the news quickly gained international attention. The Cargill meatpacking plant, overwhelmingly staffed by temporary foreign workers with no permanent status or citizenship rights, was the site of the largest single coronavirus outbreak in Canada.

Transcriptome Analysis Identifies GATA3-AS1 as a Long Noncoding RNA Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients.

Breast cancer is one of the leading causes of mortality in women worldwide, and neoadjuvant chemotherapy has emerged as an option for the management of locally advanced breast cancer. Extensive efforts have been made to identify new molecular markers to predict the response to neoadjuvant chemotherapy. Transcripts that do not encode proteins, termed long noncoding RNAs (lncRNAs), have been shown to display abnormal expression profiles in different types of cancer, but their role as biomarkers in response to neoadjuvant chemotherapy has not been extensively studied.

Transcriptional Profiles Reveal Deregulation of Lipid Metabolism and Inflammatory Pathways in Neurons Exposed to Palmitic Acid.

The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated.

Primary care provider expectations of addiction services and patients in Spain.

Background: Primary care (PC) is crucial in the care of substance use disorder (SUD) patients. However, the relationship between PC and addiction settings is complex and collaboration issues stand out. Available evidence suggests that integration of SUD and PC services can improve physical and mental health of SUD patients and reduce health expenses.

Comparative transcriptome analysis reveals key epigenetic targets in SARS-CoV-2 infection.

COVID-19 is an infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2), which has caused a global outbreak. Current research efforts are focused on the understanding of the molecular mechanisms involved in SARS-CoV-2 infection in order to propose drug-based therapeutic options. Transcriptional changes due to epigenetic regulation are key host cell responses to viral infection and have been studied in SARS-CoV and MERS-CoV; however, such changes are not fully described for SARS-CoV-2.

Hiding for Survival: Highlighting the Lived Experiences of Precarity and Labour Abuse Among Filipino Non-status Migrants in Canada.

are individuals who do not hold a valid immigration document or official status to stay in Canada. This paper presents a case study on the experiences of non-status migrants seeking access to health, social, and community services. Through interviews with five non-status migrants, the authors explore the specific needs, rights, services and barriers they encountered.

Magnetically-stimulated transformations in nanostructure of lipid mesophases: Effect of structure of iron oxide nanoparticles.

Nanostructured lipid-based liquid crystalline (LLC) systems can display different drug release rates and also be stimuli-responsive, rendering them the potential to serve as 'on-demand' drug delivery systems. In this study, a magnetically-responsive cubic phase nanocomposite was engineered by doping iron oxide nanoparticles (IONPs) into a phytantriol (PHYT)-based lipid that exhibits transformation in nanostructure under external alternating magnetic field (AMF). The effects of IONP surface hydrophilicity/hydrophobicity, size and concentration were determined in dispersed systems, and the effect of hydration state of the system was also assessed.

A functional genetic screen identifies the Mediator complex as essential for SSX2-induced senescence.

The senescence response to oncogenes is believed to be a barrier to oncogenic transformation in premalignant lesions, and describing the mechanisms by which tumor cells evade this response is important for early diagnosis and treatment. The male germ cell-associated protein SSX2 is ectopically expressed in many types of cancer and is functionally involved in regulating chromatin structure and supporting cell proliferation. Similar to many well-characterized oncogenes, SSX2 has the ability to induce senescence in cells.

De Novo Pathway-Based Classification of Breast Cancer Subtypes.

Breast cancer is a heterogeneous disease for which various clinically relevant subtypes have been reported. These subtypes are characterized by molecular differences which direct treatment selection. The state of the art for breast cancer subtyping utilizes histochemistry or gene expression to measure a few selected markers.

De Novo Pathway Enrichment with KeyPathwayMiner.

Biomolecular networks such as protein-protein interaction networks provide a static picture of the interplay of genes and their products, and, consequently, they fail to capture dynamic changes taking place during the development of complex diseases. KeyPathwayMiner is a software platform designed to fill this gap by integrating previous knowledge captured in molecular interaction networks with OMICS datasets (DNA microarrays, RNA sequencing, genome-wide methylation studies, etc.) to extract connected subnetworks with a high number of deregulated genes.