A new mouse model of elastin haploinsufficiency highlights the importance of elastin to vascular development and blood pressure regulation

Supravalvular aortic stenosis (SVAS) is an autosomal dominant disease resulting from elastin (ELN) haploinsufficiency. Individuals with SVAS typically develop a thickened arterial media with an increased number of elastic lamellae and smooth muscle cell (SMC) layers and stenosis superior to the aortic valve. A mouse model of SVAS (El

BZINB Model-Based Pathway Analysis and Module Identification Facilitates Integration of Microbiome and Metabolome Data

Integration of multi-omics data is a challenging but necessary step to advance our understanding of the biology underlying human health and disease processes. To date, investigations seeking to integrate multi-omics (e.g., microbiome and metabolome) employ simple correlation-based network analyses; however, these methods are not always well-suited for microbiome analyses because they do not accommodate the excess zeros typically present in these data. In this paper, we introduce a bivariate zero-inflated negative binomial (BZINB) model-based network and module analysis method that addresses this limitation and improves microbiome–metabolome correlation-based model fitting by accommodating excess zeros. We use real and simulated data based on a multi-omics study of childhood oral health (ZOE 2.0; investigating early childhood dental caries, ECC) and find that the accuracy of the BZINB model-based correlation method is superior compared to Spearman’s rank and Pearson correlations in terms of approximating the underlying relationships between microbial taxa and metabolites. The new method, BZINB-iMMPath, facilitates the construction of metabolite–species and species–species correlation networks using BZINB and identifies modules of (i.e., correlated) species by combining BZINB and similarity-based clustering. Perturbations in correlation networks and modules can be efficiently tested between groups (i.e., healthy and diseased study participants). Upon application of the new method in the ZOE 2.0 study microbiome–metabolome data, we identify that several biologically-relevant correlations of ECC-associated microbial taxa with carbohydrate metabolites differ between healthy and dental caries-affected participants. In sum, we find that the BZINB model is a useful alternative to Spearman or Pearson correlations for estimating the underlying correlation of zero-inflated bivariate count data and thus is suitable for integrative analyses of multi-omics data such as those encountered in microbiome and metabolome studies

An open-source device for measuring food intake and operant behavior in rodent home-cages

Feeding is critical for survival, and disruption in the mechanisms that govern food intake underlies disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: the Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs

Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer\u27s Disease-Relevant Phenotypes in Mice.

Obesity is recognized as a significant risk factor for Alzheimer\u27s disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model wit

Comprehensive Bayesian analysis of FRB-like bursts from SGR 1935+2154 observed by CHIME/FRB

The bright millisecond-duration radio burst from the Galactic magnetar SGR 1935+2154 in 2020 April was a landmark event, demonstrating that at least some fast radio burst (FRB) sources could be magnetars. The two-component burst was temporally coincident with peaks observed within a contemporaneous short X-ray burst envelope, marking the first instance where FRB-like bursts were observed to coincide with X-ray counterparts. In this study, we detail five new radio burst detections from SGR 1935+2154, observed by the CHIME/FRB instrument between October 2020 and December 2022. We develop a fast and efficient Bayesian inference pipeline that incorporates state-of-the-art Markov chain Monte Carlo techniques and use it to model the intensity data of these bursts under a flexible burst model. We revisit the 2020 April burst and corroborate that both the radio sub-components lead the corresponding peaks in their high-energy counterparts. For a burst observed in 2022 October, we find that our estimated radio pulse arrival time is contemporaneous with a short X-ray burst detected by GECAM and HEBS, and Konus-Wind and is consistent with the arrival time of a radio burst detected by GBT. We present flux and fluence estimates for all five bursts, employing an improved estimator for bursts detected in the side-lobes. We also present upper limits on radio emission for X-ray emission sources which were within CHIME/FRB's field-of-view at trigger time. Finally, we present our exposure and sensitivity analysis and estimate the Poisson rate for FRB-like events from SGR 1935+2154 to be $0.005^{+0.082}_{-0.004}$ events/day above a fluence of $10~\mathrm{kJy~ms}$ during the interval from 28 August 2018 to 1 December 2022, although we note this was measured during a time of great X-ray activity from the source.Comment: 22 pages, 6 figures, 4 tables. To be submitted to Ap

Progress on improving Agricultural Nitrogen use efficiency: UK-China viortual joint centers on Nitrogen Agronomy

Two virtual joint centers for nitrogen agronomy were established between the UK and China to facilitate collaborative research aimed at improving nitrogen use efficiency (NUE) in agricultural production systems and reducing losses of reactive N to the environment. Major focus areas were improving fertilizer NUE, use of livestock manures, soil health, and policy development and knowledge exchange. Improvements to fertilizer NUE included attention to application rate in the context of yield potential and economic considerations and the potential of improved practices including enhanced efficiency fertilizers, plastic film mulching and cropping design. Improved utilization of livestock manures requires knowledge of the available nutrient content, appropriate manure processing technologies and integrated nutrient management practices. Soil carbon, acidification and biodiversity were considered as important aspects of soil health. Both centers identified a range of potential actions that could be taken to improve N management, and the research conducted has highlighted the importance of developing a systemslevel approach to assessing improvement in the overall efficiency of N management and avoiding unintended secondary effects from individual interventions. Within this context, the management of fertilizer emissions and livestock manure at the farm and regional scales appear to be particularly important targets for mitigation

QT dispersion in patients with systemic lupus erythematosus: the impact of disease activity

<p>Abstract</p> <p>Background</p> <p>Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.</p> <p>Methods and Results</p> <p>One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10).</p> <p>QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; <it>P </it>< 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, <it>P </it>= 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, <it>P </it>= 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (<it>P </it>< 0.004).</p> <p>Conclusions</p> <p>QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.</p> <p>Trial registration</p> <p>Clinicaltrial.gov registration <a href="http://www.clinicaltrials.gov/ct2/show/NCT01031797">NCT01031797</a></p

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study