bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population size interacts with reproductive longevity to shape the germline mutation rate
Authors: Zhu Luke , Beichman Annabel , Harris Kelley 
Published: December 2023

AbstractMutation rates vary across the tree of life by many orders of magnitude, with lower mutation rates in species that reproduce quickly and maintain large effective population sizes. A compelling explanation for this trend is that large effective population sizes facilitate selection against weakly deleterious “mutator alleles” such as variants that interfere with the molecular efficacy of DNA repair. However, in multicellular organisms, the relationship of the mutation rate to DNA repair efficacy is complicated by variation in reproductive age. Long generation times leave more time for mutations to accrue each generation, and late reproduction likely amplifies the fitness consequences of any DNA repair defect that creates extra mutations in the sperm or eggs. Here, we present theoretical and empirical evidence that a long generation time amplifies the strength of selection for low mutation rates in the spermatocytes and oocytes. This leads to the counterintuitive prediction that the species with the highest germline mutation rates per generation are also the species with most effective mechanisms for DNA proofreading and repair in their germ cells. In contrast, species with different generation times accumulate similar mutation loads during embryonic development. Our results parallel recent findings that the longest-lived species have the lowest mutation rates in adult somatic tissues, potentially due to selection to keep the lifetime mutation load below a harmful threshold.Significance StatementAll cells accumulate mutations due to DNA damage and replication errors. When mutations occur in germ tissues including sperm, eggs, and the early embryo, they create changes in the gene pool that can be passed down to future generations. Here, we examine how rates of germline mutations vary within and between mammalian species, and we find that species which reproduce at older ages tend to accumulate fewer mutations per year in their sperm and eggs. This finding suggests that the evolution of humans’ long reproductive lifespan created evolutionary pressure to improve the fidelity of DNA maintenance in germ tissues, paralleling the pressure to avoid accumulating too many mutations in the body over a long lifespan.
Glial swip-10expression controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis
Authors: Rodriguez Peter , Kalia Vrinda , Gibson Chelsea L. , Gichi Zayna , Rajoo Andre , Matier Carson D. , Pezacki Aidan T. , Xiao Tong , Carvelli Lucia , Chang Christopher J. , Miller Gary W. , Khamoui Andy V. , Boerner Jana , Blakely Randy D. 
Published: December 2023

AbstractCuprous copper (Cu(I)) is an essential cofactor for enzymes supporting many cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly dependent on these pathways, with multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, associated with their dysfunction. Key features of Cu(I) contributions to neuronal healthin vivoremain to be defined, owing largely to the complex processes involved in Cu(I) production, intracellular transport, and systemic redistribution. Here, we provide genetic and pharmacological evidence thatswip-10is a critical determinant of systemic Cu(I) levels inC. elegans, with deletion leading to systemic deficits in mitochondrial respiration, production of oxidative stress, and neurodegeneration. These phenotypes can be reproduced in wild-type worms by Cu(I)-specific chelation and offset inswip-10mutants by growth on the Cu(I) enhancing molecule elesclomol, as well as by glial expression of wildtypeswip-10.MBLAC1, the most closely related mammalian ortholog toswip-10, encodes for a pre-mRNA processing enzyme for H3 histone, a protein whose actions surprisingly include an enzymatic capacity to produce Cu(I) via the reduction of Cu(II). Moreover, genome-wide association studies and post-mortem molecular studies implicate reductions ofMBLAC1expression in risk for AD with cardiovascular disease comorbidity. Consistent with these studies, we demonstrate that the deposition of β-amyloid plaques, an AD pathological hallmark, in worms engineered to express human Aβ1-42,is greatly exaggerated by mutation ofswip-10. Together, these studies identify a novel glial-expressed, and pathway for Cu(I) production that may be targeted for the treatment of AD and other neurodegenerative diseases.Significance StatementDevastating neurodegenerative diseases such as Alzheimer’s disease, and Parkinson’s disease are associated with disruptions in copper (Cu) homeostasis. Alterations in Cu(I) give rise to increased oxidative stress burden, mitochondrial and metabolic dysfunction, and can accelerate production and/or potentiate toxicity of disease-associated protein aggregates. Here, using the model systemCaenorhabditis elegans, we establish a role for the geneswip-10in systemic Cu(I) homeostasis. Perturbation of this pathway in worms recapitulates biochemical, histological, and pathological features seen in human neurodegenerative disease. We reveal that these changes can be suppressed pharmacologically and arise whenswip-10expression is eliminated from glial cells. Our work implicatesswip-10and orthologs as key players in Cu(I) homeostasis that may be exploitable to treat multiple neurodegenerative diseases.
Reversibly-bonded Microfluidic Devices for Stable Cell Culture and Rapid, Gentle Cell Extraction
Authors: Feng Xiaohan , Wai Cheng Lily Kwan , Lin Xuyan , Wu Angela Ruohao 
Published: December 2023

AbstractMicrofluidics chips have emerged as significant tools in cell culture due to their capacity for supporting cells to adopt more physiologically relevant morphology in 3D compared with traditional cell culture in 2D. Currently, irreversible bonding methods commonly used in chip fabrication mean that chips cannot be detached from their substrate without destroying the chip structure, which makes it challenging to do further analysis on cells that have been cultured on-chip. Some reversible bonding techniques exist but are restricted to certain materials, or require complex processing procedures. Here, we demonstrate a simple and reversible polydimethylsiloxane (PDMS)-polystyrene (PS) bonding technique that allows devices to withstand extended operation while pressurized, and supports long-term stable cell cultures. Importantly, it allows rapid and gentle live cell extraction for further downstream manipulation and characterization after long-term on-chip culturing, or even further subculturing. Our new approach could greatly facilitate microfluidic chip-based tissue and cell cultures, overcoming current analytical limitations and opening up new avenues for downstream uses of on-chip cultures, including 3D-engineered tissue structures for biomedical applications.
Linking root-associated fungal and bacterial functions to root economics
Authors: Wu Ran , Zeng Xiaoyue , McCormack M. Luke , Fernandez Christopher W. , Yang Yin , Guo Hui , Xi Meijie , Liu Yu , Qi Xiangbin , Liang Shuang , Juenger Thomas E. , Koide Roger T. , Chen Weile 
Published: December 2023

AbstractTree roots form symbioses with soil microbes to acquire nutrients, but the relationships between root nutrient acquisition strategies and microbial community composition remain poorly understood. Here, we measured root traits and root-associated fungal and bacterial guilds in 336 trees of 52 species from a subtropical forest. We found a fungal gradient from ectomycorrhizal to saprotrophic dominance, which corresponded with a shift from organic to mineral nutrient economics. This fungal gradient was aligned with the increase of root nitrogen concentration, suggesting a linkage from simple root trait to fungal-mediated carbon-nutrient cycling. We also found that the functional composition of fungal and bacterial communities was closely correlated with host root-zone pH, which often varied among coexisting trees. Root-zone pH was independent of the common root traits, underpinning a potential new gradient in the root trait space. Our findings integrate microbial functions into the root economics framework, thereby advancing the understanding of diversity of nutrient acquisition strategies across forest trees.
Poverty trajectories and child and mother wellbeing outcomes in Ireland: findings from an Irish prospective cohort
Authors: Driscoll David J O , Kiely Elizabeth , Keeffe Linda M O , Khashan Ali S 
Published: December 2023

AbstractBackgroundPoverty is associated with poor outcomes, yet exposure to distinct poverty trajectories in early childhood is not well understood.ObjectiveTo understand the prevalence of different trajectories of household poverty and their association with mid-childhood and primary-parent(mother) indicators of physical health and psychopathology in Ireland.MethodsWe used a nationally representative, prospective cohort (Growing-up-in-Ireland– Infant-Cohort). Household poverty included lowest third income decile, subjective poverty and material deprivation when children were aged 9-months(m),3,5,9-years(y). We used group based multi-trajectory-cluster-modelling to classify trajectories of poverty. Using multivariate logistic regression, adjusted with separate child and mother confounders, we assessed the association of poverty trajectories from 9m to 9y with child outcomes (overweight, any longstanding illness and psychopathology) at age 9y and the same poverty trajectories over the same 9y period with mother outcomes (overweight, any longstanding illness and depression).ResultsOf 11,134 participants, four trajectories were identified: never-in-poverty (43.1%), material/subjective>monetary-poverty (16.1%), monetary>material-poverty (25.6%), and persistent-poverty (15.2%). Children in persistent-poverty compared with never in poverty experienced higher odds of being overweight at 9y (adjusted odds ratio aOR 1.70,95% CI 1.34, 2.16), having a longstanding illness (aOR 1.51,95% CI 1.20, 1.91) and psychopathology (aOR 2.06,95% CI 1.42, 2.99). The outcomes for primary parent (99.7% were mothers) had higher odds of being overweight (aOR 1.49,95% CI 1.16, 1.92), having a longstanding illness (aOR 2.13,95% CI 1.63, 2.79), and depression (aOR 3.54,95% CI 2.54, 4.94).ConclusionsAny poverty trajectory was associated with poorer psychopathology and physical wellbeing in late childhood for children and their mothers in Ireland.Take home messageWhat is already known on this subject?Poverty is understood as having both objective (e.g. low household income) and subjective dimensions (e.g., perception of being poor relative to others, poverty related anxiety). Evidence highlights the association between child poverty exposure and child and mother wellbeing outcomes.What this study adds?Our study examined predicted trajectories of multi-dimensional poverty and child and mother outcomes using a large national cohort. We identified that any poverty trajectory in childhood had a higher odds of being associated with poor well-being outcomes.How this study might affect research, practice or policy?This study highlights the need for strategies to ameliorate any poverty exposure as all poverty trajectories resulted in poorer wellbeing outcomes. Strategies should be considered to ameliorate any poverty exposure in early childhood (e.g., school based resourcing).
DISCHARGE PLANNING PATIENT STROKE A NURSING SCIENCE PHILOSOPHY: SYSTEMATIC REVIEW
Authors: Retnaningsih Dwi , Pandin Moses Glorino Rumambo , Nursalam Nursalam , Ramadhani Desi 
Published: December 2023

ABSTRACTObjectivesThe quality of life and health of the patient are strongly influenced by the high incidence of stroke in a particular community or population. After the early recovery phase, recovery planning is crucial, as individuals who have suffered a stroke face uncertainty about the long-term recovery process as well as adjustments in everyday life. The objective of the research is to discuss the philosophical review of discharge planning for stroke patients from the points of view of ontology, epistemology, and axiology, with a focus on the philosophy of nursing science.Materials and methodsIn accordance with PRISMA (2017–2023) criteria, the study is a review of the literature. Keyword searches for “discharge planning,” “stroke,” “patients,” and “RCT” were conducted in the databases of Scopus, Science Direct, and ProQuest. The inclusion criteria encompassed quantitative research design, English-language publications, studies involving adult stroke patients, interventions related to discharge planning, and analysis evaluating discharge planning for stroke patients, yielding 281 identified papers. The Rayyan application is used in the selection process. PICO synthesis and grouping, which are based on the Cochrane Handbook for Systematic Review, are used in the analysis. Using the Joanna Briggs Institute Critical Assessment methodology, methodological quality assessment demonstrates that a multidisciplinary approach through ontological, epistemological, and axiological investigations offers a solid basis for enhancing health information systems and clinical practice.ResultsThere are twenty-two quantitative research findings that show the features of the respondents, who were family caregivers and stroke patients. Ensuring that stroke victims receive the best care possible when they leave the hospital is the aim of recovery planning. In the process, families, patients, and health care providers collaborate. Patient assessment, treatment planning, medication scheduling, patient and family education, advanced care planning, mental and spiritual health support, health service coordination, medical recordkeeping, and monitoring are all essential elements of recovery planning.ConclusionThorough recovery planning guarantees effective monitoring of medical records and coordination of treatment, improving the post-hospital experience for stroke patients. With an emphasis on the best possible recovery, this planning aims to offer focused and well-coordinated treatment. Stroke patients should anticipate comprehensive and well-coordinated post-hospital treatment, which will benefit both patients and families, thanks to the cooperation of health care professionals, patients, and families.
Assisted reproductive technology (ART) patient information-seeking behavior: a qualitative study
Authors: Mayette Emma , Scalise Ariel , Li Angela , McGeorge Nicolette , James Kaitlyn , Mahalingaiah Shruthi 
Published: December 2023

AbstractObjectiveTo investigate patient interaction with information sources while undergoing assisted reproductive treatment.MethodsSemi-structured interviews with fifteen individuals were conducted between August and October 2022. Interview participants underwent assisted reproductive treatment including embryo transfer between January 2017 and April 2022 within a large urban healthcare system. Thematic analysis of the interview transcripts was performed.ResultsParticipants reported that they engaged in informed decision-making with their provider. Three main themes were identified. Participants 1) utilized clinic-provided information and then turned to outside sources to fill knowledge gaps; 2) struggled to learn about costs and insurance; 3) had difficulty identifying mental health resources to support care.ConclusionPatients prefer clinic-provided resources and then utilize academic sources, the internet, and social media when they have unfulfilled information needs. Knowledge gaps related to cost, insurance, and mental health support were identified.Practice ImplicationsART clinics should consider providing more information about cost, insurance, and mental health support to patients.
Rapid dexamethasone treatment inhibits LPS-induced cytokine storm in mice
Authors: Zhang Fen , Xiao Lanlan , Li Yujia , Feng Rilu , Zhou Menghao , Tang Shima , Liebe Roman , Ebert Matthias P , Dooley Steven , Li Lanjuan , Weng Hong-Lei 
Published: December 2023

AbstractSevere infection-induced cytokine storm is an urgent medical syndrome with high mortality. To date, no therapy is available. This study shows that high concentrations of lipopolysaccharide (LPS) induce cytokine storm within 48h and thus kill most experimental mice. Rapid, but not late dexamethasone administration remarkably inhibits cytokine storm and rescues LPS-treated mice. Monocytes and macrophages are the major source of cytokine storm. In these cells, pro-inflammatory genes (i.e.,Tnf,Il6andIl1β) have preassembled RNA polymerase II (RNA Pol II), but stay at the pause stage of transcriptional elongation in the absence of stimulation. LPS rapidly activates transcription of these “pre-loaded” genes within 2h. Administration of dexamethasone within this time window inhibits RNA Pol II ser2 binding to the core promoters of pro-inflammatory genes and thus reduces LPS-induced cytokine transcription. Therefore, rapid utilization of dexamethasone might be efficacious to prevent severe bacterium-induced cytokine storm in clinical practice.
Golgi-associated retrograde protein (GARP) complex recruits retromer to trans-Golgi network for FgKex2 and FgSnc1 recycling, necessary for development and pathogenicity ofFusarium graminearum
Authors: Long Yunfei , Chen Xin , Chen Jia , Zhang Haoran , Lin Ying , Cheng Shuyuan , Pu Neng , Zhou Xuandong , Sheng Renzhi , Abubakar Yakubu Saddeeq , Zheng Huawei , Yun Yingzi , Lu Guodong , Wang Zonghua , Zheng Wenhui 
Published: December 2023

AbstractIn eukaryotic cells, the retromer complex plays a crucial role in orchestrating the sorting and retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN). Despite its significance, the molecular details of this intracellular trafficking process remain unclear. Here, we identified a Golgi-associated retrograde protein (GARP) complex as a mediator of vesicular transport, facilitating the recruitment of the retromer complex to TGN to exert its functions. The GARP complex is mainly localized to the TGN, where it interacts with the retromer complex. This interaction is evolutionarily conserved across different species. Furthermore, we identified FgKex2 and Fgsnc1 as cargo proteins in the GARP/retromer-mediated recycling pathway. Loss of GARP or retromer results in a complete mis-sorting of FgKex2 and FgSnc1 to the vacuolar degradation pathway, which affects the growth, development, toxisome biogenesis, and pathogenicity ofF. graminearum. In summary, we assert that GARP facilitates the recruitment of retromer from endosomes to the TGN, orchestrating the recycling of FgKex2 and FgSnc1. This is integral to sustaining continuous growth, development and contributes significantly to the pathogenicity ofF. graminearum.
Low-dimensional neural geometry underlies distributed goal representations in working memory
Authors: Zhang Mengya , Yu Qing 
Published: December 2023

AbstractSuccessful goal-directed behavior requires the maintenance and implementation of abstract task goals on concrete stimulus information in working memory. Previous working memory research has revealed distributed neural representations of task information across cortex. However, how the distributed task representations emerge and communicate with stimulus-specific information to implement flexible goal-directed computations is still unclear. Here, leveraging EEG and fMRI along with state space analyses, we provided converging evidence in support of a low-dimensional neural geometry of goal information consistent with a designed task space, which first emerged in frontal cortex during goal maintenance and then transferred to posterior sensory cortex through frontomedial-to-posterior theta coherence for implementation on stimulus-specific representations. Importantly, the fidelity of the goal geometry predicted memory performance. Collectively, our findings suggest that abstract goals in working memory are represented in an organized, low-dimensional neural geometry for communications from frontal to posterior cortex to enable computations necessary for goal-directed behaviors.
A precise IDMS-based method for absolute quantification of phytohemagglutinin, a major antinutritional component in common bean
Authors: Li Lan , Chu Zhanying , Ning Kang , Zhu Manman , Zhai Rui , Xu Pei 
Published: December 2023

AbstractPhytohemagglutinin (PHA), a natural tetramer comprising PHA-E and PHA-L subunits that preferentially bind to red and white blood cells, respectively, constitutes a significant antinutritional and allergenic factor in common bean seeds. The accurate measurement of PHA content is a prerequisite for ensuring food safety inspections and facilitating genetic improvements in common bean cultivars with reduced PHA levels. Currently, mainstream methods for PHA quantification involve hemagglutination assays and immunodetection, but these methods often require fresh animal blood and lack specificity and accuracy. In this study, we present a novel LC-MS/MS-based method for PHA quantification, leveraging the advantages of isotope dilution mass spectrometry (IDMS). Two signature peptides each for PHA-E and PHA-L, along with a common signature peptide, were identified and employed for quantification, allowing differentiation between PHA-E and PHA-L subunits. The incorporation of amino acid analysis-isotope dilution mass spectrometry (AAA-IDMS) enabled precise determination of the synthetic signature peptides’ purity during measurement, enhancing metrological accuracy. In addition, the TCA-acetone protocol was established as the optimized method for total protein extraction from dry bean seeds. Quantitative analysis of PHA-E and PHA-L subunits in six common bean varieties using the developed method demonstrated excellent linearity (r > 0.999), sensitivity (limit of detection and quantitation as low as 2.32 ng/mg and 7.73 ng/mg, respectively), recovery (94.18-104.47%), and repeatability (relative standard deviation < 3.45%). This method has the potential to serve as a standard for measuring PHA contents in common beans and other agricultural products containing PHA.