590 research outputs found
Spatial organization of bacterial transcription and translation
In bacteria such as , DNA is compacted into a
nucleoid near the cell center, while ribosomesmolecular complexes that
translate messenger RNAs (mRNAs) into proteinsare mainly localized at the
poles. We study the impact of this spatial organization using a minimal
reaction-diffusion model for the cellular transcriptional-translational
machinery. Our model predicts that of mRNAs are segregated to the
poles and reveals a "circulation" of ribosomes driven by the flux of mRNAs,
from synthesis in the nucleoid to degradation at the poles. To address the
existence of non-specific, transient interactions between ribosomes and mRNAs,
we developed a novel method to efficiently incorporate such transient
interactions into reaction-diffusion equations, which allowed us to quantify
the biological implications of such non-specific interactions, e.g. for
ribosome efficiency
Application of adaptive multilevel splitting to high-dimensional dynamical systems
Stochastic nonlinear dynamical systems can undergo rapid transitions relative
to the change in their forcing, for example due to the occurrence of multiple
equilibrium solutions for a specific interval of parameters. In this paper, we
modify one of the methods developed to compute probabilities of such
transitions, Trajectory-Adaptive Multilevel Sampling (TAMS), to be able to
apply it to high-dimensional systems. The key innovation is a projected
time-stepping approach, which leads to a strong reduction in computational
costs, in particular memory usage. The performance of this new implementation
of TAMS is studied through an example of the collapse of the Atlantic Ocean
Circulation
Shelf slope convection: A note for antarctic regions
Some basic processes associated with buoyancy-driven convection in the presence of coastal upwellingcurren ts were investigated in a 2.5D framework near the Adelie Coast of Antarctica. The surface buoyancy forcingw as derived from
coolingand brine deposition due to ice formation, and was specified over a persistent off-shore polynya maintained by the off-shore katabatic winds. Rotational effects and
the formation of a turbulent surface mixed layer were included in the model. The representation of topography was done via the VBM (virtual Boundary Method) that utilizes equivalent body forces in the momentum equation, thus enabling the use of very efficient Poisson solvers for the pressure, based on FFTs. The simulations were carried out near longitude 143E, between latitude 68S and 65S, over the nearshore shelf region. The hydrography was initialized with the 1/4 deg Levitus annual climatology. Two cases of idealized meteorological forcing were considered: constant
winds blowingalong -shore and off-shore. The resultant motions in each case were characterized by interaction between the wind-driven upwellingmotions and the downward movingdense convection plumes, but with marked differences: a) the formation of a strongfron t under the open sea edge of the polynya only by off-shore winds; b) the periodic suppression of the surface off-shore currents and of the coastal upwelling only by the along-shore winds; c) the formation of deep upwelling currents along the slope between 400 and 200 meters only for along-shore winds, and d) the rapid filling of the surface layers (depths < 100m) with high salinities under the whole polynya by the
off-shore forcing, vs. the delayed fillingof a narrow region
near the downwellingplume with intermediate salinity values by the along-shore forcing
Association of a homozygous GCK missense mutation with mild diabetes
Background: Homozygous inactivating GCK mutations have been repeatedly reported to cause severe hyperglycemia, presenting as permanent neonatal diabetes mellitus (PNDM). Conversely, only two cases of GCK homozygous mutations causing mild hyperglycemia have been so far described. We here report a novel GCK mutation (c.1116G>C, p.E372D), in a family with one homozygous member showing mild hyperglycemia. Methods: GCK mutational screening was carried out by Sanger sequencing. Computational analyses to investigate pathogenicity and molecular dynamics (MD) were performed for GCK-E372D and for previously described homozygous mutations associated with mild (n = 2) or severe (n = 1) hyperglycemia, used as references. Results: Of four mildly hyperglycemic family-members, three were heterozygous and one, diagnosed in the adulthood, was homozygous for GCK-E372D. Two nondiabetic family members carried no mutations. Fasting glucose (p = 0.016) and HbA1c (p = 0.035) correlated with the number of mutated alleles (0–2). In-silico predicted pathogenicity was not correlated with the four mutations’ severity. At MD, GCK-E372D conferred protein structure flexibility intermediate between mild and severe GCK mutations. Conclusions: We present the third case of homozygous GCK mutations associated with mild hyperglycemia, rather than PNDM. Our in-silico analyses support previous evidences suggesting that protein stability plays a role in determining clinical severity of GCK mutations
A family history of type 2 diabetes as a predictor of fatty liver disease in diabetes-free individuals with excessive body weight
Comprehensive screening for non-alcoholic fatty liver disease (NAFLD) may help prompt clinical management of fatty liver disease. A family history, especially of diabetes, has been little studied as a predictor for NAFLD. We characterized the cross-sectional relationship between a family history of type 2 diabetes (FHT2D) and NAFLD probability in 1185 diabetes-free Apulian (Southern-Italy) subjects aged > 20 years with overweight or obesity not receiving any drug or supplementation. Clinical data and routine biochemistry were analysed. NAFLD probability was defined using the fatty liver index (FLI). A first-degree FHT2D was assessed by interviewing subjects and assigning a score of 0, 1, or 2 if none, only one, or both parents were affected by type 2 diabetes mellitus (T2DM). Our study population featured most females (70.9%, N = 840), and 48.4% (N = 574) of the sample had first-degree FHT2D. After dividing the sample by a FHT2D, we found a higher BMI, Waist Circumference (WC), and diastolic blood pressure shared by FHT2D subjects; they also showed altered key markers of glucose homeostasis, higher triglyceride levels, and worse liver function. FLI scores were significantly lower in subjects without a first-degree FHT2D. After running logistic regression models, a FHT2D was significantly associated with the NAFLD probability, even adjusting for major confounders and stratifying by age (under and over 40 years of age). A FHT2D led to an almost twofold higher probability of NAFLD, regardless of confounding factors (OR 2.17, 95% CI 1.63 to 2.89). A first-degree FHT2D acts as an independent determinant of NAFLD in excess weight phenotypes, regardless of the age group (younger or older than 40 years). A NAFLD risk assessment within multidimensional screening might be useful in excess weight subjects reporting FHT2D even in the absence of diabetes
Spaces with Noetherian cohomology
Is the cohomology of the classifying space of a p-compact group, with Noetherian twisted coefficients, a Noetherian module? In this paper we provide, over the ring of p-adic integers, such a generalization to p-compact groups of the Evens-Venkov Theorem. We consider the cohomology of a space with coefficients in a module, and we compare Noetherianity over the field with p elements with Noetherianity over the p-adic integers, in the case when the fundamental group is a finite p-grou
Role of the Tracy-Widom distribution in the finite-size fluctuations of the critical temperature of the Sherrington-Kirkpatrick spin glass
We investigate the finite-size fluctuations due to quenched disorder of the
critical temperature of the Sherrington-Kirkpatrick spin glass. In order to
accomplish this task, we perform a finite-size analysis of the spectrum of the
susceptibility matrix obtained via the Plefka expansion. By exploiting results
from random matrix theory, we obtain that the fluctuations of the critical
temperature are described by the Tracy-Widom distribution with a non-trivial
scaling exponent 2/3
Efficacy and safety of GLP-1 receptor agonists as add-on to SGLT2 inhibitors in type 2 diabetes mellitus: A meta-analysis
GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) have been associated with improved glycemic control, body weight loss and favorable changes in cardiovascular risk factors and outcomes. We conducted a systematic review and meta-analysis to evaluate the effects of the addition of GLP-1RA to SGLT2i in patients with type 2 diabetes mellitus and inadequate glycemic control. Six databases were searched until March 2019. Randomized controlled trials (RCT) with a follow-up of at least 24 weeks reporting on HbA1c, body weight, systolic blood pressure, lipids, achievement of HbA1c < 7%, requirement of rescue therapy due to hyperglycemia and hypoglycemic events were selected. Four RCTs were included. Compared to SGLT2i, the GLP-1RA/SGLT2i combination was associated with greater reduction in HbA1c (−0.74%), body weight (−1.61 kg), and systolic blood pressure (−3.32 mmHg). A higher number of patients achieved HbA1c < 7% (RR = 2.15), with a lower requirement of rescue therapy (RR = 0.37) and similar incidence of hypoglycemia. Reductions in total and LDL cholesterol were found. The present review supports treatment intensification with GLP-1RA in uncontrolled type 2 diabetes on SGLT2i. This drug regimen could provide improved HbA1c control, together with enhanced weight loss and blood pressure and lipids control
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