Those men with higher levels of 1,25(OH)2D had greater α-diversity, even after adjusting for previously characterized determinants of microbial diversity including age, geographical origin, race, PPI, and antibiotic use
This study reports robust correlations between the vitamin D metabolites, 1,25(OH)2D and 24,25(OH)2D, and the gut microbiome in 567 older men representing six geographic sites across the United States
Kathryn M. Spitler, Shwetha K. Shetty, Emily M. Cushing, Kelli L. Sylvers-Davie, Brandon S.J. Davies
Published: Nov 2020
Elevated plasma triglyceride levels are associated with metabolic disease. Angiopoietin-like protein 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). Our aim was to investigate the role of tissue-specific ANGPTL4 expression in the setting of high fat diet. Adipocyte- and hepatocyte-specific ANGPTL4 deficient mice were fed a high fat diet (60% kCal from fat) for either 12 weeks or 6 months. We performed plasma metabolic measurements, triglyceride clearance and uptake assays, LPL activity assays, and assessed glucose homeostasis. Mice lacking adipocyte ANGPTL4 recapitulated the triglyceride phenotypes of whole-body ANGPTL4 deficiency, whereas mice lacking hepatocyte ANGPTL4 had few triglyceride phenotypes. When fed a high fat diet (HFD), mice deficient in adipocyte ANGPTL4 gained more weight, had enhanced adipose LPL activity, and initially had improved glucose and insulin sensitivity. However, this improvement was largely lost after 6 months on HFD. Conversely, mice deficient in hepatocyte ANGPTL4 initially displayed no differences in glucose homeostasis, but began to manifest improved glucose tolerance after 6 months on HFD. We conclude that it is primarily adipocyte-derived ANGPTL4 that is responsible for regulating plasma triglyceride levels. Deficiency in adipocyte- or hepatocyte-derived ANGPTL4 may confer some protections against high fat diet induced dysregulation of glucose homeostasis.
Bile acids (BAs) not only facilitate fat digestion but also protect against obesity. Here, we show that a genetic mouse model for BA overload (Farnesoid X receptor; Small heterodimer double knockout (DKO)) exhibits mitochondrial dysfunction resulting in a thermogenic defect. By housing DKO mice at thermoneutrality, the poor mitochondrial function in brown fat protects them from diet-induced obesity. Compared to control, we find higher adipose BA levels with excess accumulation of taurocholic acid in the DKO mice. We report that the expression of genes responsible for BA de novo synthesis, conjugation and transporters and accumulation of BAs are present in both brown and white adipocytes. We determine that BA overload is sufficient to cause adipocyte mitochondrial dysfunction and induce the expression of cellular senescence genes in vitro. Taken together, we uncover that BA levels within the adipose tissue may modulate its overall function.
Mouse model of BA overload exhibits adipose defects, which is partially restored by housing at thermoneutrality.
BAs are present in detectable concentrations in both BAT and WAT.
Adipocytes express genes responsible for de novo synthesis, conjugation and transport of BAs, and accumulate BAs.
Pathological accumulation of BAs impairs mitochondrial function leading to thermogenic
Plant photosynthesis is a major part of the global carbon cycle and climate system. Carbon capture by C3 plants is most often modelled using the Farquhar-von-Caemmerer-Berry (FvCB) equations. We undertook a global synthesis of all parameters required to solve the FvCB model. The publicly available dataset we assembled includes 3663 observations from 336 different C3 plant species among 96 taxonomic families coming from every major vascular plant clade (lycophytes, ferns, gymnosperms, magnoliids, eudicots and monocots). Geographically, the species in the database have distributions that span the majority of the globe. We used the model to predict photosynthetic rates for a hypothetical average plant in each major terrestrial plant clade and find that generally plants have dramatically increased their photosynthetic abilities through evolutionary time, with the average monocot (the youngest clade) achieving maximum rates of photosynthesis almost double that of the average lycophyte (the oldest clade). We also solved the model for different hypothetical average plant functional types (PFTs) and find that herbaceous species generally have much higher rates of photosynthesis compared to woody plants. Indeed, the maximum photosynthetic rate of graminoids is almost three times the rate of the average tree. The resulting functional responses to increasing CO2 in average hypothetical PFTs would suggest that most groups are already at or near their maximum rate of photosynthesis. However, phylogenetic analysis showed that there was no evidence of niche conservatism with most variance occurring within, rather than among clades (K=0.357, p=0.001). This high within-group variability suggests that average PFTs may obscure important plant responses to increasing CO2. Indeed, when we solved the model for each of the 3663 individual observations, we found that, contrary to the predictions of hypothetical average PFTs, that most plants are predicted to be able to increase their photosynthetic rates. These results suggest that global models should seek to incorporate high within-group variability to accurately predict plant photosynthesis in response to a changing climate.
Electromyographic activity of eight upper limb muscles was recorded during cereal grinding in an athletic sample of 10 female rowers and a nonathletic sample of 25 females and analyzed using both an eight- and four-muscle model
Andrew J Lutkewitte, Yi-Chun Chen, Jeffrey L Hansen, Patrick T Fueger
Published: Nov 2020
Hyperlipidemia associated with obesity and type 2 diabetes (T2D) promotes excess hepatic lipid storage (steatosis) and endoplasmic reticulum (ER) stress, thereby reducing hepatic cell proliferation and survival. An important receptor tyrosine kinase controlling liver proliferation and survival is the epidermal growth factor receptor (EGFR). EGFR expression and activation are decreased during steatosis in humans and several animal models of obesity. Therefore, restoring EGFR activation in obesity-induced ER stress and diabetes could restore the liver's capacity for survival and regeneration. As an inducible feedback inhibitor of EGFR activity, mitogen-inducible gene 6
Andrea Bizzego, Giulio Gabrieli, Cesare Furlanello, Gianluca Esposito
Published: Nov 2020
A key access point to the functioning of the Autonomic Nervous System is the investigation of peripheral signals. Wearable Devices (WDs) enable the acquisition and quantification of peripheral signals in a wide range of contexts, from personal uses to scientific research. WDs have lower costs and higher portability than medical-grade devices. But achievable data quality can be lower, subject to artifacts due to body movements and data losses. It is therefore crucial to evaluate the reliability and validity of WDs before their use in research. In this study we introduce a data analysis procedure for the assessment of WDs for multivariate physiological signals. The quality of cardiac and Electrodermal Activity signals is validated with a standard set of Signal Quality Indicators. The pipeline is available as a collection of open source Python scripts based on the pyphysio package. We apply the indicators for the analysis of signal quality on data simultaneously recorded from a clinical-grade device and two WDs. The dataset provides signals of 6 different physiological measures collected from 18 subjects with WDs. This study indicates the need of validating the use of WD in experimental settings for research and the importance of both technological and signal processing aspects to obtain reliable signals and reproducibility of results.
Objective: Maintenance of glucose homeostasis requires the precise regulation of hormone secretion from the endocrine pancreas. Free-fatty acid receptor 4 (FFAR4/GPR120) is a G protein-coupled receptor whose activation in islets of Langerhans promotes insulin and glucagon secretion and inhibits somatostatin secretion. However, the contribution of individual islet cell types (alpha, beta, and delta cells) to the insulinotropic and glucagonotropic effects of GPR120 remains unclear. As gpr120 mRNA is enriched in somatostatin-secreting delta cells, we hypothesized that GPR120 activation
Background/Objective In the field of Physical Medicine and Rehabilitation, it is essential to measure individual functional capacity, which could be evaluated through walking tests. Aside from the commonly used six minutes walking test (6MWT), four meter gait speed (4MGS) are widely used for its practicality. This study aimed to assess the agreement between 4 MGS and the 6MWT in Indonesian healthy adults.
Methods This agreement analysis study had recruited 61 healthy and sedentary Indonesians aged 18 until 50 years old, and they were instructed to perform three tests, namely 6MWT and 4MGS with six meters and eight meters track. These gait speed were then compared to assess validity.
Results Mean gait speed results for males in 6MWT is 1.602 m/s, whereas 4MGS in six meter track is 2.114 m/s and similarly 2.108 m/s in the eight meter track. Females on the other hand, achieved 1.462 m/s for 6MWT, 1.908 m/s and 1.986 m/s for 4MGS in six and eight meter simultaneously. Bland Altman Agreement test between the 6MWT and 4MGS shows scatter dots with close limit of agreement, thus showing a good agreement between the 6MWT and 4 MGS with both tracks.
Discussion Both track length of 4 MGS were in a good agreement with 6MWT for functional capacity assessment.
Conclusions In response to the COVID-19 pandemic era, shorter track of 4MGS (six meters) can be feasibly utilized. It is evident that shorter duration and track will boost the tests practicality in assessing functional capacity for both inpatient and outpatient settings.
Background Longevity is of considerable interest. Collation of recent data after World War II by the Human Mortality Database allowed analyses, previously unattainable, of modal death-ages for sufficient numbers of large European pooled cohorts.
Objective To track modes, means and medians (≥60 years old (y)) of all-cause mortality for both sexes.
Methods The only highest-quality, large-number Lexis data available were pooled from nine European countries: Denmark, Finland, France, Iceland, Italy, Netherlands, Norway, Sweden and Switzerland; raw-data modes (and means/medians ≥60y, plus thin-plate-splines), were analyzed, plus loess-smoothed equivalents for individual countries.
Results Here we show that for ∼25-30 years (cohorts 1880-∼1909) dramatic overall sex differences existed between pooled raw-death-age changes: male modal ages being near-constant (77.2y ±; standard deviation 1.58y); females’ increased. Overall, for available cohorts (1880-1904) male raw medians were exactly constant (76y); male means showed slight increase (0.0193y/year; compare female: 0.146y/year). Male deaths ≥60≤76y compared with >76y, as percentages of total, were near-equal, whereas in females the former decreased. Only after ∼1910 did male modal ages rapidly increase (other averages not calculable). Individual country results showed that males in Finland, France, Switzerland were affected less than other countries.
Conclusions Results clarify previously knowledge concerning sex differences during this period. Despite improved environment during late adulthood, this did not translate into increased male longevity and earlier events might have sealed their fate, especially in Denmark, Italy, Netherlands, Norway, and Sweden. One hypothesis concerns long-term effects of the 1918-1919 influenza pandemic, perhaps directly relevant to the Covid-19 pandemic at present.
Eedann McCord, Goragot Wisedchaisri, William A. Catterall
Published: Nov 2020
Voltage-gated sodium channels initiate action potentials in prokaryotes and in many eukaryotic cells, including vertebrate nerve and muscle. Their activation is steeply voltage-dependent, but it is unclear how the voltage sensitivity is set or whether it can be broadly shifted to positive voltages. Here we show that the voltage dependence of activation (VA) of the ancestral bacterial sodium channel NaVAb can be progressively shifted from −118 mV to +35 mV in chimeras with increasing numbers of amino acid residues from the extracellular half of the voltage sensor of human NaV1.7 channels. In a minimal chimera in which only 32 residues were transferred, we analyzed the effects of six additional mutations of conserved amino acid residues singly, in pairs, and as triple mutations. The resulting chimeric mutants exhibited a broad range of voltage sensitivity from VA=−118 mV to VA=+120 mV. Three mutations (N48K, L112A, and M119V) shifted VA to +61 mV when substituted in NaVAb itself, and substitution of two additional Cys residues in the Cys-free background of NaVAb further shifted VA to +105 mV. In these mutants, measurement of gating currents revealed that the voltage dependence of gating charge movement (VQ) shifted to positive membrane potentials as much or more than VA, confirming that the gating charges are trapped in their resting positions by these VA-shifting mutations. Our results demonstrate broadband shifting of VA and VQ of a sodium channel across a range of 240 mV and provide a toolbox of methods and constructs to analyze sodium channel structure and function in the resting state at 0 mV and in activated states at positive membrane potentials.