Browse Articles

Open-channel block of human TRPV6 by polyamine spermine

Abstract Polyamines are organic cations that are present at sub-millimolar concentrations in the cytoplasm and extracellular fluids and serve as versatile modulators of TRP channels, fine-tuning their functions in physiological and pathological contexts, including pain, inflammation and cancer. Despite extensive functional studies, the structural basis by which polyamines regulate TRP channels remains unclear. Here, we combine calcium imaging, electrophysiology, cryo-electron microscopy, mutagenesis and molecular dynamics simulations to study regulation of human TRPV6 by polyamine spermine. Our functional experiments demonstrate voltage-dependent block of TRPV6-mediated currents by spermine. Cryo-electron microscopy reveals that spermine binds in the open pore of TRPV6, extending along the pore axis through the selectivity filter and central cavity. Mutagenesis and molecular dynamics simulations confirm the main binding site of spermine in the selectivity filter and suggest a stepwise molecular mechanism of channel block that includes two more binding sites in the pore transiently occupied by spermine. Our findings enrich the knowledge about TRPV6 regulation by endogenous factors and provide details of the ion channel blocking mechanism that can be explored for inhibition of this channel in disease conditions.

An Atom-Precise Approach to Damp First-Order Phase Transitions and Its Implications for Neuromorphic Signal Processing

Ex vivo accuracy of three electronic apex locators under various irrigants

Transfer learning reveals large discrepancies between air and land surface temperatures in cities

Computational Insights into the Activation Mechanism of CXCR4: Implications for the Design of Small Molecule Agonists

Geological mapping of the Adrar Souttouf mafic complex in the Northern West African Craton using remote sensing and geophysical data

Abstract Geological mapping of the Adrar Souttouf Mafic Complex (ASMC) is constrained by its remote arid mountainous setting, where logistical limitations hinder traditional field surveys; however, advances in satellite data have provided powerful, cost-effective tools for high-resolution lithological and structural mapping. This research presents the first synergistic use of Sentinel-1 radar, Sentinel-2 and Landsat-8 optical imagery, and airborne gamma-ray spectrometry data to decipher the main structural and lithological characteristics of the Adrar Souttouf mafic complex within Morocco’s Oulad Dlim Massif. To achieve this, image processing—including color composites, band ratios, Principal Component Analysis (PCA), and radiometric terrain correction (RTC) —was employed for lithological mapping at regional and local scales. These spectral results were integrated with airborne gamma-ray spectrometry (K%, Th ppm, U ppm), providing the geochemical constraints necessary to differentiate lithological units and update existing geological maps. The study revealed that the highly complex geology with a variety of facies. These facies can be classified into three main categories: (i) (minor) ultramafic cumulates (ii) massive isotropic gabbros that represent magmatic intrusions that correspond to interconnected laccolites through a network of feeding dykes, and (iii) evolved silica-rich facies corresponding to charnockites, that are found either in undeformed massifs, or in elliptical bodies. The latter are situated under the broad gneissified massif of Hassi Bougaffa. All these magmatic facies were emplaced within a strongly deformed gabbroic body and are structurally controlled by fault systems. The most significant faults are oriented E-W and NNE-SSW. The result validation by fieldwork aided by remote sensing and gamma-ray spectrometry maps have clearly helped in better distinguishing between the various lithological units. This led to update the litho-structural map of the study area.

Protonation and magnesium ions shape the transition state diversity of phosphoanhydride hydrolysis in water

Iron-Catalyzed Selective C(sp ² )–C(sp ³ ) Coupling of Nitro(hetero)arenes and Alkyl Bromides by Paired Electrolysis

Intranasal infection of Rift Valley fever virus in the ferret model suggests multiple routes of neuroinvasion with consequential encephalitis and ophthalmitis

Abstract Rift Valley fever virus (RVFV) causes haemorrhagic fever, ophthalmitis, and in severe cases, encephalitis in humans. Despite the well-recognised neurotropism, the mechanisms of central nervous system (CNS) invasion remain poorly understood. We investigated RVFV ingress into the CNS and resulting neuropathogenesis following intranasal inoculation in ferrets ( Mustela putorius furo ) ( n  = 15). At 3 DPI, before RVFV dissemination to the CNS, mild multifocal suppurative rhinitis and multifocal interstitial pneumonia were detected in the nasal cavity and lungs respectively, supported by detection of viral antigen and genome. From 6 DPI, infected ferrets exhibited neurological signs; by 6 − 8 DPI, a mild-to-moderate non-suppurative meningoencephalitis and myelitis was observed, progressing rostrally to caudally, with ophthalmitis observed from 7 DPI and 100% mortality by 8 DPI. Mild-to-moderate hyperaemia of the meninges was identified macroscopically in all infected ferrets. An immune response to infection was unable to prevent neuropathogenesis and clinical disease. Although our results suggest that neuroinvasion occurs via the olfactory route through the nasal turbinates to cranial nerves, virus replication in the lungs and presence of viremia implies that haematogenous dissemination into the CNS as a secondary route is possible. This relevant experimental ferret model may further contribute to understanding the pathogenesis of human RVFV infection.

Water engineering via surfactant coacervates enables efficient and robust solar hydrogen evolution

Transformer-based 3D pose estimation pipeline with modular SmoothNet integration for animation generation

Pneumococcus uses COMMD2 to alter host cellular immunity

Abstract NF-κB driven cellular immunity is essential for both pro- and anti-inflammatory responses to microbes, which makes it one of the most frequently targeted pathways by bacteria during pathogenesis. How NF-κB tunes the epithelial response to Streptococcus pneumoniae across the spectrum of commensal to pathogenic outcomes is not fully understood. In this study, we compare a commensal-like 6B ST90 strain to an invasive TIGR4 strain and demonstrate, through comparative mass spectrometry of the p65 interactome, that TIGR4 challenge triggers interaction of COMMD2 with p65 and p62. Mechanistically, we show this complex mediates export of p65 for degradation and COMMD2 is necessary for altering host cellular immunity. With these results, we reveal a bacterial pathogenesis mechanism to repress host inflammatory response though COMMD2 and p65 degradation while presenting a paradigm for diverging NF-κB responses to pneumococcus.

Tailored Synergistic Vibronic Progression and Charge Transfer in 1,2-BN-Heteroarenes for Efficient and Stable Narrowband Electroluminescence

Risk factors associated with rectal carriage of extended spectrum beta-lactamases producing Enterobacterales among inpatients at a tertiary hospital in Northern Nigeria: A cross-sectional study

Extensive variation between chromosomes of North American and European hop

Abstract Hop is an essential ingredient in brewing, providing beer with its characteristic bitterness and aroma. Most modern hop cultivars are hybrids between European and North American hop lineages, but how these ancestries contribute to bitter acid content, the most important trait in hop breeding, remains unclear. Here, we report chromosome-scale, haplotype-resolved assemblies of the hybrid hop cultivar Apollo, assign European and North American ancestry across the genome, and identify varying levels of recombination suppression between chromosomes of either origin. Using this reference, we uncover genetic and chemical diversity in core bittering pathways between European and North American hops. We further show additive effects of beneficial European and North American alleles on bitter acid content, providing a foundation for genomics-assisted hop breeding.

Covalent Chemical Tagging of Transmembrane Transport Proteins Illuminates the Internalization Pathways of Xenosiderophores

Anemia as an independent risk factor for sarcopenia in older adults: a cohort study based on CHARLS and ELSA

Abstract This study examined the prospective association between anemia and incident sarcopenia using two large-scale aging cohorts: the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). This prospective, population-based cohort study included participants aged ≥ 45 years without sarcopenia at baseline from CHARLS (Wave 1, 2011) and ELSA (Wave 4, 2008–2009). Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, lifestyle, and health-related confounders. Subgroup analyses and sensitivity analyses were conducted to test robustness. After full adjustment, baseline anemia was significantly associated with an increased risk of incident sarcopenia in both CHARLS ( n  = 1,407; HR = 1.73, 95% CI: 1.07–2.79) and ELSA ( n  = 2,921; HR = 2.62, 95% CI: 1.50–4.56). In ELSA, a stronger association was observed among females (HR = 4.72, 95% CI: 2.25–9.93), with a marginal sex interaction (P for interaction = 0.054). No significant sex interaction was detected in CHARLS.Sensitivity analyses using sequential adjustment models confirmed consistent results (CHARLS: HR = 1.53, 95% CI: 1.17–2.01; ELSA: HR = 2.59, 95% CI: 1.30–5.18). This bicohort study suggests that baseline anemia is associated with a higher risk of developing sarcopenia in older adults from two distinct populations (Chinese and British). The strength of this association and the susceptible subgroups differed between cohorts. Further studies are needed to determine whether correcting anemia can reduce sarcopenia incidence and whether risk stratification based on anemia improves prevention strategies.

Caspase-4 transgenic mice exhibit cytoplasmic TDP-43 accumulation and age-dependent neuropathology

A Persistent Ni(0)–Pentalene Complex with High Fluxionality: Does Stronger Antiaromaticity Promote Metal–Ligand Interactions?

Industrial energy use and oil dependence as conditional drivers of carbon emissions in Saudi Arabia — evidence from quantile regression