bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerated Nitrogen Cycling on Seagrass Leaves in a High-CO2World
Authors: Berlinghof Johanna , Montilla Luis M. , Peiffer Friederike , Quero Grazia M. , Marzocchi Ugo , Meador Travis B. , Margiotta Francesca , Abagnale Maria , Wild Christian , Cardini Ulisse 
Published: May 2023

AbstractSeagrass meadows form highly productive and diverse ecosystems in coastal areas worldwide, where they are increasingly exposed to ocean acidification (OA). Efficient nitrogen (N) cycling and uptake are essential to maintain plant productivity, but the effects of OA on N transformations in these systems are poorly understood. Here we show that complete N cycling occurs on leaves of the Mediterranean seagrassPosidonia oceanica, with OA affecting both N gain and loss while the prokaryotic community structure remains largely unaffected. Daily leaf-associated N2fixation contributed to 35% of the plant’s N demand under ambient pH, whereas it contributed to 45% under OA. Nitrification potential was only detected under OA, and N-loss via N2production increased, although the balance remained decisively in favor of enhanced N gain. Our work highlights the role of the N-cycling microbiome in seagrass adaptation to OA, with key N transformations accelerating towards increased N gain.
Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair
Authors: Saraswathy Vishnu Muraleedharan , Zhou Lili , Mokalled Mayssa H. 
Published: May 2023

ABSTRACTAdult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity between 1 and 3 weeks post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.
Scaling the Discrete-time Wright Fisher model to biobank-scale datasets
Authors: Spence Jeffrey P. , Zeng Tony , Mostafavi Hakhamanesh , Pritchard Jonathan K. 
Published: May 2023

AbstractThe Discrete-Time Wright Fisher (DTWF) model and its large population diffusion limit are central to population genetics. These models describe the forward-in-time evolution of the frequency of an allele in a population and can include the fundamental forces of genetic drift, mutation, and selection. Computing like-lihoods under the diffusion process is feasible, but the diffusion approximation breaks down for large sample sizes or in the presence of strong selection. Unfortunately, existing methods for computing likelihoods under the DTWF model do not scale to current exome sequencing sample sizes in the hundreds of thousands. Here we present an algorithm that approximates the DTWF model with provably bounded error and runs in time linear in the size of the population. Our approach relies on two key observations about Binomial distributions. The first is that Binomial distributions are approximately sparse. The second is that Binomial distributions with similar success probabilities are extremely close as distributions, allowing us to approximate the DTWF Markov transition matrix as a very low rank matrix. Together, these observations enable matrix-vector multiplication in linear (as opposed to the usual quadratic) time. We prove similar properties for Hypergeometric distributions, enabling fast computation of likelihoods for subsamples of the population. We show theoretically and in practice that this approximation is highly accurate and can scale to population sizes in the billions, paving the way for rigorous biobank-scale population genetic inference. Finally, we use our results to estimate how increasing sample sizes will improve the estimation of selection coefficients acting on loss-of-function variants. We find that increasing sample sizes beyond existing large exome sequencing cohorts will provide essentially no additional information except for genes with the most extreme fitness effects.
Mycolactone A vs. B: Does localization or association explain isomer-specific toxicity?
Authors: Nguyen John D. M. , da Hora Gabriel C. A. , Swanson Jessica M. J. 
Published: May 2023

ABSTRACTMycolactone is an exotoxin produced byMycobacterium ulceransthat causes the neglected tropical skin disease Buruli ulcer. This toxin inhibits the Sec61 translocon in the endoplasmic reticulum (ER), preventing the host cell from producing many secretory and transmembrane proteins, resulting in cytotoxic and immunomodulatory effects. Interestingly, only one of the two dominant isoforms of mycolactone is cytotoxic. Here, we investigate the origin of this specificity by performing extensive molecular dynamics (MD) simulations with enhanced free energy sampling to query the association trends of the two isoforms with both the Sec61 translocon and the ER membrane, which serves as a toxin reservoir prior to association. Our results suggest that mycolactone B (the cytotoxic isoform) has a stronger association with the ER membrane than mycolactone A due to more favorable interactions with membrane lipids and water molecules. This could increase the reservoir of toxin proximal to the Sec61 translocon. Isomer B also interacts more closely with the lumenal and lateral gates of the translocon, the dynamics of which are essential for protein translocation. These interactions induce a more closed conformation, which has been suggested to block signal peptide insertion and subsequent protein translocation. Collectively, these findings suggest that isomer B’s unique cytotoxicity is a consequence of both increased localization to the ER membrane and channel-locking association with the Sec61 translocon, facets that could be targeted in the development of Buruli Ulcer diagnostics and Sec61-targeted therapeutics.
Cardiomyocyte-specific deletion of PTP1B protects against HFD-induced cardiomyopathy through direct regulation of cardiac metabolic signaling
Authors: Sun Yan , Chanrasekhar Vasanth , Kessinger Chase W. , Tang Peiyang , Gao Yunan , Kamli-Salino Sarah , Nelson Katherine , Delibegovic Mirela , Abel E. Dale , Kontaridis Maria I. 
Published: May 2023

BackgroundHeart failure is the number one cause of death worldwide and mortality is directly correlated with the high incidence of obesity and diabetes. Indeed, the epidemic phenomenon of obesity was projected to reach 50% in the US by the year 2030. However, the mechanisms linking metabolic dysfunction with heart disease are not clear. Protein Tyrosine Phosphatase 1B (PTP1B), a negative regulator of insulin signaling, is considered to be an emerging therapeutic target against the development of obesity, insulin resistance, and diabetes. Increased PTP1B levels and activity have been observed in brain, muscle and adipose tissues isolated from obese and/or diabetic animals, as well as in human obese human patients. Its role, however, and the mechanisms by which it modulates metabolic processes in the heart remain unknown.Method and ResultsWe generated cardiomyocyte (CM)-specific PTP1B knock-out (PTP1Bfl/fl::ꭤMHCCre/+) mice to investigate the cardiomyocyte-specific role of PTP1B in response to high fat diet (HFD)-induced cardiac dysfunction. While we did not observe any physiological or functional cardiac differences at baseline, in response to HFD, we found that PTP1Bfl/fl::ꭤMHCCre/+mice were protected against development of cardiac hypertrophy, mitochondrial dysfunction, and diminished cardiac steatosis. Metabolomics data revealed that hearts with CM-specific deletion of PTP1B had increased fatty acid oxidation and NAD+metabolism, but reduced glucose metabolism; we further validated these findings by real-time qPCR analysis. Mechanistically, we identified a novel PTP1B PKM2-AMPK axis in the heart, which acts as a molecular switch to promote fatty acid oxidation. In this regard, we identified that hearts from PTP1Bfl/fl::ꭤMHCCre/+mice had upregulated levels of nicotinamide adenine dinucleotide (NAD+) and NAD phosphate (NADPH), leading to higher levels of nicotinamide phosphoribosyl transferase (NAMPT), the rate-limiting step of the NAD+salvage pathway and an enzyme associated with obesity and diabetes.ConclusionsTogether, these results suggest that CM-specific deletion of PTP1B mediates a substrate switch from glucose to fatty acid metabolism, protecting hearts against development of HFD-induced cardiac hypertrophy and dysfunction through mechanisms involving a novel PTP1B/PKM2/AMPK axis that is critical for the regulation of NAMPT and NAD+biosynthesis.
Protocol for Generation of a Patient-Reported Outcome Measure of Quality of Life in Heart Valve Disease: The VALVQ
Authors: Pons Ariel , Whalley Gillian , Jenkinson Crispin , Morley David , Coffey Sean 
Published: May 2023

ABSTRACTBackgroundThere is an increasing prevalence of people worldwide with heart valve diseases (HVD), especially rheumatic heart disease, aortic stenosis, and mitral regurgitation, as well as people with a previous valve repair or replacement. Treatment decisions for HVD can be complex, making quality of life an important factor, but no questionnaire to measure quality of life across the lifespan of HVD exists. In this article, we describe the protocol for the development of such a questionnaire.Methods and ResultsThe project will occur over four phases. First, people with HVD, family members and clinical experts will be interviewed to generate a list of questions (‘items’) that comprehensively describe participants’ quality of life. In the second phase, this will be formatted into a questionnaire that is pilot tested for functionality. In the third phase, items will be selected according to item distributions, factor analysis and rotation, and item response theory using the Graded Response Model to generate a final questionnaire containing only the best-performing items, which will then be tested for validity.Validity assessments will be repeated after final questionnaire administration in a new sample in the fourth phase.ConclusionThe article gives a template for development of a patient report outcome measure (PROM) in the health sciences. It is expected that the final questionnaire, called the VALVQ, will allow clinical trials to more sensitively assess quality of life changes across the spectrum and lifespan in HVD.
Carcinogenesis is associated with sex-biased tissue environments and imbalances between estrogen receptor alpha and thyroid hormone receptors
Authors: Zhang Feng , Deng Minghua 
Published: May 2023

AbstractThere is extensive evidence of sex differences in the susceptibility and prognosis of non-reproductive cancers. In addition to external factors, biological sex bias (e.g., sex chromosomes, hormones, and immune function) is suspected to function as a selective pressure that influences the evolutionary process of carcinogenesis. However, there remains a lack of clarity concerning the extent of the effect of sex bias on carcinogenesis, as well as the underlying mechanism. In this study, we show that tissue sex bias, correlated to gonadotropin-releasing hormone, varies among tissues and is associated with two distinct age-specific patterns of cancer incidence: parallel and nonparallel. Additionally, we reveal that imbalances in estrogen receptor alpha and thyroid hormone receptors are associated with levels of hypoxia-inducible factors, which have three phases (hypoxia, hyperoxia, and “chaotic-oxia”) that exist in most cancers and are linked to specific cancer subtypes, including cancers with microsatellites, the CpG island methylator phenotype, or hypermethylation. Our results suggest that sex-biased tissue environments and hormonal imbalances may influence the incidence pattern and direction of carcinogenesis, emphasizing the importance of maintaining hormonal homeostasis for cancer prevention and providing insights toward improving therapies for cancer types with hormonal imbalances.Plain English summarySex bias has been long observed in cancer susceptibility and prognosis. Hormone difference between the two sexes was believed to play a role. However, the mechanism is still largely unknown. Our study has shown that the activity of one hormone secreted from pituitary, namely gonadotropin-releasing hormone, are correlated to sex-biased tissue environment, which was speculated to influence incidence patterns of carcinogenesis. Furthermore, hormonal imbalance, particularly imbalance in receptors of estrogen and thyroid hormone, which is associated with specific cancer subtypes, was speculated to influence the direction of carcinogenesis.HighlightsThere are two distinct patterns of cancer age-specific incidence curve between the two sexes: parallel and nonparallel.The parallel and nonparallel patterns are associated with sex bias in tissue environments which is correlated with sex-biased activity of gonadotropin-releasing hormone.Three sex-biased mutated genes:PTEN,PGM5andLARP4B, have tissue-specific hotspot mutations which are associated with microsatellite instability (MSI), and the proportion of MSI exhibit sex bias in stomach cancer.Three hypoxia induce factors (HIFs) phases: hypoxia, hyperoxia, and “chaotic-oxia”, exist in most cancers and are linked to specific cancer subtypes, including cancers with MSI, the CpG island methylator phenotype, and hypermethylation.The phases of HIFs are associated with imbalances between estrogen receptor alpha and thyroid hormone receptors.
Convergent mutations in phage virion assembly proteins enable evasion of Type I CBASS immunity
Authors: Richmond-Buccola Desmond , Hobbs Samuel J. , Garcia Jasmine M. , Toyoda Hunter , Gao Jingjing , Shao Sichen , Lee Amy S. Y. , Kranzusch Philip J. 
Published: May 2023

SUMMARYCBASS is an anti-phage defense system that protects bacteria from phage infection and is evolutionarily related to human cGAS-STING immunity. cGAS-STING signaling is initiated by viral DNA but the stage of phage replication which activates bacterial CBASS remains unclear. Here we define the specificity of Type I CBASS immunity using a comprehensive analysis of 975 operon-phage pairings and show that Type I CBASS operons composed of distinct CD-NTases, and Cap effectors exhibit striking patterns of defense against dsDNA phages across five diverse viral families. We demonstrate that escaper phages evade CBASS immunity by acquiring mutations in structural genes encoding the prohead protease, capsid, and tail fiber proteins. Acquired CBASS resistance is highly operon-specific and typically does not affect overall fitness. However, we observe that some resistance mutations drastically alter phage infection kinetics. Our results define late-stage virus assembly as a critical determinant of CBASS immune activation and evasion by phages.
Achieving popularity to attract more patients via free knowledge sharing in the online health community
Authors: Ouyang Peng , Liu Jiaming , Zhang Xiaofei 
Published: May 2023

PurposeFree knowledge sharing in the online health community has been widely documented. However, whether free knowledge sharing can help physicians accumulate popularity and further the accumulated popularity can help physicians attract patients remain unclear. To unveil these gaps, this study aims to examine how physicians' popularity are affected by their free knowledge sharing, how the relationship between free knowledge sharing and popularity is moderated by professional capital, and how the popularity finally impacts patients' attraction.Design/methodology/approachThe authors collect a panel dataset from Hepatitis B within an online health community platform with 10,888 observations from April 2020 to August 2020. The authors develop a model that integrates free knowledge sharing, popularity, professional capital, and patients' attraction. The hierarchical regression model is used to for examining the impact of free knowledge sharing on physicians' popularity and further investigating the impact of popularity on patients' attraction.FindingsThe authors find that the quantity of articles acted as the heuristic cue and the quality of articles acted as the systematic cue have positive effect on physicians' popularity, and this effect is strengthened by physicians' professional capital. Furthermore, physicians' popularity positively influences their patients' attraction.Originality/valueThis study reveals the aggregation of physicians' popularity and patients' attraction within online health communities and provides practical implications for managers in online health communities.
The choice of destination country of international franchise networks: the case of Mexican franchisors
Authors: Flores Villanueva Cesario Armando , Gaytán Ramírez María del Carmen , Núñez García Aleida 
Published: May 2023

PurposeThis article examines the influence of market opportunity, risk, and distance on the choice of destination country for Mexican franchises.Design/methodology/approachThe research hypotheses are developed under the theoretical approaches of institutional theory, agency theory, and transaction costs theory and were contrasted on the data obtained from 52 Mexican international franchisors operating in 37 countries as of 2016. This study uses linear regression with ordinary minimums using the STATA 13.1 software.FindingsThe results reveal that a larger market size, a greater level of economic freedom, and a smaller geographic distance are determining factors in the choice of destination country. No statistical significance was found in the variables GDP per capita, level of democracy and cultural distance.Originality/valueThis research contributes to the theoretical and practical field. On the theoretical side, this study integrates institutional theory, agency theory, and transaction cost theory to evaluate the factors of the destination country that influence the internationalization process of the franchise. Another contribution of this study is to apply theories and models of developed economies to the process of internationalization of franchises in an emerging economy. Additionally, this study is based on a model that considers the distance, opportunities and risks that are considered by Mexican franchisors in the selection of the international markets in which they maintain operations. This study contains important practical implications that can serve as relevant information for decision-making in the franchise sector and its internationalization. This data is valuable for new models of Mexican franchises that decide to start their internationalization process.
Connection between corporate diversification, CSR and firm performance in South Asia
Authors: Shira Ruba Khalid 
Published: May 2023

PurposeThe manufacturing sector plays an important role in any economy. The sector opts for diversification techniques and CSR initiatives in a competitive business environment for growth, survival and reputation. This study examined the impact of corporate diversification and CSR on the financial performance of South Asian manufacturing firms.Design/methodology/approachData is obtained from the financial statements of 350 listed South Asian manufacturing firms as well as the respective stock exchanges of these countries. The data for research analysis ranges from 2010 to 2020. Diversification is measured using product diversification and geographic diversification. CSR is quantified in terms of social contribution value. Accounting measurements (ROA and ROE) are also used to capture corporate performance. For hypothesis testing, the study also uses fixed effect panel regression, and for assessing the robustness of the findings, the two-step dynamic panel system-GMM regression approach is used.FindingsFindings of study indicate a positive impact of product and geographic diversification on financial performance measured with ROA. However, geographic diversification is insignificantly linked with ROA and ROE. Further, CSR positively impacts the performance of firms in South Asia with both performance measures.Originality/valueThe study has several policy implications based on the findings, including the need for the manufacturing sector to practice and implement appropriate diversification approaches and CSR initiatives to improve its financial performance and reputation.
Purchase intention of organic foods from the perspective of consumers
Authors: Eberle Luciene , Milan Gabriel Sperandio , Graciola Ana Paula , Borchardt Miriam , Pereira Giancarlo Medeiros 
Published: May 2023

PurposeThe present research had the objectives of proposing, testing and validating a theoretical model that includes ecological awareness, healthy consumption, consumer attitude and price awareness as determinants of the purchase intention of organic foods and analyzing the moderating effect of gender, educational level and income of families in the relationship between price awareness and purchase intention.Design/methodology/approachA survey research was implemented with 382 Brazilians who consume organic foods from a non-probabilistic sample for convenience. For data analysis, structural equation modeling was used to test the proposed theoretical model and its respective relationships.FindingsThe results showed that ecological awareness, healthy consumption, consumer attitude and price awareness are determinants of the purchase intention of organic foods 79.1% of the variance of purchase intention of organic foods could be explained by such determinants. Another relevant result is that gender and family income has a positive moderating effect on the relationship between price awareness and the intention to purchase organic food.Originality/valueEnvironmental problems and their adverse impacts on humans have become an important issue to be analyzed by academics (researchers), governments and organizations, and their managers, especially when organic foods are considered.