Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions

Sr2+ triggers neurotransmitter release similar to Ca2+, but less efficiently. We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca2+- and Sr2+-induced release is selectively impaired, suggesting that both cations partly act by binding to synaptotagmin 1. Both the C(2)A and the C2B domain of synaptotagmin 1 bind Ca2+ in phospholipid complexes, but only the C2B domain forms Sr2+/phospholipid complexes; therefore, Sr2+ binding to the C2B domain is sufficient to trigger fast release, although with decreased efficacy. Ca2+ induces binding of the synaptotagmin C, domains to SNARE proteins, whereas Sr2+ even at high concentrations does not. Thus, triggering of the fast component of release by Sr2+ as a Ca2+ agonist involves the formation of synaptotagmin/ phospholipid complexes, but does not require stimulated SNARE binding

Rudder Gap Flow Control for Cavitation Suppression

For the suppression of rudder cavitation, especially within and around the gap between the stationary and movable parts, flow control devices were developed. In the present study, both experimental and computational analyses of the flow control devices were carried out. The new rudder system is equipped with cam devices, which effectively close the gap between the stationary horn/pintle and movable flaps. Model scale experiments of surface pressure measurements, flow field visualization near the gap using PIV, and cavitation behavior observation were conducted in a cavitation tunnel. The experiments were simulated using a computational fluid dynamics tool and the results are compared for validation. It is confirmed that the flow control devices effectively suppresses the rudder gap cavitation and, at the same time, augments lifthttp://deepblue.lib.umich.edu/bitstream/2027.42/84266/1/CAV2009-final70.pd

Calcium Silicate-Based Biocompatible Light-Curable Dental Material for Dental Pulpal Complex

Dental caries causes tooth defects and clinical treatment is essential. To prevent further damage and protect healthy teeth, appropriate dental material is a need. However, the biocompatibility of dental material is needed to secure the oral environment. For this purpose, biocompatible materials were investigated for incorporated with dental capping material. Among them, nanomaterials are applied to dental materials to enhance their chemical, mechanical, and biological properties. This research aimed to study the physicochemical and mechanical properties and biocompatibility of a recently introduced light-curable mineral trioxide aggregate (MTA)-like material without bisphenol A-glycidyl methacrylate (Bis-GMA). To overcome the compromised mechanical properties in the absence of Bis-GMA, silica nanoparticles were synthesized and blended with a dental polymer for the formation of a nano-network. This material was compared with a conventional light-curable MTA-like material that contains Bis-GMA. Investigation of the physiochemical properties followed ISO 4049. Hydroxyl and calcium ion release from the materials was measured over 21 days. The Vickers hardness test and three-point flexural strength test were used to assess the mechanical properties. Specimens were immersed in solutions that mimicked human body plasma for seven days, and surface characteristics were analyzed. Biological properties were assessed by cytotoxicity and biomineralization tests. There was no significant difference between the tested materials with respect to overall physicochemical properties and released calcium ions. The newly produced material released more calcium ions on the third day, but 14 days later, the other material containing Bis-GMA released higher levels of calcium ions. The microhardness was reduced in a low pH environment, and differences between the specimens were observed. The flexural strength of the newly developed material was significantly higher, and different surface morphologies were detected. The recently produced extract showed higher cell viability at an extract concentration of 100%, while mineralization was clear at the conventional concentration of 25%. No significant changes in the physical properties between Bis-GMA incorporate material and nanoparticle incorporate materials

The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II).

Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1960

NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs.

Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been detected in mitochondrial transcriptome, however its biogenesis has not been investigated in details. Mammalian NOP2/Sun RNA Methyltransferase Family Member 2 (NSUN2) has been characterized as an RNA methyltransferase introducing m5C in nuclear-encoded tRNAs, mRNAs and microRNAs and associated with cell proliferation and differentiation, with pathogenic variants in NSUN2 being linked to neurodevelopmental disorders. Here we employ spatially restricted proximity labelling and immunodetection to demonstrate that NSUN2 is imported into the matrix of mammalian mitochondria. Using three genetic models for NSUN2 inactivation-knockout mice, patient-derived fibroblasts and CRISPR/Cas9 knockout in human cells-we show that NSUN2 is necessary for the generation of m5C at positions 48, 49 and 50 of several mammalian mitochondrial tRNAs. Finally, we show that inactivation of NSUN2 does not have a profound effect on mitochondrial tRNA stability and oxidative phosphorylation in differentiated cells. We discuss the importance of the newly discovered function of NSUN2 in the context of human disease.Medical Research Council, UK [MC_UU_00015/4 to M.M.]; EMBO [ALFT 701-2013 to L.V.H.]; National Research Foundation of Korea [NRF-2019R1A2C3008463 to S.Y.L and H.W.R.]; Cancer Research UK [C13474/A18583, C6946/A14492 to E.A.M.]; Wellcome Trust [104640/Z/14/Z, 092096/Z/10/Z to E.A.M.]. Funding for open access charge: MRC

Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design

<p>Abstract</p> <p>Background</p> <p>Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people.</p> <p>Methods</p> <p>Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation.</p> <p>Results</p> <p>Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003).</p> <p>Conclusions</p> <p>The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.</p

Dynamic skin deformation using finite difference solutions for character animation

We present a new skin deformation method to create dynamic skin deformations in this paper. The core elements of our approach are a dynamic deformation model, an efficient data-driven finite difference solution, and a curve-based representation of 3D models. We first reconstruct skin deformation models at different poses from the taken photos of a male human arm movement to achieve real deformed skin shapes. Then, we extract curves from these reconstructed skin deformation models. A new dynamic deformation model is proposed to describe physics of dynamic curve deformations, and its finite difference solution is developed to determine shape changes of the extracted curves. In order to improve visual realism of skin deformations, we employ data-driven methods and introduce skin shapes at the initial and final poses into our proposed dynamic deformation model. Experimental examples and comparisons made in this paper indicate that our proposed dynamic skin deformation technique can create realistic deformed skin shapes efficiently with a small data size

Gender differences in the association between self-rated health and hypertension in a Korean adult population

<p>Abstract</p> <p>Background</p> <p>Self-rated health (SRH) has been reported as a predictor of mortality in previous studies. This study aimed to examine whether SRH is independently associated with hypertension and if there is a gender difference in this association.</p> <p>Methods</p> <p>16,956 community dwelling adults aged 20 and over within a defined geographic area participated in this study. Data on SRH, socio-demographic factors (age, gender, marital status, education) and health behaviors (smoking status, alcohol consumption, physical activity) were collected. Body mass index and blood pressure were measured. Logistic regression models were used to determine a relationship between SRH and hypertension.</p> <p>Results</p> <p>32.5% of the participants were found to have hypertension. Women were more likely than men to rate their SRH as poor (<it>p </it>< 0.001), and the older age groups rated their SRH more negatively in both men and women (<it>p </it>< 0.001). While the multivariate-adjusted odds ratio (OR, 95% CI) of participants rating their SRH as very poor for hypertension in men was OR 1.70 (1.13-2.58), that in women was OR 2.83 (1.80-4.44). Interaction between SRH and gender was significant (<it>p </it>< 0.001).</p> <p>Conclusions</p> <p>SRH was independently associated with hypertension in a Korean adult population. This association was modified by gender.</p