Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

*S Supporting Information ABSTRACT: Two nicotinamide adenine dinucleotide (NAD +) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD + (6-N-methyl nicotinamide adenosine 5′-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5′-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5′-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5′-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5′-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1cIDPR-induced Ca 2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5′-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling

Managing sedentary behavior to reduce the risk of diabetes and cardiovascular disease

Modern human environments are vastly different from those of our forebears. Rapidly advancing technology in transportation, communications, workplaces, and home entertainment confer a wealth of benefits, but increasingly come with costs to human health. Sedentary behavior—too much sitting as distinct from too little physical activity—contributes adversely to cardiometabolic health outcomes and premature mortality. Findings from observational epidemiology have been synthesized in meta-analyses, and evidence is now shifting into the realm of experimental trials with the aim of identifying novel mechanisms and potential causal relationships. We discuss recent observational and experimental evidence that makes a compelling case for reducing and breaking up prolonged sitting time in both the primary prevention and disease management contexts. We also highlight future research needs, the opportunities for developing targeted interventions, and the potential of population-wide initiatives designed to address too much sitting as a health risk

Sedentary time, breaks in sedentary time and metabolic variables in people with newly diagnosed type 2 diabetes

Aims/hypothesis We investigated whether objectively measured sedentary time and interruptions in sedentary time are associated with metabolic factors in people with type 2 diabetes. Methods We studied 528 adults (30–80 years) with newly diagnosed type 2 diabetes, who were participants in a diet and physical activity intervention. Waist circumference (WC), fasting HDL-cholesterol, insulin and glucose levels, HOMA of insulin resistance (HOMA-IR) and physical activity (accelerometer) were measured at baseline and at 6 months follow-up. Linear regression models were used to investigate cross-sectional and longitudinal associations of accelerometer-derived sedentary time and breaks in sedentary time (BST) with metabolic variables. Results In cross-sectional analyses each hour of sedentary time was associated with larger WC (unstandardised regression coefficient [B] [95% CI] 1.89 cm [0.94, 2.83]; p < 0.001), higher insulin (B = 8.22 pmol/l [2.80, 13.65]; p = 0.003) and HOMA-IR (B = 0.42 [0.14, 0.70]; p = 0.004), and lower HDL-cholesterol (B = −0.04 mmol/l [−0.06, −0.01]; p = 0.005). Adjustment for WC attenuated all associations. Each BST was associated with lower WC (B = −0.15 cm [− 0.24, −0.05]; p = 0.003) and there was evidence of a weak linear association with HDL-cholesterol, but no association with insulin levels or HOMA-IR. Volume of sedentary time at baseline predicted HDL-cholesterol (B = −0.05 mmol/l [−0.08, −0.01]; p = 0.007), insulin levels (B = 8.14 pmol/l [0.1.51, 14.78]; p = 0.016) and HOMA-IR (B = 0.49 [0.08, 0.90]; p = 0.020) at 6 months, though not WC. Baseline BST did not substantially predict any metabolic variables at follow-up. No change was seen in sedentary time or BST between baseline and 6 months follow-up. Conclusions/interpretation Higher sedentary time is associated with a poorer metabolic profile in people with type 2 diabetes

Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and β-adrenoceptors

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role. Bladder relaxation, which is required for urine storage, is mediated by β-adrenoceptors, in most species involving a strong β3-component. An excessive stimulation of contraction or a reduced relaxation of the detrusor smooth muscle during the storage phase of the micturition cycle may contribute to bladder dysfunction known as the overactive bladder. Therefore, interference with the signal transduction of these receptors may be a viable approach to develop drugs for the treatment of overactive bladder. The prototypical signaling pathway of M3 receptors is activation of phospholipase C (PLC), and this pathway is also activated in the bladder. Nevertheless, PLC apparently contributes only in a very minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder contraction involves voltage-operated Ca2+ channels and Rho kinase. The prototypical signaling pathway of β-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to β-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in β-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and β-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder

Statistical analysis of data from pulsed electric field tests to extract polyphenols

During the last decade, pulsed electric field (PEF) treatment was found to be a useful non-thermal and minimally invasive processing method for breakage of cellular tissue. The strong electric field causes electroporation of plant cells, an increase in their permeability and in some cases, disruption of their structural integrity. Because the integrity of the cell membrane is important to the overall quality of the components within the cell, membrane permeabilization is dependent on several factors such as electric field strength (E), pulse duration (PD), number of pulses (N), and pause between pulses (PBP). In this work, design of experiments for PEF assisted extraction of polyphenols from leaf plant tissues will be presented. The disturbance factors E, PD, N, and PBP were varied to find a suitable combination to maximize extraction yield. For this purpose, multivariate techniques have been used for preliminary evaluation of experimental factors as well as for determination of critical conditions (maximum or minimum) of these factors. Central composite, Box-Behnken and Doehlert designs were among the principal response surface methodologies used in experimental design. Furthermore, the Box-Behnken design of experiments was employed to minimize the number of required experiments. Analysis of variance (ANOVA) was used as a statistical method to quantify main disturbances effects. The key finding is that moderate electric field strength has significant effect on the extraction yield. Moreover, results suggested that higher extraction yield could be achieved under moderate electric field strength and longer treatment time (number of pulses and duration of pulses). The outcome of the statistical analysis will be used to develop surface response models that will be used to optimize the settings for the PEF unit in such way that the extraction yield is maximized

Statistical analysis of data from pulsed electric field tests to extract polyphenols

During the last decade, pulsed electric field (PEF) treatment was found to be a useful non-thermal and minimally invasive processing method for breakage of cellular tissue. The strong electric field causes electroporation of plant cells, an increase in their permeability and in some cases, disruption of their structural integrity. Because the integrity of the cell membrane is important to the overall quality of the components within the cell, membrane permeabilization is dependent on several factors such as electric field strength (E), pulse duration (PD), number of pulses (N), and pause between pulses (PBP). In this work, design of experiments for PEF assisted extraction of polyphenols from leaf plant tissues will be presented. The disturbance factors E, PD, N, and PBP were varied to find a suitable combination to maximize extraction yield. For this purpose, multivariate techniques have been used for preliminary evaluation of experimental factors as well as for determination of critical conditions (maximum or minimum) of these factors. Central composite, Box-Behnken and Doehlert designs were among the principal response surface methodologies used in experimental design. Furthermore, the Box-Behnken design of experiments was employed to minimize the number of required experiments. Analysis of variance (ANOVA) was used as a statistical method to quantify main disturbances effects. The key finding is that moderate electric field strength has significant effect on the extraction yield. Moreover, results suggested that higher extraction yield could be achieved under moderate electric field strength and longer treatment time (number of pulses and duration of pulses). The outcome of the statistical analysis will be used to develop surface response models that will be used to optimize the settings for the PEF unit in such way that the extraction yield is maximized