[Ser7]neurotensin: isolation from guinea pig intestine

AbstractUsing three antisera to neurotensin of defined regional specificity, a novel neurotensin has been identified in extracts of guinea pig brain and small intestine. The primary structure of the peptide was established as: pGlu Leu Tyr GIu Asn Lys Ser Arg Arg Pro Tyr He Leu. Guinea pig neurotensin differs from bovine neurotensin by substitution of a prolyl residue by a seryl residue at position 7. Synthetic [Ser7]neurotensin showed identical Chromatographie and immunochemical properties to guinea pig neurotensin. This difference in primary structure may account for some of the anomalous pharmacological effects of bovine neurotensin on guinea pig tissues

Emerging Field of Cardiomics: High-Throughput Investigations into Transcriptional Regulation of Cardiovascular Development and Disease

Congenital heart defects remain a leading cause of infant mortality in the western world, despite decades of research focusing on cardiovascular development and disease,. With the recent emergence of several high-throughput technologies including RNA sequencing, chromatin immunoprecipitation-coupled sequencing, mass spectrometry-based proteomics analyses, and the numerous variations of these strategies, investigations into cardiac development have been transformed from candidate-based studies into whole-genome, -transcriptome, and -proteome undertakings. In this review, we discuss several reports that have emerged from our lab and others over the last five years that emphasize the versatility of large dataset-based investigations of cardiogenic transcription factors, from phenotypic validations and new gene implications to the identification of novel roles of well-studied transcriptional regulators

Effects of Product Availability: Experimental Evidence

Product availability impacts many industries such as transportation, events, and retail, yet little empirical evidence documents the importance of stocking decisions for firm profits, vertical relationships, or consumers. We conduct several experiments, exogenously removing top-selling products from a set of vending machines and analyzing substitution patterns and profit impacts of the changed product availability using nonparametric analyses and structural demand estimation. We find substantial switching to alternate products, and evidence of misaligned incentives between upstream and downstream firms in the choice of which products to carry. We discuss the trade-offs of both empirical approaches for analyzing product availability effects generally.

Development and Evaluation of an Automated Algorithm to Estimate the Nutrient Intake of Infants from an Electronic Complementary Food Frequency Questionnaire

Background: We previously validated a four-day complementary food frequency questionnaire (CFFQ) to estimate the nutrient intake in New Zealand infants aged 9-12 months. However, manual entry of the CFFQ data into nutritional analysis software was time-consuming. Therefore, we developed an automated algorithm and evaluated its accuracy by comparing the nutrient estimates with those obtained from the nutritional analysis software.Methods: We analysed 50 CFFQ completed at 9- and 12-months using Food Works nutritional analysis software. The automated algorithm was programmed in SAS by multiplying the average daily consumption of each food item by the nutrient content of the portion size. We considered the most common brands for commercially prepared baby foods. Intakes of energy, macronutrients, and micronutrients were compared between methods using Bland-Altman analysis.Results: The automated algorithm did not have any significant bias for estimates of energy (kJ) (MD 15, 95% CI -27, 58), carbohydrate (g) (MD -0.1, 95% CI -1.2,1.0), and fat (g) (-0.1, 95% CI -0.3,0.1), but slightly underestimated intake of protein (MD -0.4 g, 95% CI -0.7,-0.1), saturated fat, PUFA, dietary fibre, and niacin. The algorithm provided accurate estimates for other micronutrients. The limits of agreement were relatively narrow.Conclusion: This automated algorithm is an efficient tool to estimate the nutrient intakes from CFFQ accurately. The small negative bias observed for few nutrients was clinically insignificant and can be minimised. This algorithm is suitable to use in large clinical trials and cohort studies without the need for proprietary software

A Multiscale Spatiotemporal Approach for Smallholder Irrigation Detection

In presenting an irrigation detection methodology that leverages multiscale satellite imagery of vegetation abundance, this paper introduces a process to supplement limited ground-collected labels and ensure classifier applicability in an area of interest. Spatiotemporal analysis of MODIS 250 m enhanced vegetation index (EVI) timeseries characterizes native vegetation phenologies at regional scale to provide the basis for a continuous phenology map that guides supplementary label collection over irrigated and non-irrigated agriculture. Subsequently, validated dry season greening and senescence cycles observed in 10 m Sentinel-2 imagery are used to train a suite of classifiers for automated detection of potential smallholder irrigation. Strategies to improve model robustness are demonstrated, including a method of data augmentation that randomly shifts training samples; and an assessment of classifier types that produce the best performance in withheld target regions. The methodology is applied to detect smallholder irrigation in two states in the Ethiopian Highlands, Tigray and Amhara, where detection of irrigated smallholder farm plots is crucial for energy infrastructure planning. Results show that a transformer-based neural network architecture allows for the most robust prediction performance in withheld regions, followed closely by a CatBoost model. Over withheld ground-collection survey labels, the transformer-based model achieves 96.7% accuracy over non-irrigated samples and 95.9% accuracy over irrigated samples. Over a larger set of samples independently collected via the introduced method of label supplementation, non-irrigated and irrigated labels are predicted with 98.3 and 95.5% accuracy, respectively. The detection model is then deployed over Tigray and Amhara, revealing crop rotation patterns and year-over-year irrigated area change. Predictions suggest that irrigated area in these two states has decreased by approximately 40% from 2020 to 2021

Working with Climate Projections to Estimate Disease Burden: Perspectives from Public Health

There is interest among agencies and public health practitioners in the United States (USA) to estimate the future burden of climate-related health outcomes. Calculating disease burden projections can be especially daunting, given the complexities of climate modeling and the multiple pathways by which climate influences public health. Interdisciplinary coordination between public health practitioners and climate scientists is necessary for scientifically derived estimates. We describe a unique partnership of state and regional climate scientists and public health practitioners assembled by the Florida Building Resilience Against Climate Effects (BRACE) program. We provide a background on climate modeling and projections that has been developed specifically for public health practitioners, describe methodologies for combining climate and health data to project disease burden, and demonstrate three examples of this process used in Florida

Resource Allocation during an Influenza Pandemic

Resource Allocation during an Influenza Pandemi

Small heat shock protein Hsp27 is required for proper heart tube formation

The small heat shock protein Hsp27 has been shown to be involved in a diverse array of cellular processes, including cellular stress response, protein chaperone activity, regulation of cellular glutathione levels, apoptotic signaling, and regulation of actin polymerization and stability. Furthermore, mutation within Hsp27 has been associated with the human congenital neuropathy Charcot-Marie Tooth (CMT) disease. Hsp27 is known to be expressed in developing embryonic tissues; however, little has been done to determine the endogenous requirement for Hsp27 in developing embryos. In this study, we show that depletion of XHSP27 protein results in a failure of cardiac progenitor fusion resulting in cardia bifida. Furthermore, we demonstrate a concomitant disorganization of actin filament organization and defects in myofibril assembly. Moreover, these defects are not associated with alterations in specification or differentiation. We have thus demonstrated a critical requirement for XHSP27 in developing cardiac and skeletal muscle tissues

Focal adhesion kinase is essential for cardiac looping and multichamber heart formation

Focal adhesion kinase (FAK) is a critical mediator of matrix- and growth factor-induced signaling during development. Myocyte-restricted FAK deletion in mid-gestation mice results in impaired ventricular septation and cardiac compaction. However, whether FAK regulates early cardiogenic steps remains unknown. To explore a role for FAK in multi-chambered heart formation, we utilized anti-sense morpholinos to deplete FAK in Xenopus laevis. Xenopus FAK morphants exhibited impaired cardiogenesis, pronounced pericardial edema, and lethality by tadpole stages. Spatial-temporal assessment of cardiac marker gene expression revealed that FAK was not necessary for midline migration, differentiation, fusion of cardiac precursors, or linear heart tube formation. However, myocyte proliferation was significantly reduced in FAK morphant heart tubes and these tubes failed to undergo proper looping morphogenesis. Collectively our data imply that FAK plays an essential role in chamber outgrowth and looping morphogenesis likely stimulated by fibroblast growth factors (and possibly other) cardiotrophic factors

Impact of Nitric Oxide-Release Kinetics on Antifungal Activity

Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species