The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.
View Article and Find Full Text PDFIntroduction: Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from nodule screening or follow-up to early lung cancer detection. This is due to improved nodule localization and biopsy confirmation with combined modalities of navigational platforms and imaging tools.
View Article and Find Full Text PDFBackground And Aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico.
Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included.
CD8 T cells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets, but how chromatin is site-specifically remodeled during their differentiation is unclear. Due to its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8 T cells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions (OCRs) at enhancers.
View Article and Find Full Text PDFCharacterization of COVID-19 in the Latinx community is necessary for guiding public health initiatives, health system policy, clinical management practices, and improving outcomes. Our aim was to describe the socioeconomic background and clinical profile of patients with COVID-19 at a large public hospital in Los Angeles to improve health disparities leading to poor outcomes during the pandemic. A single center retrospective cross-sectional study of all patients with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to Los Angeles County (LAC)+University of Southern California (USC) Medical Center between March 15, 2020 and April 30, 2020.
View Article and Find Full Text PDFBackground: Postpartum depression is common and adversely affects children of afflicted mothers; postpartum depression recognition and treatment may improve outcomes. Hospitalization represents a potential health encounter for expanding screening and intervention.
Objective: We aimed to assess for postpartum depression at infant hospitalization and examine postpartum depression risk factors in this population.
Bivalves are used as sentinel species to detect chemical contaminants in the marine environment, but biological effects on indigenous populations that result from chemical exposure are largely unknown. We assessed age-weight, length-weight relationships, age structure, and reproductive status (i.e.
View Article and Find Full Text PDFBackground: Chagas disease kills approximately 45 thousand people annually and affects 10 million people in Latin America and the southern United States. The parasite that causes the disease, Trypanosoma cruzi, can be transmitted by insects of the family Reduviidae, subfamily Triatominae. Any study that attempts to evaluate risk for Chagas disease must focus on the ecology and biogeography of these vectors.
View Article and Find Full Text PDFFluorescence optical detection in sedimentation velocity analytical ultracentrifugation allows the study of macromolecules at nanomolar concentrations and below. This has significant promise, for example, for the study of systems of high-affinity protein interactions. Here we describe adaptations of the direct boundary modeling analysis approach implemented in the software SEDFIT that were developed to accommodate unique characteristics of the confocal fluorescence detection system.
View Article and Find Full Text PDFAnalytical ultracentrifugation (AUC) and steady-state fluorescence anisotropy were used to measure the equilibrium dissociation constant (Kd) for formation of dimers by the amino-terminal domains (ATDs) of the GluA2 and GluA3 subtypes of AMPA receptor. Previous reports on GluA2 dimerization differed in their estimate of the monomer-dimer Kd by a 2,400-fold range, with no consensus on whether the ATD forms tetramers in solution. We find by sedimentation velocity (SV) analysis performed using absorbance detection a narrow range of monomer-dimer Kd values for GluA2, from 5 to 11 nM for six independent experiments, with no detectable formation of tetramers and no effect of glycosylation or the polypeptide linker connecting the ATD and ligand-binding domains; for GluA3, the monomer-dimer Kd was 5.
View Article and Find Full Text PDFContext: Latino and black adolescents are disproportionately affected by STDs, including HIV, and unintended pregnancies. Few parent-based interventions have targeted these youth, focused on early adolescence and had high participation rates.
Methods: Between 2003 and 2009, a randomized clinical trial was conducted with 2,016 Latino and black mother-adolescent dyads in New York City.
J Matern Fetal Neonatal Med
December 2011
Objective: The adipocyte-derived hormone leptin regulates food intake and body weight via the activation of JAK-STAT pathway in mammalian adult hypothalamic neurons. To investigate whether endogenous leptin is metabolically active in newborn rat pups, the JAK-STAT leptin signaling pathway was analyzed following leptin antagonist challenge.
Methods: One day old male control pups were injected with either (i) saline, (ii) leptin (10 μg/g, s.
Objective: The authors studied the lifetime prevalence of DSM-IV-TR psychiatric disorders in a population of adults with the fragile X premutation.
Method: The Structured Clinical Interview for DSM-IV was conducted, from 2007-2008, in 85 individuals with the fragile X premutation, 47 with the fragile X-associated tremor/ataxia syndrome (FXTAS; 33 male, 14 female; mean age = 66 years) and 38 without FXTAS (16 male, 22 female; mean age = 52 years). Lifetime prevalence for mood and anxiety disorders among carriers with and without FXTAS was compared to available age-specific population estimates from the National Comorbidity Survey Replication (NCS-R).
Background: Because fragile X syndrome (FXS) is prevalent, it has become the subject of newborn and high-risk screening efforts. International screening, however, can be financially and logistically prohibitive, particularly in countries where resources may be scarce. Recently, we have developed a screening test on blood spot that can detect expanded alleles from the normal through the full mutation range in both males and females.
View Article and Find Full Text PDFJ Matern Fetal Neonatal Med
July 2009
Objective: We determined the impact of maternal food restriction during gestation and lactation or lactation alone on basal inflammation and lipopolysaccharide (LPS)-stimulated cytokine induction in adult female offspring.
Study Design: From 10 days of gestation to term, pregnant rats received either ad libitum (control) feed or were 50% food restricted (FR). Pups were either nursed by their own dams or were cross-fostered to give three groups, namely, Control (AdLib/AdLib), FR during lactation (AdLib/FR) and FR during pregnancy and lactation (FR/FR).
Background: The incidence and prevalence of pregnancy and sexually transmitted infections among American adolescents remain unacceptably high.
Purpose: This research examines adolescent intentions to have sexual intercourse, their expectancies about having sexual intercourse, and maternal communication about the expectancies of engaging in sexual intercourse.
Methods: Six hundred sixty-eight randomly selected inner-city middle school students and their mothers completed self-administered questionnaires.
Feeding dysregulation may manifest as either under-nourishment (e.g., anorexia) or excessive eating leading to obesity.
View Article and Find Full Text PDFBioorg Med Chem Lett
February 2004
The nonsteroidal anti-inflammatory drugs flurbiprofen and ibuprofen were modified in an attempt to alter the kinetics of inhibitor binding by COX-1. Contrary to prior predictions, a halogen substituent is not sufficient to confer slow tight-binding behavior. Conversion of the carboxylate moiety of flurbiprofen to an ester or amide abolishes slow tight-binding behavior, regardless of halogenation state.
View Article and Find Full Text PDFArch Environ Contam Toxicol
January 2003
A selected suite of cytochemical parameters in Mytilus edulis are altered in response to field and laboratory exposure to chemical contaminants. These biomarkers include lysosomal stability, nicotinamide adenine dinucleotide phosphate (NADPH)-ferrihemoprotein reductase activity, liposfuscin deposition, and accumulation of lysosomal and cytoplasmic unsaturated neutral lipid. Normal variations in physiological processes (influenced by exogenous seasonal changes in temperature, salinity, food availability, etc.
View Article and Find Full Text PDFTwo common problems in applying and interpreting invertebrate bioassays and fish biomarkers in sediment toxicology are the wide gap between significant effects concentrations determined by these two approaches, and a general lack of ecological context. We have devised an exposure system that is able to reconcile much of the disparity between invertebrate bioassay and fish biomarker results by incorporating realistic ecological processes based on deposit feeding and predator-prey interactions. This system relates the disturbance of interest (sediment contamination) to biologically meaningful effects in a resource of interest (marine flatfish) via a realistic contaminant vector (a deposit-feeding polychaete worm).
View Article and Find Full Text PDFThe relationship between hemic neoplasia, a blood cell disorder in bivalve molluscs, and chemical contaminants was evaluated in the common mussel (Mytilus edulis complex). Hemic neoplasia (HN) is endemic to mussel populations in Puget Sound. The prevalence of hemic neoplasia ranged from 0 to 30% in mussels from nine sites in Puget Sound, Washington.
View Article and Find Full Text PDFArch Environ Contam Toxicol
November 1997
Bioaccumulation of chlorinated hydrocarbons (CHs) from field-contaminated sediments by two infaunal invertebrates, Rhepoxynius abronius (a non-deposit feeding amphipod) and Armandia brevis (a nonselective, deposit-feeding polychaete), was examined and species responses were compared. Sediments were selected over a large geographical area of the Hudson-Raritan estuary to assess the potential for bioaccumulation from a typical urban estuary. Unlike polycyclic aromatic hydrocarbons (PAHs) from these sediments, concentrations of CHs in interstitial water (IW) indicated that partition coefficients (Koc) were generally as expected, especially when based on predicted, nonsorbed, interstitial water CH concentrations (IWfree).
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