Assessment of the Cutaneous Hormone Landscapes and Microbiomes in Vulvar Lichen Sclerosus.

Vulvar lichen sclerosus (VLS) is a progressive skin disease of unknown etiology. In this longitudinal case-control exploratory study, we evaluated the hormonal and microbial landscapes in 18 postmenopausal females (mean [SD] age: 64.4 [8.

CLSTN3B enhances adipocyte lipid droplet structure and function via endoplasmic reticulum contact.

Interorganelle contacts facilitate material exchanges and sustain the structural and functional integrity of organelles. Lipid droplets (LDs) of adipocytes are responsible for energy storage and mobilization responding to body needs. LD biogenesis defects compromise the lipid-storing capacity of adipocytes, resulting in ectopic lipid deposition and metabolic disorders, yet how the uniquely large LDs in adipocytes attain structural and functional maturation is incompletely understood.

A Proline-Squaraine Ligand Framework (Pro-SqEB) for Stereoselective Rhodium(II)-Catalyzed Cyclopropanations.

A proline-squaraine ligand (Pro-SqEB) that demonstrates high levels of stereoselectivity in olefin cyclopropanations when anchored to a Rh scaffold is introduced. High yields and enantioselectivities were achieved in the cyclopropanation of alkenes with diazo compounds in the presence of Rh(Pro-SqEB). Notably, the unique electronic and steric design of this catalyst enabled the use of polar solvents that are otherwise incompatible with most Rh complexes.

Association of Vaginal Progesterone Treatment With Prevention of Recurrent Preterm Birth.

Importance: Preterm birth (PTB) is the leading cause of infant morbidity and mortality worldwide. It has been suggested that vaginal progesterone (VP) treatment may reduce the recurrence of PTB.

Objective: To evaluate the association of VP treatment with prevention of recurrent PTB among patients with a singleton pregnancy.

Cutaneous Hormone Production Is Distinct between Anatomical Sites and between Males and Females.

The skin acts as an endocrine organ capable of hormone production and response. Moreover, many skin conditions clinically improve with antiandrogen therapies. Despite their importance, we have an incomplete understanding of the composition of hormones produced by the skin.

Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.

Deregulation of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) plays a significant role in developmental brain defects, early-onset neurodegeneration, neuronal cell loss, dementia, and several types of cancer. Herein, we report the discovery of three new classes of N-heterocyclic DYRK1A inhibitors based on the potent, yet toxic kinase inhibitors, harmine and harmol. An initial in vitro evaluation of the small molecule library assembled revealed that the core heterocyclic motifs benzofuranones, oxindoles, and pyrrolones, showed statistically significant DYRK1A inhibition.

Interleukins 4 and 13 drive lipid abnormalities in skin cells through regulation of sex steroid hormone synthesis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin dryness, inflammation, and itch. A major hallmark of AD is an elevation of the immune cytokines IL-4 and IL-13. These cytokines lead to skin barrier disruption and lipid abnormalities in AD, yet the underlying mechanisms are unclear.

Snx14 proximity labeling reveals a role in saturated fatty acid metabolism and ER homeostasis defective in SCAR20 disease.

Fatty acids (FAs) are central cellular metabolites that contribute to lipid synthesis, and can be stored or harvested for metabolic energy. Dysregulation in FA processing and storage causes toxic FA accumulation or altered membrane compositions and contributes to metabolic and neurological disorders. Saturated lipids are particularly detrimental to cells, but how lipid saturation levels are maintained remains poorly understood.

Decreased 11β-hydroxysteroid dehydrogenase 1 in lungs of steroid receptor coactivator (Src)-1/-2 double-deficient fetal mice is caused by impaired glucocorticoid and cytokine signaling.

Our previous research revealed that steroid receptor coactivators (Src)-1 and -2 serve a critical cooperative role in production of parturition signals, surfactant protein A and platelet-activating factor, by the developing mouse fetal lung (MFL). To identify the global landscape of genes in MFL affected by Src-1/-2 double-deficiency, we conducted RNA-seq analysis of lungs from 18.5 days post-coitum (dpc) Src-1 /-2 (dKO) vs.

Diverse species-specific phenotypic consequences of loss of function sorting nexin 14 mutations.

Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) in both humans and dogs. Studies implicating the phenotypic consequences of SNX14 mutations to be consequences of subcellular disruption to autophagy and lipid metabolism have been limited to in vitro investigation of patient-derived dermal fibroblasts, laboratory engineered cell lines and developmental analysis of zebrafish morphants. SNX14 homologues Snz (Drosophila) and Mdm1 (yeast) have also been conducted, demonstrated an important biochemical role during lipid biogenesis.

Cholesterol accessibility at the ciliary membrane controls hedgehog signaling.

Previously we proposed that transmission of the hedgehog signal across the plasma membrane by Smoothened is triggered by its interaction with cholesterol (Luchetti et al., 2016). But how is cholesterol, an abundant lipid, regulated tightly enough to control a signaling system that can cause birth defects and cancer? Using toxin-based sensors that distinguish between distinct pools of cholesterol, we find that Smoothened activation and Hedgehog signaling are driven by a biochemically-defined, small fraction of membrane cholesterol, termed accessible cholesterol.

Drosophila Snazarus Regulates a Lipid Droplet Population at Plasma Membrane-Droplet Contacts in Adipocytes.

Adipocytes store nutrients as lipid droplets (LDs), but how they organize their LD stores to balance lipid uptake, storage, and mobilization remains poorly understood. Here, using Drosophila fat body (FB) adipocytes, we characterize spatially distinct LD populations that are maintained by different lipid pools. We identify peripheral LDs (pLDs) that make close contact with the plasma membrane (PM) and are maintained by lipophorin-dependent lipid trafficking.

Three-phase liquid extraction: a simple and fast method for lipidomic workflows.

An unbiased sample preparation free of interferents (i.e., competing analytes, detergents, plastics) is critical to any lipid MS workflow.

Polyphenols from the sagebrush ssp. affect the redox state of cultured hepatocytes by direct and indirect mechanisms.

Basin big sagebrush ( Nutt. ssp. (Asteraceae)), is a widespread North American shrub which produces a variety of polyphenolic compounds.

Aroyl Isocyanates as 1,4-Dipoles in a Formal [4 + 1]-Cycloaddition Approach toward Oxazolone Construction.

A formal phosphine-mediated [4 + 1]-cycloaddition between a 1,2-dicarbonyl and an aroyl isocyanate to provide oxazolones bearing a disubstituted C5 center is described. By exploiting the carbene-like reactivity of oxyphosphonium enolates as C1 synthons and aroyl isocyanates as formal 1,4-dipoles, oxazolones and spiroooxindole oxazolones are constructed in high yields (39-99%).

GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment.

The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here, we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway.