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Atmospheric ice nucleating particles (INPs) influence global climate by altering cloud formation, lifetime, and precipitation efficiency. The role of secondary organic aerosol (SOA) material as a source of INPs in the ambient atmosphere has not been well defined. Here, we demonstrate the potential for biogenic SOA to activate as depositional INPs in the upper troposphere by combining field measurements with laboratory experiments. Ambient INPs were measured in a remote mountaintop location at -46 °C and an ice supersaturation of 30% with concentrations ranging from 0.1 to 70 L-1. Concentrations of depositional INPs were positively correlated with the mass fractions and loadings of isoprene-derived secondary organic aerosols. Compositional analysis of ice residuals showed that ambient particles with isoprene-derived SOA material can act as depositional ice nuclei. Laboratory experiments further demonstrated the ability of isoprene-derived SOA to nucleate ice under a range of atmospheric conditions. We further show that ambient concentrations of isoprene-derived SOA can be competitive with other INP sources. This demonstrates that isoprene and potentially other biogenically-derived SOA materials could influence cirrus formation and properties.Nature has protein channels (e.g., aquaporins) that preferentially transport water molecules while rejecting even the smallest hydrated ions. Aspirations to create robust synthetic counterparts have led to the development of a few one-dimensional channels. However, replicating the performance of the protein channels in these synthetic water channels remains a challenge. In addition, the dimensionality of the synthetic water channels also imposes engineering difficulties to align them in membranes. Here we show that zero-dimensional porous organic cages (POCs) with nanoscale pores can effectively reject small cations and anions while allowing fast water permeation (ca. 109 water molecules per second) on the same magnitude as that of aquaporins. Water molecules are found to preferentially flow in single-file, branched chains within the POCs. This work widens the choice of water channel morphologies for water desalination applications.Here we uncovered the involved subcellular mechanisms that sulforaphane-cysteine (SFN-Cys) inhibited invasion in human glioblastoma (GBM). SFN-Cys significantly upregulated 45 and downregulated 14 microtubule-, mitophagy-, and invasion-associated proteins in GBM cells via HPLC-MS/MS and GEO ontology analysis; SFN-Cys disrupted microtubule by ERK1/2 phosphorylation-mediated downregulation of α-tubulin and Stathmin-1 leading to the inhibition of cell migration and invasion; SFN-Cys downregulated invasion-associated Claudin-5 and S100A4, and decreased the interaction of α-tubulin to Claudin-5. Knockdown of Claudin-5 and S100A4 significantly reduced the migration and invasion. Besides, SFN-Cys lowered the expressions of α-tubulin-mediated mitophagy-associated proteins Bnip3 and Nix. Transmission electron microscopy showed more membrane-deficient mitochondria and accumulated mitophagosomes in GBM cells, and mitochondria fusion might be downregulated because that SFN-Cys downregulated mitochondrial fusion protein OPA1. SFN-Cys increased the colocalization and interplay of LC3 to lysosomal membrane-associated protein LAMP1, aggravating the fusion of mitophagosome to lysosome. Nevertheless, SFN-Cys inhibited the lysosomal proteolytic capacity causing LC3II/LC3I elevation but autophagy substrate SQSTM1/p62 was not changed, mitophagosome accumulation, and the inhibition of migration and invasion in GBM cells. These results will help us develop high-efficiency and low-toxicity anticancer drugs to inhibit migration and invasion in GBM.High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.
Obesity is becoming more prevalent in older people. A management strategy in obese, young adults is to increase dietary protein relative to other macronutrients. It is not clear if this is effective in obese, older individuals. Obesity may be associated with diminished sensitivity to nutrients. We have reported that a 30-g whey protein drink slows gastric emptying more, and suppresses energy intake less, in older, than younger, non-obese men. The aim of this study was to determine the effect of a 30 g whey protein drink on energy intake, GE and glycaemia in obese, older and younger men.
In randomized, double-blind order, 10 younger (age 27 ± 2 years; BMI 36 ± 2 kg/m²), and 10 older (72 ± 1 years; 33 ± 1 kg/m²), obese men were studied twice. After an overnight fast, subjects ingested a test drink containing 30 g whey protein (120 kcal) or control (2 kcal). Postprandial gastric emptying (antral area, 2D Ultrasound) and blood glucose concentrations were measured for 180 min. At t = 180 min subjects were given a buffet meal and ad libitum energy intake was assessed.
Older subjects ate non-significantly less (~20%) that the younger subjects (effect of age, P = 0.16). Whey protein had no effect on subsequent energy intake (kcal) compared to control in either the younger (decrease 3 ± 8%) or older (decrease 2 ± 8%) obese men (age effect P > 0.05, protein effect P = 0.46, age × protein interaction effect P = 0.84). Whey protein slowed gastric emptying, to a similar degree in both age groups (50% emptying time control vs. protein young men 255 ± 5 min vs. Cinchocaine nmr 40 ± 7 min; older men 16 ± 5 min vs. 50 ± 8 min; protein effect P = 0.001, age effect P = 0.93, age × protein interaction effect P = 0.13).
Our data suggest that obesity may blunt/abolish the age-related effect of whey protein on suppression of energy intake.
Our data suggest that obesity may blunt/abolish the age-related effect of whey protein on suppression of energy intake.
Homepage: https://www.selleckchem.com/products/cinchocaine.html
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