bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein catabolites as blood-based biomarkers of aging physiology: Findings from the Dog Aging Project
Authors: Harrison Benjamin R. , Partida-Aguilar Maria , Marye Abbey , Djukovic Danijel , Kauffman Mandy , Dunbar Matthew D. , Mariner Blaise L. , McCoy Brianah M. , Algavi Yadid M. , Muller Efrat , Baum Shiri , Bamberger Tal , Raftery Dan , Creevy Kate E. ,   Dog Aging Project Consortium, Avery Anne , Borenstein Elhanan , Snyder-Mackler Noah , Promislow Daniel E. 
Published: October 2024

AbstractOur understanding of age-related physiology and metabolism has grown through the study of systems biology, including transcriptomics, single-cell analysis, proteomics and metabolomics. Studies in lab organisms in controlled environments, while powerful and complex, fall short of capturing the breadth of genetic and environmental variation in nature. Thus, there is now a major effort in geroscience to identify aging biomarkers and to develop aging interventions that might be applied across the diversity of humans and other free-living species. To meet this challenge, the Dog Aging Project (DAP) is designed to identify cross-sectional and longitudinal patterns of aging in complex systems, and how these are shaped by the diversity of genetic and environmental variation among companion dogs. Here we surveyed the plasma metabolome from the first year of sampling of the Precision Cohort of the DAP. By incorporating extensive metadata and whole genome sequencing information, we were able to overcome the limitations inherent in breed-based estimates of genetic and physiological effects, and to probe the physiological and dietary basis of the age-related metabolome. We identified a significant effect of age on approximately 40% of measured metabolites. Among other insights, we discovered a potentially novel biomarker of age in the post-translationally modified amino acids (ptmAAs). The ptmAAs, which can only be generated by protein hydrolysis, covaried both with age and with other biomarkers of amino acid metabolism, and in a way that was robust to diet. Clinical measures of kidney function mediated about half of the higher ptmAA levels in older dogs. This work identifies ptmAAs as robust indicators of age in dogs, and points to kidney function as a physiological mediator of age-associated variation in the plasma metabolome.
Self-pruning in tree crowns is influenced by functional strategies and neighborhood interactions
Authors: Kothari Shan , Urgoiti Jon , Messier Christian , Keeton William S. , Paquette Alain 
Published: October 2024

AbstractAs canopy closure causes forest stands to face increasing light limitation, trees’ lower branches begin to die back. This process, called self-pruning, defines a crown’s base and depth and shapes the structure of entire stands. Self-pruning is often thought to occur after shading causes individual branches to transition from net carbon sources to sinks. Under this explanation, we would expect resource-conservative and shade-tolerant species to initiate self-pruning under deeper shade because their branches need less light to maintain a positive carbon balance. However, the notion that branches are fully autonomous may be complicated by ‘correlative inhibition,’ in which plants preferentially allocate resources towards sunlit branches. Consistent with this idea, we predicted that within species, trees with sunlit tops would initiate self-pruning at a higher light threshold. Lastly, we predicted that plot-level diversity in self-pruning strategies would correlate with productivity and total crown volume. We tested these predictions in an experiment where 12 temperate tree species were planted in plots of varying diversity and composition. We measured characteristics of crown size and position as well as the light level at the crown base (denotedLbase), which we took as an estimate of the light threshold of self-pruning. As we predicted, more shade-tolerant and resource-conservative species self-pruned at a deeper level of shade (lowerLbase). In addition, most species had higherLbasewhen they had more light at the crown top, suggestive of correlative inhibition. With respect to their neighbors’ traits, though, conservative and acquisitive species showed contrary patterns of plasticity: conservative species had lowerLbasearound conservative neighbors, while acquisitive species had lowerLbasearound acquisitive neighbors. However, all species declined in crown depth when they grew alongside larger, more acquisitive neighbors. As predicted, plots with a greater interspecific diversity ofLbasehad greater basal area and crown volume. Using simulations, we showed that plasticity in crown depth between monocultures and mixtures strengthened the relationship with crown volume, primarily due to competitive release experienced by acquisitive species. By placing shade-induced self-pruning in a comparative context, we clarify how forest function emerges from competition for light between individual trees.
Loss of virulence ofBotrytis cinereamutants defective in phytotoxin production is restored by modifying inoculation medium
Authors: Qin Si , Shi-Kunne Xiaoqian , Chen Jie , Beenen Henriek G. , You Yaohua , van Kan Jan A. L. 
Published: October 2024

AbstractBotrydial, botcinic acid and their derivatives are major phytotoxic metabolites produced by the necrotrophic fungal pathogenBotrytis cinerea. These phytotoxins are able to induce programmed cell death in the host and thereby promote plant susceptibility toB. cinerea.We observed that aΔbot2Δboa6double mutant strain, which synthesizes neither botrydial nor botcinic acid, was almost avirulent on tomato leaves when the disease assay was performed using synthetic minimal Gamborg B5 medium. However, virulence of this mutant was restored when the inoculation medium was supplemented with yeast extract. Further virulence assays which compared the double mutant with other multiple mutants using both inoculation media, revealed a prominent contribution of botrydial and botcinic acid to the full virulence ofB. cinerea. Therefore, we performed an RNA-sequencing experiment to identifyB. cinereagenes that contribute to the phenotypic switch from an “incompatible” to a “compatible” interaction between tomato and theΔbot2Δboa6double mutant. Four genes encoding cell death-inducing effector proteins were upregulated inB. cinereaby the addition of yeast extract, and their transcript profiles grouped within a co-expression module that was positively correlated with the compatible interaction. Functional analyses of these effector genes were performed by overexpressing them individually in theΔbot2Δboa6background, followed by disease assays with the Gamborg B5 medium without yeast extract.ImportanceThe grey mould fungusBotrytis cinereais a model for necrotrophic plant pathogens due to its wide host range, economic impact, well-assembled genome, and versatile mechanisms for inducing host cell death during colonization. Botrydial and botcinic acid have previously been characterized as major phytotoxins produced byB. cinerea. However, studies from different groups reported variable results regarding the contributions of these phytotoxins to fungal virulence. Here we demonstrate that botrydial and botcinic acid make a prominent contribution to the full virulence ofB. cinerea, by performing infection assays with mutants that are defective in phytotoxin production and/or multiple cell death-inducing proteins using different inoculation media. This work highlights the pivotal roles of these phytotoxins as compared to other virulence factors, as well as the significant impact of inoculation conditions on compatible and incompatible interactions between the fungus and its hosts.
Validation of a Novel Smartphone Pupillometer Application Compared to a Dedicated Clinical Pupillometer in the Measurement of the Pupillary Light Reflex of Healthy Volunteers
Authors: Middleton PM , Davies W , Buzytsky I 
Published: October 2024

AbstractAimThis study aimed to assess the correlation between the PLR curves of 25 healthy volunteers, generated with the MindMirror mobile telephone application, with PLR data from a dedicated clinical pupillometer.Materials & methodsPaired pupillary light reflex curves were recorded from 25 healthy volunteers using the MindMirror mobile telephone application, and a Neuroptics NPi 200 clinical pupillometer. The curves were analysed for correlation using a Pearson correlation coefficient across both curve sets.ResultsClose correlation was demonstrated between all parameters except maximum and mean pupillary constriction velocity. These values were consistently lower in the MindMirror derived curves and may be explained by the intensity of the light stimulus available from a mobile telephone being significantly less that that used by the clinical pupillometer.ConclusionA mobile telephone equipped with a MindMirror mobile phone application may provide a reliable, low cost and widely available alternative to a clinical pupillometer in the assessment of the pupillary light reflex.Plain language summaryClinical pupillometry allows objective measurement of Pupillary Light Reflex (PLR) parameters, giving reproducible measurements shown to be independent predictors of adverse outcomes in patients with various neurological insults, and is increasingly being used as a clinical assessment tool among ambulatory patients outside of the hospital setting, particularly for concussion assessment in sports medicine. The MindMirror™ smartphone application uses artificial intelligence to identify and measure changes in important PLR components, and was shown to deliver variables with high levels of correlation and agreement with existing measurement tools such as the Neuroptics NPi-200TM Automated Pupillometer.Tweetable abstractA novel smartphone-based AI tool identifies potential predictors of neurological insults such as concussion with similar performance to dedicated tools.
Reversal of vein of Galen aneurysmal malformation by stimulation of flow-mediated vessel fusion
Authors: Martin-Valiente Edwige , Du Yao , Goemans Chloé , Zindy Egor , Adam Myckel , Scheid Benoît , Vikkula Miikka , Lubicz Boris , Vanhollebeke Benoit , Baeyens Nicolas 
Published: October 2024

AbstractCongenital vascular malformations arise from defective homeostatic development of the vascular tree1. The aneurysmal malformation of the Vein of Galen (VGAM) is the most frequent neurovascular malformation in neonates, with limited therapeutic options and poor outcomes in the most severe cases2. This congenital disease is consecutive to germline genetic mutation ofRASA1orEPHB43,4, but little is known about the mechanisms leading to its development. We generated mutantrasa1aandephb4adeficiency models in zebrafish reproducing the genetic and structural characteristics of the VGAM in the dorsal longitudinal vein of the cerebral vasculature. We link the development of the malformation to a failure of the fusion of precursor blood vessels into a draining vessel for the choroidal type malformations and to a failure to constrict for the mural type malformations. The fusion process is driven by blood flow, sensed and integrated by endothelial cells. RASA1 deficiency destabilizes the homeostatic response to blood flow and contributes to impaired flow-mediated activation of MAPK and PI3K signaling. We targeted these defective mechanotransduction mechanisms pharmacologically in bothrasa1aandephb4amutant models, successfully reestablishing the fusion and constriction processes in preexisting malformations. This work identifies molecular actors of the flow-mediated blood vessel fusion mechanism, a specific angiogenetic program, and provides ground for treating VGAM and other vascular remodeling disorders.
The effect of surfactants and film-forming polymers on pulmonary surfactant function measuredin vitrois dose-rate dependent
Authors: Sengupta Sreyoshee , Barlow Hugh J. , Baltazar Maria T. , Sørli Jorid B. 
Published: October 2024

SummarySurfactants and film-forming polymers are common ingredients in consumer spray products such as cleaning products, hair care products, and anti-perspirants. Spraying eases application by creating aerosolised droplets of the product that can distribute evenly over the treated surface. However, these aerosols can potentially be inhaled during their normal application. Droplets that reach the alveoli can interact with the pulmonary surfactant; a complex mixture of phospholipids and proteins that regulates the surface tension at the air-liquid interface. This interaction could elevate the minimum surface tension at maximum compression and change the surface rheology of the pulmonary surfactant at the interface. We tested four surfactants and seven polymers for their ability to inhibit pulmonary surfactant functionin vitroand investigated if the inhibition is dose-rate dependent i.e., the product of the concentration (mg/mL) and aerosolisation rate (mL/min). We found that independent of chemical class (surfactant or polymer) there was a clear dose-rate dependent inhibition of pulmonary surfactant function and that different chemicals inhibited function at different dose-rates. We compared the points of departure of inhibitory chemicals to a polymer with known dose-rate dependent lung toxicity. When assessing the risk of chemicals that might be inhaled, it is essential to ensure normal use would not inhibit pulmonary surfactant function leading to immediate effects on the lungs.Lay summarySpray products create a cloud of tiny droplets in the air when they are used. This cloud can be inhaled, and if it reaches the deepest parts of the lungs, it can interact with the thin layer of liquid, called pulmonary surfactant, that covers the cells. It protects the lung tissue during the constant movement of breathing. Droplets can sometimes disrupt the pulmonary surfactant function, making breathing difficult. Chemicals that are used in spray products must be tested to assess if they are harmful if inhaled. In this project we studied the effect of chemicals that are commonly found in spray products on the functioning of the pulmonary surfactantin vitro. The results can be combined with otherin vitromethods to test if chemicals are harmful to inhale without testing on animals.
Modelling human social vision with cinematic stimuli
Authors: Santavirta Severi , Paranko Birgitta , Seppälä Kerttu , Hyönä Jukka , Nummenmaa Lauri 
Published: October 2024

AbstractSociability is central for humans. Visual information ranging from low-level physical features (e.g. luminance) to semantic information (e.g. face recognition) and high-level social inference (e.g. emotional valence of social interactions) is constantly sampled for navigating the social world. Here we utilize large-scale eye tracking during natural vision for mapping how different levels of visual information guide the perception of social scenes. In three experiments, participants (N = 166) watched full-length films and short movie clips with varying social content (total duration: 193 minutes) during eye tracking. To model the association between the perceptual features and spatiotemporal eye movement parameters (gaze position, gaze synchronization, pupil size and blinking), we extracted 39 stimulus features from the movies including low-level audiovisual features (e.g. luminance, motion), presence and location of mid-level semantic categories (e.g. faces, objects) and high-level social information (e.g. body movements, pleasantness). Pupil size was modulated by luminance, scene cuts and emotional arousal while gaze position was most accurately predicted by a combination of the presence of human faces, local motion and entropy. Faces and eyes were prioritized over other semantic categories and blinking rate decreased during periods of attentional engagement. Altogether the results show that human social vision is primarily guided by low-level physical features and mid-level semantic categories, while high-level social features such as emotional arousal primarily modulate pupillary responses.
Helminthic parasite infections of endangered western hoolock gibbons (Hoolock hoolock) in degraded habitats of Bangladesh
Authors: Kabir M Tarik , Lappan Susan , Acharjee Rajib , Pomy Jesmin Sultana , Sah Shahrul Anuar Mohd , Ruppert Nadine 
Published: October 2024

ABSTRACTAlthough habitat degradation and anthropogenic disturbance can increase the risk of parasitic infections for many animals, including primates, little information about parasitism in wild gibbons is available, and almost nothing is known about the prevalence of helminth infection in wild populations. Globally threatened western hoolock gibbons (Hoolock hoolock, Harlan 1834) are exposed to significant anthropogenic disturbances across their range. We examined faecal samples from wild gibbons in three highly degraded and fragmented forests in Bangladesh: Lawachara National Park, Saltila forest, and Sheikh Jamal Inani National Park, for helminths, and identified two helminthic parasites,Bunostomumsp., andEnterobiussp. Overall helminthic parasite prevalence (percentage of samples containing parasites) and intensity (mean number of parasites individuals per sample) in faecal samples from wild gibbons were 82% and 12.1, respectively. This is the first report ofBunostomumsp. andEnterobiussp. infections in wild individuals of western hoolock gibbons or any other small ape. Habitat fragmentation, degradation, human encroachment, and other anthropogenic disturbances in Bangladesh may contribute to higher infection risk and transmission of zoonotic diseases in this highly arboreal gibbon species, with unknown consequences for their health and long-term survival. As parasitic infections can be transmitted within and across species, affecting humans, other primates, and other wild and domesticated animals, habitat protection and restoration and public awareness campaigns applying the One Health approach should be used to mitigate the spread of zoonotic disease in shared landscapes.HIGHLIGHTSFirst reported helminthic parasite infections withBunostomumsp. andEnterobiussp. in wild gibbonsOut of 50 collected fecal samples from the endangered Western hoolock gibbon in three degraded forests in Bangladesh, 41 (82%) tested positive for helminthic infectionsParasite intensity ranged from 1 to 45 individuals per gram, with a median intensity of 9Lower parasite intensity (≤5) was more common in winter than in the monsoon season indicating seasonal variationsGRAPHICAL ABSTRACT
Polymorphisms in rs2069845 are associated with IL-6 and soluble IL-6 receptor levels during total joint replacement
Authors: Anderson Kyle D. , Dulion Bryan , Wong John , Patel Niyati , Debenedetti Anne , Della Valle Craig J. , Ross Ryan D. 
Published: October 2024

AbstractAs the number of patients undergoing total joint replacement (TJR) surgery increases, so does the number of revision surgeries. One driver of implant failure and subsequent revision surgery is peri-implant osteolysis, which is driven by inflammation-mediated bone loss. IL-6 is an inflammatory marker that is elevated during the peri-operative period. Early elevations in IL-6 levels have been linked to osteolysis development. The current study asked whether there is genetic contribution to the IL-6-related peri-operative inflammatory reaction to TJR surgery. Patients undergoing primary TJR (total hip or total knee) provided pre-operative and post-operative blood samples for measurement of the circulating levels of IL-6 and the soluble IL-6 receptor (sIL-6r) and evaluation of allele status of three single nucleotide polymorphisms (SNPs) linked to IL-6 or sIL-6r levels - rs2069845, rs228145, and rs4537545. Circulating sIL-6r levels were associated with allele status in the rs2228145 SNP. More interestingly, allele status in the rs2069845 SNP was associated with the change in circulating IL-6 levels following TJR surgery. Specifically, patients with the A,A allele had increasing levels of IL-6, while those harboring the G,A allele had decreasing levels of IL-6. Although the study was not designed to follow implant survival, due to the critical role of IL-6 in driving peri-implant osteolysis development, the results may suggest that the rs2069845 allele has a role in the success of orthopedic implants. rs2069845 polymorphisms may be a useful patient-specific marker of inflammatory response to TJR surgery.
A genome-to-proteome atlas charts natural variants controlling proteome diversity and forecasts their fitness effects
Authors: Jakobson Christopher M. , Hartl Johannes , Trébulle Pauline , Mülleder Michael , Jarosz Daniel F. , Ralser Markus 
Published: October 2024

SummaryDespite abundant genomic and phenotypic data across individuals and environments, the functional impact of most mutations on phenotype remains unclear. Here, we bridge this gap by linking genome to proteome in 800 meiotic progeny from an intercross between two closely relatedSaccharomyces cerevisiaeisolates adapted to distinct niches. Modest genetic distance between the parents generated remarkable proteomic diversity that was amplified in the progeny and captured by 6,476 genotype-protein associations, over 1,600 of which we resolved to single variants. Proteomic adaptation emerged through the combined action of numerouscis- andtrans-regulatory mutations, a regulatory architecture that was conserved across the species. Notably,trans-regulatory variants often arose in proteins not traditionally associated with gene regulation, such as enzymes. Moreover, the proteomic consequences of mutations predicted fitness under various stresses. Our study demonstrates that the collective action of natural genetic variants drives dramatic proteome diversification, with molecular consequences that forecast phenotypic outcomes.Highlights- Proteome diversity arises from natural genetic variants, with divergent proteomes in closely related parents and progeny.-Cis-regulatory elements had strong individual impacts, but coherenttranseffects combined to dominate protein expression.- Directional selection and frequent transgression suggest much of the proteome is under selective pressure.- Manytrans-regulators are enzymes or transporters, with fewer than 4% of pQTLs linking known interactors.- Genome-to-proteome connections predicted the fitness impact of mutations under various stresses, including a strong but hidden causal variant inIRA2/NF1.
Comparative Genome Study of Multidrug-resistantSerratia marcescensstrain IU-BTGE-M-3 Isolated from a Diarrheal Patient Reveals Antibiotic Resistance Profile
Authors: Hossain Md. Shohorab , Mamun Md. Abdullah Al , Alshaya Dalal Sulaiman , Attia KOTB A , Han Changhee , Haque AKM Ariful , Rahman Md Mafizur 
Published: October 2024

AbstractSerratia marcescensis a notable pathogen known for its intrinsic and acquired antimicrobial resistance, posing challenges in healthcare. The study investigates the multidrug-resistant (MDR)Serratia marcescensstrain BTGE-M-3, focusing on its genomic features and antibiotic resistance. The strain was identified using both morphological and molecular approaches, and its genome, which measured 4.97 Mbp and exhibited a GC content of 59.7%, was sequenced. The genome has 4,827 genes, including essential antibiotic resistance genes, such astet(41) for tetracyclines,aac(6′)-Icfor aminoglycosides,OqxBfor fluoroquinolones, andblaSST-1 beta-lactam, alongside various virulence determinants. Comparative genomics revealed high similarity (98.06% ANI) toS. marcescensstrain KS10, supporting its classification within the same species. Additionally, the genome analysis showed thatS. marcescensstrain IU-BTGE-M-3 comprises of 4390 gene clusters, 4564 genes, and 244 unique singleton genes. To summarize, the results showed thatS. marcescensstrain IU-BTGE-M-3 exhibited a high level of genomic diversity as well as diverse metabolic, cellular, and biological functions, and it is hypothesized that frequent strain exchanges resulted in the horizontal transfer of drug resistance genes. This study underscores the importance of genomic surveillance in understanding and combating antibiotic resistance in therapeutic settings.