Endothelial knockdown of the tumor suppressor, , increases inflammation in ventilator-induced lung injury.

Chronic cigarette smoke exposure decreases lung expression of which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of -silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). -silenced ECs as well as those isolated from endothelial cell knockout (EC KO) mice were subjected to cyclic stretch (18% elongation, 0.

WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12.

WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322).

an Immune-Related Long Non-Coding RNA Associated with Early-Stage Breast Cancer Progression.

Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this study was to characterize expression, localization, and phenotypic and molecular effects in non-invasive and invasive breast cancer cells.

Innovation and immunization program management: traceability and quality in Latin America and the Caribbean, laying the groundwork for a regional action plan.

Introduction: The Latin American Society of Pediatric Infectious Diseases (SLIPE by its Spanish acronyms) is working to understand the current situation, gaps, and opportunities for traceability of the quality vaccination process in Latin America and the Caribbean.

Areas Covered: On September 24th and 25th, a Latin American forum of experts in immunization programs was held through the Zoom platform; the topics discussed included: computerized systems for recording immunizations, vaccination programs traceability, challenges, and information systems for the integrated management of vaccination.

Expert Opinion: Latin American countries have transitioned from having a nominal registration system to a nominal tracking system, with many of them not migrating their platforms to new technologies; therefore, the low-quality data, fragmented databases, and slow information traffic present a challenge that must be taken on.

Wwox Binding to the Murine Brca1-BRCT Domain Regulates Timing of Brip1 and CtIP Phospho-Protein Interactions with This Domain at DNA Double-Strand Breaks, and Repair Pathway Choice.

Wwox-deficient human cells show elevated homologous recombination, leading to resistance to killing by double-strand break-inducing agents. Human Wwox binds to the Brca1 981-PPLF-984 Wwox-binding motif, likely blocking the pChk2 phosphorylation site at Brca1-S988. This phosphorylation site is conserved across mammalian species; the PPLF motif is conserved in primates but not in rodents.

Interaction of Wwox with Brca1 and associated complex proteins prevents premature resection at double-strand breaks and aberrant homologous recombination.

Down regulation of Wwox protein expression occurs in many cancers, contributing to insensitivity to ionizing radiation (IR) and platinum drug treatments. Patients with reduced Wwox expression in their cancer tissue show decreased overall survival following these treatments, in accord with our earlier finding that reduced Wwox protein expression in cancers is associated with changes in choice of DNA double-strand break (DSB) repair pathway. Our current investigation of mechanisms underlying the initial choice of repair by homologous recombination/single-strand annealing (HR/SSA) in Wwox-deficient cells, showed immediate DNA end-resection at DSBs following IR, abrogating initial repair by the expected non-homologous end-joining (NHEJ) pathway.

Modulated Pathways in Early-Stage Breast Cancer Progression.

The long-non-coding HOX transcript antisense intergenic RNA () was identified as significantly upregulated in breast ductal carcinoma (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by in early-stage breast cancer progression. We determined that induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and growth in normal and DCIS breast cell lines.

The non-adiabatic nanoreactor: towards the automated discovery of photochemistry.

The nanoreactor has previously been introduced to automate reaction discovery for ground state chemistry. In this work, we present the nonadiabatic nanoreactor, an analogous framework for excited state reaction discovery. We automate the study of nonadiabatic decay mechanisms of molecules by probing the intersection seam between adiabatic electronic states with hyper-real metadynamics, sampling the branching plane for relevant conical intersections, and performing seam-constrained path searches.

RHBDD2‑WWOX protein interaction during proliferative and differentiated stages in normal and breast cancer cells.

Rhomboid pseudoproteases are catalytically inactive members of the rhomboid superfamily that modulate the traffic, turnover and activity of their target proteins. Rhomboid domain containing 2 () is a rhomboid family member overexpressed during mammary gland development and advanced stages of breast cancer. Interactome profiling studies have identified RHBDD2 as a novel binding partner of WW domain‑containing oxidoreductase (WWOX) protein.

Experimental and Theoretical Characterization of Ultrafast Water-Soluble Photochromic Photoacids.

UV-visible transient absorption spectroscopy and quantum mechanical simulations are combined to elucidate the photochemical mechanism of two metastable merocyanine/spiropyran photoacids, 2-[()-2-(2-hydroxyphenyl)ethenyl]-3,3-dimethyl-1-(3-sulfopropyl)-3-indol-1-ium (phenylhydroxy-MCH) and 2-[()-2-(1-indazol-7-yl)ethenyl]-3-(3-sulfopropyl)-1,3-benzothiazol-3-ium (indazole-MCH). Transient absorption spectra demonstrate that -acid isomerization to the form results in deprotonation on a picosecond time scale. Ring closure to form spiropyran follows promptly from the appropriate conformation or follows at longer time delays (≫3.

Genomic Alterations during the to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System.

The drivers of ductal carcinoma (DCIS) to invasive ductal carcinoma (IDC) transition are poorly understood. Here, we conducted an integrated genomic, transcriptomic, and whole-slide image analysis to evaluate changes in copy-number profiles, mutational profiles, expression, neoantigen load, and topology in 6 cases of matched pure DCIS and recurrent IDC. We demonstrate through combined copy-number and mutational analysis that recurrent IDC can be genetically related to its pure DCIS despite long latency periods and therapeutic interventions.

WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders.

The gene was initially discovered as a putative tumor suppressor. More recently, its association with multiple central nervous system (CNS) pathologies has been recognized. biallelic germline pathogenic variants have been implicated in spinocerebellar ataxia type 12 (SCAR12; MIM:614322) and in early infantile epileptic encephalopathy (EIEE28; MIM:616211).

The Mechanics of the Bicycle Pedal Photoisomerization in Crystalline -1,4-Diphenyl-1,3-butadiene.

Direct irradiation of crystalline -1,4-diphenyl-1,3-butadiene (cc-DPB) forms -1,4-diphenyl-1,3,-butadiene via a concerted two-bond isomerization called the bicycle pedal (BP) mechanism. However, little is known about photoisomerization pathways in the solid state and there has been much debate surrounding the interpretation of volume-conserving isomerization mechanisms. The bicycle pedal photoisomerization is investigated using the quantum mechanics/molecular mechanics complete active space self-consistent field/Amber force-field method.

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels.

a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression.

Long intergenic non-protein coding RNA 885 () was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by in non-invasive and invasive breast cancer models. We determined that induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines.

Deletion in Mouse B Cells Leads to Genomic Instability, Neoplastic Transformation, and Monoclonal Gammopathies.

(WW domain containing oxidoreductase) expression loss is common in various cancers and characteristic of poor prognosis. Deletions, translocations, and loss of expression affecting the gene are a common feature of various B cell neoplasms such as certain B cell lymphomas and multiple myeloma. However, the role of this common abnormality in B cell tumor initiation and/or progression has not been defined.

Delineating WWOX Protein Interactome by Tandem Affinity Purification-Mass Spectrometry: Identification of Top Interactors and Key Metabolic Pathways Involved.

It has become clear from multiple studies that WWOX (WW domain-containing oxidoreductase) operates as a "non-classical" tumor suppressor of significant relevance in cancer progression. Additionally, WWOX has been recognized for its role in a much wider array of human pathologies including metabolic conditions and central nervous system related syndromes. A myriad of putative functional roles has been attributed to WWOX mostly through the identification of various binding proteins.

Discovery of conical intersection mediated photochemistry with growing string methods.

Conical intersections (CIs) are important features of photochemistry that determine yields and selectivity. Traditional CI optimizers require significant human effort and chemical intuition, which typically restricts searching to only a small region of the CI space. Herein, a systematic approach utilizing the growing string method is introduced to locate multiple CIs.

WWOX, the FRA16D gene: A target of and a contributor to genomic instability.

WWOX is one of the largest human genes spanning over 1.11 Mbp in length at chr16q23.1-q23.

Wwox deletion leads to reduced GABA-ergic inhibitory interneuron numbers and activation of microglia and astrocytes in mouse hippocampus.

The association of WW domain-containing oxidoreductase WWOX gene loss of function with central nervous system (CNS) related pathologies is well documented. These include spinocerebellar ataxia, epilepsy and mental retardation (SCAR12, OMIM: 614322) and early infantile epileptic encephalopathy (EIEE28, OMIM: 616211) syndromes. However, there is complete lack of understanding of the pathophysiological mechanisms at play.

Genomic and Expression Analyses Identify a Disease-Modifying Variant for Fibrostenotic Crohn's Disease.

Background And Aims: Crohn's disease [CD] is a chronic inflammatory disease with unpredictable behaviour. More than half of CD patients eventually develop complications such as stenosis, for which they then require endoscopic dilatation or surgery, as no anti-fibrotic drugs are currently available. We aim to identify disease-modifying genes associated with fibrostenotic CD.

Wwox-Brca1 interaction: role in DNA repair pathway choice.

In this study, loss of expression of the fragile site-encoded Wwox protein was found to contribute to radiation and cisplatin resistance of cells, responses that could be associated with cancer recurrence and poor outcome. WWOX gene deletions occur in a variety of human cancer types, and reduced Wwox protein expression can be detected early during cancer development. We found that Wwox loss is followed by mild chromosome instability in genomes of mouse embryo fibroblast cells from Wwox-knockout mice.

DMBA induced mouse mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations.

Controversy always existed on the utility of chemically induced mouse mammary carcinogenesis models as valid equivalents for the study of human breast cancer. Here, we performed whole exome and RNA sequencing on long latency mammary tumors (218 ± 27 days) induced by the carcinogen 7,12-Dimethylbenzathracene (DMBA) and short latency tumors (65 ± 11 days) induced by the progestin Medroxyprogesterone Acetate (MPA) plus DMBA in CD2F1 mice. Long latency tumors displayed a high frequency of Pi3kca and/or Pten mutations detected in 11 of 13 (85%) long latency cases (14/22, 64% overall).

Conformance contrast testing between rates of pulmonary tuberculosis in Ecuadorian border areas.

Objective: To estimate rates of cases of respiratory symptomatic subjects and the incidence rate of pulmonary tuberculosis in two border areas of Ecuador, and contrast them with official figures.

Materials And Methods: Cross-sectional survey in the southeastern (SEBA), and the Andean southern Ecuadorian border areas (ASBA), which were conducted, respectively, in 1 598 and 2 419 persons aged over 15 years recruited over periods of three weeks. In identified respiratory symptomatic cases, a sputum sample was taken for smear testing.

A Molecular Portrait of High-Grade Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer whereas others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs.