This study elucidates the physical mechanisms underlying internal and forced components of winter surface air temperature (SAT) trends over North America during the past 50 years (1963–2012) using a ...combined observational and modeling framework. The modeling framework consists of 30 simulations with the Community Earth System Model (CESM) at 1° latitude–longitude resolution, each of which is subject to an identical scenario of historical radiative forcing but starts from a slightly different atmospheric state. Hence, any spread within the ensemble results from unpredictable internal variability superimposed upon the forced climate change signal. Constructed atmospheric circulation analogs are used to estimate the dynamical contribution to forced and internal components of SAT trends: thermodynamic contributions are obtained as a residual. Internal circulation trends are estimated to account for approximately one-third of the observed wintertime warming trend over North America and more than half locally over parts of Canada and the United States. Removing the effects of internal atmospheric circulation variability narrows the spread of SAT trends within the CESM ensemble and brings the observed trends closer to the model’s radiatively forced response. In addition, removing internal dynamics approximately doubles the signal-to-noise ratio of the simulated SAT trends and substantially advances the “time of emergence” of the forced component of SAT anomalies. The methodological framework proposed here provides a general template for improving physical understanding and interpretation of observed and simulated climate trends worldwide and may help to reconcile the diversity of SAT trends across the models from phase 5 of the Coupled Model Intercomparison Project (CMIP5).
Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal ...barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2−/−Tlr4−/− mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
•Pregnane X receptor (PXR) is a physiologic regulator of intestinal permeability•Microbial-derived indoles can regulate intestinal barrier function through PXR•PXR regulates intestinal barrier function through TLR4•Specific indole-producing bacteria can reduce intestinal inflammation
How commensal microbial metabolites affect mucosal integrity and barrier function is unclear. Mani and colleagues show that indole 3 propionic acid regulates intestinal barrier permeability through the PXR-TLR4 pathway.
Pyridoxal-5′-phosphate (PLP) is a versatile cofactor that enzymes use to catalyze a wide variety of reactions of amino acids, including transamination, decarboxylation, racemization, β- and ...γ-eliminations and substitutions, retro-aldol and Claisen reactions. These reactions depend on the ability of PLP to stabilize, to a varying degree, α-carbanionic intermediates. Furthermore, oxidative decarboxylations and rearrangements suggest that PLP can stabilize radical intermediates as well. The reaction mechanisms of two PLP-dependent enzymes are discussed, kynureninase and tyrosine phenol-lyase (TPL). Kynureninase catalyzes a retro-Claisen reaction of kynurenine to give anthranilate and alanine. The key step, hydration of the γ-carbonyl, is assisted by acid–base catalysis with the phosphate of the PLP, mediated by a conserved tyrosine, and an oxyanion hole. TPL catalyzes the reversible elimination of phenol, a poor leaving group, from l-tyrosine. In TPL, the Cβ–Cγ bond cleavage is accelerated by ground state strain from the bending of the substrate ring out of the plane with the Cβ–Cγ bond. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
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•PLP-dependent enzymes catalyze a wide variety of reactions of amino acids and amines.•Kynureninase catalyzes a retro-Claisen reaction of kynurenine to anthranilate and alanine.•Kynureninase utilizes the PLP as both an electrophilic catalyst and acid–base catalyst.•Tyrosine phenol-lyase catalyzes the elimination of phenol, a poor leaving group, from tyrosine.•Tyrosine phenol-lyase introduces strain into the substrate to accelerate the reaction rate.
The relative contributions of external forcing and internal processes to the observed spatial and temporal characteristics of “Atlantic Multidecadal Variability” (AMV) are still under debate. Here, ...the efficacy of the commonly‐used “global temperature residual method” for isolating the internal component of AMV is investigated by means of model Large Ensembles where the truth is known a priori. In this method, local sea surface temperature variability associated with global‐mean temperature (G) is removed via linear regression, and the residuals regressed upon the North Atlantic residual timeseries. We show that this method introduces spurious connections over the Indo‐Pacific due to the fact that G in any single realization includes both external and internal components: the latter dominated by influences from Pacific Decadal Variability independent of AMV. This methodological shortcoming can be overcome by using the forced component of G in the residual method applied to individual model realizations and to observations.
Plain Language Summary
The phenomenon known as “Atlantic Multidecadal Variability” (AMV) has been widely studied and has important climate effects over Africa, Asia, Europe, and eastern North America. Recently, there has been considerable debate regarding the relative contributions of natural processes within the coupled ocean‐atmosphere system versus human influences related to aerosol emissions on the spatial and temporal character of AMV. An accurate separation of these natural and anthropogenic contributions has proven challenging due to limitations of the data record. Statistical techniques aimed at isolating the natural component of AMV often yield conflicting results. Here, we investigate one widely‐used approach based on removing variability associated with global‐mean temperatures. We show that the conventional application of this method aliases another well‐known phenomenon, “Interdecadal Pacific Variability,” onto the pattern of natural AMV. However, with a simple modification to the method, the true pattern of natural AMV can be recovered.
Key Points
A common method for isolating the internal component of Atlantic Multidecadal Variability is to remove fluctuations associated with global‐mean temperature
This method introduces spurious Indo‐Pacific connections in model Large Ensembles and observations due to internal variations in global‐mean temperature
A revised method based on removing fluctuations associated with the forced component of global‐mean temperature mitigates this issue
There is a need to better understand the survivorship of discarded fishes, both for commercial stocks and species of conservation concern. Within European waters, the landing obligations that are ...currently being phased in as part of the European Union's reformed common fisheries policy means that an increasing number of fish stocks, with certain exceptions, should not be discarded unless it can be demonstrated that there is a high probability of survival. This study reviews the various approaches that have been used to examine the discard survival of elasmobranchs, both in terms of at‐vessel mortality (AVM) and post‐release mortality (PRM), with relevant findings summarized for both the main types of fishing gear used and by taxonomic group. Discard survival varies with a range of biological attributes (species, size, sex and mode of gill ventilation) as well as the range of factors associated with capture (e.g. gear type, soak time, catch mass and composition, handling practices and the degree of exposure to air and any associated change in ambient temperature). In general, demersal species with buccal‐pump ventilation have a higher survival than obligate ram ventilators. Several studies have indicated that females may have a higher survival than males. Certain taxa (including hammerhead sharks Sphyrna spp. and thresher sharks Alopias spp.) may be particularly prone to higher rates of mortality when caught.
In 2013, New York began requiring hospitals to follow protocols for the early identification and treatment of sepsis. However, there is controversy about whether more rapid treatment of sepsis ...improves outcomes in patients.
We studied data from patients with sepsis and septic shock that were reported to the New York State Department of Health from April 1, 2014, to June 30, 2016. Patients had a sepsis protocol initiated within 6 hours after arrival in the emergency department and had all items in a 3-hour bundle of care for patients with sepsis (i.e., blood cultures, broad-spectrum antibiotic agents, and lactate measurement) completed within 12 hours. Multilevel models were used to assess the associations between the time until completion of the 3-hour bundle and risk-adjusted mortality. We also examined the times to the administration of antibiotics and to the completion of an initial bolus of intravenous fluid.
Among 49,331 patients at 149 hospitals, 40,696 (82.5%) had the 3-hour bundle completed within 3 hours. The median time to completion of the 3-hour bundle was 1.30 hours (interquartile range, 0.65 to 2.35), the median time to the administration of antibiotics was 0.95 hours (interquartile range, 0.35 to 1.95), and the median time to completion of the fluid bolus was 2.56 hours (interquartile range, 1.33 to 4.20). Among patients who had the 3-hour bundle completed within 12 hours, a longer time to the completion of the bundle was associated with higher risk-adjusted in-hospital mortality (odds ratio, 1.04 per hour; 95% confidence interval CI, 1.02 to 1.05; P<0.001), as was a longer time to the administration of antibiotics (odds ratio, 1.04 per hour; 95% CI, 1.03 to 1.06; P<0.001) but not a longer time to the completion of a bolus of intravenous fluids (odds ratio, 1.01 per hour; 95% CI, 0.99 to 1.02; P=0.21).
More rapid completion of a 3-hour bundle of sepsis care and rapid administration of antibiotics, but not rapid completion of an initial bolus of intravenous fluids, were associated with lower risk-adjusted in-hospital mortality. (Funded by the National Institutes of Health and others.).
This study highlights the relative importance of internally generated versus externally forced climate trends over the next 50 yr (2010–60) at local and regional scales over North America in two ...global coupled model ensembles. Both ensembles contain large numbers of integrations (17 and 40): each of which is subject to identical anthropogenic radiative forcing (e.g., greenhouse gas increase) but begins from a slightly different initial atmospheric state. Thus, the diversity of projected climate trends within each model ensemble is due solely to intrinsic, unpredictable variability of the climate system. Both model ensembles show that natural climate variability superimposed upon forced climate change will result in a range of possible future trends for surface air temperature and precipitation over the next 50 yr. Precipitation trends are particularly subject to uncertainty as a result of internal variability, with signal-to-noise ratios less than 2. Intrinsic atmospheric circulation variability is mainly responsible for the spread in future climate trends, imparting regional coherence to the internally driven air temperature and precipitation trends. The results underscore the importance of conducting a large number of climate change projections with a given model, as each realization will contain a different superposition of unforced and forced trends. Such initial-condition ensembles are also needed to determine the anthropogenic climate response at local and regional scales and provide a new perspective on how to usefully compare climate change projections across models.
Abstract
Background
sarcopenia in ageing is a progressive decrease in muscle mass, strength and/or physical function. This review aims to summarise the definitions of sarcopenia in community-dwelling ...older adults and explore similarities and differences in prevalence estimates by definition.
Methods
a systematic review was conducted to identify articles which estimated sarcopenia prevalence in older populations using search terms for sarcopenia and muscle mass. Overall prevalence for each sarcopenia definition was estimated stratified by sex and ethnicity. Secondary analyses explored differences between studies and within definitions, including participant age, muscle mass measurement techniques and thresholds for muscle mass and gait speed.
Results
in 109 included articles, eight definitions of sarcopenia were identified. The lowest pooled prevalence estimates came from the European Working Group on Sarcopenia/Asian Working Group on Sarcopenia (12.9%, 95% confidence interval: 9.9–15.9%), International Working Group on Sarcopenia (9.9%, 3.2–16.6%) and Foundation for the National Institutes of Health (18.6%, 11.8–25.5%) definitions. The highest prevalence estimates were for the appendicular lean mass (ALM)/weight (40.4%, 19.5–61.2%), ALM/height (30.4%, 20.4–40.3%), ALM regressed on height and weight (30.4%, 20.4–40.3%) and ALM / body mass index (24.2%, 18.3–30.1%) definitions. Within definitions, the age of study participants and the muscle mass cut points used were substantive sources of between-study differences.
Conclusion
estimates of sarcopenia prevalence vary from 9.9 to 40.4%, depending on the definition used. Significant differences in prevalence exist within definitions across populations. This lack of agreement between definitions needs to be better understood before sarcopenia can be appropriately used in a clinical context.
The Pacific Decadal Oscillation, Revisited Newman, Matthew; Alexander, Michael A.; Ault, Toby R. ...
Journal of climate,
06/2016, Letnik:
29, Številka:
12
Journal Article
Recenzirano
The Pacific decadal oscillation (PDO), the dominant year-round pattern of monthly North Pacific sea surface temperature (SST) variability, is an important target of ongoing research within ...themeteorological and climate dynamics communities and is central to the work of many geologists, ecologists, natural resource managers, and social scientists. Research over the last 15 years has led to an emerging consensus: the PDO is not a single phenomenon, but is instead the result of a combination of different physical processes, including both remote tropical forcing and local North Pacific atmosphere–ocean interactions, which operate on different time scales to drive similar PDO-like SST anomaly patterns. How these processes combine to generate the observed PDO evolution, including apparent regime shifts, is shown using simple autoregressive models of increasing spatial complexity. Simulations of recent climate in coupled GCMs are able to capture many aspects of the PDO, but do so based on a balance of processes often more independent of the tropics than is observed. Finally, it is suggested that the assessment of PDO-related regional climate impacts, reconstruction of PDO-related variability into the past with proxy records, and diagnosis of Pacific variability within coupled GCMs should all account for the effects of these different processes, which only partly represent the direct forcing of the atmosphere by North Pacific Ocean SSTs.
Unloading-induced atrophy is a relatively uncomplicated form of muscle loss, dependent almost solely on the loss of mechanical input, whereas in disease states associated with inflammation (cancer ...cachexia, AIDS, burns, sepsis, and uremia), there is a procatabolic hormonal and cytokine environment. It is therefore predictable that muscle loss mainly due to disuse alone would be governed by mechanisms somewhat differently from those in inflammatory states. We suggest that in vivo measurements made in human subjects using arterial-venous balance, tracer dilution, and tracer incorporation are dynamic and thus robust by comparison with static measurements of mRNA abundance and protein expression and/or phosphorylation in human muscle. In addition, measurements made with cultured cells or in animal models, all of which have often been used to infer alterations of protein turnover, appear to be different from results obtained in immobilized human muscle in vivo. In vivo measurements of human muscle protein turnover in disuse show that the primary variable that changes facilitating the loss of muscle mass is protein synthesis, which is reduced in both the postabsorptive and postprandial states; muscle proteolysis itself appears not to be elevated. The depressed postprandial protein synthetic response (a phenomenon we term "anabolic resistance") may even be accompanied by a diminished suppression of proteolysis. We therefore propose that most of the loss of muscle mass during disuse atrophy can be accounted for by a depression in the rate of protein synthesis. Thus the normal diurnal fasted-to-fed cycle of protein balance is disrupted and, by default, proteolysis becomes dominant but is not enhanced.
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