Activation of Extracellular-signal Regulated Kinase (ERK1/2) by Fluid Shear is Ca\u3csup\u3e2+\u3c/sup\u3e- and ATP-dependent in MC3T3-E1 Osteoblasts

To determine the role of Ca2+ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca2+ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 min of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Cai2+ was chelated with BAPTA or when Ca2+ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca2+ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced pERK1/2. This inhibition did not result from blockage of intracellular Ca2+ release, but a loss of PKC activation. Recent data suggests a role of ATP release and purinergic receptor activation in mechanotransduction. Apyrase-mediated hydrolysis of extracellular ATP completely blocked FSS-induced phosphorylation of ERK1/2, while the addition of exogenous ATP to static cells mimicked the effects of FSS on pERK1/2. Two P2 receptors, P2Y2 and P2X7, have been associated with the anabolic responses of bone to mechanical loading. Using both iRNA techniques and primary osteoblasts isolated from P2X7 knockout mice, we found that the P2X7, but not the P2Y2, purinergic receptor was involved in ERK1/2 activation under FSS. These data suggest that FSS-induced ERK1/2 phosphorylation requires Ca2+-dependent ATP release, however both increased Cai2+ and PKC activation are needed for complete activation. Further, this ATP-dependent ERK1/2 phosphorylation is mediated through P2X7, but not P2Y2, purinergic receptors

Large-scale detector testing for the GAPS Si(Li) Tracker

Lithium-drifted silicon [Si(Li)] has been used for decades as an ionizing radiation detector in nuclear, particle, and astrophysical experiments, though such detectors have frequently been limited to small sizes (few cm$^2$) and cryogenic operating temperatures. The 10-cm-diameter Si(Li) detectors developed for the General Antiparticle Spectrometer (GAPS) balloon-borne dark matter experiment are novel particularly for their requirements of low cost, large sensitive area (~10 m$^2$ for the full 1440-detector array), high temperatures (near -40\,^\circC), and energy resolution below 4 keV FWHM for 20--100-keV x-rays. Previous works have discussed the manufacturing, passivation, and small-scale testing of prototype GAPS Si(Li) detectors. Here we show for the first time the results from detailed characterization of over 1100 flight detectors, illustrating the consistent intrinsic low-noise performance of a large sample of GAPS detectors. This work demonstrates the feasibility of large-area and low-cost Si(Li) detector arrays for next-generation astrophysics and nuclear physics applications.Comment: Updated to version accepted in IEEE Trans Nucl Sci. Minor changes to text, fixed plotting error on Fig. 5. Conclusions unchange

Age-Related Changes in Brain Prodynorphin Gene Expression in the Rat

Dynorphin has a well-established role in feeding and gustation. Alterations in taste perception and feeding behavior are common with age. We hypothesized that proDynorphin gene expression in brain areas involved in taste and feeding declines with age. Male Sprague-Dawley rats were housed individually with ad libitum access to food and water. Brain punches of the selected regions were dissected out in groups of rats aged 4-6, 12-14 and 18-21 months. ProDynorphin mRNA (measured using a cDNA probe) decreased significantly with age in arcuate nucleus and amygdala; increased significantly with age in hippocampus; and was not significantly affected in nucleus of the solitary tract, cortex, caudate putamen or hypothalamic paraventricular nucleus. These data suggest an age-related decrease in the synthesis of dynorphin in two brain regions strongly associated with feeding behavior, and an increase in dynorphin synthesis in a brain region associated with learning and memory

Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice

Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. The authors tested whether specific changes in the microbiome modulate depressive-like behaviors. Stools from learned helpless, non-learned helpless, and non-shocked mice were analyzed by V4 16S RNA sequencing to identify gut bacteria associated with learned helplessness and to quantify the level of the quorum-sensing molecule autoinducer-2 (AI-2). T cells were analyzed by flow cytometry, and serum amyloid proteins (SAA) were analyzed by quantitative real-time polymerase chain reaction. Fecal transfer approach and administration of oleic acid and AI-2 were used to determine the effects of the microbiome and quorum-sensing molecules on depressive-like behaviors. Mice deficient in segmented filamentous bacteria (SFB) were resilient to the induction of depressive-like behavior, and were resensitized when SFB was reintroduced in the gut. SFB produces the quorum-sensing AI-2 and promotes the production of SAA1 and SAA2 by the host, which increases T helper 17 (Th17) cell production. Th17 cells were required to promote depressive-like behaviors by AI-2, as AI-2 administration did not promote susceptibility to depressive-like behaviors or SAA1 and SAA2 production in Th17-deficient mice after stress. Oleic acid, an AI-2 inhibitor, exhibited antidepressant properties, reducing depressive-like behavior, intestinal SAA1 and SAA2 production, and hippocampal Th17 cell accumulation. Stool samples from 10 people with current depressive symptoms and 10 matched healthy control subjects were analyzed as well. Patients with current major depressive disorder exhibited increased fecal interleukin 17A, SAA, and SFB levels. The study results reveal a novel mechanism by which bacteria alter mood

Life Cycle Analysis of Thin-Film Photovoltaic Thermal Systems for Different Tropical Regions

Different energy solutions are required to satisfy the energy demand of the world’s ever-growing population. Photovoltaic Thermal systems (PVT) could propose resolutions to tackle real-time issues regarding power generation. Life Cycle Analysis (LCA) is performed to compare the environmental impact and measure the energy across different PVT modules consisting of a-Si, CdTe, and CIS thin-film solar cells. The authors performed LCA to calculate the energy payback time (EPBT) and life-cycle CO2 emissions of residential rooftop and open-field PVT systems. The primary energy needed to produce thin-film PVT modules of 1 m2 cell area was considered in the present life cycle analysis studies operated using water as the working fluid. The annual net electrical energy savings at various Indian weather conditions, such as New Delhi, Jodhpur, and Ladakh, have been calculated. For the thin-film PVT systems, the calculated values of annual energy yield for three locations with average solar radiation levels and peak sun hours in the range of 600–1000 W/m2 and 6–8 h were reported. Results show that the CO2 emissions for rooftop installation of CdTe and CIS are around 200 and 156 kg/annually, which is lower than the open field installation of the same, where CO2 emissions were found to be 295 and 250 kg/year

Life Cycle Analysis of Thin-Film Photovoltaic Thermal Systems for Different Tropical Regions

Different energy solutions are required to satisfy the energy demand of the world’s ever-growing population. Photovoltaic Thermal systems (PVT) could propose resolutions to tackle real-time issues regarding power generation. Life Cycle Analysis (LCA) is performed to compare the environmental impact and measure the energy across different PVT modules consisting of a-Si, CdTe, and CIS thin-film solar cells. The authors performed LCA to calculate the energy payback time (EPBT) and life-cycle CO2 emissions of residential rooftop and open-field PVT systems. The primary energy needed to produce thin-film PVT modules of 1 m2 cell area was considered in the present life cycle analysis studies operated using water as the working fluid. The annual net electrical energy savings at various Indian weather conditions, such as New Delhi, Jodhpur, and Ladakh, have been calculated. For the thin-film PVT systems, the calculated values of annual energy yield for three locations with average solar radiation levels and peak sun hours in the range of 600–1000 W/m2 and 6–8 h were reported. Results show that the CO2 emissions for rooftop installation of CdTe and CIS are around 200 and 156 kg/annually, which is lower than the open field installation of the same, where CO2 emissions were found to be 295 and 250 kg/year