Browse Articles
Discover research articles across all indexed journals
Designing an oxidase toolbox for site-directed oxidation of taxanes
Research on changes in psychological, physical fatigue and emotional states in the National Youth Orienteering Preparation Camp
Cryo-EM structure of renal AL amyloid fibrils from a patient with λ1 light chain amyloidosis
Abstract Systemic light-chain amyloidosis (AL) is characterized by the misfolding and aggregation of immunoglobulin light chains (LCs) into amyloid fibrils, leading to multiorgan deposition and dysfunction, with the kidneys being one of the most commonly involved organs. Here, we report high-resolution cryo-electron microscopy (cryo-EM) structures of AL amyloid fibrils from the kidney of a male patient with renal AL amyloidosis. Two distinct polymorphic fibril structures, polymorph A and polymorph B, were identified, both featuring ordered cores (Gln16-Ser95) with β-sheet-rich architectures stabilized by interchain hydrogen bonds and salt bridges. Notably, six mutations in the IGLV1-44*01 gene sequence, including Gln39His and Tyr37Phe, were identified within the fibril core. These mutations influence fibril stability and aggregation by altering intramolecular and intermolecular interactions, such as CH-π stacking and salt bridge formation. Comparative analysis with previously reported heart-derived IGLV1-44 fibrils reveals structural variations linked to light-chain sequence differences. Our findings provide critical insights into the molecular determinants of fibril assembly and organ tropism in AL amyloidosis.
CCL8 suppresses ovarian cancer progression via M1 macrophage polarization and NF-κB-mediated apoptosis
Enantioselective protein affinity selection mass spectrometry (E-ASMS)
In-silico identification, characterization and expression analysis of salt overly sensitive-2 (SOS2) gene family in Gossypium hirsutum L. against abiotic stresses
PhaseT3M: 3D imaging at 1.6 Å resolution via electron cryo-tomography with nonlinear phase retrieval
Development of a cost-effectiveness analysis model for Duchenne muscular dystrophy utilizing the national registry in Japan
TMEM65-dependent Ca2+ extrusion safeguards mitochondrial homeostasis
Rehandling-aware stowage planning for RoRo ships using exclusive subgraph modeling and affinity-based cargo ordering
Current protected areas provide limited benefits for European river biodiversity
Abstract Protected areas are a principal conservation tool for addressing biodiversity loss. Such protection is especially needed in freshwaters, given their greater biodiversity losses compared to terrestrial and marine ecosystems. However, broad-scale evaluations of protected area effectiveness for freshwater biodiversity are lacking. Here, we provide a continental-scale analysis of the relationship between protected areas and freshwater biodiversity using 1,754 river invertebrate community time series sampled between 1986 and 2022 across ten European countries. Protected areas primarily benefited poor-quality communities (indicative of higher human impacts) that were protected, or that gained protection, across a substantial proportion of their upstream catchment. Protection had little to no influence on moderate- and high-quality communities, although high-quality communities potentially provide less scope for effect. Our results reveal the overall limited effectiveness of current protected areas for freshwater biodiversity, likely because they are typically designed and managed to achieve terrestrial conservation goals. Broadly improving effectiveness for freshwater biodiversity requires catchment-scale management approaches involving larger and more continuous upstream protection, and efforts to address remaining stressors. These approaches would also benefit connected terrestrial and coastal ecosystems, thus generally helping bend the curve of global biodiversity loss.
The chain mediating effect of mindfulness and self-regulation in the relationship between parental warmth and adolescent study engagement
Vegetation biogeography is a main source of uncertainty in modelling the land carbon cycle
Molecular assessment of the HIV pol gene and use of computational vaccine design targeting Pakistani isolates
A Meta-Analysis of Social and Contextual Correlates of Migrant Adaptation to Living in Receiving Societies
Abstract International migration has been consistently rising in modern times, and understanding what factors are associated with the successful inclusion of migrants is urgent. This meta-analysis helps pinpoint such factors by identifying the most robust social and contextual correlates of successful migrant adaptation to living in the receiving societies. Here, we meta-analyze 5,066 effects from 1,114 primary studies among 571,260 first-generation migrants, international students, business expatriates, and refugees. We show that migrant adaptation is most strongly negatively associated with the presence of stressors, especially acculturative stressors and perceived discrimination, and positively with the availability of social resources, especially feelings of connectedness with the social context and not feeling lonely. The role of variables related to culture learning, namely exposure to social groups within the new culture, and the distance between the new culture and one’s heritage culture, was more limited. This pattern was found across the different migrant groups.
Modulation of peroxisome proliferator activated receptor genes and gamma glutamyl transferase in rats by high intensity interval training and livergol
Abstract Obesity is a global health concern affecting multiple organs and is influenced by genetics, diet, and physical activity. Peroxisome proliferator-activated receptor gamma (PPARγ) regulates lipid and glucose metabolism, while gamma-glutamyl transferase (GGT) is a marker of liver function.The combined effect of high-intensity interval training (HIIT) and livergol, a liver-protective supplement, on these markers in obesity remains unclear. The primary aim of this study was to specifically examine the effects of 8 weeks of HIIT and livergolsupplementation, administered individually and in combination, on the gene expression levels of PPARγ and the enzymatic activity of GGT in the liver and adipose tissues of obese male Wistar rats. In this experimental study, forty male Wistar rats (8 weeks old, weighing 246 ± 15 g) were fed a high-fat diet to induce obesity, then randomly divided into four groups ( n = 10): control, HIIT, livergol, and HIIT + livergol. The interventions lasted for 8 weeks. The study setting was laboratory-based. Adipose tissue and liver samples were collected one day after the last session in a fasting state and analyzed in the reference laboratory. The primary outcome measures were PPARγ gene expression (RT-PCR) in adipose tissues and GGT enzymatic activity (biochemical assay) in liver samples. Data were analyzed using Shapiro-Wilk, Levene, two-way ANOVA, and Bonferroni post hoc ( P ≤ 0.05) tests. Results are presented as mean ± standard deviation with 95% confidence interval (CI). Among 40 obese male Wistar rats, HIIT combined with Livergolsupplementation markedly improved metabolic health by substantially upregulating PPARγ expression in the HIIT and HIIT + Livergolgroups ( P < 0.05) while reducing GGT activity compared to controls (where GGT was significantly higher( P < 0.05). PPARγ expression increased by 317% in the HIIT group, 267% in the livergolgroup, and 435% in the HIIT + livergolgroup compared with controls. GGT activity decreased by 27.4%, 32.3%, and 23.9% in HIIT, livergol, and HIIT + livergolgroups, respectively, compared with the control group. Enhanced expression of PPARγ likely drives improved adipocyte differentiation, fatty acid oxidation, and insulin signaling in adipose and liver tissues, thereby attenuating dyslipidemia and hyperglycemia; these effects are amplified in the combined group. Simultaneously, the observed reductions in GGT activity indicate diminished hepatic oxidative stress and inflammation. Livergol’s silymarin content appears to potentiate this hepatoprotection by scavenging reactive oxygen species, and High-Intensity Interval Training (HIIT) emerges as a promising adjunctive strategy for obesity management.
Single-cell dynamics of genome-nucleolus interactions captured by nucleolar laser microdissection (NoLMseq)
Abstract Gene positioning in nuclear space is central to regulation, with repressive chromatin domains often contacting the nuclear lamina or nucleoli. The nucleolus undergoes structural changes in different cellular states, potentially altering genome organization. Yet, how nucleolar states influence 3D-genome architecture remains underexplored, largely due to the lack of methods able to map nucleolar-associated domains (NADs) in single cells and stressed nucleoli. We developed NoLMseq, a technique combining laser-capture microdissection and DNA sequencing to map NADs in single cells. NoLMseq uncovered unexplored features of chromosome organization around nucleoli, including NAD heterogeneity in mouse embryonic stem cells, yielding two major populations with distinct chromatin and developmental states. NADs predominantly contact nucleoli monoallelically, with contact frequency correlating with gene expression and chromatin states. Under nucleolar stress, NoLMseq revealed extensive chromosome reorganization, highlighting the importance of nucleolus integrity in genome organization. Thus, NoLMseq provides a critical tool to study 3D-genome responses to nucleolar states in health and disease.
Omega-3 fatty acids modulate acetamiprid and emamectin benzoate-induced testicular toxicity in rats by modulating Nrf2/NFkB pathway and apoptotic signaling
Abstract Pesticides are well-known harmful substances that cause oxidative stress and testicular dysfunction in both humans and animals, whereas omega-3 fatty acids (ω3FAs) have been demonstrated to possess antioxidant and anti-inflammatory properties. Thus, the primary focus of this investigation was the protective role of (ω3FAs) and their related molecular mechanism in testicular dysfunction induced by acetamiprid plus emamectin benzoate in rats. Rats were divided into four groups: control, omega-3 fatty acids (ω3FA; 300 mg/kg BW), insecticide mixture (Insec Mix; Acetamiprid (30 mg/kg BW) and emamectin benzoate (9 mg/kg BW)), and ω3FA + Insec Mix, respectively. ω3FA was taken orally an hour before insecticide treatment for three weeks daily. The results demonstrated that lipid peroxidation markers and lactate dehydrogenase activity were significantly elevated in rats intoxicated with pesticides; however, enzymatic antioxidants, aminotransferases, phosphatases, and reduced glutathione decreased. Furthermore, notable changes in testicular Bax, Cas-3, Bcl-2, P53, IL-1β, TNF-α, NFkB, Nrf2, hormones, sperm quality, testis structure, and Ki-67 protein expression were detected. Otherwise, ω3FA pre-treatment before insecticide intoxication substantially recovered most of the molecular and biochemical indicators and improved testicular cellular structure. Conclusively, ω3FA was highly effective in mitigating testicular toxicity conferred by acetamiprid and emamectin benzoate insecticides.