Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity

TRPM6 is crucial for human Mg2+ homeostasis as patients carrying TRPM6 mutations develop hypomagnesemia and secondary hypocalcemia (HSH). However, the activation mechanism of TRPM6 has remained unknown. Here we demonstrate that phosphatidylinositol-4,5-bisphophate (PIP2) controls TRPM6 activation and Mg2+ influx. Stimulation of PLC-coupled M1-receptors to deplete PIP2 potently inactivates TRPM6. Translocation of over-expressed 5-phosphatase to cell membrane to specifically hydrolyze PIP2 also completely inhibits TRPM6. Moreover, depolarization-induced-activation of the voltage-sensitive-phosphatase (Ci-VSP) simultaneously depletes PIP2 and inhibits TRPM6. PLC-activation induced PIP2-depletion not only inhibits TRPM6, but also abolishes TRPM6-mediated Mg2+ influx. Furthermore, neutralization of basic residues in the TRP domain leads to nonfunctional or dysfunctional mutants with reduced activity by PIP2, suggesting that they are likely to participate in interactions with PIP2. Our data indicate that PIP2 is required for TRPM6 channel function; hydrolysis of PIP2 by PLC-coupled hormones/agonists may constitute an important pathway for TRPM6 gating, and perhaps Mg2+ homeostasis

Local context effects during emotional item directed forgetting in younger and older adults

This paper explored the differential sensitivity young and older adults exhibit to the local context of items entering memory. We examined trial-to-trial performance during an item directed forgetting task for positive, negative, and neutral (or baseline) words each cued as either to-be-remembered (TBR) or to-be-forgotten (TBF). This allowed us to focus on how variations in emotional valence (independent of arousal) and instruction (TBR vs. TBF) of the previous item (trial n-1) impacted memory for the current item (trial n) during encoding. Different from research showing impairing effects of emotional arousal, both age groups showed a memorial boost for stimuli when preceded by items high in positive or negative valence relative to those preceded by neutral items. This advantage was particularly prominent for neutral trial n items that followed emotional items suggesting that, regardless of age, neutral memories may be strengthened by a local context that is high in valence. A trending age difference also emerged with older adults showing greater sensitivity when encoding instructions changed between trial n-1 and n. Results are discussed in light of age-related theories of cognitive and emotional processing, highlighting the need to consider the dynamic, moment-to-moment fluctuations of these systems

Facile Fabrication of Ultrafine Hollow Silica and Magnetic Hollow Silica Nanoparticles by a Dual-Templating Approach

The development of synthetic process for hollow silica materials is an issue of considerable topical interest. While a number of chemical routes are available and are extensively used, the diameter of hollow silica often large than 50 nm. Here, we report on a facial route to synthesis ultrafine hollow silica nanoparticles (the diameter of ca. 24 nm) with high surface area by using cetyltrimethylammmonium bromide (CTAB) and sodium bis(2-ethylhexyl) sulfosuccinate (AOT) as co-templates and subsequent annealing treatment. When the hollow magnetite nanoparticles were introduced into the reaction, the ultrafine magnetic hollow silica nanoparticles with the diameter of ca. 32 nm were obtained correspondingly. Transmission electron microscopy studies confirm that the nanoparticles are composed of amorphous silica and that the majority of them are hollow

Synthesis and Characterization of Glomerate GaN Nanowires

Glomerate GaN nanowires were synthesized on Si(111) substrates by annealing sputtered Ga2O3/Co films under flowing ammonia at temperature of 950 °C. X-ray diffraction, scanning electron microscopy, high resolution transmission electron microscopy and Fourier transformed infrared spectra were used to characterize the morphology, crystallinity and microstructure of the as-synthesized samples. Our results show that the samples are of hexagonal wurtzite structure. For the majority of GaN nanowires, the length is up to tens of microns and the diameter is in the range of 50–200 nm. The growth process of the GaN nanowires is dominated by Co–Ga–N alloy mechanism

A TRPV4-dependent neuroimmune axis in the spinal cord promotes neuropathic pain

Microglia, resident macrophages of the CNS, are essential to brain development, homeostasis, and disease. Microglial activation and proliferation are hallmarks of many CNS diseases, including neuropathic pain. However, molecular mechanisms that govern the spinal neuroimmune axis in the setting of neuropathic pain remain incompletely understood. Here, we show that genetic ablation or pharmacological blockade of transient receptor potential vanilloid type 4 (TRPV4) markedly attenuated neuropathic pain-like behaviors in a mouse model of spared nerve injury. Mechanistically, microglia-expressed TRPV4 mediated microglial activation and proliferation and promoted functional and structural plasticity of excitatory spinal neurons through release of lipocalin-2. Our results suggest that microglial TRPV4 channels reside at the center of the neuroimmune axis in the spinal cord, which transforms peripheral nerve injury into central sensitization and neuropathic pain, thereby identifying TRPV4 as a potential new target for the treatment of chronic pain

Hybrid light emitting diodes based on stable, high brightness all-inorganic CsPbI3 perovskite nanocrystals and InGaN

Despite important advances in the synthesis of inorganic perovskite nanocrystals (NCs), the long-term instability and degradation of their quantum yield (QY) over time need to be addressed to enable the further development and exploitation of these nanomaterials. Here we report stable CsPbI3 perovskite NCs and their use in hybrid light emitting diodes (LEDs), which combine in one system the NCs and a blue GaN-based LED. Nanocrystals with improved morphological and optical properties are obtained by optimizing the post-synthesis replacement of oleic acid ligands with iminodibenzoic acid: the NCs have a long shelf-life (>2 months), stability under different environmental conditions, and a high QY, of up to 90%, in the visible spectral range. Ligand replacement enables the engineering of the morphological and optical properties of the NCs. Furthermore, the NCs can be used to coat the surface of a GaN-LED to realize a stable diode where they are excited by blue light from the LED under low current injection conditions, resulting in emissions at distinct wavelengths in the visible range. The high QY and fluorescence lifetime in the nanosecond range are key parameters for visible light communication, an emerging technology that requires high-performance visible light sources for secure, fast energy-efficient wireless transmission

The recent decline and recovery of Indian summer monsoon rainfall: relative roles of external forcing and internal variability

The Indian summer monsoon (ISM) rainfall affects a large population in South Asia. Observations show a decline in ISM rainfall from 1950-1999 and a recovery from 1999-2013. While the decline has been attributed to global warming, aerosol effects, deforestation, and a negative-to-positive phase transition of the Interdecadal Pacific Oscillation (IPO), the cause for the recovery remains largely unclear. Through analyses of a 57-member perturbed-parameter ensemble of model simulations, this study shows that the externally-forced rainfall trend is relatively weak and is overwhelmed by large internal variability during both 1950-1999 and 1999-2013. The IPO is identified as the internal mode that helps modulate the recent decline and recovery of the ISM rainfall. The IPO induces ISM rainfall changes through moisture convergence anomalies associated with an anomalous Walker circulation and meridional tropospheric temperature gradients and the resultant anomalous convection and zonal moisture advection. The negative-to-positive IPO phase transition from 1950-1999 reduces what would have been an externally-forced weak upward rainfall trend of 0.01 mm day-1 decade-1 to −0.15 mm day-1 decade-1 during that period, while the rainfall trend from 1999-2013 increases from the forced value of 0.42 to 0.68 mm day-1 decade-1 associated with a positive-to-negative IPO phase transition. Such a significant modulation of the historical ISM rainfall trends by the IPO is confirmed by another 100-member ensemble of simulations using perturbed initial conditions. Our findings highlight that the interplay between the effects of external forcing and the IPO needs be considered for climate adaptation and mitigation strategies in South Asia

ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel

<p>Abstract</p> <p>Background</p> <p>One of the major challenges in currently chemotherapeutic theme is lacking effective biomarkers for drug response and sensitivity. Our current study focus on two promising biomarkers, ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer susceptibility gene 1). To investigate their potential role in serving as biomarkers for drug sensitivity in cancer patients with metastases, we statistically measure the mRNA expression level of ERCC1 and BRCA1 in tumor cells isolated from malignant effusions and correlate them with cisplatin and/or docetaxel chemosensitivity.</p> <p>Methods</p> <p>Real-time quantitative PCR is used to analysis related genes expression in forty-six malignant effusions prospectively collected from non-small cell lung cancer (NSCLC), gastric and gynecology cancer patients. Viable tumor cells obtained from malignant effusions are tested for their sensitivity to cisplatin and docetaxel using ATP-TCA assay.</p> <p>Results</p> <p>ERCC1 expression level is negatively correlated with the sensitivity to cisplatin in NSCLC patients (P = 0.001). In NSCLC and gastric group, BRCA1 expression level is negatively correlated with the sensitivity to cisplatin (NSCLC: P = 0.014; gastric: P = 0.002) while positively correlated with sensitivity to docetaxel (NSCLC: P = 0.008; gastric: P = 0.032). A significant interaction is found between ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P = 0.010, n = 45).</p> <p>Conclusion</p> <p>Our results demonstrate that ERCC1 and BRCA1 mRNA expression levels are correlated with <it>in vitro </it>chemosensitivity to cisplatin and/or docetaxel in malignant effusions of NSCLC and gastric cancer patients. And combination of ERCC1 and BRCA1 may have a better role on predicting the sensitivity to cisplatin than the single one is considered.</p