Ethyl 1-[(2-chloro-1,3-thia­zol-5-yl)methyl]-5-methyl-1H-1,2,3-triazole-4-carboxylate

In the title compound, C10H11ClN4O2S, the triazole ring carries methyl and ethoxy­carbonyl groups and is bound via a methyl­ene bridge to a chloro­thia­zole unit. There is also evidence for significant electron delocalization in the triazolyl system. Intra- and inter­molecular C—H⋯O hydrogen bonds together with strong π–π stacking inter­actions [centroid–centroid distance 3.620 (1) Å] stabilize the structure

Low Vitamin D and Its Association with Cognitive Impairment and Dementia

Vitamin D is a neurosteroid hormone that regulates neurotransmitters and neurotrophins. It has anti-inflammatory, antioxidant, and neuroprotective properties. It increases neurotrophic factors such as nerve growth factor which further promotes brain health. Moreover, it is also helpful in the prevention of amyloid accumulation and promotes amyloid clearance. Emerging evidence suggests its role in the reduction of Alzheimer’s disease hallmarks such as amyloid-beta and phosphorylated tau. Many preclinical studies have supported the hypothesis that vitamin D leads to attentional, behavioral problems and cognitive impairment. Cross-sectional studies have consistently found that vitamin D levels are significantly low in individuals with Alzheimer’s disease and cognitive impairment compared to healthy adults. Longitudinal studies and meta-analysis have also exhibited an association of low vitamin D with cognitive impairment and Alzheimer’s disease. Despite such evidence, the causal association cannot be sufficiently answered. In contrast to observational studies, findings from interventional studies have produced mixed results on the role of vitamin D supplementation in the prevention and treatment of cognitive impairment and dementia. The biggest issue of the existing RCTs is their small sample size, lack of consensus over the dose, and age of initiation of vitamin D supplements to prevent cognitive impairment. Therefore, there is a need for large double-blind randomized control trials to assess the benefits of vitamin D supplementation in the prevention and treatment of cognitive impairment

Cenomanian-Turonian transition in a shallow water sequence of the Sinai, Egypt

Environmental and depositional changes across the Late Cenomanian oceanic anoxic event (OAE2) in the Sinai, Egypt, are examined based on biostratigraphy, mineralogy, delta(13)C values and phosphorus analyses. Comparison with the Pueblo, Colorado, stratotype section reveals the Whadi El Ghaib section as stratigraphically complete across the late Cenomanian-early Turonian. Foraminifera are dominated by high-stress planktic and benthic assemblages characterized by low diversity, low-oxygen and low-salinity tolerant species, which mark shallow-water oceanic dysoxic conditions during OAE2. Oyster biostromes suggest deposition occurred in less than 50 m depths in low-oxygen, brackish, and nutrient-rich waters. Their demise prior to the peak delta(13)C excursion is likely due to a rising sea-level. Characteristic OAE2 anoxic conditions reached this coastal region only at the end of the delta(13)C plateau in deeper waters near the end of the Cenomanian. Increased phosphorus accumulations before and after the delta(13)C excursion suggest higher oxic conditions and increased detrital input. Bulk-rock and clay mineralogy indicate humid climate conditions, increased continental runoff and a rising sea up to the first delta(13)C peak. Above this interval, a dryer and seasonally well-contrasted climate with intermittently dry conditions prevailed. These results reveal the globally synchronous delta(13)C shift, but delayed effects of OAE2 dependent on water depth

Apical Localization of Inositol 1,4,5-Trisphosphate Receptors Is Independent of Extended Synaptotagmins in Hepatocytes

Extended synaptotagmins (E-Syts) are a recently identified family of proteins that tether the endoplasmic reticulum (ER) to the plasma membrane (PM) in part by conferring regulation of cytosolic calcium (Ca2+) at these contact sites (Cell, 2013). However, the mechanism by which E-Syts link this tethering to Ca2+ signaling is unknown. Ca2+ waves in polarized epithelia are initiated by inositol 1,4,5-trisphosphate receptors (InsP3Rs), and these waves begin in the apical region because InsP3Rs are targeted to the ER adjacent to the apical membrane. In this study we investigated whether E-Syts are responsible for this targeting. Primary rat hepatocytes were used as a model system, because a single InsP3R isoform (InsP3R-II) is tethered to the peri-apical ER in these cells. Additionally, it has been established in hepatocytes that the apical localization of InsP3Rs is responsible for Ca2+ waves and secretion and is disrupted in disease states in which secretion is impaired. We found that rat hepatocytes express two of the three identified E-Syts (E-Syt1 and E-Syt2). Individual or simultaneous siRNA knockdown of these proteins did not alter InsP3R-II expression levels, apical localization or average InsP3R-II cluster size. Moreover, apical secretion of the organic anion 5-chloromethylfluorescein diacetate (CMFDA) was not changed in cells lacking E-Syts but was reduced in cells in which cytosolic Ca2+ was buffered. These data provide evidence that E-Syts do not participate in the targeting of InsP3Rs to the apical region. Identifying tethers that bring InsP3Rs to the apical region remains an important question, since mis-targeting of InsP3Rs leads to impaired secretory activity