Browse Articles

Calumenin prevents fibroblast senescence and lung aging by promoting vimentin proteostasis

Progressive lung fibrosis is linked to aging-related dysfunction in fibroblasts, which remains poorly understood. To investigate the alterations in fibroblasts, particularly the molecular programs driving this profibrotic evolution in the aging lung, we isolated senescent lung fibroblasts from aged mice. We observed aberrant vimentin aggregates, which correlate with accelerated fibroblast senescence. CRISPR-based screening identified calumenin as a chaperone protein essential for vimentin proteostasis. A fibroblast-specific knockout of calumenin promotes the accumulation of vimentin aggregates and profibrotic factors migracytosis, exacerbating fibroblast senescence and lung aging. Mechanistically, calumenin collaborates with the TRiC complex to facilitate proper vimentin folding and recruits the chaperonin subunit Chaperonin Containing TCP1 Subunit 2 (CCT2) to degrade misfolded vimentin aggregates. Pathologically, external profibrotic stimuli trigger calcium transients and induce calumenin degradation, resulting in fibroblast senescence and the initiation of fibrosis. The natural product 9-85, derived from high-content screening, specifically targets and disrupts vimentin aggregates upon stimulation, alleviating aging-related lung fibrosis. Our findings reveal that calumenin coordinates vimentin quality control to shape cell structure and suppress the secretome of senescent fibroblasts, providing a promising therapeutic strategy for aging-related organ fibrosis.

High prevalence of Trypanosoma spp. and apparent trypanocidal drugs inefficacy in cattle in Al Radom National Park, Sudan

Abstract Trypanosomosis is a major infectious disease affecting cattle in Sudan. In South Darfur, data on cattle trypanosomosis has been limited since the Darfur civil war (2003–2007). This study assessed the prevalence and distribution of Trypanosoma spp. in cattle in the tsetse fly endemic Al Radom National Park, and collected questionnaire data on trypanocide use and apparent efficacy. Blood from 509 cattle across four regions was analysed. Of these, 3.1%, 19.8% and 35.8% tested positive for trypanosomes by microscopy, buffy coat technique and PCR, respectively. At the regional level, prevalence was 50.0%, 42.9%, 27.3% and 22.9% in Al Radom Livestock Market, Kafindibei, Al Radom town and Murayrayah, respectively. Trypanosoma congolense savannah (15.7%), Trypanosoma vivax (9.6%), Trypanosoma brucei (0.8%) and Trypanosoma theileri (13.4%) were identified. Prevalence was significantly correlated with region and age ( P  < 0.05). Older cattle showed significantly higher prevalence (44.7%) than 1–3 years old (29.7%) and < 1 year old cattle (22.7%). Most cattle (86.8%) had received trypanocides within 30 days before sample collection, mainly diminazene aceturate, either alone or combined with isometamidium chloride and/or quinapyramine. Despite treatment, 30.7% were Trypanosoma -positive by PCR. In conclusion, trypanosomes are prevalent in Al Radom National Park, even in treated cattle, indicating apparent drug inefficacy, which requires further research and control measures.

Constraints on the impactor flux to the Earth–Moon system from oxygen isotopes of the lunar regolith

The impactor flux record to Earth has largely been erased by active tectonics, weathering, and continual reworking of the crust. Instead, a record of highly siderophile elements (HSE: Re, Os, Ir, Ru, Rh, Pt, Pd, and Au) in lunar impactites has been used as a proxy for the type of impactor material added to the Earth–Moon system. Quantifying impactor mass and flux with the HSE can potentially be complicated by numerous secondary processes, however, including silicate–metal segregation and multiple impact heritage. In contrast, because oxygen has an invariant geochemical affinity, triple oxygen isotope compositions have the potential to offer a robust long-term record of impactor fluxes in complex mixtures such as regolith. Here, we use high-precision triple oxygen isotopes to deconvolve the influences of meteorite addition and silicate vaporization and identify a ubiquitous impactor contaminant comprised of partially evaporated CM or ureilite-like material representing at least 1 wt% of the lunar regolith. Water delivered to Earth by meteorite material over 4 billion years therefore is only a fraction of an ocean’s worth of water but is a significant contributor to the ice reservoir of the lunar cold traps.

Active optical boundary recognition with boron powder injection in a magnetic confinement device

Abstract Accurate determination of the plasma boundary—especially the Last Closed Flux Surface (LCFS)—is crucial for understanding equilibrium, optimizing confinement, and achieving effective control in magnetic confinement devices. Conventional detection methods, such as magnetic reconstructions (e.g., EFIT) and passive optical diagnostics, have limitations during transient or low-emission conditions. We present an innovative plasma boundary identification technique that uses boron powder injection in the EXL-50U spherical torus device. When the boron particles ablate at the plasma boundary, they emit a strong localized line radiation of boron in the visible spectral range, serving as a clear, real-time marker for LCFS detection. By combining precise camera calibration with boron-filter-based contrast enhancement, our method provides high spatial accuracy and fast response with minimal hardware complexity. We describe the principles of the technique, experimental setup, and data processing workflow, and compare its performance to established boundary detection methods. Lastly, we explore the potential of active boron injection for advanced plasma control in future high-performance fusion devices, emphasizing its ability to meet the demanding requirements of long-pulse and reactor-grade plasmas.

How much of the forest sink is passive? Case of the United States

Over time, carbon sequestered in temperate forests has increased, but the relative effects of passive and active drivers remain unclear. This study uses plot-level data to disentangle the contributions of six drivers (temperature, precipitation, CO 2 , management, age composition, and area) to these increases in 14 forest groups of the conterminous United States. From 2005 to 2022, the passive drivers (CO 2 , temperature, and precipitation) increased live tree carbon (C) by 66 teragrams (Tg) C y −1 with CO 2 fertilization contributing most of the change. Among the anthropogenic drivers, declining forest area reduced live tree C by 31 Tg C y −1 while tree planting increased it by 23 Tg C y −1 . Changes in age composition, driven by both passive traits and anthropogenic choices, increased live tree C by 89 Tg C y −1 . By quantifying the share of removals attributable to passive uptake, this approach enables nations with national forest inventories to better utilize their forests to meet net-zero requirements.

N-acetyl cysteine amide mitigates oxidative stress and apoptosis in a rat model of renal ischemia-reperfusion injury

Scaling the glassy dynamics of active particles: Tunable fragility and reentrance

Understanding the influence of activity on dense amorphous assemblies is crucial for biological processes such as wound healing, embryogenesis, or cancer progression. Here, we study the effect of self-propulsion forces of amplitude f 0 and persistence time τ p in dense assemblies of soft repulsive particles by simulating a model particle system that interpolates between particulate active matter and biological tissues. We identify the fluid and glass phases of the three-dimensional phase diagram obtained by varying f 0 , τ p , and the packing fraction ϕ . The morphology of the phase diagram accounts for a nonmonotonic evolution of the relaxation time with τ p , which is a direct consequence of the crossover in the dominant relaxation mechanism, from glassy to jamming. A second major consequence is the evolution of the glassy dynamics from sub-Arrhenius to super-Arrhenius. We show that this tunable glass fragility extends to active systems analogous observations reported for passive particles. This analogy allows us to apply a dynamic scaling analysis proposed for the passive case, in order to account for our results for active systems. Finally, we discuss similarities and differences between our results and recent findings in the context of computational models of biological tissues.

GeneticNAS: a novel self-evolving neural architecture for advanced ASD screening

Evolutionary adaptations to the hormonal regulation of vascular tissue development

Vascular tissues provide long-distance transport and physical support in the vascular plant lineage, providing a significant adaptive advantage. Although the cross talk between auxin and cytokinin in promoting both vascular cell proliferation and differentiation has been well studied in angiosperms such as Arabidopsis thaliana , little is known about this regulation in other vascular plant lineages. Here, we found that unlike the hormonal cross talk found in all other species under study, the lycophyte Selaginella moellendorffii shows clear task separation, with auxin driving vascular cell proliferation only and cytokinin specifically triggering cell differentiation. Using a cross-species transcriptomics approach, we found that members of the AUXIN / INDOLE-ACETIC ACID ( AUX / IAA ) and CYTOKININ OXIDASE ( CKX ) gene families exhibited divergent expression patterns in response to auxin and cytokinin treatments. Despite these regulatory differences, we show that AUX/IAA and CKX proteins are functionally conserved between Arabidopsis and Selaginella. Taken together, our findings suggest an evolutionary adaptation to the hormonal regulation of vascular tissue development in which core protein functions are conserved, but regulatory circuits diverged in lycophytes.

Data-driven quantification and visualization of resilience metrics of power distribution systems

Noncanonical genetic markers resolve the pre-GOE emergence of aerobic bacteria in Earth’s history

The transition from anaerobic to aerobic life was a pivotal adaptation in Earth’s history, yet the timing and genomic drivers remain poorly resolved. Traditional approaches relying on oxygen-utilizing genes need improvement for obligate anaerobes and fragmentary environmental genomes, where gene absence may reflect poor assembly rather than phenotype. We developed a machine learning model (GBDT40-LR) to predict microbial oxygen requirements using 40 broadly conserved genes, 35 without direct oxygen roles. This approach overcomes incompleteness biases in environmental genomes. Applied to 80,787 bacterial genomes [including metagenome-derived assemblies (MAGs)], the model classified 42,014 aerobes and 38,775 anaerobes, enabling large-scale ancestral reconstruction. Molecular clock dating indicates an emergence of aerobic bacterium prior to the Great Oxidation Event (GOE, 2.5 to 2.3 Ga), likely around ~2.7 Ga. Aerobic lineages subsequently diversified during the GOE and Neoproterozoic Oxygenation Event (NOE, 0.8 to 0.55 Ga), with persistent anaerobe diversity across Earth’s oxygenation. This establishes that aerobic bacteria originated planetary oxygenation, potentially by 200 to 400 My, providing insights into phenotypic evolution and prolonged anaerobe–aerobe coexistence.

Correlation of inflammatory mediators with osteophyte formation in end-stage knee osteoarthritis

Widespread terrestrial ecosystem disruption at the onset of the Paleocene–Eocene Thermal Maximum

The Paleocene–Eocene Thermal Maximum (PETM, ~56 Mya) interval was marked by massive 13 C-depleted carbon emissions into the ocean/atmosphere system, manifested as a negative carbon isotope excursion (CIE) in sedimentary components, and ~5 °C global average warming. Episodes of hydrological perturbations and soil-erosion have been widely documented for the PETM but their link with vegetation- and carbon cycle changes remain poorly constrained. Here, we present organic microfossil evidence showing a strong increase in fern-dominated pioneer vegetation that replaced coniferous forests on the margin of the Norwegian Sea during the first millennia of the CIE. With the present stratigraphic constraints, the “fern spike” occurred simultaneously in terrestrial settings along the North Sea, Arctic Ocean, the US east coast and in southern Australia, indicating that pioneer vegetation persisted for several millennia following a partial collapse of previously stable terrestrial ecosystems. Both the ferns and influx of microcharcoal imply recurrent physical disturbance, including soil destabilization and erosion, potentially linked to droughts, wildfires, and strong hydrological forcing resulting from extreme climate change. Together with evidence for reworked clay minerals and ancient organic matter (kerogen), these findings show that highly disturbed terrestrial ecosystems were widespread across mid- and high-latitude regions globally. Carbon cycle model simulations suggest that a substantial loss of standing and buried biomass, along with oxidation of soil organic matter, acted as important positive feedbacks during the onset of the CIE. Additionally, enhanced kerogen weathering likely contributed as another major positive feedback throughout both the onset and main phase of the CIE.

Nuclear receptor corepressor 1 is a potential diagnostic and prognostic biomarker in clear cell renal cell carcinoma

Liganded LolCDE structures reveal a common substrate-LolE interaction guiding bacterial lipoprotein transport

Bacterial lipoproteins are key structural components of the outer membrane in Gram-negative bacteria and vital components of machineries required for its biosynthesis and maintenance. The Lol system, essential for viability, directs transport of lipoproteins from the site of biosynthesis on the inner membrane to the outer membrane and has been the target of extensive efforts to develop novel antimicrobial drugs. In the first stage of this transport process, newly synthesized lipoproteins are released from the inner membrane by the ABC transporter LolCDE and passed to the periplasmic chaperone, LolA. Here, we show cryo-EM structures of LolCDE in complex with three different lipoprotein substrates, Lpp, Pal, and LolB, with the latter two bearing a disordered peptide linker between the acyl chains and the globular domain. Our work reveals that when the mature lipoprotein lacks an unstructured linker, the N-terminal portion of the protein is in an unfolded state for transport. The lipoproteins make a sequence-independent but structurally conserved interaction with a cleft on the surface of the periplasmic domain of LolE that promotes efficient transport. We propose a model of lipoprotein export where this interaction acts as pivot point for the peptide portion of the lipoprotein allowing the acyl chains to rotate 180° from their initial position in LolCDE to their binding site in LolA. Our results demonstrate how LolCDE can extrude lipoproteins of diverse sequence and structure and reveal an important detail of a transport process fundamental to bacterial physiology.

Network based analysis of student self governance networks and predictive role in civic participation outcomes

Effects of wireless local area network exposure on testicular morphology and VEGF levels

Abstract This study investigated the effects of exposure to a 2.45 GHz electromagnetic field (EMF) on rat testicular tissue, focusing on histological alterations and the potential activation of the HIF1A-VEGF pathway. Twenty-four adult male albino Wistar rats were divided into a control group ( n  = 12) with no EMF exposure and an experimental group ( n  = 12) exposed to 2.45 GHz microwave radiation (3 V/m, SAR 0.00208 W/kg) for one hour daily over 60 days. Following the exposure period, testicular tissues were analyzed for histopathological changes, VEGFA and HIF1A gene expression levels, and VEGFA protein concentration. In rat testicular tissue, while VEGFA gene expression ( p  < 0.05) and protein levels ( p  < 0.001) increased in the EMF group, no significant change was detected in HIF1A gene expression levels in the EMF group compared to the control group. Histological examination revealed a significant reduction in seminiferous tubule diameter ( p  < 0.001), epithelial thickness ( p  < 0.001), tubule density ( p  < 0.001), and Sertoli cell count ( p  = 0.0098) in the EMF-exposed group. It may be concluded that EMF at 2.45 GHz increases HIF1A-independent VEGF levels, and EMF exposure may cause testicular damage by increasing VEGF gene expression levels.

Optimization based load forecasting and demand management in smart building microgrids with Greylag Goose and Bi level graph models

The mediating and moderating effects of learning engagement and physical exercise on the mobile phone addiction and academic burnout

Integrated transcriptome analysis of jejunum and liver to identify key genes and pathways associated with body weight in chickens

Abstract This study investigates the transcriptomic variations in the jejunum and liver of Golden Montazah (GM) chickens to better understand the biological mechanisms influencing poultry growth and production. Given the vital role of poultry in fulfilling global protein demands, especially with the rising consumer preference for chicken, it is essential to explore these underlying genetic and molecular factors that drive growth. From a larger cohort of 480 GM chickens, the top 10 males in both the high-weight (HW) and low-weight (LW) groups were selected for RNA sequencing. Tissues from their jejunum and liver were collected for transcriptomic analysis. The results revealed 38 up- and 36 down-regulated genes in the jejunum, while the liver exhibited 109 up- and 74 down-regulated genes. Among these, notable differentially expressed genes (DEGs) such as CHST14 and LOC429682 in the jejunum, alongside RBP2 and STC2 in the liver, appeared to be integral to growth regulation, immune response, and metabolic processes. Functional enrichment analyses using GO and KEGG pathways highlighted processes like cytokine-cytokine receptor interactions in the jejunum and steroid biosynthesis in the liver. Additionally, protein–protein interaction networks identified key hub genes essential for various biological functions. Overall, our findings emphasize the distinct gene expressions profiles associated with body weight in the jejunum and liver, providing valuable insights for genetic improvement in poultry breeding. Understanding these molecular mechanisms paves the way for targeted strategies to enhance growth performance in the poultry industry.