reshapes mucosal immunity toward a Type 2 response that attenuates inflammatory bowel-like diseases.

Diarrheal diseases are the second leading cause of death in children worldwide. Epidemiological studies show that co-infection with decreases the severity of diarrhea. Here, we show that is highly prevalent in the stools of asymptomatic school-aged children.

Management of de novo metastatic hormone-sensitive prostate cancer: A comprehensive report of a single-center experience.

Background: Upfront docetaxel or novel hormonal agents (NHA) such as abiraterone and enzalutamide have become the standard of care for metastatic hormone sensitive prostate cancer (mHSPC). We evaluated real-world management of patients treated with these agents at a single center.

Patients And Methods: Patients with de novo mHSPC treated with upfront docetaxel or an NHA between January 2014 and April 2019 at Mount Sinai Health System were included.

Mice Expressing Cosegregating Single Nucleotide Polymorphisms (D298G and N397I) in TLR4 Have Enhanced Responses to House Dust Mite Allergen.

Asthma is a common and ubiquitous chronic respiratory disease that is associated with airway inflammation and hyperreactivity resulting in airway obstruction. It is now accepted that asthma is controlled by a combination of host genetics and environment in a rather complex fashion; however, the link between sensing of the environment and development and exacerbation of allergic lung inflammation is unclear. Human populations expressing cosegregating D299G and T399I polymorphisms in the gene are associated with a decreased risk for asthma in adults along with hyporesponsiveness to inhaled LPS, the TLR4 ligand.

Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers With Lung Adenocarcinoma.

Introduction: Historically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (ADC). In the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis.

Methods: All Mount Sinai patients between January 1, 2015, and June 1, 2020, with a diagnosis of ADC of any stage with known smoking status who received genomic testing were included.

Impact of body mass index on the efficacy of aromatase inhibitors in patients with metastatic breast cancer.

Purpose: Higher levels of estrogen in obese patients may lead to incomplete inhibition by aromatase inhibitors (AIs). The aim of this study was to determine the impact of body mass index (BMI) on efficacy of AIs in patients with metastatic hormone receptor (HR)-positive breast cancer (BC).

Methods: We performed a retrospective chart review of all female patients with metastatic HR-positive BC on an AI in first- or second-line settings and seen at our academic institution between 2001 and 2020.

USP8 and TP53 Drivers are Associated with CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors.

Context: Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropin (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown.

Objective: To investigate genomic drivers of corticotroph tumors at risk for aggressive behavior.

Giardia lamblia: Laboratory Maintenance, Lifecycle Induction, and Infection of Murine Models.

Giardia lamblia is a protozoan parasite that is found ubiquitously throughout the world and is a major contributor to diarrheal disease. Giardia exhibits a biphasic lifestyle existing as either a dormant cyst or a vegetative trophozoite. Infections are typically initiated through the consumption of cyst-contaminated water or food.

Recent insights into innate and adaptive immune responses to Giardia.

Infection with Giardia produces a wide range of clinical outcomes. Acutely infected patients may have no overt symptoms or suffer from severe cramps, diarrhea, nausea and even urticaria. Recently, post-infectious irritable bowel syndrome and chronic fatigue syndrome have been identified as long-term sequelae of giardiasis.

Proliferation of Resident Macrophages Is Dispensable for Protection during Infections.

Infection with the intestinal parasite is one of the most common causes of diarrheal disease in the world. Previous work has demonstrated that the cells and mechanisms of the adaptive immune system are critical for clearance of this parasite. However, the innate system has not been as well studied in the context of infection.

Distinction of Fly Artifacts from Human Blood using Immunodetection.

Insect stains produced by necrophagous flies are indistinguishable morphologically from human bloodstains. At present, no diagnostic tests exist to overcome this deficiency. As the first step toward developing a chemical test to recognize fly artifacts, polyclonal antisera were generated in rats against three distinct antigenic sequences of fly cathepsin D-like proteinase, an enzyme that is structurally distinct in cyclorrhaphous Diptera from other animals.

The Intersection of Immune Responses, Microbiota, and Pathogenesis in Giardiasis.

Giardia lamblia is one of the most common infectious protozoans in the world. Giardia rarely causes severe life-threatening diarrhea, and may even have a slight protective effect in this regard, but it is a major contributor to malnutrition and growth faltering in children in the developing world. Giardia infection also appears to be a significant risk factor for postinfectious irritable bowel and chronic fatigue syndromes.

Identification of a novel somatic mutation in a -mutated corticotroph adenoma.

Cushing's disease (CD) is caused by pituitary corticotroph adenomas that secrete excess adrenocorticotropic hormone (ACTH). In these tumors, somatic mutations in the gene have been identified as recurrent and pathogenic and are the sole known molecular driver for CD. Although other somatic mutations were reported in these studies, their contribution to the pathogenesis of CD remains unexplored.

Development and clinical application of an integrative genomic approach to personalized cancer therapy.

Background: Personalized therapy provides the best outcome of cancer care and its implementation in the clinic has been greatly facilitated by recent convergence of enormous progress in basic cancer research, rapid advancement of new tumor profiling technologies, and an expanding compendium of targeted cancer therapeutics.

Methods: We developed a personalized cancer therapy (PCT) program in a clinical setting, using an integrative genomics approach to fully characterize the complexity of each tumor. We carried out whole exome sequencing (WES) and single-nucleotide polymorphism (SNP) microarray genotyping on DNA from tumor and patient-matched normal specimens, as well as RNA sequencing (RNA-Seq) on available frozen specimens, to identify somatic (tumor-specific) mutations, copy number alterations (CNAs), gene expression changes, gene fusions, and also germline variants.

Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant-KRas NSCLC Models.

Background: The capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival.

Spatial characterization of proteolytic enzyme activity in the foregut region of the adult necrophagous fly, Protophormia terraenovae.

The spatial distribution of proteolytic enzymes in the adult foregut of Protophormia terraenovae was studied in the context of protein digestion and regurgitation. Based on substrate specificity, pH optima, and use of specific protease inhibitors, all adults tested displayed enzyme activity in the foregut consistent with pepsin, trypsin and chymotrypsin. Chymotrypsin-like and trypsin-like enzyme activity were detected in all gut fluids and tissues tested, with chymotrypsin displaying the highest activity in saliva and salivary gland tissue, whereas maximal trypsin activity was evident in the crop.

Survival of HER2-Positive Breast Cancer Cells: Receptor Signaling to Apoptotic Control Centers.

HER2 is overexpressed in a subset of breast cancers and controls an oncogenic signaling network that inhibits tumor cell death through the specific biochemical regulation of apoptotic pathways. In particular, the mitochondrial pathway for apoptosis is important for death induced by inhibitors of HER2. This review focuses on the connections between this oncogenic signaling network and individual components of the mitochondrial pathway.

Research resource: Gonadotropin-releasing hormone receptor-mediated signaling network in LbetaT2 cells: a pathway-based web-accessible knowledgebase.

The GnRH receptor (GnRHR), expressed at the cell surface of the anterior pituitary gonadotrope, is critical for normal secretion of gonadotropins LH and FSH, pubertal development, and reproduction. The signaling network downstream of the GnRHR and the molecular bases of the regulation of gonadotropin expression have been the subject of intense research. The murine LbetaT2 cell line represents a mature gonadotrope and therefore is an important model for the study of GnRHR-signaling pathways and modulation of the gonadotrope cell by physiological regulators.

Plato's cave algorithm: inferring functional signaling networks from early gene expression shadows.

Improving the ability to reverse engineer biochemical networks is a major goal of systems biology. Lesions in signaling networks lead to alterations in gene expression, which in principle should allow network reconstruction. However, the information about the activity levels of signaling proteins conveyed in overall gene expression is limited by the complexity of gene expression dynamics and of regulatory network topology.

Structure of the GnRH receptor-stimulated signaling network: insights from genomics.

The GnRH receptor influences gene expression in the gonadotrope through activating signaling cascades that modulate transcription factor expression and activity. A longstanding question in neuroendocrinology is how instructions received at the membrane in the form of the pattern of receptor stimulation are processed into specific biosynthetic changes at each gonadotropin promoter. Signal transduction from the membrane to preformed transcription factors relies on recognition of altered conformations.

Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface.

The function of adhesion receptors in both cell adhesion and migration depends critically on interactions with the cytoskeleton. During cell adhesion, cytoskeletal interactions stabilize receptors to strengthen adhesive contacts. In contrast, during cell migration, adhesion proteins are believed to interact with dynamic components of the cytoskeleton, permitting the transmission of traction forces through the receptor to the extracellular environment.