Carltonchung4140

In the yeast Saccharomyces cerevisiae, the mitochondrial branched-chain amino acid (BCAA) aminotransferase Bat1 plays an important role in the synthesis of BCAAs (valine, leucine, and isoleucine). find more Our upcoming study (Large et al. bioRχiv. 10.1101/2020.06.26.166157, Large et al. 2020) will show that the heterozygous tetraploid beer yeast strain, Wyeast 1056, which natively has a variant causing one amino acid substitution of Ala234Asp in Bat1 on one of the four chromosomes, produced higher levels of BCAA-derived fusel alcohols in the brewer's wort medium than a derived strain lacking this mutation. Here, we investigated the physiological role of the A234D variant Bat1 in S. cerevisiae. Both bat1∆ and bat1A234D cells exhibited the same phenotypes relative to the wild-type Bat1 strain-namely, a repressive growth rate in the logarithmic phase; decreases in intracellular valine and leucine content in the logarithmic and stationary growth phases, respectively; an increase in fusel alcohol content in culture medium; and a decrease in the carbon dioxide productivity. These results indicate that amino acid change from Ala to Asp at position 234 led to a functional impairment of Bat1, although homology modeling suggests that Asp234 in the variant Bat1 did not inhibit enzymatic activity directly. KEY POINTS • Yeast cells expressing Bat1A234D exhibited a slower growth phenotype. • The Val and Leu levels were decreased in yeast cells expressing Bat1A234D. • The A234D substitution causes a loss-of-function in Bat1. • The A234D substitution in Bat1 increased fusel alcohol production in yeast cells.Aim of our study was to analyze the association between serum sodium (Na) variability and acute kidney injury (AKI) development. We performed a retrospective observational cohort study on the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 1, 2010 and December 31, 2014 with inclusion of adult patients with ≥ 2 Na and ≥ 2 serum creatinine measurements. We included only patients with ≥ 2 Na measurements before AKI development. The outcome of interest was AKI. The exposures of interest were hyponatremia, hypernatremia and Na fluctuations before AKI development. Na variability was evaluated using the coefficient of variation (CV). Multivariable Cox proportional hazards and logistic regression models were fitted to obtain hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the exposures of interest and AKI. Overall, 56,961 patients met our inclusion criteria. During 1541 person-years of follow-up AKI occurred in 1450 patients. In multivariable hazard models, patients with pre-existent dysnatremia and those who developed dysnatremia had a higher risk of AKI compared with patients with normonatremia. Logistic models suggested a higher risk for AKI in the 3rd (OR 1.41, 95% CI 1.18, 1.70, p  less then  0.001) and 4th (OR 1.53, 95% CI 1.24, 1.91, p  less then  0.001) highest quartiles of Na CV with a significant linear trend across quartiles (p trend  less then  0.001). This association was also independent from Na highest and lowest peak value. Dysnatremia is a common condition and is positive associated with AKI development. Furthermore, high Na variability might be considered an independent early indicator for kidney injury development.Streptobacillus felis is a fastidious microorganism and a novel member of the potentially zoonotic bacteria causing rat bite fever. Since its description, this is the second isolation of S. felis in a diseased member of the Felidae. Interestingly, the strain from this study was isolated from a zoo held, rusty-spotted cat (Prionailurus rubiginosus), with pneumonia, thereby indicating a possible broader host range in feline species. A recent preliminary sampling of domestic cats (Felis silvestris forma catus) revealed that this microorganism is common in the oropharynx, suggesting that S. felis is a member of their normal microbiota. Due to unawareness, fastidiousness, antibiotic sensitivity and lack of diagnostics the role of S. felis as a cat and human pathogen might be under-reported as with other Streptobacillus infections. More studies are necessary to elucidate the role of S. felis in domestic cats and other Felidae in order to better estimate its zoonotic potential.

Previous studies demonstrated that tiotropium/olodaterol reduced rates of exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this should be examined in a wider population.

This post hoc analysis pooled data from TONADO

1 + 2 and DYNAGITO

, three 52-week, parallel-group, randomised, double-blind, phaseIII trials investigating patients with moderate-to-very severe COPD, with and without previous exacerbations, who received tiotropium/olodaterol 5/5µg or tiotropium 5µg. Subgroup analyses were conducted on patients stratified by exacerbation history, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 2-4 disease severity and baseline inhaled corticosteroid (ICS) use.

In 9942 patients, tiotropium/olodaterol was associated with lower rates of moderate/severe exacerbations (0.68 vs. 0.77 per patient-year; rate ratio (RR) vs. tiotropium 0.89, 95% confidence interval (CI) 0.84, 0.95; P = 0.0003) and exacerbations requiring hospitalisation (0.11 vs. 0.13 per l together and people who were taking tiotropium alone. We showed that, across a wide range of people, treatment with tiotropium/olodaterol was generally better at reducing exacerbations than tiotropium. Tiotropium/olodaterol also decreased the number of exacerbations that led to hospitalisation compared with tiotropium. Overall, our results support the use of combined tiotropium/olodaterol in people at different stages of COPD.Many neurodegenerative diseases such as Alzheimer's disease (AD), multiple sclerosis, and traumatic brain injury (TBI) are associated with systemic inflammation. Inflammation itself results in increased blood content of fibrinogen (Fg), called hyperfibrinogenemia (HFg). Fg is not only considered an acute phase protein and a marker of inflammation, but has been shown that it can cause inflammatory responses. Fibrin deposits have been associated with memory reduction in neuroinflammatory diseases such as AD and TBI. link2 Reduction in short-term memory has been seen during the most common form of TBI, mild-to-moderate TBI. Fibrin deposits have been found in brains of patients with mild-to-moderate TBI. The vast majority of the literature emphasizes the role of fibrin-activated microglia as the mediator in the neuroinflammation pathway. However, the recent discovery that astrocytes, which constitute approximately 30% of the cells in the mammalian central nervous system, manifest different reactive states warrants further investigations in the causative role of HFg in astrocyte-mediated neuroinflammation. link3 Our previous study showed that Fg deposited in the vasculo-astrocyte interface-activated astrocytes. However, little is known of how Fg directly affects astrocytes and neurons. In this review, we summarize studies that show the effect of Fg on different types of cells in the vasculo-neuronal unit. We will also discuss the possible mechanism of HFg-induced neuroinflammation during TBI.

The aim of this prospective study was to validate the diagnostic performance of computed tomography angiography (CTA) in endoprosthesis stenosis in the superior mesenteric artery (SMA) using mean arterial pressure (MAP) gradients during angiography as a reference method.

Twenty-nine patients with mesenteric atherosclerotic disease underwent 45 paired measurements of endoprosthesis stenosis in the SMA with CTA and MAP gradients between March 2009 and July 2015. The grade of endoprosthesis stenosis in the SMA at CTA using the TeraRecon Aquarius workstation was correlated with MAP gradients.

Grade of endoprosthesis stenosis in the SMA (r = 0.37, p = 0.013) correlated with MAP gradients. The intraclass correlations between the first and second CTA rater was 0.76 (95% CI 0.56-0.87) for estimation of grade of endoprosthesis stenosis in the SMA. The area under the receiver operating characteristics curve was 0.79 for diagnosis of significant endoprosthesis stenosis in the SMA at CTA for different threshold values using MAP gradient of ≥ 10mmHg as reference. Sensitivity, specificity and positive predictive value for endoprosthesis stenosis in the SMA ≥ 50% at CTA were 52.4% (95% CI 31.0-73.7), 87.5% (95% CI 74.3-100.0) and 78.6 (95% CI 57.1-1.00), respectively.

Grading endoprosthesis stenosis in the SMA with CTA performed fair when using trans-stenotic MAP gradient as reference. Software development towards reduction of endoprosthesis artefacts may result in more accurate CTA assessment of the narrowest part.

Grading endoprosthesis stenosis in the SMA with CTA performed fair when using trans-stenotic MAP gradient as reference. Software development towards reduction of endoprosthesis artefacts may result in more accurate CTA assessment of the narrowest part.Host-guest binding remains a major challenge in modern computational modelling. The newest 7th statistical assessment of the modeling of proteins and ligands (SAMPL) challenge contains a new series of host-guest systems. The TrimerTrip host binds to 16 structurally diverse guests. Previously, we have successfully employed the spherical coordinates as the collective variables coupled with the enhanced sampling technique metadynamics to enhance the sampling of the binding/unbinding event, search for possible binding poses and calculate the binding affinities in all three host-guest binding cases of the 6th SAMPL challenge. In this work, we report a retrospective study on the TrimerTrip host-guest systems by employing the same protocol to investigate the TrimerTrip host in the SAMPL7 challenge. As no binding pose is provided by the SAMPL7 host, our simulations initiate from randomly selected configurations and are proceeded long enough to obtain converged free energy estimates and search for possible binding poses. The calculated binding affinities are in good agreement with the experimental reference, and the obtained binding poses serve as a nice starting point for end-point or alchemical free energy calculations. Note that as the work is performed after the close of the SAMPL7 challenge, we do not participate in the challenge and the results are not formally submitted to the SAMPL7 challenge.

In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce.

We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression.

Higher maternal androgen levels associated with lower BMIz at birth (β = -0.