Browse Articles

24-hour ambulatory blood pressure and associated factors in women with polycystic ovary syndrome compared with ovulatory controls

An experimentally-informed polymer model reveals high resolution organization of genomic loci

Abstract Gene expression patterns are governed by the hierarchical organization of the genome. Numerous efforts, leveraging both polymer physics-based models and experimental imaging technologies, have sought to elucidate the structure-function relationship of chromatin fibers. However, a major challenge is posed by the multi-scale nature of chromatin organization. Here, we present an experimentally informed, polymer physics-based model capable of reconstructing chromatin structural ensembles by integrating low-resolution contact data with MNase-derived nucleosome positioning information. We apply our approach to multiple human genomic loci. Our analysis shows distinct structural features associated with active and inactive chromatin states, providing insights into the relationship between genomic organization and transcriptional activity. These findings offer a framework for understanding genome structure-function relationships.

Collaborative strategies for planning post-earthquake waste disposal facilities: a bounded rationality perspective

Reversibly Redox-Active Iron Oxide Structures in FeNC Catalysts Identified by Microscopy and Spectroelectrochemical EPR and Mössbauer Methods

A multivalent adaptor mechanism drives the nuclear import of proteasomes

Abstract Nuclear protein homeostasis, including transcription factor turnover, critically depends on the nuclear proteasomes that must be imported after cell division. This dynamic process requires AKIRIN2, a small unstructured protein whose mechanistic role has remained elusive despite its essential function. Using an integrated approach combining protein-wide saturation mutagenesis screens, cryo-EM, and biochemical reconstitution, we characterize AKIRIN2 as a scaffold protein that coordinates the assembly of an importin cluster around the proteasome. AKIRIN2 binds in multiple copies to the 20S proteasome and simultaneously interacts with importin IPO9 and the KPNA2/KPNB1 heterodimer. In the nucleus, RanGTP triggers importin dissociation, releasing the proteasome, while AKIRIN2 undergoes ubiquitin-independent degradation. Our findings reveal how AKIRIN2’s multivalency facilitates the recruitment of multiple importins to the proteasome, a critical adaptation for transporting this large macromolecular complex into the nucleus and maintaining the nuclear proteome.

Reference gene variability across age and sex in 5XFAD mice highlights normalization challenges in Alzheimer’s models

Indolent primary cutaneous B-cell lymphomas resemble persistent antigen reactions without signs of dedifferentiation

Abstract Primary cutaneous B-cell lymphoma encompass clinically heterogeneous entities. While primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) is aggressive, primary cutaneous follicle centre lymphoma (pcFCL) and primary cutaneous marginal zone lymphoma (pcMZL) typically follow an indolent course. To clarify their pathophysiological basis, we perform single-cell RNA sequencing on pcFCL, pcMZL, and pcDLBCL-LT, alongside reactive B-cell rich lymphoid proliferations (rB-LP), gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and systemic counterparts. Here we show that the indolent pcMZL, pcFCL, and rB-LP exhibit a persistent germinal centre reaction, not observed in pcDLBCL-LT or gastric MALT lymphoma. Further, pcMZL top expanded clones develop within lesions from naïve and not post-germinal centre B cells as currently presumed. Our data thus indicate that pcMZL and pcFCL, similar to rB-LP may be driven by (a yet unknown) antigen. While our data indicates that pcFCL exhibits some features of true lymphomas, it clearly supports the classification of pcMZL as a lymphoproliferative disease.

Patterns of brown bear damages to agro-livestock activities in North-Eastern Italy across 15 years

Injectable hydrogel bioelectrostimulator for wireless deep brain neuromodulation

Abstract Deep brain stimulation (DBS) is effective for treating neurological and psychiatric disorders. However, its tethered configuration, invasiveness, and limited tissue compatibility motivate wireless, minimally invasive alternatives. Here, we develop an in situ-gelled injectable conductive hydrogel (ICH), enabling wireless neuromodulation via electric-field localization under volume conduction. The ICH forms in vivo through bio-catalyzed polymerization and electrostatic self-assembly, yielding a stable, highly conductive, tissue-soft, and biocompatible network. Under high-frequency capacitive coupling, impedance difference between the ICH and surrounding brain tissue induces interfacial polarization and charge accumulation, locally concentrating the electric field to activate nearby neurons. This mechanism is supported by enhanced calcium signaling, increased c-Fos expression, and electrophysiological evidence of balanced basal ganglia-cortical activity. In a Parkinson’s disease rat model, ICH-mediated stimulation improved locomotor behavior, preserved dopaminergic neurons, and restored functional connectivity and structural integrity as revealed by fMRI. This injectable hydrogel bioelectronics provides a platform for minimally invasive, wireless neuromodulation therapies.

Author Correction: Assessment of the safety of hypoxia-primed mesenchymal stem cells derived from umbilical cord and adipose tissues in animals

Author Correction: Buried deep freshwater reserves beneath salinity-stressed coastal Bangladesh

Two paired HPV-59 cervical cancer cell lines with distinct chemoradioresistant phenotypes

Predator-prey temporal niche partitioning under human disturbance: a meta-analysis

Cordyceps sinensis enhances the efficacy of anti-PD-1 immunotherapy in Lewis lung adenocarcinoma

Inhibition mechanism of the fungal β−1,3-glucan synthases by triterpenoid antifungal drugs

Multimodal imaging evaluation of hypoxic bone marrow microenvironment and type H vascular injury in diabetes

Ampere-level CO2 electroreduction to multi-carbon oxygenates in acidic electrolyte through surface microenvironment reconstruction

Direct evaluation of the electrocardiographic spatial QRS-T angle without the need for orthogonal transformation

Abstract Increased electrocardiogram (ECG) spatial QRS-T wave angle is a recognised risk factor. Standard evaluation of the angle requires deriving orthogonal ECG leads, either by general transformation matrices into XYZ leads or by singular value decomposition (SVD). This study shows that the transformation is not needed, and that the spatial QRS-T angle can be calculated directly from the original ECG leads. The direct computation was tested using long-term 12-lead ECGs of 523 healthy volunteers (259 females). A total of 659,313 individual 10-second ECG samples were obtained providing 7,350,733 individual beats which were analysed both by the direct method using 8 algebraically independent leads and by the conventional XYZ and SVD transformations. On average, the results of the direct non-transformation method were closer to the SVD-based results (averaged differences below 1 degree) than to the XYZ-based results (averaged differences below 2 degrees). The subject-specific regressions to the underlying heart rate showed that the proposed direct method was significantly more reproducible ( p  < 0.0001) and that it showed more compact variability within individual ECG samples ( p  < 0.0001). Thus, the study shows not only that the QRS-T angle can be computed without any orthogonal transformation but that the results of the direct computation are also more precise.

Neural and computational mechanisms underlying one-shot perceptual learning in humans

Ginsenoside Rg5 inhibits colorectal cancer, at least partially by blocking the lysosomal degradation of colorectal cancer cells