Bioscience Reports最新文献

{"title":"Bacterial heteroresistance mechanisms, dynamics, and emerging diagnostic approaches.","authors":"Sophie Brameyer","doi":"10.1042/BSR20260035","DOIUrl":"10.1042/BSR20260035","url":null,"abstract":"<p><p>Antibiotic heteroresistance is a form of within-isolate susceptibility heterogeneity in which an apparently susceptible bacterial population contains rare subpopulations capable of growth at substantially higher antibiotic concentrations. It is commonly defined as resistant minorities occurring at frequencies ≥10-7 and growing at concentrations at least eight-fold above those that inhibit the dominant population, as demonstrated by population analysis profiling or related assays. This phenomenon has been described in diverse Gram-negative and Gram-positive pathogens and across multiple drug classes and is frequently characterized by instability, with resistant subpopulations expanding under treatment and contracting once drug pressure is relieved. This dynamic behavior contributes to systematic under-detection by routine antimicrobial susceptibility testing, which is optimized for population-average endpoints and may miss clinically relevant resistant tails, helping explain treatment failure despite 'susceptible' results. Mechanistically, heteroresistance spans a continuum from genotypic processes, including gene amplification, plasmid copy-number variation, transposition, and point mutations, to phenotypic mechanisms driven by reversible regulatory and physiological states such as transcriptional reprogramming, stochastic expression variability, and intergenerational phenotypic memory. These mechanisms can coexist and shift under antibiotic selection, supporting the view that heteroresistance may act as an evolutionary intermediate linking susceptibility and stable resistance. Recent advances in single-cell phenotyping, copy-number-aware genomics, transcriptomics, pharmacodynamic and population modeling, and machine-learning-assisted diagnostics offer new opportunities to detect and interpret susceptibility distributions. Integrating these approaches into clinical microbiology and stewardship will be essential to improve risk stratification, guide therapy, and predict resistance evolution.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":"46 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13333382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of correlations between serum and urinary vitamin D metabolites using LC-MS/MS.","authors":"Shixing Wu, Nau Ishimine, Riho Shimizu, Harue Suzuki, Yoko Usami, Taichi Shimazaki, Koji Takahashi, Masaki Takiwaki, Kentaro Abe, Sota Yoshimura, Ryota Sakamoto, Rino Tsutsumi, Kazuo Nagasawa","doi":"10.1042/BSR20260223","DOIUrl":"10.1042/BSR20260223","url":null,"abstract":"<p><p>Vitamin D (VD) is involved in bone health, immunity, cardiovascular function, and cancer prevention. Recent studies suggested the potential of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] and the VD metabolite ratio (VMR = [24,25(OH)2D3/25(OH)D] × 100) as indicators of VD levels. An assessment of VD levels relies on serum measurements. The present study investigated the utility of urinary VD metabolites as a non-invasive alternative and their potential as surrogate markers for serum VD metabolites. We used residual serum and urine from the annual health check-ups of employees at Shinshu University Hospital, Japan (n = 506). Urine samples were mixed with β-glucuronidase. Serum and urine were processed via solid-phase extraction, followed by DAP-PA derivatization. LC-MS/MS was used to quantify serum and urinary 25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, and 24,25(OH)2D3 and urinary 23,25(OH)2D3. Serum whole parathyroid hormone (PTH) levels were measured, and urinary VD metabolites were adjusted for urinary creatinine. We also investigated whether serum and urinary VD metabolites correlated with PTH. The results showed that urinary 24,25(OH)2D3 and 23,25(OH)2D3 strongly correlated with serum 25(OH)D [25(OH)D3 + 25(OH)D2] (all ρ >0.7, P<0.001). Urinary 24,25(OH)2D3, 23,25(OH)2D3, and VMR had stronger inverse correlations with whole PTH (ρ = -0.297, -0.274, -0.308, respectively; all P<0.001), whereas serum 25(OH)D showed a weak correlation (ρ = -0.174, P<0.001). In conclusion, urinary VD metabolites, particularly 24,25(OH)2D3, 23,25(OH)2D3 and the VMR, correlated with serum values and PTH, suggesting their potential as non-invasive markers for the VD status.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal serum from 'high-stress' pregnancies demonstrates bioactivity capable of attenuating neurite growth through a TNFα-dependent pathway in SH-SY5Y cells.","authors":"Clara Deady, Lars Wilmes, Fergus P McCarthy, Ali S Khashan, Gerard Clarke, James Keane, Cathal McCarthy, Gerard W O'Keeffe, Siobhain M O'Mahony","doi":"10.1042/BSR20260125","DOIUrl":"10.1042/BSR20260125","url":null,"abstract":"<p><p>Prenatal stress is associated with deleterious neurodevelopmental consequences in affected offspring. Prenatal stress via exposure to high physiological levels of inflammation in utero may induce an inflammatory state in the fetal brain. However, inflammation is not only associated with disease-states but also can be seen in a healthy pregnancy. There is limited research examining the potential that exposure to biological mediators of stress may have on neurodevelopment. We aim to determine whether certain circulating biological markers in maternal serum influence neurite growth in partially differentiated SH-SY5Y cells as a potential mechanism impacting neurodevelopment. Blood was collected at 20-weeks' gestation as part of the SCOPE pregnancy cohort study. These factors, including pro-inflammatory cytokines, markers of tryptophan metabolism, and gut permeability that were previously analysed, were used to stratify women into low (n = 10) and high (n = 10) biological stress groups. Exposure to the serum categorised as 'high-stress' significantly reduced neurite length in comparison to serum categorised as 'low-stress', with tumour necrosis factor-α playing a substantial role in mediating this reduction. The 'high-stress' serum was subsequently found to increase the levels of phospho-Ser536-p65. Phosphorylation of p65 Ser536 has previously been shown to switch NF-κΒ from promoting neuronal growth, to inhibiting it. The reduction in neurite length seen following exposure to the 'high-stress' serum was prevented when NF-κΒ p65 was knocked down. The present study emphasises the potential negative impact that circulating factors may have on neuronal growth, and the mechanism behind it.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13279720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148013356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An open-source code to analyze mitochondrial intracellular distribution from fluorescence microscopy images.","authors":"Giovanna C Cavalcante, Alicia J Kowaltowski","doi":"10.1042/BSR20260140","DOIUrl":"10.1042/BSR20260140","url":null,"abstract":"<p><p>Mitochondria have a plethora of roles in cells, many of which are related to dynamic changes in their size, shape, and intracellular location. Mitochondrial morphology is commonly assessed by microscopy with targeted fluorescent probes. However, tools to easily estimate mitochondrial localization within a cell are still lacking. A code was designed to estimate per-cell mitochondrial radial localization (perinuclear or peripheral) from fluorescence microscopy files in a variety of formats and using different mitochondrial markers (https://github.com/cavalcantegc/mito_localization.git). Three case studies with different cell types and stainings demonstrate that mitochondrial localization can be easily extracted and plotted with this code.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13329321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative role of orexigenic peptides in neuroprotection and neurodegenerative disease modulation.","authors":"Zuzana Sopko, Andrea Pačesová, Blanka Železná, Lenka Maletínská","doi":"10.1042/BSR20250362","DOIUrl":"10.1042/BSR20250362","url":null,"abstract":"<p><p>The neuroprotective properties of several anorexigenic peptides, including leptin and glucagon-like peptide-1, are well established across models of neurodegenerative diseases. However, less is known about the role of orexigenic neuropeptides-including neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, orexins, galanin, and peripherally released hormone ghrelin-that are best known for their role in energy balance and stimulation of food intake. Growing evidence highlights their broader neuroprotective properties across preclinical models of Alzheimer's disease (AD) and Parkinson's disease (PD). In AD, these peptides reduce hallmark pathologies such as amyloid burden, tau phosphorylation, oxidative stress, and neuroinflammation, while enhancing synaptogenesis, neurogenesis, and cognitive function. In PD models, ghrelin protects nigrostriatal dopaminergic neurons by restoring autophagic flux, suppressing endoplasmic reticulum stress-mediated apoptosis, and reducing microglial activation, whereas orexin A and B preserve tyrosine hydroxylase expression, promote neuronal excitability, and improve motor and cognitive outcomes. Taken together, these findings position orexigenic peptides as promising modulators of neurodegeneration and highlight their potential as therapeutic targets in AD and PD.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural characterization of the human CC2D1A fragment associated with non-syndromic intellectual disability (NSID).","authors":"Yi-Hung Yeh, Min-Guan Lin, Xing-Han Sun, Yo-You Shen, Pin Ling, Chwan-Deng Hsiao","doi":"10.1042/BSR20253955","DOIUrl":"10.1042/BSR20253955","url":null,"abstract":"<p><p>CC2D1A is a multidomain scaffold protein implicated in transcriptional regulation and autosomal recessive non-syndromic intellectual disability (NSID), yet its molecular mechanism is still poorly understood due to a lack of structural information. Here, we present the crystal structure of the human CC2D1A491-810 fragment, encompassing the fourth DM14 domain, a coiled-coil region, and a C-terminal C2 domain. These elements form a compact, integrated architecture, with the C2 domain mediating symmetric dimerization through conserved electrostatic interactions. In addition, a unique antiparallel β1-β10 sheet connects the coiled-coil and C2 domains, stabilizing the tertiary structure. Fluorescence polarization assays reveal micromolar DNA-binding affinity, likely mediated by the basic surface of the DM14 domain. Comparison with the Drosophila homolog Lgd highlights conserved topology with added structural features, offering insights into CC2D1A's vertebrate-specific functions and NSID-related mutations.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quorum sensing in streptococci and its peptide-mediated modulation.","authors":"Clay P Renshaw, Keely M Rodriguez, Yftah Tal-Gan","doi":"10.1042/BSR20260162","DOIUrl":"10.1042/BSR20260162","url":null,"abstract":"<p><p>Quorum sensing (QS) is a density-dependent communication process that enables bacteria to coordinate group behaviors, including competence, biofilm formation, bacteriocin production, and virulence. Early observations of genetic transformation in Streptococcus pneumoniae and density-dependent bioluminescence in marine bacteria laid the foundation for the eventual unification of these phenomena under the QS framework. In streptococci, QS is mediated primarily by secreted peptide pheromones that are processed, exported, and sensed through either membrane-associated two-component signal transduction systems or intracellular RRNPP-family regulators. These signaling pathways control tightly regulated and often transient physiological states, most notably competence, through interconnected regulatory circuits such as ComABCDE and ComRS. Increasing evidence indicates that, in some streptococci, these systems do not operate in isolation but instead form integrated and, in some cases, noncanonical networks that respond to environmental and metabolic cues. The chemical accessibility of peptide signals has enabled detailed structure-activity relationship studies, revealing key determinants of receptor activation and specificity. In particular, systematic modification of competence-stimulating peptides (CSPs) and sigX-inducing peptides (XIPs) has led to the identification of residues critical for activity and enabled the development of peptide analogs that act as agonists or competitive antagonists of QS pathways. These studies have demonstrated that synthetic peptides can modulate QS-regulated phenotypes, including competence, and in some cases attenuate infection in vivo. Collectively, these advances establish streptococcal QS as a chemically tractable system and highlight peptide-based modulation as a strategy for probing and influencing bacterial communication.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147961976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synaptic vesicle architecture modulates α-synuclein conformation and pathogenic transitions in Parkinson's disease.","authors":"Priyatosh Ranjan","doi":"10.1042/BSR20260364","DOIUrl":"10.1042/BSR20260364","url":null,"abstract":"<p><p>α-Synuclein (α-Syn) is a presynaptic protein implicated in the regulation of synaptic vesicle (SV) organization, soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, and neurotransmitter release through reversible interactions with curved lipid membranes. Increasing evidence indicates that α-Syn functions as a curvature-sensitive membrane adaptor whose N-terminal amphipathic helices selectively recognize the nanoscale architecture of SVs, thereby promoting vesicle tethering, clustering, and membrane fusion dynamics essential for synaptic transmission. Recent structural and biophysical studies demonstrate that SVs act as catalytic platforms in which membrane curvature, lipid packing defects, molecular crowding, and local physicochemical conditions determine whether α-Syn remains membrane-bound or transitions into pathogenic assemblies. Post-translational modifications, including phosphorylation, nitration, acetylation, and ubiquitination, dynamically regulate α-Syn conformation, membrane engagement, proteostatic turnover, aggregation propensity, and intracellular localization by modulating its structural plasticity and interactions with synaptic membranes. These modifications can alter electrostatic interactions, destabilize amphipathic helices, and shift α-Syn from functional membrane-associated states toward soluble oligomeric and amyloidogenic species. Aging further exacerbates these transitions through alterations in SV lipid composition, membrane fluidity, oxidative membrane damage, impaired proteostasis, and defective vesicle trafficking, thereby destabilizing α-Syn-membrane interactions. The present review discusses how membrane remodeling, vesicle lipid composition, post-translational modifications, protein conformational dynamics, and aging collectively regulate α-Syn phase behavior, membrane binding, and pathological aggregation at the presynaptic terminal. Integrating structural biology, lipidomics, proteomics, and live-cell imaging approaches will identify mechanistic transitions linking physiological membrane engagement to neurodegenerative synucleinopathies and reveal therapeutic opportunities for preventing synaptic dysfunction, toxic condensate formation, and neurodegeneration in Parkinson's disease and related disorders associated with pathological α-Syn aggregation.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of peroxisomal membrane proteins PEX13 and PEX14 disrupts fatty acid oxidation and drives lipid imbalance.","authors":"Navia Vinoy, Gary Huang, Daniel Wallace, V Nathan Subramaniam","doi":"10.1042/BSR20260048","DOIUrl":"10.1042/BSR20260048","url":null,"abstract":"<p><p>Peroxisomal disorders arise from severe peroxisome dysfunction and are frequently linked to liver pathology. Metabolic dysfunction-associated steatotic liver disease, which affects up to 38% of adults worldwide, has driven extensive efforts to identify genes that contribute to its development. In the present study, we investigated the role of two peroxisomal membrane proteins, PEX13 and PEX14, by performing single and dual small interfering RNA-mediated knockdowns in a liver cell line, HUH-7. Steatosis was induced using free fatty acids, and changes in lipid-metabolism gene expression were assessed by quantitative real-time polymerase chain reaction. Knockdown efficiency reached 90% for both genes, and Oil-Red-O staining confirmed successful induction of steatosis. Both single and combined knockdown of PEX13 and PEX14 altered the expression of genes involved in lipid sensing, fatty acid uptake, synthesis, and oxidation. These findings suggest that peroxisomal dysfunction disrupts hepatic metabolic pathways, promoting increased fatty acid uptake and synthesis. Such alterations may contribute to the liver dysfunction observed in patients with peroxisome biogenesis disorders, highlighting the importance of peroxisomal integrity in maintaining lipid homeostasis.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147484301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in GPCR signalling in appetite regulation.","authors":"Holly R Brittain, Caroline M Gorvin","doi":"10.1042/BSR20250120","DOIUrl":"10.1042/BSR20250120","url":null,"abstract":"<p><p>The balance between energy intake and energy expenditure determines whether we gain weight, and appetite regulatory circuits in the brain have a critical role in this energy balance. G protein-coupled receptors (GPCRs), the largest family of transmembrane proteins, have an important role in appetite regulation. They function in the leptin-melanocortin pathway of the hypothalamic arcuate nucleus, which plays a central role in the regulation of energy balance and appetite, integrating peripheral metabolic cues with central neural circuits to promote satiety. GPCRs also mediate the function of the orexigenic hormone ghrelin, the suppression of appetite and hedonic reward circuitry by serotonin, and the incretin receptors are targets for several drugs that currently dominate the weight loss market. Human genetic studies and animal models of obesity have revealed important physiological roles in appetite regulation and weight gain for several additional GPCRs, some of which are still classified as orphan receptors. In this review, we discuss twelve GPCRs with roles in appetite regulation, focussing on developments within the last 5-10 years where possible. We discuss evidence from animal models, proposed mechanisms of action, and relevance to human disease for each of these receptors. Finally, we evaluated, where applicable, the current position and future prospects for therapeutically targeting these receptors for use in treatments for weight loss or gain.</p>","PeriodicalId":8926,"journal":{"name":"Bioscience Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}