Bariatric surgical procedures such as vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most potent treatments available to produce sustained reductions in body weight and ...improvements in glucose regulation. While traditionally these effects are attributed to mechanical aspects of these procedures, such as restriction and malabsorption, a growing body of evidence from mouse models of these procedures points to physiological changes that mediate the potent effects of these surgeries. In particular, there are similar changes in gut hormone secretion, bile acid levels, and composition after both of these procedures. Moreover, loss of function of the nuclear bile acid receptor (FXR) greatly diminishes the effects of VSG. Both VSG and RYGB are linked to profound changes in the gut microbiome that also mediate at least some of these surgical effects. We hypothesize that surgical rearrangement of the gastrointestinal tract results in enteroplasticity caused by the high rate of nutrient presentation and altered pH in the small intestine that contribute to these physiological effects. Identifying the molecular underpinnings of these procedures provides new opportunities to understand the relationship of the gastrointestinal tract to obesity and diabetes as well as new therapeutic strategies to harness the effectiveness of surgery with less-invasive approaches.
•Bariatric surgery is highly effective for treating obesity and diabetes•These surgeries alter gut function, resulting in effects on weight and metabolism•Gut adaptation contributes to the effects of these surgeries on energy balance
Various bariatric surgery procedures are the most potent treatments for both obesity and type 2 diabetes. This is not a result of mechanical restriction or malabsorption, but rather a result of alterations in gut function and signaling. Hypotheses about these physiological changes are presented in this review.
Saccharomyces cerevisiae is traditionally used for alcoholic beverage and bioethanol production; however, its performance during fermentation is compromised by the impact of ethanol accumulation on ...cell vitality. This article reviews studies into the molecular basis of the ethanol stress response and ethanol tolerance of S. cerevisiae; such knowledge can facilitate the development of genetic engineering strategies for improving cell performance during ethanol stress. Previous studies have used a variety of strains and conditions, which is problematic, because the impact of ethanol stress on gene expression is influenced by the environment. There is however some commonality in Gene Ontology categories affected by ethanol assault that suggests that the ethanol stress response of S. cerevisiae is compromised by constraints on energy production, leading to increased expression of genes associated with glycolysis and mitochondrial function, and decreased gene expression in energy-demanding growth-related processes. Studies using genome-wide screens suggest that the maintenance of vacuole function is important for ethanol tolerance, possibly because of the roles of this organelle in protein turnover and maintaining ion homoeostasis. Accumulation of Asr1 and Rat8 in the nucleus specifically during ethanol stress suggests S. cerevisiae has a specific response to ethanol stress although this supposition remains controversial.
Monthly GRACE gravity field models from the three science processing centers (CSR, GFZ, and JPL) are analyzed for the period from February 2003 to April 2005 over the ocean. The data are used to ...estimate maps of the mass component of sea level at smoothing radii of 500 km and 750 km. In addition to using new gravity field models, a filter has been applied to estimate and remove systematic errors in the coefficients that cause erroneous patterns in the maps of equivalent water level. The filter is described and its effects are discussed. The GRACE maps have been evaluated using a residual analysis with maps of altimeter sea level from Jason‐1 corrected for steric variations using the World Ocean Atlas 2001 monthly climatology. The mean uncertainty of GRACE maps determined from an average of data from all 3 processing centers is estimated to be less than 1.8 cm RMS at 750 km smoothing and 2.4 cm at 500 km smoothing, which is better than was found previously using the first generation GRACE gravity fields.
Unlike in land plants, photosynthesis in many aquatic plants relies on bicarbonate in addition to carbon dioxide (CO
) to compensate for the low diffusivity and potential depletion of CO
in water. ...Concentrations of bicarbonate and CO
vary greatly with catchment geology. In this study, we investigate whether there is a link between these concentrations and the frequency of freshwater plants possessing the bicarbonate use trait. We show, globally, that the frequency of plant species with this trait increases with bicarbonate concentration. Regionally, however, the frequency of bicarbonate use is reduced at sites where the CO
concentration is substantially above the air equilibrium, consistent with this trait being an adaptation to carbon limitation. Future anthropogenic changes of bicarbonate and CO
concentrations may alter the species compositions of freshwater plant communities.
Sea level observations suggest that the rate of sea level rise has accelerated during the last 20 years. However, the presence of considerable decadal‐scale variability, especially on a regional ...scale, makes it difficult to assess whether the observed changes are due to natural or anthropogenic causes. Here we use a regression model with atmospheric pressure, wind, and climate indices as independent variables to quantify the contribution of internal climate variability to the sea level at nine tide gauges from around the world for the period 1920–2011. Removing this contribution reveals a statistically significant acceleration (0.022 ± 0.015 mm/yr2) between 1952 and 2011, which is unique over the whole period. Furthermore, we have found that the acceleration is increasing over time. This acceleration appears to be the result of increasing greenhouse gas concentrations, along with changes in volcanic forcing and tropospheric aerosol loading.
Key Points
We detect a sea level acceleration between 1952 and 2011
The sea level acceleration appears to be increasing over time
The acceleration is due to both anthropogenic and natural external forcing
Decadal sea level variations from tide gauge records along the western European coast and in the Mediterranean Sea commencing in the late 19th and early 20th centuries are examined relative to ...large‐scale atmospheric forcing. Recent studies have provided evidence for a link between sea level in the eastern North Atlantic and atmospheric forcing, however the nature of this relationship is still unclear. Here the outputs of a regional barotropic model and a nearly global baroclinic model are used in conjunction with wind stress and heat flux data to explore the physical mechanisms responsible for the observed sea level variability. All tide gauge records show significant decadal variability (up to 15 cm) and are highly correlated with the NAO and among themselves at decadal periods. There is a coherent sea level signal that affects the eastern boundary of the North Atlantic northward of 25°N and is limited to a narrow band of the order of a few hundred kilometers along the coast. This band tends to become narrower towards higher latitudes. We find that longshore wind and wave propagation along the boundary are the major contributors to coastal sea level variability but no significant contribution from mass redistribution linked to changes in the strength of the subtropical gyre is observed. The mass component dominates sea level in the Mediterranean and is mainly driven by mass exchanges with the Atlantic, which explains the correlation between both regions. Southward of 25°N, sea level changes are mainly driven by heat advection through Ekman fluxes.
Key Points
Coherent sea level signal along the eastern boundary of the North Atlantic
Longshore wind is a major contributor
Cells continually assess their energy and nutrient state to maintain growth and survival and engage necessary homeostatic mechanisms. Cell-autonomous responses to the fed state require the ...surveillance of the availability of amino acids and other nutrients. The mammalian target of rapamycin complex 1 (mTORC1) integrates information on nutrient and amino acid availability to support protein synthesis and cell growth. We identify the G protein-coupled receptor (GPCR) T1R1/T1R3 as a direct sensor of the fed state and amino acid availability. Knocking down this receptor, which is found in most tissues, reduces the ability of amino acids to signal to mTORC1. Interfering with this receptor alters localization of mTORC1, downregulates expression of pathway inhibitors, upregulates key amino acid transporters, blocks translation initiation, and induces autophagy. These findings reveal a mechanism for communicating amino acid availability through a GPCR to mTORC1 in mammals.
► The T1R1/T1R3 GPCR senses extracellular amino acids promoting mTORC1 activation ► T1R1/T1R3 is required for proper localization of mTOR to the lysosomal compartment ► Silencing T1R1/T1R3 induces changes characteristic of a starvation response ► Small molecule inhibitors of T1R1/T1R3 acutely block mTORC1 activity
Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To ...test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-9-39 (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist. Unexpectedly, Ex-9 had no effect on blood glucose in mice with restoration of intestinal Gcg. In contrast, pancreatic reactivation of Gcg fully restored the effect of Ex9 to impair both oral and i.p. glucose tolerance. These findings suggest an alternative model whereby islet GLP-1 also plays an important role in regulating glucose homeostasis.
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•Intestinally secreted GLP-1 is presumed to regulate glucose via incretin action•Exendin-9 does not alter glucose in mice that only produce GLP-1 in the intestine•Exendin-9 does impair glucose in mice that only produce GLP-1 in the pancreas•Alternative to the incretin model, islet GLP-1 is crucial for gluco-regulation
GLP-1 is necessary for normal gluco-regulation, and it has been widely presumed that this function is the action of peptide released from enteroendocrine L cells. The data from Chambers et al. challenge this dogma and find that intestinally produced GLP-1 is dispensable, while pancreatic production of GLP-1 is necessary for gluco-regulation.
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