128 research outputs found
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
Objective and Self-Rated Sedentary Time and Indicators of Metabolic Health in Dutch and Hungarian 10β12 Year Olds: The ENERGY-Project
Background: The association between objectively assessed sedentary time and metabolic risk factors in childhood have rarely been studied. Therefore, we examined the independent relationship between objectively assessed and self-rated sedentary time and indicators of metabolic health in Dutch and Hungarian 10β12 year olds. Methodology/Principal Findings: We performed a cross-sectional survey in primary schools. Participants were Dutch and Hungarian girls (n = 73, aged 12.260.6 years, 18 % overweight/obese) and boys (n = 69, aged 12.260.7 years, 38% overweight/obese). Sedentary time and physical activity were assessed by the Actigraph accelerometer. TV and PC time were assessed by self-report. Adiposity indicators included body weight, height, and waist circumference (WC). Fasting plasma glucose, C-peptide, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides were determined in capillary blood and summed into a metabolic risk score. Linear regression analyses were adjusted for physical activity, number of sedentary bouts and WC. Children spent on average 7.6 hours of their daily waking time in sedentary behavior and self-reported 116664 min/day watching TV and 85657 min/day using the computer. Comparing the 1 st and 4 th quartile of objectively assessed sedentary time, C-Peptide levels, WC and BMI were significantly higher in the most sedentary quartile, while the difference in metabolic risk score was borderline significant (p = 0.09). Comparing the 1 st and 4 th quartile of TV time, BMI was significantly higher in the most sedentary quartile, while th
Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and Ξ²-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 Ξ²-adrenoceptors, in most species involving a strong Ξ²3-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 Ξ²-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to Ξ²-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in Ξ²-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and Ξ²-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder
Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5β²-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 5β²-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5β²-diphosphoribose, 11), whereas 6-thio NHD + (nicotinamide 6-mercaptopurine 5β²-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 5β²-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5β²-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 5β²-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
At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension
Hypertension affects 1β5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12Β years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review
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 (30β80 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]; pβ<β0.001), higher insulin (Bβ=β8.22 pmol/l [2.80, 13.65]; pβ=β0.003) and HOMA-IR (Bβ=β0.42 [0.14, 0.70]; pβ=β0.004), and lower HDL-cholesterol (Bβ=ββ0.04 mmol/l [β0.06, β0.01]; pβ=β0.005). Adjustment for WC attenuated all associations. Each BST was associated with lower WC (Bβ=ββ0.15 cm [β 0.24, β0.05]; pβ=β0.003) 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 (Bβ=ββ0.05 mmol/l [β0.08, β0.01]; pβ=β0.007), insulin levels (Bβ=β8.14 pmol/l [0.1.51, 14.78]; pβ=β0.016) and HOMA-IR (Bβ=β0.49 [0.08, 0.90]; pβ=β0.020) 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
- β¦