The actin-microtubule cross-linking activity of Drosophila Short stop is regulated by intramolecular inhibition

Actin and microtubule dynamics must be precisely coordinated during cell migration, mitosis, and morphogenesis—much of this coordination is mediated by proteins that physically bridge the two cytoskeletal networks. We have investigated the regulation of the Drosophila actin-microtubule cross-linker Short stop (Shot), a member of the spectraplakin family. Our data suggest that Shot's cytoskeletal cross-linking activity is regulated by an intramolecular inhibitory mechanism. In its inactive conformation, Shot adopts a “closed” conformation through interactions between its NH2-terminal actin-binding domain and COOH-terminal EF-hand-GAS2 domain. This inactive conformation is targeted to the growing microtubule plus end by EB1. On activation, Shot binds along the microtubule through its COOH-terminal GAS2 domain and binds to actin with its NH2-terminal tandem CH domains. We propose that this mechanism allows Shot to rapidly cross-link dynamic microtubules in response to localized activating signals at the cell cortex

Dietary adaptation for weight loss maintenance at Yale (DAWLY): Protocol and predictions for a randomized controlled trial

BackgroundCurrent therapies for obesity treatment are effective at producing short-term weight loss, but weight loss maintenance remains a significant challenge. Here we investigate the impact of pre-intervention dietary fat intake on the efficacy of a dietary supplement to support weight loss maintenance. Preclinical work demonstrates that a vagal afferent pathway critical for sensing dietary lipids is blunted by a high-fat diet (HFD), resulting in a reduced preference for a low-fat emulsion and severe blunting of the dopamine (DA) response to the gastric infusion of lipids. Infusion of the gut lipid messenger oleoylethanolamide (OEA), which is also depleted by HFD, immediately reverses this DA blunting and restores preference for the low-fat emulsion. Studies of OEA supplementation for weight loss in humans have had limited success. Given the strong effect of HFD on this pathway, we designed a study to test whether the efficacy of OEA as a weight loss treatment is related to pre-intervention habitual intake of dietary fat.Methods/DesignWe employed a randomized, double-blind, placebo-controlled trial in which 100 adults with overweight/obesity (OW/OB) were randomized to receive either OEA or placebo daily for 16 months. Following a baseline evaluation of diet, metabolic health, adiposity, and brain response to a palatable an energy dense food, participants in both groups underwent a 4-month behavioral weight loss intervention (LEARN®) followed by a 1-year maintenance period. The study aims are to (1) determine if pre-intervention dietary fat intake moderates the ability of OEA to improve weight loss and weight loss maintenance after a gold standard behavioral weight loss treatment; (2) identify biomarkers that predict outcome and optimize a stratification strategy; and (3) test a model underlying OEA’s effectiveness.DiscussionFocusing on interventions that target the gut-brain axis is supported by mounting evidence for the role of gut-brain signaling in food choice and the modulation of this circuit by diet. If successful, this work will provide support for targeting the gut-brain pathway for weight loss maintenance using a precision medicine approach that is easy and inexpensive to implement.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT04614233]

Radical-Initiated Brown Carbon Formation in Sunlit Carbonyl–Amine–Ammonium Sulfate Mixtures and Aqueous Aerosol Particles

Brown carbon (BrC) formed from glyoxal+ammonium sulfate (AS) and methylglyoxal+AS reactions photobleaches quickly, leading to the assumption that BrC formed overnight by Maillard reactions will be rapidly destroyed at sunrise. Here, we tested this assumption by reacting glyoxal, methylglyoxal, glycolaldehyde, or hydroxyacetone in aqueous mixtures with reduced nitrogen species at pH 4–5 in the dark and in sunlight (\u3e350 nm) for at least 10 h. The absorption of fresh carbonyl+AS mixtures decreased when exposed to sunlight, and no BrC formed, as expected from previous work. However, the addition of amines (either methylamine or glycine) allowed BrC to form in sunlight at comparable rates as in the dark. Hydroxyacetone+amine+AS aqueous mixtures generally browned faster in sunlight than in the dark, especially in the presence of HOOH, indicating a radical-initiated BrC formation mechanism is involved. In experiments with airborne aqueous aerosol containing AS, methylamine, and glyoxal or methylglyoxal, browning was further enhanced, especially in sunlight (\u3e300 nm), forming aerosol with optical properties similar to “very weak” atmospheric BrC. Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analysis of aerosol filter extracts indicates that exposure of methylglyoxal+AS aqueous aerosol to methylamine gas, sunlight, and cloud processing increases incorporation of ammonia, methylamine, and photolytic species (e.g., acetyl radicals) into conjugated oligomer products. These results suggest that when amines are present, photolysis of first-generation, “dark reaction” BrC (imines and imidazoles) initiates faster, radical-initiated browning processes that may successfully compete with photobleaching, are enhanced in aqueous aerosol particles relative to bulk liquid solutions, and can produce BrC consistent with atmospheric observations

Stabilized tilted-octahedra halide perovskites inhibit local formation of performance-limiting phases.

Efforts to stabilize photoactive formamidinium (FA)–based halide perovskites for perovskite photovoltaics have focused on the growth of cubic formamidinium lead iodide (α-FAPbI3) phases by empirically alloying with cesium, methylammonium (MA) cations, or both. We show that such stabilized FA-rich perovskites are noncubic and exhibit ~2° octahedral tilting at room temperature. This tilting, resolvable only with the use of local nanostructure characterization techniques, imparts phase stability by frustrating transitions from photoactive to hexagonal phases. Although the bulk phase appears stable when examined macroscopically, heterogeneous cation distributions allow microscopically unstable regions to form; we found that these transitioned to hexagonal polytypes, leading to local trap-assisted performance losses and photoinstabilities. Using surface-bound ethylenediaminetetraacetic acid, we engineered an octahedral tilt into pure α-FAPbI3 thin films without any cation alloying. The templated photoactive FAPbI3 film was extremely stable against thermal, environmental, and light stressors

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages