Benzene-1,3,5-tricarbonyl trichloride

In the title molecule, C9H3Cl3O3, there are three short interactions involving the benzene H atoms and the chloro­formyl Cl atoms. In the crystal, mol­ecules stack along the a axis with no significant non-bonded inter­actions

Clay mineral transformation mechanism modelling of shale reservoir in Da’anzhai Member, Sichuan Basin, Southern China

Shale reservoirs often undergo intense clay mineral transformation, which plays a crucial role in the formation and evolution of pores. The reservoir lithofacies types of Da’anzhai Member in the Sichuan Basin are complex, the heterogeneity is strong, and the transformation mechanism of clay minerals is unclear, limiting the understanding of reservoir diagenesis and reservoir formation mechanism. In this study, we selected the typical shale reservoir in the Da’anzhai Member of the eastern Sichuan Basin and innovatively introduced the multiphase fluid-chemical-thermal multi-field coupled numerical simulation technique to focus on the dissolution, precipitation and transformation laws of diagenetic minerals in the shale reservoir. We calculated the transformation of diagenetic minerals and their physical response under different temperatures, pressure and fluid conditions and identified the main controlling factors of mineral transformation in shale reservoirs in the study area. The results show that the transformation of smectite to illite in the Da’anzhai Member is a complex physicochemical process influenced by various factors such as temperature, pressure, fluid, and lithology. The increase in temperature can promote illitization until the critical temperature of 110°C–115°C, below which the conversion rate of smectite to illite increases as the temperature increases. However, when it is higher than the critical temperature, the degree of illitization decreases. In specific K-rich fluids, organic acids significantly affect the conversion of clay minerals in the Da’anzhai Member of the formation. The acidic fluid promotes the dissolution of minerals such as K-feldspar and releases K+, thus provides the material basis for illitization. The research results provide theoretical support for the diagenetic and formation mechanism of the shale reservoir in the Da’anzhai Member of the Sichuan Basin and even for the efficient exploration and development of shale gas

The East-Asian VLBI Network

The East-Asian VLBI Network (EAVN) is the international VLBI facility in East Asia and is conducted in collaboration with China, Japan, and Korea. The EAVN consists of VLBI arrays operated in each East Asian country, containing 21 radio telescopes and three correlators. The EAVN will be mainly operated at 6.7 (C-band), 8 (X-band), 22 (K-band), and 43 GHz (Q-band), although the EAVN has an ability to conduct observations at 1.6 - 129 GHz. We have conducted fringe test observations eight times to date at 8 and 22 GHz and fringes have been successfully detected at both frequencies. We have also conducted science commissioning observations of 6.7 GHz methanol masers in massive star-forming regions. The EAVN will be operational from the second half of 2017, providing complementary results with the FAST on AGNs, massive star-forming regions, and evolved stars with high angular resolution at cm- to mm-wavelengths.Comment: 6 pages, 3 figures, 2 tables. To appear in the proceedings of "Frontiers in Radio Astronomy and FAST Early Sciences Symposium 2015" ed. Lei Qian (ASP Conf. Ser.

Pathological Tau From Alzheimer’s Brain Induces Site-Specific Hyperphosphorylation and SDS- and Reducing Agent-Resistant Aggregation of Tau in vivo

Neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau are a histopathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Hyperphosphorylation of tau is responsible for its loss of normal physiological function, gain of toxicity and its aggregation to form NFTs. Injection of misfolded tau seeds into mouse brain induces tau aggregation, but the nature of tau phosphorylation in pathologic tau seeded pathology is unclear. In the present study, we injected hyperphosphorylated and oligomeric tau isolated from AD brain (AD P-tau) into hippocampus of human tau transgenic mice and found that in addition to tau aggregation/pathology, tau was hyperphosphorylated at Ser202/Thr205, Thr212, Ser214, Thr217, Ser262, and Ser422 in AD P-tau injected hippocampus and at Ser422 in the contralateral hippocampus and in the ipsilateral cortex. AD P-tau-induced AD-like high molecular weight aggregation of tau that was SDS- and reducing agent-resistant and site-specifically hyperphosphorylated in the ipsilateral hippocampus. There were no detectable alterations in levels of tau phosphatases or tau kinases in AD P-tau-injected brains. Furthermore, we found that hyperphosphorylated tau was easier to be captured by AD P-tau and that aggregated tau was more difficult to be dephosphorylated than the non-aggregated tau by protein phosphatase 2A (PP2A). Based on these findings, we speculate that AD P-tau seeds hyperphosphorylated tau to form aggregates, which resist to the dephosphorylation by PP2A, resulting in hyperphosphorylation and pathology of tau

Exome sequencing revealed PDE11A as a novel candidate gene for early-onset Alzheimer\u27s disease

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer\u27s disease (AD), whole-exome sequencing was performed in 215 early-onset AD (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOAD. Both variants are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation and are classified as pathogenic. Furthermore, we found significantly decreased protein levels of PDE11A in brain samples of AD patients. Expression of PDE11A variants and knockdown experiments with specific short hairpin RNA (shRNA) for PDE11A both resulted in an increase of AD-associated Tau hyperphosphorylation at multiple epitopes in vitro. PDE11A variants or PDE11A shRNA also caused increased cyclic adenosine monophosphate (cAMP) levels, protein kinase A (PKA) activation and cAMP response element-binding protein phosphorylation. In addition, pretreatment with a PKA inhibitor (H89) suppressed PDE11A variant-induced Tau phosphorylation formation. This study offers insight into the involvement of Tau phosphorylation via the cAMP/PKA pathway in EOAD pathogenesis and provides a potential new target for intervention

Spectrochemical analyses of growth phase-related bacterial responses to low (environmentally-relevant) concentrations of tetracycline and nanoparticulate silver

Exposure to environmental insults generally occurs at low levels, making it challenging to measure bacterial responses to such interactions. Additionally, microbial behaviour and phenotype varies in differing bacterial types or growth phases, likely giving rise to growth- or species-specific responses to environmental stimuli. The present study applied a spectrochemical tool, infrared (IR) spectral interrogation coupled with multivariate analysis, to investigate the growth- and species-specific responses of two bacterial strains, Gram-negative Pseudomonas fluorescens and Gram-positive Mycobacterium vanbaalenii, to low concentrations of tetracycline, nanoparticulate silver (AgNP) or mixtures thereof. Results indicate the tendency for tetracycline-induced biospectral alterations to occur in outer-cellular components, e.g., phospholipids or proteins, while AgNPs-induced changes are mainly associated with proteins (∼964 cm−1, ∼1485 cm−1, ∼1550 cm−1, ∼1650 cm−1). The primary altered targets are correlated with bacterial membranes or outer-cellular components. Furthermore, significant lipid changes at 1705–1750 cm−1 were only present in P. fluorescens cells compared to M. vanbaalenii, owing to differences in cell wall structure between Gram-positive and -negative bacteria. This study also found distinct biospectral alterations in non-log phase compared to log phase, confirming bacterial growth-dependent responses to environmental exposures. It implies that previous studies on log phase only may underestimate the impacts from exposures of interest in situ, where bacteria stay in different growth stages. Our work proves the feasibility of biospectroscopy in determining bacterial responses to low-level environmental exposures in a fast and efficient manner, revealing sufficient biochemical information continuously through growth phases. As a nondestructive approach, biospectroscopy may provide deeper insights into the actual and in situ interactions between microbes and environmental stimuli, regardless of the exposure level, growth phase, or bacterial types

Spectrochemical determination of unique bacterial responses following long-term low-level exposure to antimicrobials

Agents arising from engineering or pharmaceutical industries may have significant environmental impacts. Particularly, antimicrobials not only act as efficient eliminators of certain microbes but also facilitate the propagation of organisms with antimicrobial resistance, giving rise to critical health issues, e.g., the bloom of multidrug-resistant bacteria. Although many investigations have examined microbial responses to antimicrobials and characterized relevant mechanisms, they have focused mainly on high-level and short-term exposures, instead of simulating real-world scenarios in which the antimicrobial exposure is at a low-level for long periods. Herein, we developed a spectrochemical tool, attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, as a high-throughput and nondestructive approach to interrogate the long-term effects of low-level antimicrobial exposure in bacterial cells. Post-exposure to nanoparticulate silver (AgNP), tetracycline or their mixtures for 12 days, Gram-positive (Mycobacterium vanbaalenii PYR-1) and Gram-negative (Pseudomonas fluorescens) bacteria exhibited distinct IR spectral alterations. Multivariate analysis coupled with multivariate regression trees (MRT) indicates nutrient depletion and exposure time as the primary factors in bacterial behaviour, followed by exposure category and bacterial type. Nutrient depletion and starvation during long-term exposure drives bacterial cells into a dormant state or to exhibit additional cellular components (e.g., fatty acids) in response to antimicrobials, consequently causing a broader range of spectral alterations compared to short-term exposure. This work is the first report highlighting the more important roles of exposure duration and nutrient depletion, instead of treatment regimens of antimicrobials, in microbial responses to low-level and prolonged environmental exposures

Excess Folic Acid Supplementation Before and During Pregnancy and Lactation Activates Fos Gene Expression and Alters Behaviors in Male Mouse Offspring

Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects and other birth defects. After 20 years mandate food fortification with FA, serum concentration of folate and unmetabolized FA increased significantly in the North American population. But whether excess FA intake impairs neurodevelopment and behavior is still controversial. Here, we treated mice with approximately 2.5-fold (moderate dose of FA, MFA) or 10-fold (high dose of FA, HFA) the dietary requirement of FA 1 week before mating and throughout pregnancy and lactation, and examined behaviors in adult male offspring using open field test, three-chamber sociability and social novelty test, elevated plus maze, rotarod and Morris water maze. We found that early life MFA supplementation increased long-term body weight gain in adults, elevated anxiety-like behavior, and impaired social preference, motor learning and spatial learning ability without modifying motor ability and spatial memory. In contrast, HFA supplementation only induced mild behavioral abnormality. RNA sequencing revealed that FA supplementation altered the expression of brain genes at weaning, among which Fos and related genes were significantly up-regulated in MFA mice compared with control and HFA mice. Quantitative real time-PCR (qRT-PCR) and western blots confirmed the increase of these genes. Our results suggested that FA supplementation during early life stage affected gene expression in weaning mice, and exhibited long-term impairments in adult behaviors in a dose-sensitive manner