Search Results (1,836)

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article

Directed cell migration orchestrates embryonic development, wound repair, immune surveillance and malignant tumor invasion. Viscotaxis—directed cell migration along spatial gradients of extracellular fluid viscosity or matrix loss modulus—has emerged as a candidate mechanotaxis modality that may guide cells through heterogeneous viscoelastic tissues; however, its biological functions and molecular underpinnings remain largely uncharacterized, and direct evidence in mammalian systems is still limited to a small number of studies. This mini-review first defines viscotaxis and distinguishes it from the related but physically different mechanical quantities with which it is frequently conflated—substrate stiffness, matrix viscoelasticity, and stress relaxation—and then summarizes its physiological and pathological relevance across development, tissue homeostasis, immunity, and cancer. We outline the putative multi-step mechanosensory cascade governing viscotactic responses, examine how viscotaxis may synergize or compete with durotaxis, haptotaxis, chemotaxis, electrotaxis, and phototaxis under mixed microenvironmental cues, and compare the distinct hydrodynamic and steric-exclusion mechanisms proposed across spiral microbes, flagellated eukaryotes, mammalian cells, and embryonic tissues. Throughout, we explicitly distinguish evidence obtained under viscosity gradients from that obtained under uniformly elevated viscosity and established findings from working hypotheses. Finally, we discuss current methodological bottlenecks and unresolved conceptual debates and propose biomaterial tools and therapeutic strategies to advance viscotaxis from a biophysical curiosity toward a core principle of cellular mechanobiology. Full article

The circadian clock, located in the mammalian hypothalamus, regulates biological rhythms with a period of approximately 24 h, influencing nearly all body functions. Its timing is synchronised daily by external cues, primarily light, which align internal rhythms with the environmental cycle. Through this entrainment, the circadian system orchestrates physiological processes such as the sleep–wake cycle, feeding behaviour, gene expression and body temperature regulation. Melatonin, secreted by the pineal gland, also plays a key role as a synchroniser by facilitating sleep onset. Changes in environmental time cues, such as those experienced by shift workers, can disrupt the body’s natural 24-h rhythms. This situation can lead to fatigue, significantly impacting accident rates and productivity, and, in the long term, to an increased risk of various health conditions. A Phase Response Curve (PRC) illustrates how the clock’s phase is affected by stimuli administered at different points in the circadian cycle. In particular, both light and melatonin can induce phase shifts, but the direction and magnitude of this shift depend on the timing of administration. Understanding the PRC enables the design of interventions to realign circadian rhythms and improve adaptation to shift work. This review explores the physiological and clinical effects of circadian disruption in shift workers and discusses strategies to mitigate its impact. Full article

Alpha-gal syndrome (AGS) is a tick-induced, IgE-mediated hypersensitivity to the oligosaccharide galactose-α-1,3-galactose (α-gal), which is expressed on glycoproteins and glycolipids of non-primate mammals but absent in humans. Gastrointestinal (GI) symptoms dominate the clinical presentation in a substantial proportion of patients yet remain systematically under-recognized, frequently being attributed to irritable bowel syndrome (IBS), non-celiac gluten sensitivity (NCGS), or lactose intolerance. This narrative review synthesizes the current evidence on the epidemiology, GI and systemic phenotype, immunological mechanisms, diagnostic strategies, management approaches, quality-of-life burden, and multi-level public health interventions for AGS, and it identifies critical knowledge gaps as of 2026. We searched PubMed/MEDLINE, Embase, and Web of Science from database inception through 31 March 2026, and synthesized the evidence narratively in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA). GI symptoms occur in 47–69% of patients with AGS, with abdominal pain (58%), diarrhea (42%), nausea (39%), and vomiting (31%) as the cardinal manifestations. A characteristic 2–6 h delay between the ingestion of mammalian-derived food and symptom onset—explained by the glycolipid–chylomicron delivery mechanism—drives diagnostic confusion with functional GI disorders. Among 295,400 tested individuals in the United States, 30.5% were α-gal IgE positive, and an estimated 96,000–450,000 Americans were affected between 2010 and 2022. Despite this burden, 42% of U.S. healthcare providers had never heard of AGS. Strict avoidance of mammalian meat improves symptoms in 53–86% of adherent patients, although the condition carries a meaningful risk of anaphylaxis even among GI-predominant presenters. AGS is a prevalent, frequently misdiagnosed, and clinically morbid condition whose GI phenotype lies squarely within the gastroenterologist’s domain. A coordinated response that integrates clinician education, institutional diagnostic algorithms, and national surveillance infrastructure is urgently needed. Full article

Although the role of the mammalian hippocampus in representing locomotor speed has been widely investigated, how the avian hippocampus represents continuous flight speed under free-flight conditions in the outdoor environment remains unclear. In this study, we used homing pigeons as a model system and synchronously recorded hippocampal formation (HF) local field potentials (LFPs), global positioning system (GPS) trajectories, and inertial measurement unit (IMU) data during natural homing flights. We aimed to determine whether and how the avian HF encodes flight speed. Flight-speed-related neural features were extracted from both frequency-domain and time-domain signals, including the 50–70 Hz power spectral density (PSD) ratio and theta-demodulated amplitude (DAmp). We then constructed models for discrete flight-speed state decoding and continuous flight-speed prediction. The results showed that the 50–70 Hz PSD ratio in the HF was significantly negatively correlated with flight speed, whereas DAmp was significantly positively correlated with flight speed. Both features exhibited consistent speed-related trends across different spatial release sites. Support vector machine (SVM)-based classification showed that PSD, DAmp, and their combined features could effectively decode four flight-speed states, including non-flight, low-speed, medium-speed, and high-speed states, with the combined features achieving the best performance. Further Gaussian process regression (GPR) analysis demonstrated that the combined features predicted continuous flight speed more accurately than either single feature. These findings provide evidence that the avian hippocampal formation encodes continuous flight speed during natural navigation through the complementary integration of frequency-domain and time-domain features, extending the known role of the avian hippocampal formation from static spatial mapping to dynamic self-motion representation. Full article

Stop codon readthrough is a noncanonical translation strategy employed by certain RNA viruses, in which a viral termination codon is either decoded by host near-cognate tRNAs or canonically recognized by the class I release factor (RF, eRF1 in eukaryotes). Ribosomal A-site competition between near-cognate tRNAs and eRF can shift decoding toward near-cognate tRNAs, thereby promoting non-canonical decoding events by transiently pausing termination and favoring readthrough. This review focuses on two viral cis-elements that modulate readthrough across four viral genera in which this decoding event has been experimentally validated: (i) primary sequences surrounding the stop codon (stop codon context), and (ii) downstream RNA structures. Effects of stop codon context have been observed more broadly in cellular genes, including nonsense suppression in bacteria, with mechanisms including inefficient RF association or tRNA interactions at adjacent sense codons. In eukaryotic systems, interactions with the ribosomal mRNA entry channel have been suggested. Diverse downstream structures, including gammaretroviral pseudoknots and specific structures in alpha- and coltiviruses, further stimulate readthrough in a location- and structure-sensitive manner. This effect has not been consistently observed in chikungunya and triatoviral structures, suggesting a strong dependence on local sequence and structural context. Compared with the larger number of cellular readthrough occurrences that can be detected at low efficiency by ribosome profiling, viral readthrough in mammalian systems is consistently high (>2%). Understanding the interplay between viral RNA elements and host translational machinery, including potential kinetic trapping at the termination codon, provides insights into this unusual elongation mechanism. These findings may have implications for antiviral strategies targeting these RNA elements. Full article

Background/Objectives: Alpha-gal syndrome (AGS) is an allergic condition that results in delayed symptoms in response to exposure to mammalian products. There is limited research on which healthcare professionals (HCPs) are diagnosing AGS, types of symptoms, time to reactions, and products that induce allergic responses in AGS. This survey study aimed to further identify the patient journey and characterize reactions for people with AGS. Methods: Adult patients with HCP-diagnosed AGS took a survey offered through social media and support organizations. Questions included diagnosing HCP type, time from exposure to symptom onset, and type of symptoms by body system. Results: Survey participants (n = 3437) were mostly white (95.8%) and female (81.5%), ranging from 18 to 86 years old, with a mean time from onset to diagnosis of 4.3 years. Most were diagnosed by an allergist (53.6%) or primary care doctor (30.7%). Participants reported gastrointestinal (86.2%), skin (83.5%), respiratory (59.8%), cardiovascular (41.3%), emotional (38.2%), motor (23.7%), and nervous system (23.3%) symptoms. Symptoms were most often reported at 4–6 h post-exposure (49.8%) and 6–8 h (28.6%), with a range from 0 min to 8+ hours. Products eliciting reactions included mammalian products (beef 97.7%, pork 87.2%, dairy 66.9%, gelatin 61.3%), prescription (41.3%) or over-the-counter medications (36.4%), and personal care products (42.0%). Most participants managed their reactions at home, and without epinephrine. Conclusions: This study demonstrates that patients with AGS may experience symptoms due to exposures from mammalian meat and a broad range of mammalian ingredient-containing products, including medications, personal care products, and dairy, with a wide range of body systems impacted. These results may be useful for educating patients and healthcare professionals to improve the accuracy and speed of AGS diagnosis. Full article

Background/objectives: The emergence of highly pathogenic avian influenza A (H5N1) virus infections in dairy cattle in the United States revealed a novel mammalian host and a potential transmission pathway involving raw milk and dairy production systems. Sustained circulation of H5N1 in dairy herds is of concern because ongoing viral adaptation in mammals may increase the risk of efficient mammalian transmission and subsequent zoonotic spread. In response to this emerging threat, we developed a chimpanzee adenovirus (ChAd)-vectored vaccine expressing the haemagglutinin 5 antigen (H5HA) from the dairy cattle isolate A/dairy cattle/Texas. Methods: Lactating dairy cows were vaccinated by either intramuscular (N = 3) or intranasal administration (N = 3). H5HA clade 2.3.4.4b antibodies in cow’s milk and sera were evaluated by ELISA. Hemagglutination and neutralisation capacity were also evaluated. Results: IgG and IgA H5HA-specific antibodies were detected in serum and milk from parenterally vaccinated animals, demonstrating the induction of a systemic immune response. The neutralising antibody responses elicited were only detected in serum of cows vaccinated via the intramuscular route. Conclusions: These preliminary findings support the feasibility of ChAd-vectored vaccination as a strategy to induce humoral immunity in cattle against emerging H5N1 influenza A viruses. Cross-reactive antibody responses against both A/dairy cattle/Texas/24-008749_001/2024 and A/Ibis/Egypt/RLQP-229S/2022 support the capacity of the vaccine to recognise antigenically related H5N1 clade 2.3.4.4b viruses circulating in mammalian and avian reservoirs. Further studies of vaccine efficacy and the immunological mechanism of protection should now be undertaken with the aim of reducing viral transmission and milk-associated shedding in dairy herds. Full article

Resveratrol is a plant-derived stilbene polyphenol that has attracted interest as a potential dietary additive for improving edible fish muscle quality. This review summarizes current evidence on pre-harvest dietary resveratrol supplementation and its possible effects on nutritional composition, flavor-related biochemical traits, and physicochemical quality of fish muscle or fillets. We distinguish nutritional quality, including proximate composition, amino-acid profiles, and fatty-acid composition, from flavor-related and sensory-relevant proxies, such as free amino acids, inosine monophosphate, volatile precursors, color, pH, water-holding capacity, and texture. Direct evidence from edible fish muscle remains limited and fragmented, and most available studies rely on biochemical or instrumental endpoints rather than trained-panel sensory evaluation or consumer acceptance testing. Reported effects suggest species- and dose-dependent changes in muscle protein deposition, amino-acid accumulation, fatty-acid composition, pH, cooking or drip loss, and texture-related traits. Putative mechanisms may involve antioxidant protection, muscle fiber remodeling, lipid metabolism, endoplasmic-reticulum stress, and delivery-dependent bioavailability; however, many mechanistic links are still inferred from hepatic tissues, mammalian models, or in vitro systems. Future studies should combine standardized dose–response feeding trials with gas chromatography–mass spectrometry (GC–MS)-based volatile profiling, lipid and protein oxidation indices, instrumental texture analysis, sensory evaluation, and shelf-life testing before resveratrol can be recommended as a robust feed-based strategy for improving edible fish muscle quality. Full article

The β-casein gene (CSN2) encodes one of the major milk proteins involved in calcium and phosphorus transport and combines a highly conserved genomic organization with extensive genetic diversity, making it an informative model for investigating mammalian genome evolution. Although numerous studies have described CSN2 polymorphisms, particularly in domestic species, the broader evolutionary history of the locus remains poorly understood. Here, we investigated the evolutionary architecture of CSN2 across Bovidae and related Cetartiodactyla by integrating coding variation, non-coding polymorphisms, retroposon insertions and recombination analyses. Comparative genomic analyses identified previously undescribed caprine haplotypes, expanded the known spectrum of β-casein variation in domestic and wild Caprinae, and revealed multiple structural configurations of the locus, including distinct retroposon architectures and intronic insertion/deletion polymorphisms. Retroposon mapping and comparative analyses supported a hierarchical accumulation of structural variants, while also indicating ancestral polymorphism and lineage-specific retention in rapidly radiating caprine lineages. A locus-level phylogenetic analysis revealed two deeply divergent allelic lineages and provided evidence of ancient interallelic recombination predating the divergence of Capra and Ovis. Comparative analyses further showed that a two-amino-acid deletion previously associated mainly with Caprinae is more widely distributed across Bovidae than previously recognized. Overall, the CSN2 locus emerges as a multilayered evolutionary system shaped by structural variation, ancestral polymorphism, incomplete lineage sorting and ancient recombination, illustrating how the integration of coding, structural and retroposon variation can improve locus-level evolutionary reconstruction in Bovidae. Full article

The neural circuits of the human brain are highly complex (due to the number of neurons and the diversity of synaptic connections), hindering the analysis of the pathological mechanisms of neurodegenerative diseases. Invertebrates with simple yet well-differentiated nervous systems have a natural advantage over mammalian model organisms in the identification of pathogenic genes and functional studies of neurodegenerative diseases. They can provide unique and profound insights into the pathogenesis of complex human neurodegenerative diseases and the formulation of intervention strategies. This article reviews the conserved mechanisms of three neurodegenerative diseases across species, including protein homeostasis imbalance and aggregation toxicity, mitochondrial dysfunction and metabolic abnormalities, axonal transport defects, and loss of synaptic function. Based on research on three invertebrates in the field of neurodegeneration, namely Caenorhabditis elegans (C. elegans), Drosophila melanogaster (D. melanogaster), and Bombyx mori (B. mori), we cover three major types of neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). The aim is to find important inspirations for the future prevention and treatment of neurodegenerative diseases from the aspects of the material basis and existing treatment strategies. Full article

Glycogenolysis is an important contributor to ATP production in contracting skeletal muscle. However, the activation of glycogen phosphorylase in resting muscle does not by itself trigger significant glycogenolysis. To elucidate the mechanisms underlying this regulation, we analyzed the functional coupling between glycogenolysis and glycolysis using a mathematical model of energy metabolism in mammalian fast-twitch (white) skeletal muscle. A system-level analysis of the model reveals an important role for inorganic phosphate (a substrate for glycogen phosphorylase) in regulating glycogenolysis rates in both resting and contracting muscle. In contracting muscle, at sufficiently high concentrations of inorganic phosphate, the activation of glycogen phosphorylase markedly increases the rate of glycogenolysis, thereby enhancing ATP production and stabilizing the cellular energy charge. In contrast, glycogen phosphorylase activation in resting muscle is unable to support glycogen breakdown due to a significant decrease in inorganic phosphate levels. Moreover, the analysis shows that forced acceleration of the glycogen phosphorylase reaction under resting conditions does not increase ATP production; instead, it promotes the accumulation of phosphorylated glycolytic intermediates, which may induce osmotic stress and cause damage to muscle cells. Full article

Polyphosphate (polyP) is an evolutionarily conserved linear polymer of orthophosphate residues with diverse functions across organisms from bacteria to mammals. In addition to its roles in phosphate and energy storage, polyP has been implicated in thrombosis, inflammation, cancer, metabolism, cytoskeletal regulation, and neurodegenerative diseases. PolyP also acts as a molecular scaffold interacting with lysine-rich proteins and may contribute to protein folding and amyloid formation. However, biochemical heterogeneity, including variation in chain-length, subcellular localisation, and supramolecular organisation together with the absence of clearly defined mammalian biosynthetic pathways, has limited mechanistic understanding of polyP biology. Reliable detection and quantification remain challenging because current methods often suffer from limited specificity, chain length bias, insufficient quantitative robustness, and interference from other highly anionic biomolecules such as DNA or RNA. This review summarises current methodologies for polyP detection and characterisation. Emerging polyP-specific probes, including recombinant polyP-binding domains derived from polyphosphatases and conserved histidine α-helical domains may improve qualitative and quantitative analysis of polyP in complex biological systems. Improved analytical strategies will be essential to define the physiological roles of polyP and evaluate its potential as a biomarker and therapeutic target. Full article

Gamma (γ)-aminobutyric acid (GABA) is a non-proteinogenic amino acid recognized for its primary function as the main inhibitory neurotransmitter in the mammalian central nervous system and its role as a stress-responsive metabolite in various microorganisms. This review critically examines the biosynthesis of GABA by lactic acid bacteria (LAB) via the glutamate decarboxylase (GAD) system and evaluates its potential applications in food and health sectors. The mechanistic details of the GAD pathway are analyzed, focusing on the integrated roles of gadA/gadB decarboxylases, the gadC antiporter, and pyridoxal−5′-phosphate (PLP) dependency in relation to acid resistance, metabolic flux, and strain variability. Taxonomic and strain-level diversity among GABA-producing LAB is assessed, with emphasis on the highly strain-specific nature of GABA production rather than broad species or genus generalizations. Fermentation optimization parameters (pH, temperature, substrate loading, and cofactor management) and scale-up challenges, including techno-economic feasibility and downstream recovery efficiency, are critically evaluated. Integration of LAB-derived GABA into fermented food matrices is discussed with attention to sensory compromises, stability, regulatory factors, and clean-label considerations. Evidence from clinical and preclinical studies is synthesized to assess the physiological significance of dietary GABA, distinguishing between purified GABA supplementation, GABA-enriched fermented foods, and probiotic effects of live LAB, while addressing the GABA paradox and gut–brain axis interactions. Significant research gaps are identified, including the need for standardized quantification methodologies, multi-omics-guided strain engineering, predictive bioprocess modeling, and rigorously designed human trials in realistic food matrices. This review provides a systems-oriented, critical framework to promote scalable and evidence-based advancement of GABA-enriched functional foods. Full article

Reactive oxygen species (ROS) regulate cellular signaling at physiological concentrations and drive tissue damage when their generation exceeds antioxidant defenses. The conceptual reframing of the field into oxidative eustress (low, controlled redox signaling) and oxidative distress (supraphysiological levels causing biomolecular damage), alongside parallel advances in detection chemistry and genetically encoded biosensors, has transformed how investigators measure ROS in living systems. This review provides a critical, methods-focused update covering the contemporary toolkit, with particular emphasis on advances from 2015 to 2026 while incorporating earlier foundational work where it remains indispensable to interpretation. Consistent with the title and reflecting both the maturity of the available chemistry and the weight of the recent literature, our emphasis falls on hydrogen peroxide and mammalian experimental systems; superoxide, the hydroxyl radical, and singlet oxygen are addressed primarily where their detection intersects with the platforms reviewed here, and non-mammalian models are considered only selectively. Readers seeking dedicated coverage of these other species or of plant, microbial, and invertebrate systems are directed to the specialized reviews cited throughout. Five complementary measurement platforms are evaluated: (i) electron paramagnetic resonance spectroscopy with classical nitrone spin traps and the newer cyclic hydroxylamine probes; (ii) small-molecule fluorescent probes, with particular emphasis on the boronate-based, activity-based sensing platform that has supplanted 2′,7′-dichlorofluorescin diacetate for hydrogen peroxide imaging; (iii) genetically encoded biosensors of the HyPer and roGFP families, which now permit ratiometric, organelle-resolved, and longitudinal measurements; (iv) mass-spectrometry-based quantification of oxidation products and radical adducts, including isoprostanes, 2-hydroxyethidium, and redox-modified cysteines via chemical proteomics; and (v) electrochemical and nanosensor approaches enabling real-time single-cell measurements. The selectivity, sensitivity, temporal resolution, spatial resolution, and quantitative capability of each platform are critically compared. Reliance on a single non-specific probe is no longer sufficient as the sole evidence base for quantitative or species-specific claims; contemporary investigators are expected to apply complementary approaches and to validate findings across modalities. Standardization of reporting, integration with single-cell omics, and clinical translation of validated mass-spectrometry biomarkers are identified as priorities for the coming decade. Full article