bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mucociliary Clearance is Impaired in Small Airways of Cystic Fibrosis Pigs
Authors: Stewart Carley G. , Hilkin Brieanna M. , Gansemer Nicholas D. , Dick David W. , Sunderland John J. , Stoltz David A. , Abou Alaiwa Mahmoud H. , Zabner Joseph 
Published: May 2024

ABSTRACTRationaleCystic fibrosis is a genetic disorder characterized by recurrent airway infections, inflammation, and progressive decline in lung function. Autopsy and spirometry data suggest that cystic fibrosis may start in the small airways which, due to the fractal nature of the airways, account for most of the airway tree surface area. However, they are not easily accessible for testing.ObjectivesHere, we tested the hypothesis that mucociliary clearance is abnormal in the small airways of newborn cystic fibrosis pigs.MethodsCurrent mucociliary clearance assays are limited therefore we developed a dynamic positron emission tomography scan assay with high spatial and temporal resolution. Each study was accompanied by a high-resolution computed tomography scan that helped identify the thin outer region of the lung that contained small airways.Measurements and Main ResultsClearance of aerosolized [68Ga]macro aggregated albumin from distal airways occurred within minutes after delivery and followed a two-phase process. In cystic fibrosis pigs, both early and late clearance rates were slower. Stimulation of the cystic fibrosis airways with the purinergic agonist UTP further impaired late clearance. Only 1 cystic fibrosis pig treated with UTP out of 6 cleared more than 20% of the delivered dose.ConclusionsThese data indicate that mucociliary transport in the small airways is fast and can easily be missed if the acquisition is not fast enough. The data also indicate that mucociliary transport is impaired in small airways of cystic fibrosis pigs. This defect is exacerbated by stimulation of mucus secretions with purinergic agonists.
The interaction between social determinants of health, health behaviors, and child’s intellectual developmental diagnosis
Authors: Tchoua Phoebe P. , Clarke Emily , Wasser Heather , Agrawal Seema , Scothorn Rebecca , Thompson Kelsey , Schenkelberg Michaela , Willis Erik A. 
Published: May 2024

AbstractINTRODUCTIONSocial determinants of health (SDOH) may impact caregivers’ ability to implement evidence-based health practices at home during early childhood, especially in families with children with intellectual and developmental disabilities (IDD). Therefore, we examined the influence of SDOH and children’s diagnosis (typically developing [TD], Down syndrome [DS], autism) on caregiver’s self-report of meeting evidence-based health practices.METHODSCaregivers (n=172) of children ages 2-6 years (TD: n=93, DS: n=40, autism: n=39) completed an online survey on SDOH and health practices related to child nutrition (CN), physical activity (PA), outdoor play (OP), and screen time (ST). A total SDOH score was computed by assigning 1 point for each favorable SDOH metric (range 0-13). Linear regressions were used to examine associations between SDOH and CN, PA, OP, ST health practices and the moderating effect of IDD diagnosis.RESULTSMost caregivers were non-Hispanic White (84.3%), female (76.7%), 18-35 years old (55.2%), and married (89.5%). The DS group had the lowest SDOH score (mean = 8.4±1.0) compared to autism (mean = 10.1±1.0) and TD (mean = 11.0±0.9). No family scored 100% in evidence-based practices for any health practice. SDOH score was significantly associated with evidence-based practices met score for CN (b = 1.94, 95% CI = 0.84, 3.04; p = 0.001) and PA (b = 4.86, 95% CI = 2.92, 6.79; p <0.0001). Moderation analysis showed no association in the DS and autism groups between SDOH score and CN percent total score, or between SDOH score and CN, PA, and OP for percent evidence-based practices met. SDOH score was also not associated with OP percent total score for the DS group.CONCLUSIONSThis study highlights the differential influence of SDOH on caregivers’ implementing health practices in families with children of different IDD diagnoses. Future research is needed to understand impacts of SDOH on non-typically developing children.
In-brain construction of receptor-based protease sensors by coupling ligand-directed chemistry and click chemistry
Authors: Sakamoto Seiji , Shiraiwa Kazuki , Wang Mengchu , Ishikawa Mamoru , Nonaka Hiroshi , Hamachi Itaru 
Published: May 2024

AbstractThe chemical modification of natural proteins in living systems is highly desirable toward the cutting-edge research in chemistry-biology interface. Recent advances in bioorthogonal protein modification have enabled the production of chemically functional proteins in cultured cell systems. However, few methods are applicablein vivobecause of the complexity of the three-dimensional constructs of living systems with diverse, heterogeneous cell populations and flow systems filled with tissue fluids. Here, we report a genetic engineering-free method to modify receptor proteins with various probes in the living mouse brain by combining in-brain ligand-directed chemistry with bioorthogonal click chemistry, and propose a chemical guideline for the reaction design. The rapid and selective tethering of a set of fluorescent peptides to AMPA-type glutamate receptors (AMPARs) allowed the construction of receptor-based fluorescent sensors. These probes enabled mapping of the activity of matrix metalloproteinase-9 proximal to AMPARs in the living brain to be realized with high spatial resolution. Our strategy provides new opportunities for the precise analysis of particularin vivomicroenvironments that has not been able to be addressed by conventional methods. Such analysis should contribute to the understanding of the molecular basis for complicatedin vivoevents, such as the regulation of neuroplasticity, the most important challenge in neuroscience.
The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catsharkScyliorhinus caniculareveal the molecular bases of sensory organ evolution in jawed vertebrates
Authors: Mayeur H. , Leyhr J. , Mulley J. , Leurs N. , Michel L. , Sharma K. , Lagadec R. , Aury J.-M. , Osborne O.G. , Mulhair P. , Poulain J. , Mangenot S. , Mead D. , Smith M. , Corton C. , Oliver K. , Skelton J. , Betteridge E. , Dolucan J. , Dudchenko O. , Omer A.D. , Weisz D. , Aiden E.L. , McCarthy S. , Sims Y. , Torrance J. , Tracey A. , Howe K. , Baril T , Hayward A. , Martinand-Mari C. , Sanchez S. , Haitina T. , Martin K. , Korsching S.I. , Mazan S. , Debiais-Thibaud M. 
Published: May 2024

AbstractCartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catsharkScyliorhinus caniculato shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging andin situgene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.
Stand Age and Climate Change Effects on Carbon Increments and Stock Dynamics
Authors: Vangi Elia , Dalmonech Daniela , Morichetti Mauro , Grieco Elisa , Giannetti Francesca , D’Amico Giovanni , Nakhavali Mahdi (Andre) , Chirici Gherardo , Collalti Alessio 
Published: May 2024

AbstractCarbon assimilation and wood production are influenced by environmental conditions and endogenous factors, such as species auto-ecology, age, and hierarchical position within the forest structure. Disentangling the intricate relationships between those factors is more pressing than ever due to climate change’s pressure. We employed the 3D-CMCC-FEM model to simulate undisturbed forests of different ages under four climate change scenarios (plus one no climate change) from five Earth System Models. In this context, carbon stocks and increment were simulated via total car-bon woody stocks and mean annual increment, which depends mainly on climate trends. We find greater differences among different age cohorts under the same scenario than in different climate scenarios under the same age class. Increasing temperature and changes in precipitation patterns led to a decline in above-ground biomass in spruce stands, espe-cially in the older age classes. On the contrary, the results show that beech forests at DK-Sor will maintain and even increase C-storage rates under most RCP scenarios. Scots pine forests show an intermediate behavior with a stable stock capacity over time and in different scenarios but with decreasing mean volume annual increment. These results confirm current observations worldwide that indicate a stronger climate-related decline in conifers forests than in broadleaves.
Hypothalamus-specific NSCs derived from hPSCs ameliorate age-associated dysfunction upon transplantation into aged mouse hypothalamus
Authors: Sulistio Yanuar Alan , Lee Yuna , Pieknell Kelvin , Hong Sebin , Kim Jumi , Seok Min Jong , Lee Na-Kyung , Park Kyu-Sang , Hong Taeui , Choi Suyeon , Kim Ki Woo , Yang Dong Joo , Park Woong-Yang , Han Kyung Yeon , Yoon Seul Gi , Kim Il Yong , Seong Je Kyung , Lee Tae Yong , Kim Min Sung , Kim Min Soo , Lee Sang-Hun 
Published: May 2024

AbstractThe hypothalamus is the brain region that regulates systemic body metabolism and multiple functions in other brain regions. In adult mice, the hypothalamus harbors neural stem/precursor cell (NSC)-like cells. Along with the dysregulation of body metabolism and physiology that occurs during aging, the NSC population in the hypothalamus declines with age. Here, we introduce a novel protocol that yields scalable and storable hypothalamus-specific NSCs (htNSCs) from human pluripotent stem cells (hPSCs). Implanting htNSCs into the medio-basal hypothalami of aged mice conspicuously ameliorated age-related declines in metabolic fitness, physical capacity, and cognitive function and produced corresponding histologic changes in various body tissues. Single transcriptome and immunohistochemical analyses of the grafted hypothalamic tissues showed that the anti-aging effects were attained by correcting glial NF-κB, TNF-α, and NLRP3 inflammasome pathways. Collectively, our findings support the potential of anti- or healthy aging therapies that target htNSCs and hypothalamic inflammation.One Sentence SummaryhPSC-derived hypothalamus NSCs mitigate age-associated physiological decline upon transplantation into the hypothalamus of aged mice.
Genomic factors shaping codon usage across the Saccharomycotina subphylum
Authors: Zavala Bryan , Dineen Lauren , Fisher Kaitlin J. , Opulente Dana A. , Harrison Marie-Claire , Wolters John F. , Shen Xing-Xing , Zhou Xiaofan , Groenewald Marizeth , Hittinger Chris Todd , Rokas Antonis , LaBella Abigail Leavitt 
Published: May 2024

AbstractCodon usage bias, or the unequal use of synonymous codons, is observed across genes, genomes, and between species. The biased use of synonymous codons has been implicated in many cellular functions, such as translation dynamics and transcript stability, but can also be shaped by neutral forces. The Saccharomycotina, the fungal subphylum containing the yeastsSaccharomyces cerevisiaeandCandida albicans, has been a model system for studying codon usage. We characterized codon usage across 1,154 strains from 1,051 species to gain insight into the biases, molecular mechanisms, evolution, and genomic features contributing to codon usage patterns across the subphylum. We found evidence of a general preference for A/T-ending codons and correlations between codon usage bias, GC content, and tRNA-ome size. Codon usage bias is also distinct between the 12 orders within the subphylum to such a degree that yeasts can be classified into orders with an accuracy greater than 90% using a machine learning algorithm trained on codon usage. We also characterized the degree to which codon usage bias is impacted by translational selection. Interestingly, the degree of translational selection was influenced by a combination of genome features and assembly metrics that included the number of coding sequences, BUSCO count, and genome length. Our analysis also revealed an extreme bias in codon usage in the Saccharomycodales associated with a lack of predicted arginine tRNAs. The order contains 24 species, and 23 are computationally predicted to lack tRNAs that decode CGN codons, leaving only the AGN codons to encode arginine. Analysis of Saccharomycodales gene expression, tRNA sequences, and codon evolution suggests that extreme avoidance of the CGN codons is associated with a decline in arginine tRNA function. Codon usage bias within the Saccharomycotina is generally consistent with previous investigations in fungi, which show a role for both genomic features and GC bias in shaping codon usage. However, we find cases of extreme codon usage preference and avoidance along yeast lineages, suggesting additional forces may be shaping the evolution of specific codons.
A dedicated caller forDUX4rearrangements from whole-genome sequencing data
Authors: Grobecker Pascal , Berri Stefano , Peden John F. , Chow Kai-Jie , Fielding Claire , Armogida Ivana , Northen Helen , McBride David J. , Campbell Peter J. , Becq Jennifer , Ryan Sarra L. , Bentley David R. , Harrison Christine J. , Moorman Anthony V. , Ross Mark T. , Mijuskovic Martina 
Published: May 2024

AbstractRearrangements involving theDUX4gene (DUX4-r) define a subtype of paediatric and adult acute lymphoblastic leukaemia (ALL) with a favourable outcome. Currently, there is no ‘standard of care’ diagnostic method for their confident identification. Here, we present an open-source software tool designed to detectDUX4-r from short-read, whole-genome sequencing (WGS) data. Evaluation on a cohort of 210 paediatric ALL cases showed that our method detects all known, as well as previously unidentified, cases ofIGH::DUX4and rearrangements with other partner genes. These findings demonstrate the possibility of robustly detectingDUX4-r using WGS in the routine clinical setting.
A sequential, RNA-derived, modified adenosine pathway safeguards cellular metabolism
Authors: Ogawa Akiko , Watanabe Satoshi , Kawakami Tomoyoshi , Tsai Allen Yi-Lun , Fuse Jirio , Araki Kimi , Sawa Shinichiro , Inaba Kenji , Wei Fan-Yan 
Published: May 2024

SUMMARYRNA contains diverse post-transcriptional modifications and its catabolic breakdown yields numerous modified nucleosides that must be properly processed, but the molecular mechanism is largely unknown. Here, we show that three RNA-derived modified adenosines,N6-methyladenosine (m6A),N6,N6-dimethyladenosine (m6,6A), andN6-isopentenyladenosine (i6A), are sequentially metabolized to inosine monophosphate (IMP) to prevent their intrinsic cytotoxicity. These modified adenosines are phosphorylated by adenosine kinase (ADK) followed by adenosine deaminase-like (ADAL)-mediated deamination in both plants and animals. ADAL knockout mice accumulateN6-modified AMPs that allosterically inhibit AMP-activated protein kinase (AMPK), leading to dysregulation of glucose metabolism. Furthermore, ADK deficiency, reported in patients with severe metabolic defects, induces aberrant elevation of m6A/m6,6A/i6A, disrupting lipid metabolism and causing early death in mouse models. The findings unveil a fundamental mechanism by which cells alleviate the toxicity of modified adenosines, and that connects modified adenosines to human disease.In briefRNA catabolism yields diverse nucleosides with modifications attached. Three RNA-derived modified adenosines (m6A, m6,6A, and i6A) are intrinsically toxic and subjected to sequential metabolism to yield inosine monophosphate. Dysregulation of this pathway impairs energy balance and contributes to metabolic diseases.HighlightsCytotoxic RNA catabolism-derived modified adenosines undergo sequential metabolismm6A, m6,6A, and i6A are phosphorylated by ADK then deaminated by ADAL to IMPm6AMP, m6,6AMP, and i6AMP allosterically inhibit AMP-mediated AMPK activationLoss of ADK causes the accumulation of m6A, m6,6A, and i6A, and abnormal lipid metabolism, which can lead to genetic disease
Subtilase SBT5.2 inactivates flagellin immunogenicity in the plant apoplast
Authors: Buscaill Pierre , Sanguankiattichai Nattapong , Kaschani Farnusch , Huang Jie , Mooney Brian C. , Li Yuge , Lyu Joy , Sueldo Daniela , Kaiser Markus , van der Hoorn Renier A. L. 
Published: May 2024

AbstractMost angiosperm plants recognise the flg22 epitope in bacterial flagellin via homologs of cell surface receptor FLS2 and mount pattern-triggered immune responses. However, flg22 is buried within the flagellin protein indicating that proteases might be required for flg22 release. Here, we demonstrate the extracellular subtilase SBT5.2 not only releases flg22, but also inactivates the immunogenicity of flagellin and flg22 by cleaving within the flg22 epitope, consistent with previous reports that flg22 is unstable in the apoplast. The prolonged lifetime of flg22 insbt5.2mutant plants results in increased bacterial immunity in priming assays, indicating that SBT5.2 counterbalances flagellin immunogenicity to provide spatial-temporal control and restrict costly immune responses and that bacteria take advantage of the host proteolytic machinery to avoid detection by flagellin having a protease-sensitive flg22 epitope.
The structure of the SufS-SufE complex reveals interactions driving protected persulfide transfer in iron-sulfur cluster biogenesis
Authors: Gogar Rajleen K. , Chhikara Nidhi , Vo Minh , Gilbert Nathaniel C. , Dunkle Jack A. , Frantom Patrick A. 
Published: May 2024

AbstractFe-S clusters are critical cofactors for redox chemistry in all organisms. The cysteine desulfurase, SufS, provides sulfur in the SUF Fe-S cluster bioassembly pathway. SufS is a dimeric, PLP-dependent enzyme that uses cysteine as a substrate to generate alanine and a covalent persulfide on an active site cysteine residue. SufS enzymes are activated by an accessory transpersulfurase protein, either SufE or SufU depending on the organism, which accepts the persulfide product and delivers it to downstream partners for Fe-S assembly. Here, usingE. coliproteins, we present the first X-ray crystal structure of a SufS/SufE complex. There is a 1:1 stoichiometry with each monomeric unit of the EcSufS dimer bound to one EcSufE subunit, though one EcSufE is rotated ∼7° closer to the EcSufS active site. EcSufE makes clear interactions with the α16 helix of EcSufS and site-directed mutants of several α16 residues were deficient in EcSufE binding. Analysis of the EcSufE structure showed a loss of electron density at the EcSufS/EcSufE interface for a flexible loop containing the highly conserved residue R119. An R119A EcSufE variant binds EcSufS but is not active in cysteine desulfurase assays and fails to support Fe-S cluster bioassembly in vivo.35S-transfer assays suggest that R119A EcSufE can receive a persulfide, suggesting the residue may function in a release mechanism. The structure of the EcSufS/EcSufE complex allows for comparison with other cysteine desulfurases to understand mechanisms of protected persulfide transfer across protein interfaces.
T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota
Authors: de Souza Patricia Rodrigues Marques , Keenan Catherine M. , Wallace Laurie E. , Habibyan Yasaman Bahojb , Davoli-Ferreira Marcela , Ohland Christina , Vicentini Fernando A. , McCoy Kathy D. , Sharkey Keith A. 
Published: May 2024

AbstractThe gut microbiota and immune system maintain intestinal homeostasis and regulate gut physiology in concert with the enteric nervous system (ENS). However, the underlying mechanisms remain incompletely understood. Using wildtype and T-cell deficient germ-free mice colonized with segmented filamentous bacteria (SFB) or specific pathogen-free (SPF) microbiota, we studied immune regulation of the ENS and intestinal motility. Colonization markedly increased Th17 cells and Treg expressing RORγ+T cells in both the ileum and colon of wildtype mice. T cells were necessary for the normalization of intestinal motility after colonization by SPF microbiota, and for SFB to restore neuronal density in the ENS of the ileum of germ-free mice. T cells were also required for neurogenic responses in myenteric neurons of the ileum, but not the colon, and for regulating the levels of nestin expression. The cytokines IL-1β and IL-17A mediate the enteric neurogenic response to an SPF microbiota but were not involved in the regulation of intestinal motility. Together, our findings provide new insights into the microbiota-neuroimmune dialogue that regulates intestinal physiology.
Chicken cecal microbial functional capacity and resistome differ by age and barn disinfection practice
Authors: Fan Yi , Ju Tingting , Bhardwaj Tulika , Korver Douglas R. , Willing Benjamin P. 
Published: May 2024

AbstractChemical disinfectants and water-wash methods are widely employed in sanitizing broiler chicken barns. Previous studies showed that chemical disinfectants affect environmental microbial composition and antibiotic resistance genes (ARGs). However, little is known regarding how barn disinfection treatments impact the chicken gut resistome and microbial functionality. The current study compared the effects of chemical disinfection and water-wash method on the gut microbiome and resistome of commercial broilers using a crossover experimental design after 2 production cycles at 7 barns. Shotgun metagenomic sequencing performed on cecal contents collected at day 7 and 30 also allowed evaluation of age-associated characteristics of microbiome. Age of the chickens had the largest effects on the resistome, with younger birds having increased relative abundance of total ARGs (P<0.05) and differences in resistance mechanism, however, functional and resistome differences were also identified by barn sanitation practice. At day 7, chickens in chemically-disinfected barns had decreased functional capacity related to amino acid synthesis compared to the water-wash group. Additionally, genes related to stringent response were enriched in chickens raised under chemically-disinfected condition (FDR-P<0.05), suggesting selection for stress resistance. Consistently, lower abundance of genetic pathways encoding amino acid biosynthesis associated with cecalHelicobacter pullorumwas observed in the disinfection group at day 30 compared to the water-wash group, with the same pattern in short-chain fatty acid biosynthesis (FDR-P<0.05). Overall, while the use of disinfectants in barn sanitation slightly affected the relative abundance of some ARGs in the gut, age had a dominant effect on the microbial functionality and resistome.ImportanceThis is the first study to evaluate the effect of sanitation practices on microbial functional capacity and resistome of chickens in a commercial setting. It is also amongst the biggest metagenomics studies on the gut microbiome of broiler chickens. It provides new insights into the changes in resistance profiles with age that agree with other studies examining maturation of the microbiome in other species. Finally, the current study provides valuable insights for informing industry sanitation practices and future studies on broiler gut microbiome and resistome.