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Since its discovery, Homo floresiensis-an extinct, short-statured, and small-brained hominin species from Flores, Indonesia-has often been ascribed unexpectedly advanced behaviors, such as hunting large game and using fire. Here, we report the results of a systematic taphonomic study sampling the proboscidean bone assemblage at Liang Bua where the frequency and locations of predatory marks, along with skeletal part profiles, show that Komodo dragons likely had primary access to these remains leaving behind only low-utility elements for H. floresiensis to scavenge. Moreover, no signs of intentional use of fire are present in the stratigraphic units associated with H. floresiensis. Together, these results suggest that H. floresiensis was not as behaviorally advanced as originally suggested and provides critical insights into the behavioral repertoire of H. floresiensis, raising important questions about its ancestry.
Developing biodegradable active packaging with improved mechanical and antimicrobial properties remains a key challenge in food preservation. This study evaluated the physical and antimicrobial performance of extruded sheets based on a base mixture of acetylated tapioca starch, glycerol and water (BMAS), chitosan (CH) and oregano essential oil (OEO). Extruded sheets with varying BMAS, CH and OEO proportions were formulated using a simplex centroid mixture design. Mechanical properties, water solubility, color and thermal behavior were analyzed. Sheets antimicrobial activity was tested in contact with a chicken meat-based food against external contamination by Escherichia coli, Listeria innocua, Enterococcus faecium, or Zygosaccharomyces bailii. Two optimal formulations (g kg-1) were identified: central point (853.3 BMAS, 93.3 CH, 53.3 OEO) and S7 (840 BMAS, 80 CH, 80 OEO), both showing the highest stress at break (≈ 1.06 MPa), but maximum (105%) and minimal (26%) deformation, respectively. Water solubility was 40% for central point and 47% for S7. OEO increased mechanical resistance but reduced solubility compared to controls without oil. Acetylation improved tensile strength, solubility and whiteness, though slightly decreasing thermal stability. Regarding antimicrobial barrier action, the effectiveness was microorganism dependent: while Z. bailii was not detected along storage, Escherichia coli was more sensitive than L. innocua and Enterococcus faecium. The present findings indicate that the developed extrudates are promising candidates for biodegradable active food packaging. The retained availability of OEO effectively contributed to microbial spoilage control, with Z. bailii and Escherichia coli exhibiting greater susceptibility compared to L. innocua and Enterococcus faecium. © 2026 Society of Chemical Industry.
Age-related changes in the heel fat pad (HFP) are not fully characterized beyond thickness measurements, despite their potential impact on foot biomechanics and function. The aim of the study was to evaluate ultrasonographic structural changes in the HFP across different age groups and to determine whether qualitative ultrasonographic parameters provide a more sensitive assessment of age-related structural degeneration than thickness measurements alone. A cross-sectional observational study was conducted, including 140 asymptomatic participants aged 18-89 years, stratified into three age groups (18-45, 46-65, and 66-89 years). Ultrasound assessment included measurements of thickness, echogenicity, echostructure, and Doppler flow. Statistical analyses were performed using one-way ANOVA, two-way ANOVA, and chi-square tests. Significant age-related differences were observed in echostructure, echogenicity, and horizontal fibrous band (HFB) integrity (p < 0.0001), characterized by progressive disruption and loss of compartmental organization, predominantly affecting the deep subcutaneous macrochamber (DSM) and fibrous septa. These alterations followed a consistent age-related pattern across groups. In contrast, thickness measurements demonstrated smaller and less consistent differences. No relevant intralesional Doppler signal was detected. Qualitative ultrasonographic abnormalities of the HFP, particularly involving echostructure, echogenicity, and HFB integrity, appear to detect age-related structural degeneration more consistently than thickness measurements alone. Incorporating qualitative ultrasound assessment may improve the evaluation of structural tissue remodeling in asymptomatic individuals.
Elevated iron levels, as seen in hemochromatosis, can damage vital organs. Although chelators are effective at removing excess iron, they have poor pharmacokinetics, which requires repeated doses and leads to adverse side effects. Here, we report on the synthesis of mesoporous silica nanoparticles (MSN) functionalized with the clinically used chelator deferoxamine (DFO). The nanoparticles have been physicochemically characterized, demonstrating the successful grafting of the chelator and chelating features comparable to those of the free drug. The MSN-DFO have been tested in a hepatocellular carcinoma cell line (HepG2), producing an expected decline in cell viability due to intracellular iron chelation, which affects metabolic processes. Nonetheless, it has been shown that cell function is restored when the nanochelator is cleared from the cells, highlighting its overall biocompatibility. Interestingly, MSN-DFO exhibited a more gradual and prolonged iron removal process in iron-overloaded HepG2 cells than DFO did. Finally, in preparation for an in vivo administration, the protein corona formed on the MSN-DFO has been thoroughly analyzed, revealing clear differences depending on the plasma origin (wild type vs. hemochromatotic mice), highlighting the role that the protein corona fingerprint might have as a predictor of diseases, and shedding light on how this nanochelator would behave in vivo.
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The urothelium is a stratified epithelium that lines the inner surfaces of organs in the urinary drainage system. It has a layered composition of basal, intermediate, and large superficial cells. The process, by which this cytoarchitecture develops from uncommitted precursor cells is not well understood. In this study, we analyzed the cellular and molecular functions of the transcription factor ΔNP63 in urothelial development in the murine ureter. ΔNP63 expression begins in epithelial progenitors of this organ at embryonic day (E)14.5 and is confined to basal and intermediate cells from late fetal stages onwards. In mice with a conditional loss of ΔNp63 in the epithelial progenitors, the ureteric urothelium presented as a folded monolayer composed predominantly of partially differentiated superficial cells around birth. At E15.5, the proliferation and division planes of epithelial cells remained unaffected. However, genes essential for cell adhesion and division in other epithelial stratification programs were downregulated, as were genes involved in B and I cell differentiation. In contrast, Ihh expression in the epithelium increased concomitantly with the premature formation of the lamina propria. Our results suggest that a conserved ΔNP63 gene regulatory module is responsible for epithelial stratification and the differentiation of basal and intermediate cells, as well as the timely differentiation of the lamina propria in fetal ureter development. The urothelial cytoarchitecture was progressively reconstituted in ΔNp63-deficient ureters after birth. This suggests that a few ΔNP63+ epithelial progenitors, which have escaped recombination, can undergo rapid proliferative expansion and differentiation into I and B cells.
Image sensors produce high-dimensional visual data for classification algorithms. Deep Neural Networks (DNNs) achieve high accuracy but require large labeled datasets and computational and energy resources, limiting their use in embedded systems. Active Learning (ALrn) can reduce labeling effort by selecting samples based on informativeness scores, but it remains computationally expensive, especially for high-dimensional images. This work presents a hardware-accelerated approach for the instance selection stage based on a query strategy in uncertainty-based ALrn for image classification using a novel in-line top-k selection algorithm that avoids conventional sorting and reduces memory and computational requirements. The algorithm is implemented on an Xilinx ZYNQ-7000 System on Chip (SoC) using a Field Programmable Gate Array (FPGA)-based accelerator operating at 110 MHz, interfacing with an embedded Advanced RISC Machine (ARM) processor for data acquisition and communication via the Python Productivity for Zynq (PYNQ) framework. Experiments on diverse multiclass datasets demonstrate correctness within an ALrn setting, showing negligible performance deviation in the learning curves compared to software baselines. The accelerator achieves speedup of 231.7× and 22.9× over software baseline and optimized software implementation of the proposed algorithm, respectively, in query-strategy computation while consuming only 0.473 W, substantially lower than conventional Central Processing Unit (CPU)- and Graphics Processing Unit (GPU)-based platforms. These results demonstrate the efficiency and extensibility of the proposed accelerator across alternative ALrn designs and hardware platforms, where the computational cost of instance selection scales with the size of the unlabeled pool.
We use rich longitudinal administrative medical records to examine the separate roles of mothers and fathers in children's health care use. We do so distinguishing between different types of care and child sex. Overall, we find limited evidence of an association between parents' education and their children's health care use. Mothers' health care use appears in general more strongly associated than fathers' health care use with that of their children. On the other hand, for some types of care (GP and specialist visits), these associations in health care use are stronger within the same-sex parent-child dyads. These results are not (fully) explained by parental nor children's health needs and health behaviors and are robust to the inclusion of GP fixed effects. These associations remain after controlling for unobserved time-invariant factors suggesting that non-health related family shocks also play a role. Our findings have potentially important policy implications, as patterns of health care seeking are established early in life, which the literature shows have long-lasting effects over people's life course.
Diabetic retinopathy (DR) and diabetic macular edema (DME) are leading causes of vision loss worldwide and represent a growing public health concern in Mexico. Despite the availability of effective treatments, including anti-vascular endothelial growth factor (anti-VEGF) therapies, adherence and persistence remain suboptimal, compromising outcomes. This study, part of the international DR Barometer project, examined the perspectives of patients, healthcare providers, and clinic staff to better understand challenges and opportunities in DR/DME care delivery in Mexico. A cross-sectional, survey-based study was conducted across five high-volume ophthalmology clinics in Mexico. Standardized, paper-based questionnaires were completed anonymously by patients with DR or DME, healthcare providers, and clinic staff. Data were collected between October and November 2023, scanned, and analyzed descriptively. A total of 1151 participants were included: 558 patients with DME, 265 patients with DR, 122 providers, and 206 clinic staff. Key barriers to adherence included financial burden of treatment (reported by 67.4% of patients with DME; emphasized by 97.5% of providers), logistical difficulties such as travel and long waiting times, and emotional concerns about being a burden to family (71.5% of patients with DME; 61.1% of patients with DR). Nonadherent patients were more likely to prioritize competing health issues and report limited support from care teams. While most patients stated that eye treatment was a priority (87-91%), only 61% of providers believed this to be true. Opportunities highlighted across stakeholders included proactive provider-patient communication, continuity of care with the same clinical team, appointment reminders, and financial assistance. Clinic staff emphasized the need for improved educational materials and better coordination of diabetes and eye care services. This study reveals substantial challenges to adherence in DR/DME management in participating Mexican referral centers, rooted in financial, logistical, and psychosocial factors. Strengthening communication, expanding financial support, and integrating coordinated, patient-centered care strategies could improve long-term treatment engagement and outcomes.
Ampicillin residues in animal-derived foods may cause allergic reactions and promote antimicrobial resistance in consumers; however, data on residue behavior in poultry remain limited. This study aimed to evaluate the depletion of ampicillin in muscle and skin plus fat of broiler chickens. Thirty birds were treated with ampicillin intramuscularly (20 mg kg-1 every 24 h for three days) and sacrificed at 0.5, 1, 2, 5, and 9 days post-administration. Samples were analyzed by liquid chromatography coupled with tandem mass spectrometry, a method successfully validated according to Commission Implementing Regulation (EU) 2021/808, VICH GL49 and GL2. Quantification was performed by linear regression from matrix-matched calibration curves. Residue depletion was evaluated following the European Medicines Agency guidelines. Ampicillin residues in muscle were detected only during the first 24 h post-administration (6.50-8.48 µg kg-1). Residues in skin plus fat remained detectable until day 5 post-administration (6.87-59.88 µg kg-1). Based on this, the withdrawal period calculated for skin plus fat was 9 days considering EU maximum residue limit (MRL) and 19 days considering method limit of quantification, with 95% confidence. These results provide critical data on ampicillin residue kinetics under controlled experimental conditions, supporting risk assessments and the establishment of MRLs in broiler chickens by the Codex Alimentarius.
Group A Streptococcus (GAS) is a human-restricted pathogen whose global incidence has surged in the post-COVID era. The ability of GAS to shift from a colonizing to invasive phenotype depends on coordinated virulence gene regulation in response to host-derived signals. However, the mechanisms by which individual stress-sensing systems interact to reshape the virulence gene regulatory landscape remain incompletely understood. Here we define the regulatory programs of two conserved transcriptional regulator paralogs, SpxA1 and SpxA2, using an integrated multi-omic approach combining RNA-seq, data-independent acquisition proteomics, NanoString-based transcriptional profiling across multiple host-relevant stress conditions, and chromatin immunoprecipitation with exonuclease treatment (ChIP-exo). RNA-seq revealed functionally distinct regulons with SpxA1 governing oxidative stress defense and SpxA2 coordinating virulence-associated gene expression linked to the CovRS two-component regulatory system. Proteomic analysis established SpxA2 as a ClpXP protease substrate in GAS and identified reciprocal paralog accumulation upon loss of either SpxA1 or SpxA2, consistent with compensatory transcriptional upregulation. NanoString profiling under bacitracin and human neutrophil peptide-1 challenge identified four gene modules with distinct stoichiometry-dependent and condition-dependent regulatory logic, revealing that the SpxA1/SpxA2 ratio rather than the activity of either paralog alone determines which transcriptional programs are engaged. ChIP-exo demonstrated that SpxA2 directly modulates CovR-DNA binding occupancy in a CovR binding motif-dependent manner, simultaneously antagonizing CovR dimer binding at an extended (25-bp) CovR motif and facilitating CovR monomer binding at the canonical ATTARA motif. These findings establish the LiaFSR-SpxA2-CovRS axis as a cross-regulatory circuit through which GAS cell envelope stress sensing is directly transduced into coordinated virulence gene regulatory changes. Group A Streptococcus (GAS) causes millions of infections annually, including a recent global surge in invasive disease. To survive in the human host, GAS must rapidly reprogram virulence gene expression in response to host-derived stresses. This study characterizes two conserved transcriptional regulators, SpxA1 and SpxA2, that govern this response through interaction with RNA polymerase to indirectly influence the DNA-binding activity of downstream transcription factors. We show that SpxA2, activated by a cell envelope stress-sensing system responding to human antimicrobial peptides, reshapes the binding of the master virulence regulator CovR in a promoter-specific manner, coupling cell envelope stress sensing to virulence gene regulation. The stoichiometric balance between SpxA1 and SpxA2 functions as a regulatory rheostat calibrating overall virulence gene regulatory tone, providing a framework for understanding how RNA polymerase-interacting regulators coordinate stress responses and virulence gene control across Gram-positive bacterial pathogens.
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A new species of the deep-sea squat lobster genus Munidopsis Whiteaves, 1874, is described from a seamount in the southeastern Arabian Sea, India. Munidopsis hindmahasagaraesp. nov. differs from its close congeners, M. alcocki Ahyong, 2014 and M. treis Ahyong & Poore, 2004 by the presence of a tooth on the distomesial margin of the antennule, a relatively longer distolateral tooth of the second antennal article, and a relatively longer distomesial tooth of the third antennal article. Gonionida comorina (Alcock & Anderson, 1899) is redescribed and illustrated based on fresh material, as well as comparison with photographs and the description of the type specimen. Its re-description enables confirmation of its placement in the genus Gonionida Macpherson & Baba, 2022, owing to a triangular fourth thoracic sternite. Juveniles of Eumunida sp. are compared with congeners from the western Indian Ocean namely, E. funambulus Gordon, 1930, E. similior Baba, 1990, and E. spiridonovi Macpherson, Rodríguez-Flores & Machordom, 2017.
Frailty in older adults is a multidimensional condition associated with physical, psychological, and sociodemographic factors that may affect functionality and quality of life during aging. The analysis of these factors often requires the management of heterogeneous information, which can represent a challenge for specialists during evaluation and follow-up processes. In this context, computational tools and data-driven approaches may support the organization and exploratory analysis of multidimensional health information. This study presents the development of a web-based computational system designed to support specialists in the collection, management, and analysis of health-related data from older adults in the State of Hidalgo, México. A web platform was developed to register and organize sociodemographic, psychological, and physical information from older adults. The system integrated questionnaires, physical measurements, statistical analysis tools, and computational intelligence techniques within a single environment. Data from 210 participants were collected and analyzed using exploratory statistical methods, feature selection techniques, and K-means clustering to identify patterns associated with functional and health-related characteristics. Internal validation metrics, including the Silhouette coefficient, Davies-Bouldin Index, and Calinski-Harabasz Index, were used to support cluster evaluation. The proposed system facilitated the structured storage, visualization, and exploratory analysis of multidimensional health information. The clustering analysis identified two differentiated groups characterized by distinct physical and psychological profiles. Differences were observed in variables such as muscular strength, calf circumference, body mass index, gratitude, and functional self-perception. The interpretation of the obtained profiles considered the demographic composition of the groups, particularly the predominance of women in one cluster, which may influence physical measurements associated with aging. Additionally, the usability assessment conducted with specialists using the SUS instrument indicated an acceptable level of usability for exploratory and research support purposes. The results suggest that integrating computational intelligence and statistical analysis techniques into a unified platform may support the exploratory assessment of multidimensional factors related to aging and frailty in older adults. The proposed system does not aim to establish clinical diagnoses, but rather to provide specialists with an additional resource for organizing and interpreting complex health-related information. This approach may contribute to the development of data-driven tools to support gerontological research and comprehensive evaluation processes in older populations. Not applicable.
Bacterial bioremediation involves bacterial strains and communities and their complex interactions with the environment, aiming to restore ecological balance by degrading contaminants in natural systems (soil, water, air). These processes rely on coordinated gene clusters encoding catabolic pathways. Many xenobiotic-catabolic gene clusters (XGCs) reside on mobile genetic elements (MGE), enabling horizontal gene transfer (HGT) and genome rearrangements that drive rapid microbial adaptation to anthropogenic contaminants. Here we review the evolutionary and ecological roles of HGT and genome restructuring in assembling and optimising biodegradative functions. We introduce the concept of metabolic HGT hubs-microbial taxa, mobile elements, and ecological features that serve as central nodes for gene exchange-facilitating metabolic innovation and cooperation within microbial consortia. These processes enhance ecosystem resilience and pollutant degradation efficiency by promoting functional redundancy and metabolic division of labour. Understanding these dynamics informs strategies for engineering microbial communities and genetic bioaugmentation to improve bioremediation outcomes. Our perspective highlights bioremediation as an extension of metabolic network evolution under anthropogenic selection, emphasising both its potential and the need to consider ecological and biosafety implications.
Pangolins face severe conservation threats globally, necessitating accurate taxonomy for effective conservation. Previous genomic research on the Chinese pangolin (Manis pentadactyla) identified two deeply divergent lineages (MPA and MPB), suggesting underestimated species diversity. The recent description of M. indoburmanica (corresponding to MPB), however, did not assess its relationship with historical names, particularly the subspecies M. p. aurita, leaving the group's taxonomic status uncertain. To resolve this issue, we employed an integrative framework, analyzing genomic and morphological data from museum specimens including the lectotype of M. p. aurita to clarify phylogenetic relationships and taxonomy within M. pentadactyla sensu lato. Our results demonstrate that MPB, which includes both M. indoburmanica and M. p. aurita, is geographically restricted to the southern Himalayas and thus distinct from other M. pentadactyla populations. Genomic analyses indicate the two clades diverged ~1.8 Ma and have remained largely isolated, with only minimal gene flow with congeners. Furthermore, morphometric analyses of both cranial and external features reveal consistent and significant differentiation between the Himalayan lineage (MPB) and M. pentadactyla sensu stricto. Collectively, these congruent findings provide unequivocal support for the revalidation of Manis aurita Hodgson, 1836, thereby establishing it as a distinct extant species of Asian pangolin.
Over 90% of Asian American (AsA) adults are first- or second-generation immigrants, undergoing substantial environmental and sociocultural transitions; yet most environmental epidemiology cohorts have included few AsA participants. The Food and Microbiome Longitudinal Investigation (FAMiLI) is an environmental health cohort enriched with AsA adults (predominantly Korean and Chinese American) and designed to capture environmental exposures, dietary acculturation, and sociocultural factors across immigration generations. Its biobank-including buccal and stool specimens-supports research on the oral and gut microbiomes, human genomics, and other multi-omics. Since its launch in 2018, FAMiLI has completed baseline recruitment and biospecimen collection for 13,183 adults aged 40-75 years. The cohort is now expanding to include an additional 3,000 Asian American adults, bringing the total to approximately 16,000 participants, with an expected distribution of ~50% Asian American and ~50% from other racial/ethnic groups. This expansion provides an opportunity to examine AsA environmental health experiences within the broader U.S. FAMiLI is a unique national resource to address priority questions in environmental health, including microbiome and exposome science, individual susceptibility, and large-scale data analytics. The cohort supports investigation of critical windows of environmental change across the immigration experience, racial and ethnic disparities, and drivers of emerging health outcomes, including cancer, cardiovascular disease, diabetes and other outcomes. This cohort offers essential data to inform prevention strategies and shape public health policy to improve health outcomes in AsA communities.
The first wave of Coronavirus disease 2019 (COVID-19), driven by the global emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affected Spain with high infection and mortality rates across the country. Although numerous common and rare genetic variants affecting immune-related pathways have been associated with susceptibility to infection and severe disease, the contribution of complement system remains comparatively understudied. In this work, we analyzed the frequencies and severity associations of complotype-related common polymorphisms and rare complement variants in whole-exome sequencing data from a Spanish cohort accounting for 154 adults hospitalized due to severe COVID-19. Our results indicate that the CFHR4 rs7417769 (p.N209S) and CFH rs1061170 (p. Y402H) common polymorphisms are significantly associated with protection against acute respiratory distress syndrome (ARDS), while the C3 rs2230199 (p.R102G) and MASP2 rs7255087 (p.D120G) polymorphisms respectively correlated with low and high C3 levels. The marked over-representation of the C1R rs117402032 and C8A rs143523574 polymorphisms and increased frequency of heterozygous carriers of alleles previously associated with low FCN2 and FCN3 levels, suggest a link beween defective complement activation and increased rates of SARS-CoV-2 infection and support a pivotal role for the lectin pathway in the pathogenesis of COVID-19. Together, these results demonstrate that common variants in complement genes modulate susceptibility to severe COVID-19 and its clinical complications. They also identify promising, testable genetic biomarkers with potential utility not only for SARS-CoV-2, but also for preparedness against future emerging infectious threats.
As food demand increases, agricultural practices have evolved, prompting increased exploration of sustainable ecological techniques and utilization of plant-associated microorganisms. In this context, plant fitness has been enhanced by plant growth-promoting microorganisms (PGPM), which stimulate growth through direct mechanisms, such as improved nutrient availability and phytohormone production, as well as indirect mechanisms, including protection against phytopathogens and suppression of soil-borne diseases. However, these innate capabilities of PGPM can be further improved through genomic modification or editing. This article reviews advances in the genomic engineering of plant-beneficial microorganisms as tools to enhance their positive effects on crop performance and environmental remediation. The genetic modification strategies analyzed here include random mutagenesis, targeted genome editing (such as CRISPR-Cas), gene over-expression, genome shuffling, RNA interference, metabolic pathway engineering, and synthetic biology approaches. These tools have enabled the optimization of functions, such as nitrogen fixation, phosphate solubilization, secondary metabolite production, biocontrol, stress tolerance, and bioremediation. However, we propose expanding the discussion of their regulation and use in various countries. Additionally, these modifications must be efficient and safe for the beneficial microbiota associated with the target crop, as well as for humans, animals, and the environment, all of which depend on sustainable agricultural practices.