Gαi and GƔ30A act downstream of Tre1 in Drosophila courtship

The role of genes in morphological development is well understood for a variety of model organisms, but there remains a gap in our understanding of how genetics mediate behavior. Are there master genes that regulate behavior? Answering this question will lead to a better understanding of the development and function of the central nervous system, eventually allowing us to map out the pathways that regulate specific behaviors. We are using Drosophila melanogaster as a model organism and the male courtship ritual as the behavior of interest to study the relationships between genes, neural development, and behavior. Trapped in endoderm 1 (Tre1), a gene encoding an orphan G-protein coupled receptor (GPCR), is required for normal courtship behavior in fruit flies, but how this receptor regulates behavior is not yet understood. Here, we characterize the signaling cascade downstream of Tre1 by testing mutations in the Drosophila G-proteins for courtship defects similar to those seen in Tre1. Our results demonstrate that Gαi is a candidate downstream effector for Tre1, while also implicating Gγ30A in courtship behavior. Future goals include completing the characterization of the G-protein mutations and conducting experiments to explore the complex interaction between G-protein signaling and courtship initiation

Immediate Early Gene Expression in D1-SPNs and D2-SPNs During a Striatum-dependent Reinforcement Learning Task

Dopamine signaling is thought to alter the excitability of the striatum’s principal neurons (D1- and D2-SPNs). We used immunohistochemistry to quantify the expression of Fos, a marker of neural activity, in mice trained in a head-fixed, striatum-dependent fear conditioning task. We observed a relative increase in Fos-expressing D1- vs D2-SPNs, which may indicate how activity in these neurons facilitates motor learning. Our findings have implications for understanding disease processes that affect the dopamine system, such as Parkinson’s disease and schizophrenia

Generating Image-Specific Text Improves Fine-grained Image Classification

Recent vision-language models outperform vision-only models on many image classification tasks. However, because of the absence of paired text/image descriptions, it remains difficult to fine-tune these models for fine-grained image classification. In this work, we propose a method, GIST, for generating image-specific fine-grained text descriptions from image-only datasets, and show that these text descriptions can be used to improve classification. Key parts of our method include 1. prompting a pretrained large language model with domain-specific prompts to generate diverse fine-grained text descriptions for each class and 2. using a pretrained vision-language model to match each image to label-preserving text descriptions that capture relevant visual features in the image. We demonstrate the utility of GIST by fine-tuning vision-language models on the image-and-generated-text pairs to learn an aligned vision-language representation space for improved classification. We evaluate our learned representation space in full-shot and few-shot scenarios across four diverse fine-grained classification datasets, each from a different domain. Our method achieves an average improvement of $4.1\%$ in accuracy over CLIP linear probes and an average of $1.1\%$ improvement in accuracy over the previous state-of-the-art image-text classification method on the full-shot datasets. Our method achieves similar improvements across few-shot regimes. Code is available at https://github.com/emu1729/GIST.Comment: The first two authors contributed equally to this wor

Air pollution dispersion from biomass stoves to neighboring homes in Mirpur, Dhaka, Bangladesh.

BACKGROUND: Indoor air pollution, including fine particulate matter (PM2.5) and carbon monoxide (CO), is a major risk factor for pneumonia and other respiratory diseases. Biomass-burning cookstoves are major contributors to PM2.5 and CO concentrations. However, high concentrations of PM2.5 (> 1000 μg/m3) have been observed in homes in Dhaka, Bangladesh that do not burn biomass. We described dispersion of PM2.5 and CO from biomass burning into nearby homes in a low-income urban area of Dhaka, Bangladesh. METHODS: We recruited 10 clusters of homes, each with one biomass-burning (index) home, and 3-4 neighboring homes that used cleaner fuels with no other major sources of PM2.5 or CO. We administered a questionnaire and recorded physical features of all homes. Over 24 h, we recorded PM2.5 and CO concentrations inside each home, near each stove, and outside one neighbor home per cluster. During 8 of these 24 h, we conducted observations for pollutant-generating activities such as cooking. For each monitor, we calculated geometric mean PM2.5 concentrations at 5-6 am (baseline), during biomass burning times, during non-cooking times, and over 24 h. We used linear regressions to describe associations between monitor location and PM2.5 and CO concentrations. RESULTS: We recruited a total of 44 homes across the 10 clusters. Geometric mean PM2.5 and CO concentrations for all monitors were lowest at baseline and highest during biomass burning. During biomass burning, linear regression showed a decreasing trend of geometric mean PM2.5 and CO concentrations from the biomass stove (326.3 μg/m3, 12.3 ppm), to index home (322.7 μg/m3, 11.2 ppm), neighbor homes sharing a wall with the index home (278.4 μg/m3, 3.6 ppm), outdoors (154.2 μg/m3, 0.7 ppm), then neighbor homes that do not share a wall with the index home (83.1 μg/m3,0.2 ppm) (p = 0.03 for PM2.5, p = 0.006 for CO). CONCLUSION: Biomass burning in one home can be a source of indoor air pollution for several homes. The impact of biomass burning on PM2.5 or CO is greatest in homes that share a wall with the biomass-burning home. Eliminating biomass burning in one home may improve air quality for several households in a community

Failure of functional imaging with gallium-68-DOTA-D-Phe1-Tyr3-octreotide positron emission tomography to localize the site of ectopic adrenocorticotropic hormone secretion: a case report

<p>Abstract</p> <p>Introduction</p> <p>The diagnostic efficacy of biochemical and imaging modalities for investigating the causes of Cushing's syndrome are limited. We report a case demonstrating the limitations of these modalities, especially the inability of functional imaging to help localize the site of ectopic adrenocorticotropic hormone secretion.</p> <p>Case presentation</p> <p>A 37-year-old Arabian woman presented with 12 months of progressive Cushing's syndrome-like symptoms. Biochemical evaluation confirmed adrenocorticotropic hormone -dependent Cushing's syndrome. However, the anatomical site of her excess adrenocorticotropic hormone secretion was not clearly delineated by further investigations. Magnetic resonance imaging of our patient's pituitary gland failed to demonstrate the presence of an adenoma. Spiral computed tomography of her chest only revealed the presence of a non-specific 7 mm lesion in her left inferobasal lung segment. Functional imaging, including a positron emission tomography scan using 18-fluorodeoxyglucose and gallium-68-DOTA-D-Phe1-Tyr3-octreotide, also failed to show increased metabolic activity in the lung lesion or in her pituitary gland. Our patient was commenced on medical treatment with ketoconazole and metyrapone to control the clinical features associated with her excess cortisol secretion. Despite initial normalization of her urinary free cortisol excretion rate, levels began to rise eight months after commencement of medical treatment. Repeated imaging of her pituitary gland, chest and pelvis again failed to clearly localize a source of her excess adrenocorticotropic hormone secretion. The bronchial nodule was stable in size on serial imaging and repeatedly reported as having a nonspecific appearance of a small granuloma or lymph node. We re-explored the treatment options and endorsed our patient's favored choice of resection of the bronchial nodule, especially given that her symptoms of cortisol excess were difficult to control and refractory. Subsequently, our patient had the bronchial nodule resected. The histological appearance of the lesion was consistent with that of a carcinoid tumor and immunohistochemical analysis revealed that the tumor stained strongly positive for adrenocorticotropic hormone. Furthermore, removal of the lung lesion resulted in a normalization of our patient's 24-hour urinary free cortisol excretion rate and resolution of her symptoms and signs of hypercortisolemia.</p> <p>Conclusion</p> <p>This case report demonstrates the complexities and challenges in diagnosing the causes of adrenocorticotropic hormone -dependent Cushing's syndrome. Functional imaging may not always localize the site of ectopic adrenocorticotropic hormone secretion.</p

Revealing the Chemical and Structural Complexity of Electrochemical Ion Exchange in Layered Oxide Materials.

Soft chemistry techniques, such as ion exchange, hold great potential for the development of battery electrode materials that cannot be stabilized via conventional equilibrium synthesis methods. Nevertheless, the intricate mechanisms governing ion exchange remain elusive. Herein, we investigate the evolution of the long-range and local structure, as well as the ion (de)intercalation mechanism during electrochemical Li-to-Na ion exchange initiated from an O3-type lithium-layered oxide cathode. The in situ-formed mixed-cation electrolyte leads to competitive intercalation of Li and Na ions. While Li ion intercalation predominates at the beginning of initial discharge, Na ion cointercalation into a different layer results in ion redistribution and phase separation, with the emergence of a P3-Na phase alongside an O3-Li phase. Further, this study spatially resolves the heterogeneous nature of electrochemical ion exchange reactions within individual particles and provides insights into the correlations between local Ni redox processes and phase separation. Overall, electrochemical ion exchange leads to a mixed-phase cathode and alters its reaction kinetics. Those findings have important implications for the development of new metastable materials for renewable energy devices and ion separation applications

OPN promotes the aggressiveness of non-small-cell lung cancer cells through the activation of the RON tyrosine kinase

Osteopontin (OPN) is identified as a diagnostic and prognostic biomarker of tumor progression and metastasis. In non-small-cell lung cancer (NSCLC), the functions of OPN have not been well characterized. The current study sought to investigate the clinical implications of OPN expression in NSCLC and the role of OPN in the aggressiveness of the lung cancer cells. Using a proteomics approach, we identified that phospho-RON (p-RON) was one of the most remarkably up-regulated proteins in OPN-overexpressing cells. The levels of OPN and RON transcripts were unveiled as independent prognostic indicators of survival in NSCLC (p = 0.001). Higher levels of OPN, RON and p-RON proteins were observed in tumor tissues. Knock down of the OPN gene suppressed the migration and invasion abilities of the A549 lung cancer cells which endogenously expresses OPN. While ectopic expression of OPN in the SK-MES-1 lung cancer cells increased levels of cellular invasion and migration. In addition, these changes were accompanied by a phosphorylated activation of RON. Small-molecule inhibition of RON or siRNA silencing of RON significantly reduced OPN-induced migration and invasion of lung cancer cells and had an inhibitory effect on the OPN-mediated cell epithelial-mesenchymal transition. Our study suggests that in NSCLC, the aberrant expression of OPN can be considered as an independent survival indicator and is associated with disease progression. OPN plays a crucial role in promoting migration and invasion properties of lung cancer cells through its phosphorylation activation of the RON signaling pathway, implying its potential as a therapeutic target in the treatment of NSCLC

Dietary Fiber and Saturated Fat Intake Associations with Cardiovascular Disease Differ by Sex in the Malmö Diet and Cancer Cohort: A Prospective Study

BACKGROUND: The aim of the study was to examine associations between intake of macronutrients and dietary fiber and incident ischemic cardiovascular disease (iCVD) in men and women. METHODS: We used data from 8,139 male and 12,535 female participants (aged 44-73 y) of the Swedish population-based Malmö Diet and Cancer cohort. The participants were without history of CVD and diabetes mellitus, and had reported stable dietary habits in the study questionnaire. Diet was assessed by a validated modified diet history method, combining a 7-d registration of cooked meals and cold beverages, a 168-item food questionnaire (covering other foods and meal patterns), and a 1-hour diet interview. Sociodemographic and lifestyle data were collected by questionnaire. iCVD cases, which included coronary events (myocardial infarctions or deaths from chronic ischemic heart disease) and ischemic strokes, were ascertained via national and local registries. Nutrient-disease associations were examined by multivariate Cox regressions. RESULTS: During a mean follow-up of 13.5 years, we identified 1,089 male and 687 female iCVD cases. High fiber intakes were associated with lower incidence rates of iCVD in women and of ischemic stroke in men. In post-hoc analysis, we discovered statistically significant interactions between intake of fiber and saturated fat; these interactions also differed between men and women (p<0.001). CONCLUSIONS: In this well-defined population, a high fiber intake was associated with lower risk of iCVD, but there were no robust associations between other macronutrients and iCVD risk. Judging from this study, gender-specific nutrient analysis may be preferable in epidemiology

Multiple M. tuberculosis Phenotypes in Mouse and Guinea Pig Lung Tissue Revealed by a Dual-Staining Approach

A unique hallmark of tuberculosis is the granulomatous lesions formed in the lung. Granulomas can be heterogeneous in nature and can develop a necrotic, hypoxic core which is surrounded by an acellular, fibrotic rim. Studying bacilli in this in vivo microenvironment is problematic as Mycobacterium tuberculosis can change its phenotype and also become acid-fast negative. Under in vitro models of differing environments, M. tuberculosis alters its metabolism, transcriptional profile and rate of replication. In this study, we investigated whether these phenotypic adaptations of M. tuberculosis are unique for certain environmental conditions and if they could therefore be used as differential markers. Bacilli were studied using fluorescent acid-fast auramine-rhodamine targeting the mycolic acid containing cell wall, and immunofluorescence targeting bacterial proteins using an anti-M. tuberculosis whole cell lysate polyclonal antibody. These techniques were combined and simultaneously applied to M. tuberculosis in vitro culture samples and to lung sections of M. tuberculosis infected mice and guinea pigs. Two phenotypically different subpopulations of M. tuberculosis were found in stationary culture whilst three subpopulations were found in hypoxic culture and in lung sections. Bacilli were either exclusively acid-fast positive, exclusively immunofluorescent positive or acid-fast and immunofluorescent positive. These results suggest that M. tuberculosis exists as multiple populations in most conditions, even within seemingly a single microenvironment. This is relevant information for approaches that study bacillary characteristics in pooled samples (using lipidomics and proteomics) as well as in M. tuberculosis drug development