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Eliminating lead-exposure in nebulization therapy by lead-free piezoelectric
Global assessment of current extinction risks and future challenges for turtles and tortoises
12,13-diHOME protects against the age-related decline in cardiovascular function via attenuation of CaMKII
Whole-exome sequencing analysis identifies risk genes for schizophrenia
Abstract Rare coding variants across many genes contribute to schizophrenia liability, but they have only been implicated in 12 genes at exome-wide levels of significance. To increase power for gene discovery, we analyse exome-sequencing data for rare coding variants in a new sample of 4650 schizophrenia cases and 5719 controls, and combine these with published sequencing data for a total of 28,898 cases, 103,041 controls and 3444 proband-parent trios. We identify associations for STAG1 and ZNF136 at exome-wide significance, genes that were previously implicated in schizophrenia by the SCHEMA study at a false discovery rate of 5%. We also find associations at a false discovery rate of 5% for six genes that did not pass this statistical threshold in the SCHEMA study (SLC6A1, PCLO, ZMYND11, BSCL2, KLC1 and CGREF1). Among these genes, SLC6A1 and KLC1 are associated with damaging missense variants alone. STAG1, SLC6A1, ZMYND11 and CGREF1 are also enriched for rare coding variants in other developmental and psychiatric disorders. Moreover, STAG1 and KLC1 have fine-mapped common variant signals in schizophrenia. These findings provide insights into the neurobiology of schizophrenia, including further evidence suggesting an aetiological role for disrupted chromatin organisation.
B cell maturation antigen (BCMA) is dispensable for the survival of long-lived plasma cells
Abstract The survival of antibody-secreting plasma cells is essential for long-lasting humoral immunity. BCMA is proposed to promote APRIL-mediated survival signals. However, extensive shedding of murine BCMA raises doubts about its role as a signaling receptor. To unequivocally establish BCMA’s function in plasma cell survival, we generate two BCMA-deficient mouse lines and examine antigen-specific plasma cells post-immunization. Contrary to previous reports, both BCMA-deficient mouse lines have comparable numbers of antigen-specific long-lived plasma cells following both protein and mRNA immunizations. Transcriptome analysis reveals no reduction in survival signaling upon BCMA deletion. Interestingly, BCMA-deficient mice show increased total plasma cell numbers in the bone marrow and mesenteric lymph nodes after boost immunizations. These results indicate that BCMA has no intrinsic role in maintaining long-lived plasma cells. Instead, we propose that BCMA’s function is limited to acting as a soluble decoy receptor for APRIL, thereby fine-tuning the plasma cell population size by limiting survival factor availability. Our findings thus provide a strong argument against the APRIL-BCMA axis being a central mechanism for plasma cell longevity.
Personalized ML-based wearable robot control improves impaired arm function
Scn2a-linked myelination deficits and synaptic plasticity alterations drive auditory processing disorders in an ASD mouse model
Neural function of Netrin-1 in precancerous lesions of the pancreas
The oceanic physical injection pump of organic carbon
Rotation-invariance is essential for accurate detection of spatially variable genes in spatial transcriptomics
Chimeric exosomes-derived immunomodulator restoring lymph nodes microenvironment for sensitizing TNBC immunotherapy
Pericytes promote metastasis by regulating tumor local vascular tone and hemodynamics
Apparent charge reduction in multipolarons crafted one-by-one in monolayer CrBr3
Assessing the real implications for CO2 as generation from renewables increases
Abstract Wind and solar electricity generation account for 14% of total electricity generation in the United States and are expected to continue to grow in the next decade. While increased renewable penetration reduces system-wide emissions, the intermittent nature of these resources disrupts conventional thermal plant operations. Generation displacement exhibits a nonlinear relationship, as thermal units forced to operate at suboptimal levels experience efficiency penalties. Here we show that as renewable generation rises, thermal plants often operate sub-optimally, increasing emissions when forced to respond to variability. Using hourly emissions and generation data from California and Texas, we find that solar and wind energy significantly reduce expected emissions under normal operating conditions - by 92.6% in California and 91.1% in Texas. However, if renewables force plants to operate inefficiently, emissions from natural gas and coal plants could increase by 12% to 26%. These results highlight the complex interactions between renewable energy growth and thermal plant emissions, indicating that careful management of renewables integration is crucial to minimizing overall system-level CO2 emissions, especially in electricity grids with inflexible thermal capacity.
Latent infection of Caenorhabditis elegans by Orsay virus induces age-dependent immunity and cross-protection
Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models
Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX expression in experimental lung fibrosis in vivo and in human fibrotic tissue ex vivo. We thus identify YAP-TEAD/LOX inhibition in alveolar type II cells as a promising potential therapy for IPF patients.