671 research outputs found
Interval training normalizes cCardiomyocyte function, diastolic Ca<sup>2+</sup> control, and SR Ca<sup>2+</sup> release synchronicity in a mouse model of diabetic cardiomyopathy
In the present study we explored the mechanisms behind excitation-contraction (EC)-coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db), and determined whether 13-weeks of aerobic interval training could restore cardiomyocyte Ca2+ cycling and EC-coupling. Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca2+ leak, reduced synchrony of Ca2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca2+ and caffeine-induced Ca2+ release. Additionally, the rate of SR Ca2+ ATPase (SERCA2a)-mediated Ca2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca2+ release indicated increased Na+/Ca2+- exchanger (NCX) activity. The increased SR-Ca2+ leak was attributed to increased Ca2+-calmodulindependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca2+ leak upon inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca2+ release synchronicity, T-tubule density, twitch Ca2+ amplitude, SERCA2a and NCX activities, and SR-Ca2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A (PKA) inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca2+ load when compared with the sedentary db/db mice. EC-coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition. These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type (WT)
The influence of νh11/2 occupancy on the magnetic moments of collective 21+ states in A∼100 fission fragments
AbstractThe magnetic moments of Iπ=21+ states in even–even A∼100 fission fragments have been measured using the Gammasphere array, using the technique of time-integral perturbed angular correlations. The data are interpreted within the context of the interacting boson model (IBA2) leading to the suggestion of a strong νh11/2 component in the deformed 21+ states of this region
A World-Volume Perspective on the Recombination of Intersecting Branes
We study brane recombination for supersymmetric configurations of
intersecting branes in terms of the world-volume field theory. This field
theory contains an impurity, corresponding to the degrees of freedom localized
at the intersection. The Higgs branch, on which the impurity fields condense,
consists of vacua for which the intersection is deformed into a smooth
calibrated manifold. We show this explicitly using a superspace formalism for
which the calibration equations arise naturally from F- and D-flatness.Comment: References adde
Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery
Background: The use of anaesthetics in the elderly surgical population (more than 60 years of age) is increasing. Postoperative delirium, an acute condition characterized by reduced awareness of the environment and a disturbance in attention, typically occurs between 24 and 72 hours after surgery and can affect up to 60% of elderly surgical patients. Postoperative cognitive dysfunction (POCD) is a new-onset of cognitive impairment which may persist for weeks or months after surgery. Traditionally, surgical anaesthesia has been maintained with inhalational agents. End-tidal concentrations require adjustment to balance the risks of accidental awareness and excessive dosing in elderly people. As an alternative, propofol-based total intravenous anaesthesia (TIVA) offers a more rapid recovery and reduces postoperative nausea and vomiting. Using TIVA with a target controlled infusion (TCI) allows plasma and effect-site concentrations to be calculated using an algorithm based on age, gender, weight and height of the patient. TIVA is a viable alternative to inhalational maintenance agents for surgical anaesthesia in elderly people. However, in terms of postoperative cognitive outcomes, the optimal technique is unknown. Objectives: To compare maintenance of general anaesthesia for elderly people undergoing non-cardiac surgery using propofol-based TIVA or inhalational anaesthesia on postoperative cognitive function, mortality, risk of hypotension, length of stay in the postanaesthesia care unit (PACU), and hospital stay. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE (1946 to November 2017), Embase (1974 to November 2017), PsycINFO (1887 to November 2017). We searched clinical trials registers for ongoing studies, and conducted backward and forward citation searching of relevant articles. Selection criteria: We included randomized controlled trials (RCTs) with participants over 60 years of age scheduled for non-cardiac surgery under general anaesthesia. We planned to also include quasi-randomized trials. We compared maintenance of anaesthesia with propofol-based TIVA versus inhalational maintenance of anaesthesia. Data collection and analysis: Two review authors independently assessed studies for inclusion, extracted data, assessed risk of bias, and synthesized findings. Main results: We included 28 RCTs with 4507 randomized participants undergoing different types of surgery (predominantly cardiovascular, laparoscopic, abdominal, orthopaedic and ophthalmic procedures). We found no quasi-randomized trials. Four studies are awaiting classification because we had insufficient information to assess eligibility. All studies compared maintenance with propofol-based TIVA versus inhalational maintenance of anaesthesia. Six studies were multi-arm and included additional TIVA groups, additional inhalational maintenance or both. Inhalational maintenance agents included sevoflurane (19 studies), isoflurane (eight studies), and desflurane (three studies), and was not specified in one study (reported as an abstract). Some studies also reported use of epidural analgesia/anaesthesia, fentanyl and remifentanil. We found insufficient reporting of randomization methods in many studies and all studies were at high risk of performance bias because it was not feasible to blind anaesthetists to study groups. Thirteen studies described blinding of outcome assessors. Three studies had a high of risk of attrition bias, and we noted differences in the use of analgesics between groups in six studies, and differences in baseline characteristics in five studies. Few studies reported clinical trials registration, which prevented assessment of risk of selective reporting bias. We found no evidence of a difference in incidences of postoperative delirium according to type of anaesthetic maintenance agents (odds ratio (OR) 0.59, 95% confidence interval (CI) 0.15 to 2.26; 321 participants; five studies; very low-certainty evidence); we noted during sensitivity analysis that using different time points in one study may influence direction of this result. Thirteen studies (3215 participants) reported POCD, and of these, six studies reported data that could not be pooled; we noted no difference in scores of POCD in four of these and in one study, data were at a time point incomparable to other studies. We excluded one large study from meta-analysis because study investigators had used non-standard anaesthetic management and this study was not methodologically comparable to other studies. We combined data for seven studies and found low-certainty evidence that TIVA may reduce POCD (OR 0.52, 95% CI 0.31 to 0.87; 869 participants). We found no evidence of a difference in mortality at 30 days (OR 1.21, 95% CI 0.33 to 4.45; 271 participants; three studies; very low-certainty evidence). Twelve studies reported intraoperative hypotension. We did not perform meta-analysis for 11 studies for this outcome. We noted visual inconsistencies in these data, which may be explained by possible variation in clinical management and medication used to manage hypotension in each study (downgraded to low-certainty evidence); one study reported data in a format that could not be combined and we noted little or no difference between groups in intraoperative hypotension for this study. Eight studies reported length of stay in the PACU, and we did not perform meta-analysis for seven studies. We noted visual inconsistencies in these data, which may be explained by possible differences in definition of time points for this outcome (downgraded to very low-certainty evidence); data were unclearly reported in one study. We found no evidence of a difference in length of hospital stay according to type of anaesthetic maintenance agent (mean difference (MD) 0 days, 95% CI -1.32 to 1.32; 175 participants; four studies; very low-certainty evidence). We used the GRADE approach to downgrade the certainty of the evidence for each outcome. Reasons for downgrading included: study limitations, because some included studies insufficiently reported randomization methods, had high attrition bias, or high risk of selective reporting bias; imprecision, because we found few studies; inconsistency, because we noted heterogeneity across studies. Authors' conclusions: We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes. © 2018 The Cochrane Collaboration
MAIC-2, a latitudinal model for the Martian surface temperature, atmospheric water transport and surface glaciation
The Mars Atmosphere-Ice Coupler MAIC-2 is a simple, latitudinal model, which
consists of a set of parameterisations for the surface temperature, the
atmospheric water transport and the surface mass balance (condensation minus
evaporation) of water ice. It is driven directly by the orbital parameters
obliquity, eccentricity and solar longitude (Ls) of perihelion. Surface
temperature is described by the Local Insolation Temperature (LIT) scheme,
which uses a daily and latitude-dependent radiation balance. The evaporation
rate of water is calculated by an expression for free convection, driven by
density differences between water vapor and ambient air, the condensation rate
follows from the assumption that any water vapour which exceeds the local
saturation pressure condenses instantly, and atmospheric transport of water
vapour is approximated by instantaneous mixing. Glacial flow of ice deposits is
neglected. Simulations with constant orbital parameters show that low
obliquities favour deposition of ice in high latitudes and vice versa. A
transient scenario driven by a computed history of orbital parameters over the
last 10 million years produces essentially monotonically growing polar ice
deposits during the most recent 4 million years, and a very good agreement with
the observed present-day polar layered deposits. The thick polar deposits
sometimes continue in thin ice deposits which extend far into the mid
latitudes, which confirms the idea of "ice ages" at high obliquity.Comment: 20 pages, 10 figures, 2 table
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Genetically engineered multicistronic allele of Pmel yielding highly specific CreERT2-mediated recombination in the melanocyte lineage
YesGenetic approaches that allow lineage tracing are essential to our future understanding of melanocytes and melanoma. To date, the approaches used to label melanocytes in mice have relied on random integration of transgenes driven by the promoters of the Tyrosinase and Dopachrome tautomerase genes, knock-in to the Dopachrome tautomerase locus or knock-in to the Mlana locus in a bacterial artificial chromosome. These strategies result in expression in other tissues such as telencephalon and other cell types such as nerves. Here we used homologous recombination in mouse embryonic stem cells to generate a targeted multicistronic allele of the Pmel locus that drives melanocyte-specific expression of CreERT2, nuclear localised H2B-Cerulean and membrane localised marcks-mKate2 allowing live imaging of melanocytes and activation of other conditional alleles. We combined this allele with R26R-EYFP mice allowing induction of EYFP expression on administration of tamoxifen or its metabolite 4-OHT. The fluorescent proteins H2B-Cerulean and marcks-mKate2 label the cell nucleus and plasma membrane respectively allowing live imaging and FACS isolation of melanoblasts and melanocytes as well as serving to provide an internal control allowing estimation of recombination efficiency after administration of tamoxifen. We demonstrate the utility of the transgene in embryonic and adult tissues.Cancer Research UK. Grant Number: A15673. Medical Research Council. Grant Number: MC_PC_U127527200. National Centre for the Replacement Refinement and Reduction of Animals in Research. Grant Number: NC/K001612/1. North West Cancer Research Fund. Grant Number: CR1132. Medical Research Scotland. Grant Number: 436FR
Droplet printing reveals the importance of micron-scale structure for bacterial ecology
Bacteria often live in diverse communities where the spatial arrangement of strains and species is considered critical for their ecology. However, a test of this hypothesis requires manipulation at the fine scales at which spatial structure naturally occurs. Here we develop a droplet-based printing method to arrange bacterial genotypes across a sub-millimetre array. We print strains of the gut bacterium Escherichia coli that naturally compete with one another using protein toxins. Our experiments reveal that toxin-producing strains largely eliminate susceptible non-producers when genotypes are well-mixed. However, printing strains side-by-side creates an ecological refuge where susceptible strains can persist in large numbers. Moving to competitions between toxin producers reveals that spatial structure can make the difference between one strain winning and mutual destruction. Finally, we print different potential barriers between competing strains to understand how ecological refuges form, which shows that cells closest to a toxin producer mop up the toxin and protect their clonemates. Our work provides a method to generate customised bacterial communities with defined spatial distributions, and reveals that micron-scale changes in these distributions can drive major shifts in ecology
The Milky Way Bulge: Observed properties and a comparison to external galaxies
The Milky Way bulge offers a unique opportunity to investigate in detail the
role that different processes such as dynamical instabilities, hierarchical
merging, and dissipational collapse may have played in the history of the
Galaxy formation and evolution based on its resolved stellar population
properties. Large observation programmes and surveys of the bulge are providing
for the first time a look into the global view of the Milky Way bulge that can
be compared with the bulges of other galaxies, and be used as a template for
detailed comparison with models. The Milky Way has been shown to have a
box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an
additional spheroidal component. In this review we summarise the global
chemical abundances, kinematics and structural properties that allow us to
disentangle these multiple components and provide constraints to understand
their origin. The investigation of both detailed and global properties of the
bulge now provide us with the opportunity to characterise the bulge as observed
in models, and to place the mixed component bulge scenario in the general
context of external galaxies. When writing this review, we considered the
perspectives of researchers working with the Milky Way and researchers working
with external galaxies. It is an attempt to approach both communities for a
fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen
E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure
Structural response of Caribbean dry forests to hurricane winds: a case study from Guanica Forest, Puerto Rico
Tropical dry forests in the Caribbean have an uniquely short, shrubby structure with a high proportion of multiple-stemmed trees compared to dry forests elsewhere in the Neotropics. Previous studies have shown that this structure can arise without the loss of main stems from cutting, grazing, or other human intervention. The Caribbean has a high frequency of hurricanes, so wind may also influence forest stature. Furthermore, these forests also tend to grow on soils with low amounts of available phosphorus, which may also influence structure. The objective of this study was to assess the role of high winds in structuring dry forest, and to determine whether soil nutrient pools influence forest response following hurricane disturbance.
Methods: Over 2000 stems in five plots were sampled for hurricane effects within 1 week after Hurricane Georges impacted field sites in 1998. Sprout initiation, growth, and mortality were analysed for 1407 stems for 2 years after the hurricane. Soil nutrient pools were measured at the base of 456 stems to assess association between nutrients and sprout dynamics.
Results: Direct effects of the hurricane were minimal, with stem mortality at \u3c 2% and structural damage to stems at 13%, although damage was biased toward stems of larger diameter. Sprouting response was high . over 10 times as many trees had sprouts after the hurricane as before. The number of sprouts on a stem also increased significantly. Sprouting was common on stems that only suffered defoliation or had no visible effects from the hurricane. Sprout survival after 2 years was also high (\u3e 86%). Soil nutrient pools had little effect on forest response as a whole, but phosphorus supply did influence sprout dynamics on four of the more common tree species. Main Conclusions: Hurricanes are able to influence Caribbean tropical dry forest structure by reducing average stem diameter and basal area and generating significant sprouting responses. New sprouts, with ongoing survival, will maintain the high frequency of multi-stemmed trees found in this region. Sprouting is not limited to damaged stems, indicating that trees are responding to other aspects of high winds, such as short-term gravitational displacement or sway. Soil nutrients play a secondary role in sprouting dynamics of a subset of species. The short, shrubby forest structure common to the Caribbean can arise naturally as a response to hurricane winds
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