Lehmanproctor8648
Finally, unilateral whisker stimulation from PND9 to PND16 enhanced WFA+ PNN density in the contralateral somatosensory cortex only in mGlu5+/+ mice, whereas whisker trimming from PND9 to PND16 reduced WFA+ PNN density exclusively in mGlu5-/- mice, suggesting that mGlu5 receptors shape the PNN response to sensory experience. These findings disclose a novel undescribed mechanism of PNN regulation, and lay the groundwork for the study of mGlu5 receptors and PNNs in neurodevelopmental disorders.Nonlinear optical effects in layered two-dimensional transition metal chalcogenides have been extensively explored recently because of the promising prospect of the nonlinear optical effects for various optoelectronic applications. However, these materials possess sizable bandgaps ranging from visible to ultraviolet region, so the investigation of narrow-bandgap materials remains deficient. Here, we report our comprehensive study on the nonlinear optical processes in palladium diselenide (PdSe2) that has a near-infrared bandgap. Interestingly, this material exhibits a unique thickness-dependent second harmonic generation feature, which is in contrast to other transition metal chalcogenides. find more Furthermore, the two-photon absorption coefficients of 1-3 layer PdSe2 (β ~ 4.16 × 105, 2.58 × 105, and 1.51 × 105 cm GW-1) are larger by two and three orders of magnitude than that of the conventional two-dimensional materials, and giant modulation depths (αs ~ 32%, 27%, and 24%) were obtained in 1-3 layer PdSe2. Such unique nonlinear optical characteristics make PdSe2 a potential candidate for technological innovations in nonlinear optoelectronic devices.Mental health disorders are a leading cause of disability worldwide. Challenges such as disease heterogeneity, incomplete characterization of the targets of existing drugs and a limited understanding of functional interactions of complex genetic risk loci and environmental factors have compromised the identification of novel drug candidates. There is a pressing clinical need for drugs with new mechanisms of action which address the lack of efficacy and debilitating side effects of current medications. Here we discuss a novel strategy for neuropsychiatric drug discovery which aims to address these limitations by identifying disease-related functional responses ('functional cellular endophenotypes') in a variety of patient-derived cells, such as induced pluripotent stem cell (iPSC)-derived neurons and organoids or peripheral blood mononuclear cells (PBMCs). Disease-specific alterations in cellular responses can subsequently yield novel drug screening targets and drug candidates. We discuss the potential of this approach in the context of recent advances in patient-derived cellular models, high-content single-cell screening of cellular networks and changes in the diagnostic framework of neuropsychiatric disorders.Heparanase (HPSE) is a kind of multifunctional extracellular hydrolase, and related to metastasis of hepatocellular carcinoma (HCC). Endothelial necroptosis promotes the metastasis of cancer cells. It is not clear whether HPSE could mediate necroptosis of microvascular endothelial cells (MVECs) to promote HCC metastasis. Here we found HPSE expression was up-regulated in HCC tissues and its over-expression was correlated with multiple tumor foci, microvascular invasion, and poor outcome of HCC patients. Non-contact co-culture experiments showed high-expressed HPSE in HCC cells mediated the necroptosis of human umbilical vein endothelial cells (HUVECs) and elevated the expression levels of syndecan-1 (SDC-1) and tumor necrosis factor-α (TNF-α) in vitro. As a result of necroptosis, trans-endothelial migration (TEM) of HCC cells was increased. Conversely, both HPSE and SDC-1 knockdowns reversed necroptosis and decreased TNF-α expression level, while HPSE over-expression increased SDC-1 and TNF-α expression and aggravated necroptosis. Animal experiments found that the nude mice, intraperitoneally injected with HPSE high expressing HCC cells, had obvious necroptosis of MVECs and high intrahepatic metastasis rate, which could be relieved by inhibitor of necroptosis. Morever, HPSE elevated the expression levels of p38 mitogen-activated protein kinase (p38 MAPK) rather than nuclear factor kappa B in vitro. Our data suggest that HPSE induces necroptosis of MVECs to promote the metastasis of HCC by activating HPSE/SDC-1/TNF-α axis and p38 MAPK pathway.Well-defined scaffold hydrogels made of self-assembling peptides have found their way into clinical products. By examining the properties and applications of two self-assembling peptides-EAK16 and RADA16-we highlight the potential for translating designer biological scaffolds into commercial products.Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P less then 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.The limited memory retention for a ferroelectric field-effect transistor has prevented the commercialization of its nonvolatile memory potential using the commercially available ferroelectrics. Here, we show a long-retention ferroelectric transistor memory cell featuring a metal-ferroelectric-metal-insulator-semiconductor architecture built from all van der Waals single crystals. Our device exhibits 17 mV dec-1 operation, a memory window larger than 3.8 V, and program/erase ratio greater than 107. Thanks to the trap-free interfaces and the minimized depolarization effects via van der Waals engineering, more than 104 cycles endurance, a 10-year memory retention and sub-5 μs program/erase speed are achieved. A single pulse as short as 100 ns is enough for polarization reversal, and a 4-bit/cell operation of a van der Waals ferroelectric transistor is demonstrated under a 100 ns pulse train. These device characteristics suggest that van der Waals engineering is a promising direction to improve ferroelectronic memory performance and reliability for future applications.