Search Results (378)

The regulation of calcium (Ca²⁺) homeostasis is a critical process in both plant and animal systems, involving complex interplay between various organelles and a diverse network of channels, pumps, and transporters. This review provides a concise overview of inter-organellar Ca²⁺ homeostasis, highlighting key regulators and mechanisms in plant and animal cells. We discuss the roles of key Ca²⁺ channels and transporters, including IP₃Rs, RyRs, TPCs, MCUs, TRPMLs, and P2XRs in animals, as well as their plant counterparts. Here, we explore recent innovations in structural biology and advanced microscopic techniques that have enhanced our understanding of these proteins’ structure, functions, and regulations. We examine the importance of membrane contact sites in facilitating Ca²⁺ transfer between organelles and the specific expression patterns of Ca²⁺ channels and transporters. Furthermore, we address the physiological implications of inter-organellar Ca²⁺ homeostasis and its relevance in various pathological conditions. For extended comparability, a brief excursus into bacterial intracellular Ca²⁺ homeostasis is also made. This meta-analysis aims to bridge the gap between plant and animal Ca²⁺ signaling research, identifying common themes and unique adaptations in these diverse biological systems. Full article

Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article

The ATP-binding cassette transporter ABCG2 plays a critical role in drug pharmacokinetics and multidrug resistance in cancer therapy. Two common nonsynonymous polymorphisms, rs2231137 (V12M) and rs2231142 (Q141K), are associated with altered ABCG2 function, drug response, and disease susceptibility. However, the functional impact of their haplotype remains poorly understood. In this study, we established Flp-In™-293 cell lines stably expressing ABCG2 (12M/141K) and systematically compared their expression and drug resistance profiles with those of cells expressing ABCG2 (12V/141Q) (WT), ABCG2 (12M/141Q), and ABCG2 (12V/141K). The mRNA of ABCG2 (12M/141K) was expressed at levels comparable to those of the other variants in cells. Cells expressing ABCG2 (12M/141K) exhibited significantly higher resistance to mitoxantrone (10.7-fold) and SN-38 (5.99-fold) than the mock cells. While ABCG2 (12M/141Q) conferred the highest resistance among the tested variants, the ABCG2 (12M/141K) haplotype showed a trend toward higher mitoxantrone resistance than the ABCG2 (12V/141Q) (WT) (p = 0.066), suggesting a haplotype-specific effect. These findings provide novel insights into haplotype-based modulation of ABCG2 function and its contribution to multidrug resistance, with potential implications for optimizing personalized chemotherapy strategies. Full article

This study was conducted using Geographic Information Systems (GISs), Remote Sensing (RS) techniques, and the SLEUTH model based on Cellular Automata (CA) to analyze the spatial and temporal dynamics of urban growth in Sanliurfa Province and to create future projections. The model in question simulates urban sprawl by using Slope, Land Use/Land Cover (LULC), Excluded Areas, urban areas, transportation, and hill shade layers as inputs. In addition, disaster risk areas and public policies that will affect the urbanization of the city were used as input layers. In the study, the spatial pattern of urbanization in Sanliurfa was determined by using Landsat satellite images of six different periods covering the years 1985–2025. The Analytical Hierarchy Process (AHP) method was applied within the scope of Multi-Criteria Decision Analysis (MCDA). Weighting was made for each parameter. Spatial analysis was performed by combining these values with data in raster format. The results show that the SLEUTH model successfully reflects past growth trends when calibrated at different spatial resolutions and can provide reliable predictions for the future. Thus, the proposed model can be used as an effective decision support tool in the evaluation of alternative urbanization scenarios in urban planning. The findings contribute to the sustainability of land management policies. Full article

We inspected a sector of the Apennines (central–southern Italy) in geographic and structural continuity with the Quaternary-active extensional belt but where clear geomorphic and seismological signatures of normal faulting are unexpectedly missing. The evidence of active tectonics in this area, between Abruzzo and Molise, does not align with geodetic deformation data and the seismotectonic setting of the central Apennines. To investigate the apparent disconnection between active deformation and the absence of surface faulting in a sector where high lithologic erodibility and landslide susceptibility may hide its structural evidence, we combined multi-scale and multi-source data analyses encompassing morphometric analysis and remote sensing techniques. We utilised high-resolution topographic data to analyse the topographic pattern and investigate potential imbalances between tectonics and erosion. Additionally, we employed aerial-photo interpretation to examine the spatial distribution of morphological features and slope instabilities which are often linked to active faulting. To discern potential biases arising from non-tectonic (slope-related) signals, we analysed InSAR data in key sectors across the study area, including carbonate ridges and foredeep-derived Molise Units for comparison. The topographic analysis highlighted topographic disequilibrium conditions across the study area, and aerial-image interpretation revealed morphologic features offset by structural lineaments. The interferometric analysis confirmed a significant role of gravitational movements in denudating some fault planes while highlighting a clustered spatial pattern of hillslope instabilities. In this context, these instabilities can be considered a proxy for the control exerted by tectonic structures. All findings converge on the identification of an ~20 km long corridor, the Castel di Sangro–Rionero Sannitico alignment (CaS-RS), which exhibits varied evidence of deformation attributable to active normal faulting. The latter manifests through subtle and diffuse deformation controlled by a thick tectonic nappe made up of poorly cohesive lithologies. Overall, our findings suggest that the CaS-RS bridges the structural gap between the Mt Porrara–Mt Pizzalto–Mt Rotella and North Matese fault systems, potentially accounting for some of the deformation recorded in the sector. Our approach contributes to bridging the information gap in this complex sector of the Apennines, offering original insights for future investigations and seismic hazard assessment in the region. Full article

Many academic introductions suffer from inconsistencies and a lack of comprehensive structure, often failing to effectively outline the core elements of the research. This not only impacts the clarity and readability of the article but also hinders the communication of its significance and objectives to the intended audience. This study aims to automate the CaRS (Creating a Research Space) model using machine learning and natural language processing techniques. We conducted a series of experiments using a custom-developed corpus of 50 biology research article introductions, annotated with rhetorical moves and steps. The dataset was used to evaluate the performance of four classification algorithms: Prototypical Network (PN), Support Vector Machines (SVM), Naïve Bayes (NB), and Random Forest (RF); in combination with six embedding models: Word2Vec, GloVe, BERT, GPT-2, Llama-3.2-3B, and TEv3-small. Multiple experiments were carried out to assess performance at both the move and step levels using 5-fold cross-validation. Evaluation metrics included accuracy and weighted F1-score, with comprehensive results provided. Results show that the SVM classifier, when paired with Llama-3.2-3B embeddings, consistently achieved the highest performance across multiple tasks when trained on preprocessed dataset, with 79% accuracy and weighted F1-score on rhetorical moves and strong results on M2 steps (75% accuracy and weighted F1-score). While other combinations showed promise, particularly NB and RF with newer embeddings, none matched the consistency of the SVM–Llama pairing. Compared to existing benchmarks, our model achieves similar or better performance; however, direct comparison is limited due to differences in datasets and experimental setups. Despite the unavailability of the benchmark dataset, our findings indicate that SVM is an effective choice for rhetorical classification, even in few-shot learning scenarios. Full article

Background/Objectives: Ellagic acid (EA) is a polyphenol found in several fruits and vegetables, including pomegranate, nuts and berries. It exhibits significant health benefits, mainly cardio- and vaso-protective; indeed, EA protects the myocardium against infarction and inhibits cardiac fibrosis. These beneficial effects may be, at least in part, promoted by calcium release from and uptake by the sarcoplasmic reticulum, which are crucial events for cardiac relaxation and contraction. Regardless, the exact mechanism is currently unclear. Methods: A deeper investigation of the role of EA in cardiac contractility and the underlying mechanism has been carried out by using an ex vivo model of isolated and perfused rat heart. Results and Discussion: EA perfusion (100 nM–10 µM) did not influence the coronary flow (CF), suggesting the absence of a vasoactivity, but significantly increased contractility parameters (LVDP and dP/dt). Interestingly, a more marked effect of EA on LVDP and dP/dt values was observed when it was perfused in the presence of AngII. Cyclopiazonic acid (CA) and red ruthenium (RR), specific antagonists of SERCA and RyRs, respectively, were used to explore the contribution of EA when the intracellular calcium handling was altered. In the presence of CA, EA, perfused at increasing concentrations, showed a very modest positive inotropism (significant only at 1 µM). Instead, RR, which significantly compromised all functional parameters, completely masked the effects of EA; furthermore, a marked reduction in CF and a dramatic impact on the positive inotropism occurred. Conclusions: These results demonstrate the positive inotropism of EA on isolated and perfused hearts and suggest that the RyRs may be a main target through which EA plays its effects, since inhibition with RR almost completely blocks the positive inotropism. Full article

Background/Objectives: Endplate lesions of the lumbar spine are often asymptomatic and frequently observed incidentally by radiological assessment. Variants in the vitamin D receptor gene (VDR) and an increase in some biochemical markers related to the osteo-cartilaginous metabolism were found in patients with endplate lesions. The aim of this study was to identify biochemical and genetic markers putatively associated with the presence of endplate lesions of the lumbar spine. Methods: Quantification of circulating bone remodeling proteins was obtained from 10 patients with endplate lesions and compared with age- and sex-matched controls. Whole exome sequencing (WES) was performed on patient genomic DNA using the Novaseq 6000 platform (Illumina, San Diego, CA, USA), obtaining a median read depth of 117×–200×, with ≥98% of regions covering at least 20×. The sequencing product was aligned to the reference genome (GRCh38.p13-hg38) and analyzed with Geneyx software. Results: We observed modifications in the levels of circulating proteins involved in bone remodeling and angiogenesis. We identified variants of interest in aggrecan (ACAN), bone morphogenetic protein 4 (BMP4), cytochrome P450 family 3 subfamily A member 4 (CYP3A4), GLI family zinc finger 2 (GLI2), heparan sulfate proteoglycan 2 (HSPG2), and mesoderm posterior bHLH transcription factor 2 (MESP2). VDR polymorphism (rs2228570) was present in nine patients, with the homozygotic ones having more severe endplate lesions and higher levels of the analyzed circulating markers in comparison with heterozygotic patients. Conclusions: These data represent interesting evidence of genetic variants, particularly in VDR, and altered levels of circulating markers of bone remodeling associated with endplate lesions, which should be confirmed in a larger population. The hypothesis suggested by our results is that the endplate lesions could be the consequence of an altered ossification mechanism at the vertebral level. Full article

The essential micronutrient zinc is known to inhibit gastric acid secretion (GAS), where its homeostasis is strictly regulated. We hypothesized that the gastric bitter taste receptors, TAS2Rs, regulate the following: (i) zinc-modulated proton secretory activity (PSA) as a key mechanism of GAS and (ii) zinc homeostasis in immortalized parietal cells. To confirm this hypothesis, human gastric tumor cells (HGT-1) were exposed to 100–1000 µM of zinc salts for 30 min in order to quantitate their TAS2R-dependent PSA and intracellular zinc concentration using a fluorescence-based pH sensor and ICP-MS, respectively. Thereby, we identified TAS2R43 as a key player in parietal cell PSA and zinc homeostasis, with both conclusions being verified by a CRISPR-Cas9 knockout approach. Moreover, by regulating the zinc importer protein ZIP14, TAS2R43 proved to perform a protective role against excessive zinc accumulation in immortalized parietal cells. Full article

Background: Heart failure (HF) is associated with an increased risk of cognitive impairment and hippocampal dysfunction, yet the underlying molecular mechanisms remain poorly understood. This study aims to investigate the role of microRNA (miRNA) networks in hippocampus-dependent memory recovery in a mouse model of HF. Methods: CaMKIIδC transgenic (TG) mice, a model for HF, were used to assess hippocampal function at 3 and 6 months of age. Memory performance was evaluated using hippocampus-dependent behavioral tasks. Small RNA sequencing was performed to analyze hippocampal miRNA expression profiles across both time points. Bioinformatic analyses identified miRNAs that potentially regulate genes previously implicated in HF-induced cognitive impairment. Results: We have previously shown that at 3 months of age, CaMKIIδC TG mice exhibited significant memory deficits associated with dysregulated hippocampal gene expression. In this study, we showed that these impairments, memory impairment and hippocampal gene expression, were no longer detectable at 6 months, despite persistent cardiac dysfunction. However, small RNA sequencing revealed a dynamic shift in hippocampal miRNA expression, identifying 27 miRNAs as “compensatory miRs” that targeted 73% of the transcripts dysregulated at 3 months but reinstated by 6 months. Notably, miR-181a-5p emerged as a central regulatory hub, with its downregulation coinciding with restored memory function. Conclusions: These findings suggest that miRNA networks contribute to the restoration of hippocampal function in HF despite continued cardiac pathology and provide an important compensatory mechanism towards memory impairment. A better understanding of these compensatory miRNA mechanisms may provide novel therapeutic targets for managing HF-related cognitive dysfunction. Full article

Objectives: A randomized, double-blind, placebo-controlled intervention study aimed to evaluate whether hawthorn fruit (HF) supplementation can influence facial skin phenotypes and leukocyte telomere length (TL) and whether these effects differ by genetic polymorphisms related to TL. Participants/Methods: Among 41 male and female adults aged 25–75 years who participated in the study, 36 completed initial and follow-up examinations over 6 months. The HF supplementation group (n = 17) was instructed to take a powdered HF supplement (900 mg/day), while controls (n = 19) were to take a cornstarch placebo (900 mg/day). Facial skin phenotypes, including pigmentation, pores, hydration, wrinkles, and elasticity, were measured before and after the intervention, and changes in these phenotype scores were calculated. Sequencing of telomerase reverse transcriptase (TERT) polymorphisms, such as rs7705526 (C>A) and rs2853669 (A>G), was conducted. Results: The HF supplementation group exhibited significantly improved hydration scores compared to the control group; the mean changes (follow-up measure—baseline measure) [standard deviation] in hydration scores over 6 months were 1.71 [8.18] and −3.00 [8.42] for the supplementation group and control group, respectively (p < 0.05) (Cohen’s d = 0.57). However, changes in other phenotypes and leukocyte TL were similar between groups. The genotype-specific analysis revealed that the improvement of hydration state was most noticeable among carriers with the CC genotype of rs7705526 (p < 0.05) (Cohen’s d = 1.50) and that the HF supplementation group exhibited reduced wrinkle scores while the control group showed increased scores among carriers of the AA genotype of rs2853669 (p < 0.05) (Cohen’s d = 1.40). In correlation analysis for all participants, hydration scores were positively correlated with leukocyte TL (Spearman correlation coefficient: 0.36; p < 0.05). Conclusions: These findings suggest that HF consumption may have potential anti-skin-aging effects. Future studies may need to elucidate the biological mechanisms underlying these effects. Full article

Background: Cognitive decline during aging is a factor that inevitably affects everyone. In some older adults, cognitive function declines more rapidly to mild cognitive impairment (MCI) and eventually dementia. Our work aimed to determine the associations between suicide-related single-nucleotide genetic polymorphisms (SNPs) and cognitive function dynamics in people over 65 years old over a three-year follow-up. Suicide-related SNPs have already shown an association with dementia in our previous study. Methods: The present study included 66 participants over 65 without subjective cognitive decline. Cognitive impairment was assessed at two follow-up points (at the start of the study in 2020–2021 and 3 years later) using the Montreal Cognitive Assessment (MoCA). Patients were also genotyped for 16 SNPs. Results: We found associations between rs10898553 and rs165774 and MoCA 3-year dynamics, with a certain genetic variant related to more significant progression. For rs7982251, associations with scale scores were found, but no effect on its dynamics. Conclusions: The research focused on analyzing genetic factors of cognitive decline in healthy older adults without subjective cognitive decline. Identifying these markers can help predict the development of pathology at early stages and start timely treatment. Full article

Background/Objectives: Most survivors of out-of-hospital cardiac arrest (OHCA) may suffer from cognitive, mental difficulties, and fatigue, which negatively impact their quality of life, despite a good physical recovery. However, no definitive data are available on this topic, so this study aims to assess the feasibility and acceptability of a centralized, sub-regional screening system for OHCA survivors in Italy and the prevalence of these disorders. Methods: OHCA survivors discharged with good neurological outcomes (Cerebral Performance Category (CPC) ≤ 2 and modified Ranking Scale (mRS) ≤ 3) from hospitals in the “Lombardia CARe” registry will be evaluated by a clinical psychologist using the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), EQ-5D-5L for quality of life, and the Impact of Event Scale-Revised (IES-R) at pre-discharge or within 15 days and then at 1, 3, 6, and 12 months. Patients with clinical issues will be referred for psychological support or to a community rehabilitation program. Feasibility will be defined as a recruitment rate ≥ 80% and acceptability as a retention rate ≥ 50% over 12 months. Results: Based on historical data from the Lombardia CARe, an estimated 350 eligible survivors are expected, which will allow estimation of a prevalence ranging between 20% and 30% with 5% precision and 95% confidence. Conclusions: This study will be the first in Italy to evaluate the feasibility and acceptability of a centralized, sub-regional system for pre-/post-discharge evaluation of cognitive impairment, mental health, and quality of life in a large cohort of OHCA survivors, documenting the prevalence of these disorders. Full article

The search for new heterocyclic compounds with biological potential is one of the current challenges in modern chemistry. Therefore, the comprehensive study of (3 + 2) cycloaddition (32CA) reactions between a series of aryl-substituted nitrile N-oxides (NOs) and (E)-3,3,3-tribromo-1-nitroprop-1-ene (TBNP) is carried out. According to the experimental research, in all tested 32CAs, the proper (4RS,5RS)-3-aryl-4-nitro-5-tribromomethyl-2-isoxazolines are obtained as only one reaction product. In turn, the quantum–chemical MEDT study shows that the creation of heterocycles occur via the polar attack of zwitterionic moderate-nucleophilic NOs to strong electrophilic TBNP. The reactions are realized according to a two-stage, one-step asynchronous mechanism, in which the formation of the O-C(CBr₃) bond takes place once the C-C(NO₂) bond is already formed. What is more, the computational analysis confirmed the experimental results. At the end, the obtained 2-isoxazolines were docked to three proteins: gelatinase B, cyclooxygenase COX-1, and Caspase-7. We hope that the presented study will be helpful for searching for the future direction of application for this class of organic compounds. Full article

Ryanodine receptors (RyRs) are large intracellular Ca²⁺ release channels primarily found in muscle and nerve cells and also present at low levels in pancreatic islet endocrine cells. This review examines the role of RyRs in islet cell function, focusing on calcium signaling and hormone secretion, while addressing the ongoing debate regarding their significance due to their limited expression. We explore conflicting experimental results and their potential causes, synthesizing current knowledge on RyR isoforms in islet cells, particularly in beta and delta cells. The review discusses how RyR-mediated calcium-induced calcium release enhances, rather than drives, glucose-stimulated insulin secretion. We examine the phosphorylation-dependent regulation of beta-cell RyRs, the concept of “leaky ryanodine receptors”, and the roles of RyRs in endoplasmic reticulum stress, apoptosis, store-operated calcium entry, and beta-cell electrical activity. The relationship between RyR dysfunction and the development of impaired insulin secretion in diabetes is assessed, noting their limited role in human diabetes pathogenesis given the disease’s polygenic nature. We highlight the established role of RyR-mediated CICR in the mechanism of action of common type 2 diabetes treatments, such as glucagon-like peptide-1, which enhances insulin secretion. By integrating findings from electrophysiological, molecular, and clinical studies, this review provides a balanced perspective on RyRs in islet cell physiology and pathology, emphasizing their significance in both normal insulin secretion and current diabetes therapies. Full article