Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

Molecular scalpels dissect new GluN1 hot spots in anti-NMDA receptor encephalitis.

Patient-derived NMDAR mAbs combined with single-particle cryo-electron microscopy reveal multiple GluN1 epitopes and distinct functional effects.

Suppression of thrombospondin-1-mediated inflammaging prolongs hematopoietic health span.

Chronic low-grade inflammation observed in older adults, termed inflammaging, is a common feature underlying a multitude of aging-associated maladies including a decline in hematopoietic activity. However, whether suppression of inflammaging can preserve hematopoietic health span remains unclear, in part because of a lack of tools to measure inflammaging within hematopoietic stem cells (HSCs). Here, we identify thrombospondin-1 (Thbs1) as an essential regulator of inflammaging within HSCs.

NEK7 phosphorylation amplifies NLRP3 inflammasome activation downstream of potassium efflux and gasdermin D.

The NLRP3 inflammasome plays a critical role in innate immunity and inflammatory diseases. NIMA-related kinase 7 (NEK7) is essential for inflammasome activation, and its interaction with NLRP3 is enhanced by K efflux. However, the mechanism by which K efflux promotes this interaction remains unknown.

SNIPR alert! Making T cells more precise killers.

A cell engineering approach demonstrates that precise regulation of cell signaling can be achieved using both endogenous and synthetic ligands.

Functional differences between rodent and human PD-1 linked to evolutionary divergence.

Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.

Multistate kinetics of the syringe-like injection mechanism of Tc toxins.

Tc toxins are pore-forming virulence factors of many pathogenic bacteria. Following pH-induced conformational changes, they perforate the target membrane like a syringe to translocate toxic enzymes into a cell. Although this complex transformation has been structurally well studied, the reaction pathway and the resulting temporal evolution have remained elusive.

Organic carbon dry deposition outpaces atmospheric processing with unaccounted implications for air quality and freshwater ecosystems.

Dry deposition is an important yet poorly constrained process that removes reactive organic carbon from the atmosphere, making it unavailable for airborne chemical reactions and transferring it to other environmental systems. Using an aircraft-based measurement method, we provide large-scale estimates of total gas-phase organic carbon deposition rates and fluxes. Observed deposition rates downwind of large-scale unconventional oil operations reached up to 100 tC hour, with fluxes exceeding 0.

Theory of giant magnetoelastic effect in soft systems.

Having been predominantly observed in rigid metal and metal alloys since 1865, the magnetoelastic effect was recently experimentally discovered in a soft matter system and used as a new working mechanism for energy and health care applications. Here, a theoretical framework is presented and proven to be universally accurate and robust in interpreting the giant magnetoelastic effect across soft systems subjected to various deformation modes, micromagnet concentrations, magnetization profiles, and geometric structures. The theory uncovers substantial, unique magnetoelastic phenomena in soft systems, including the magnetic pole reversal under localized compression.

A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.

Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.

Transcriptional coupling of telomeric retrotransposons with the cell cycle.

Unlike most species that use telomerase for telomere maintenance, many dipterans, including , rely on three telomere-specific retrotransposons (TRs)-, , and -to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription.

The importance of shear on the collective charge transport in CDWs revealed by an XFEL source.

Charge transport in materials has an impact on a wide range of devices based on semiconductor, battery, or superconductor technology. Charge transport in sliding charge density waves (CDW) differs from all others in that the atomic lattice is directly involved in the transport process. To obtain an overall picture of the structural changes associated to the collective transport, the large coherent x-ray beam generated by an x-ray free-electron laser (XFEL) source was used.

Enhancing cathode composites with conductive alignment synergy for solid-state batteries.

Enhancing transport and chemomechanical properties in cathode composites is crucial for the performance of solid-state batteries. Our study introduces the filler-aligned structured thick (FAST) electrode, which notably improves mechanical strength and ionic/electronic conductivity in solid composite cathodes. The FAST electrode incorporates vertically aligned nanoconducting carbon nanotubes within an ion-conducting polymer electrolyte, creating a low-tortuosity electron/ion transport path while strengthening the electrode's structure.

Transcriptional regulation of adipocyte lipolysis by IRF2BP2.

Adipocyte lipolysis controls systemic energy levels and metabolic homeostasis. Lipolysis is regulated by posttranslational modifications of key lipolytic enzymes. However, less is known about the transcriptional mechanisms that regulate lipolysis.

Global niche partitioning of purine and pyrimidine cross-feeding among ocean microbes.

Cross-feeding involves microbes consuming exudates of other surrounding microbes, mediating elemental cycling. Characterizing the diversity of cross-feeding pathways in ocean microbes illuminates evolutionary forces driving self-organization of ocean ecosystems. Here, we uncover a purine and pyrimidine cross-feeding network in globally abundant groups.

Wide-ranging predictions of new stable compounds powered by recommendation engines.

The computational search for new stable inorganic compounds is faster than ever, thanks to high-throughput density functional theory (DFT). However, stable compound searches remain highly expensive because of the enormous search space and the cost of DFT calculations. To aid these searches, recommendation engines have been developed.

Imaging interlayer exciton superfluidity in a 2D semiconductor heterostructure.

Excitons, which are Coulomb bound electron-hole pairs, are composite bosons and thus at low temperature can form a superfluid state with a single well-defined amplitude and phase. We directly image this macroscopic exciton superfluid state in an hBN-separated MoSe-WSe heterostructure. At high density, we identify quasi-long-range order over the entire active area of our sample, through spatially resolved coherence measurements.

Ubiquitination of OsCSN5 by OsPUB45 activates immunity by modulating the OsCUL3a-OsNPR1 module.

The COP9 signalosome (CSN) is a highly conserved protein complex in eukaryotes, with CSN5 serving as its critical catalytic subunit. However, the role of CSN5 in plant immunity is largely unexplored. Here, we found that suppression of in rice enhances resistance against the fungal pathogen and the bacterial pathogen pv.

Deciphering neutrophil dynamics: Enhanced phagocytosis of elastic particles and impact on vascular-targeted carrier performance.

Particle elasticity has widely been established to substantially influence immune cell clearance and circulation time of vascular-targeted carriers (VTCs). However, prior studies have primarily investigated interactions with macrophages, monocytic cell lines, and in vivo murine models. Interactions between particles and human neutrophils remain largely unexplored, although they represent a critical aspect of VTC performance.

cSTAR analysis identifies endothelial cell cycle as a key regulator of flow-dependent artery remodeling.

Fluid shear stress (FSS) from blood flow sensed by vascular endothelial cells (ECs) determines vessel behavior, but regulatory mechanisms are only partially understood. We used cell state transition assessment and regulation (cSTAR), a powerful computational method, to elucidate EC transcriptomic states under low shear stress (LSS), physiological shear stress (PSS), high shear stress (HSS), and oscillatory shear stress (OSS) that induce vessel inward remodeling, stabilization, outward remodeling, or disease susceptibility, respectively. Combined with a publicly available database on EC transcriptomic responses to drug treatments, this approach inferred a regulatory network controlling EC states and made several notable predictions.

Its own architect: Flipping cardiolipin synthase.

Current dogma assumes that lipid asymmetry in biological membranes is actively maintained and dispensable for cell viability. The inner (cytoplasmic) membrane (IM) of is asymmetric. However, the molecular mechanism that maintains this uneven distribution is unknown.

Transcriptomic DN3 clock neuron subtypes regulate sleep.

Circadian neurons within animal brains orchestrate myriad physiological processes and behaviors, but the contribution of these neurons to the regulation of sleep is not well understood. To address this deficiency, we leveraged single-cell RNA sequencing to generate a comprehensive census of transcriptomic cell types of clock neurons. We focused principally on the enigmatic DN3s, which constitute most fly brain clock neurons and were previously almost completely uncharacterized.

Comprehensive characterization of the transcriptional landscape in Alzheimer's disease (AD) brains.

Alzheimer's disease (AD) is the leading dementia among the elderly with complex origins. Despite extensive investigation into the AD-associated protein-coding genes, the involvement of noncoding RNAs (ncRNAs) and posttranscriptional modification (PTM) in AD pathogenesis remains unclear. Here, we comprehensively characterized the landscape of ncRNAs and PTM events in 1460 samples across six brain regions sourced from the Mount Sinai/JJ Peters VA Medical Center Brain Bank Study and Mayo cohorts, encompassing 33,321 long ncRNAs, 92,897 enhancer RNAs, 53,763 alternative polyadenylation events, and 900,221 A-to-I RNA editing events.

High-resolution cryo-EM using a common LaB 120-keV electron microscope equipped with a sub-200-keV direct electron detector.

High-resolution cryo-electron microscopy (cryo-EM) requires costly 200- to 300-keV cryo-transmission electron microscopes (cryo-TEMs) with field emission gun (FEG) sources, stable columns, constant-powered lenses, autoloader, and direct electron detectors (DED). Recent advances in 100-keV imaging with the emergence of sub-200-keV optimized DED technology promises the development of more affordable cryo-TEMs. So far, 100-keV imaging has required microscopes with FEG sources.

The Utility of Preoperative Phenylephrine Testing in Müller Muscle Conjunctival Resection Surgery for Involutional Ptosis.

Purpose: Phenylephrine testing prior to Müller muscle conjunctival resection has traditionally been used to predict postoperative outcomes. The purpose of this study is to determine if preoperative phenylephrine testing impacts postoperative changes in eyelid position.

Methods: In this multicenter cross-sectional cohort study, 270 eyelids of participants with involutional ptosis and levator function >12 mm who underwent Müller muscle conjunctival resection were divided into 2 comparison groups.