Dietary Magnesium May Be Protective for Aging of Bone and Skeletal Muscle in Middle and Younger Older Age Men and Women: Cross-Sectional Findings from the UK Biobank Cohort.

Although fragility fractures, osteoporosis, sarcopenia, and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral to bone and muscle physiology, the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently to date. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass-FFM), grip strength, and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and was expressed as the percentage of body weight (FFM%) or as divided by body mass index (FFMBMI). Adjusted mean grip strength, FFM%, FFMBMI, and BMD were calculated according to quintiles of dietary magnesium, while correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women, respectively, of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFMBMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes, indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and has relevance for population prevention strategies for sarcopenia, osteoporosis, and fractures

Therapeutic interventions alter ecological interactions among cystic fibrosis airway microbiota

The airways of people with cystic fibrosis (CF) often harbor a diverse microbiota and in recent years, much effort has been invested in cataloguing these. In spite of providing a wealth of insight, this cataloguing tells us little about how the organisms interact with one another in the CF airways. However, such relationships can be inferred using the theoretical framework of the Lotka-Volterra (LV) model. In the current work, we use a generalized Lotka-Volterra model to interrogate the nationwide data collected and curated by the UK CF Registry. This longitudinal dataset (covering the period 2008–2020) contains annual depositions that record the presence/absence of microbial taxa in each patient, their medication, and their CF genotype. Specifically, we wanted to identify trends in ecological relationships between the CF microbiota at a nationwide level, and whether these are potentially affected by medication. Our results show that some medications have a distinct influence on the microbial interactome, especially those that potentially influence the “gut-lung axis” or mucus viscosity. In particular, we found that patients treated with a combination of antimicrobial agents (targeting the airway microbiota), digestive enzymes (assisting in the assimilation of dietary fats and carbohydrates), and DNase (to reduce mucus viscosity) displayed a distinctly different airway interactome compared with patients treated separately with these medications

Dynamic S0 Galaxies: a Case Study of NGC 5866

S0 galaxies are often thought to be passively evolved from spirals after star formation is quenched. To explore what is occurring in S0s, we present a multi-wavelength study of NGC5866--an isolated nearby edge-on S0. This study shows strong evidence for dynamic activities in the interstellar medium, which are most likely driven by supernova explosions in the galactic disk and bulge. We utilize Chandra, HST, and Spitzer data as well as ground-based observations to characterize the content, structure, and physical state of the medium and its interplay with stars in NGC5866. A cold gas disk is detected with an exponential scale height of 100pc. Numerous off-disk dusty spurs are clearly present: prominent ones can extend as far as 300pc from the galactic plane and are probably produced by individual SNe, whereas faint filaments can have ~ kpc scale and are likely produced by SNe collectively in disk/bulge. We also detect substantial amounts of diffuse Ha- and Pa-emitting gas with a comparable scale height as the cold gas. We find that the heating of the dust and warm ionized gas cannot be explained by the radiation from evolved stars alone, strongly indicating the presence of young stars in the disk at a low formation rate of ~ 0.05Msun/yr. We reveal the presence of diffuse X-ray-emitting hot gas, which extends as far as 3.5kpc from the disk and can be heated easily by Type Ia SNe in the bulge. However, the temperature of this gas is ~ 0.2keV, substantially lower than what might be expected from the mass-loss of evolved stars and Type Ia SNe heating alone, indicating mass loading from cool gas is important. The total masses of the cold, warm and hot gases are ~ 5*10^8, 10^4 and 3*10^7Msun. The relative richness of the gases, undergoing circulations between disk/halo, is perhaps a result of its relative isolation.Comment: 27 pages, 6 figures, 3 tables, ApJ in press, comments are welcom

Prediction of MET Overexpression in Non-Small Cell Lung Adenocarcinomas from Hematoxylin and Eosin Images

MET protein overexpression is a targetable event in non-small cell lung cancer (NSCLC) and is the subject of active drug development. Challenges in identifying patients for these therapies include lack of access to validated testing, such as standardized immunohistochemistry (IHC) assessment, and consumption of valuable tissue for a single gene/protein assay. Development of pre-screening algorithms using routinely available digitized hematoxylin and eosin (H&E)-stained slides to predict MET overexpression could promote testing for those who will benefit most. While assessment of MET expression using IHC is currently not routinely performed in NSCLC, next-generation sequencing is common and in some cases includes RNA expression panel testing. In this work, we leveraged a large database of matched H&E slides and RNA expression data to train a weakly supervised model to predict MET RNA overexpression directly from H&E images. This model was evaluated on an independent holdout test set of 300 over-expressed and 289 normal patients, demonstrating an ROC-AUC of 0.70 (95th percentile interval: 0.66 - 0.74) with stable performance characteristics across different patient clinical variables and robust to synthetic noise on the test set. These results suggest that H&E-based predictive models could be useful to prioritize patients for confirmatory testing of MET protein or MET gene expression status

Molecular Gas in NUclei of GAlaxies (NUGA) XIV. The barred LINER/Seyfert 2 galaxy NGC 3627

We present CO(1-0) and CO(2-1) maps of the interacting barred LINER/Seyfert 2 galaxy NGC 3627 obtained with the IRAM interferometer at resolutions of 2.1" x 1.3" and 0.9" x 0.6", respectively. The molecular gas emission shows a nuclear peak, an elongated bar-like structure of ~18" (~900 pc) diameter in both CO maps and, in CO(1-0), a two-arm spiral feature from r~9" (~450 pc) to r~16" (~800 pc). The inner ~18" bar-like structure, with a north/south orientation (PA = 14{\deg}), forms two peaks at the extremes of this elongated emission region. The kinematics of the inner molecular gas shows signatures of non-circular motions associated both with the 18" bar-like structure and the spiral feature detected beyond it. The 1.6 micron H-band 2MASS image of NGC 3627 shows a stellar bar with a PA = -21{\deg}, different from the PA (= 14{\deg}) of the CO bar-like structure, indicating that the gas is leading the stellar bar. The torques computed with the HST-NICMOS F160W image and our PdBI maps are negative down to the resolution limit of our images, ~60 pc in CO(2-1). If the bar ends at ~3 kpc, coincident with corotation (CR), the torques are negative between the CR of the bar and the nucleus, down to the resolution limit of our observations. This scenario is compatible with a recently-formed rapidly rotating bar which has had insufficient time to slow down because of secular evolution, and thus has not yet formed an inner Lindblad resonance (ILR). The presence of molecular gas inside the CR of the primary bar, where we expect that the ILR will form, makes NGC 3627 a potential smoking gun of inner gas inflow. The gas is fueling the central region, and in a second step could fuel directly the active nucleus.Comment: 24 pages, 28 figures, 2 tables. Accepted for publication in Astronomy and Astrophysic

Differential variability analysis of gene expression and its application to human diseases

Motivation: Current microarray analyses focus on identifying sets of genes that are differentially expressed (DE) or differentially coexpressed (DC) in different biological states (e.g. diseased versus non-diseased). We observed that in many human diseases, some genes have a significantincrease or decrease in expression variability (variance). Asthese observed changes in expression variability may be caused by alteration of the underlying expression dynamics, such differential variability (DV) patterns are also biologically interesting

Sustained replication of synthetic canine distemper virus defective genomes in vitro and in vivo

Defective interfering (DI) genomes have long been considered inconvenient artifacts that suppressed viral replication in vitr

Mechanobiology as a tool for addressing the genotype-to- phenotype problem in microbiology

The central hypothesis of the genotype–phenotype relationship is that the phenotype of a developing organism (i.e., its set of observable attributes) depends on its genome and the environment. However, as we learn more about the genetics and biochemistry of living systems, our understanding does not fully extend to the complex multiscale nature of how cells move, interact, and organize; this gap in understanding is referred to as the genotype-to-phenotype problem. The physics of soft matter sets the background on which living organisms evolved, and the cell environment is a strong determinant of cell phenotype. This inevitably leads to challenges as the full function of many genes, and the diversity of cellular behaviors cannot be assessed without wide screens of environmental conditions. Cellular mechanobiology is an emerging field that provides methodologies to understand how cells integrate chemical and physical environmental stress and signals, and how they are transduced to control cell function. Biofilm forming bacteria represent an attractive model because they are fast growing, genetically malleable and can display sophisticated self-organizing developmental behaviors similar to those found in higher organisms. Here, we propose mechanobiology as a new area of study in prokaryotic systems and describe its potential for unveiling new links between an organism\u27s genome and phenome

Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis

The commensal fungus Candida albicans causes oropharyngeal candidiasis (OPC; thrush) in settings of immunodeficiency. Although disseminated, vaginal, and oral candidiasis are all caused by C. albicans species, host defense against C. albicans varies by anatomical location. T helper 1 (Th1) cells have long been implicated in defense against candidiasis, whereas the role of Th17 cells remains controversial. IL-17 mediates inflammatory pathology in a gastric model of mucosal candidiasis, but is host protective in disseminated disease. Here, we directly compared Th1 and Th17 function in a model of OPC. Th17-deficient (IL-23p19−/−) and IL-17R–deficient (IL-17RA−/−) mice experienced severe OPC, whereas Th1-deficient (IL-12p35−/−) mice showed low fungal burdens and no overt disease. Neutrophil recruitment was impaired in IL-23p19−/− and IL-17RA−/−, but not IL-12−/−, mice, and TCR-αβ cells were more important than TCR-γδ cells. Surprisingly, mice deficient in the Th17 cytokine IL-22 were only mildly susceptible to OPC, indicating that IL-17 rather than IL-22 is vital in defense against oral candidiasis. Gene profiling of oral mucosal tissue showed strong induction of Th17 signature genes, including CXC chemokines and β defensin-3. Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors

Coapplication of magnesium supplementation and vibration modulate macrophage polarization to attenuate sarcopenic muscle atrophy through PI3K/Akt/mTOR signaling pathway

Sarcopenia is an age-related geriatric syndrome characterized by the gradual loss of muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to be beneficial to structural and functional outcomes of skeletal muscles, while magnesium (Mg) is a cofactor associated with better indices of skeletal muscle mass and strength. We hypothesized that LMHFV, Mg and their combinations could suppress inflammation and sarcopenic atrophy, promote myogenesis via PI3k/Akt/mTOR pathway in senescence-accelerated mouse P8 (SAMP8) mice and C2C12 myoblasts. Results showed that Mg treatment and LMHFV could significantly decrease inflammatory expression (C/EBPα and LYVE1) and modulate a CD206-positive M2 macrophage population at month four. Mg treatment also showed significant inhibitory effects on FOXO3, MuRF1 and MAFbx mRNA expression. Coapplication showed a synergistic effect on suppression of type I fiber atrophy, with significantly higher IGF-1, MyoD, MyoG mRNA (p < 0.05) and pAkt protein expression (p < 0.0001) during sarcopenia. In vitro inhibition of PI3K/Akt and mTOR abolished the enhancement effects on myotube formation and inhibited MRF mRNA and p85, Akt, pAkt and mTOR protein expressions. The present study demonstrated that the PI3K/Akt/mTOR pathway is the predominant regulatory mechanism through which LMHFV and Mg enhanced muscle regeneration and suppressed atrogene upregulation