bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-function logic gates based on CRISPRi
Authors: Yao Zhiwu , Guo Shaobin 
Published: October 2024

AbstractDeveloping logic gate circuits that are programmable and reliable for specific functions is a central goal in synthetic biology. Traditional synthetic circuits often rely on protein regulators, which face scalability and resource burden limitations. To overcome these challenges, we introduce a novel approach utilizing dual-function and multi-level logic gates based on the CRISPRi system with dCas9 and sgRNA. This method, implemented in an in vitro transcription system, enables the rapid design and validation of complex logic gates. Our dual-function and multi-level design strategies achieve robust functionality in NOR, NAND, AND, and OR gates, allowing different logic outputs by altering only the inputs while reusing all other modules. This showcases significant advancements in efficiency and scalability for synthetic circuit construction. This work reduces development time and simplifies circuit design, paving the way for more efficient synthetic biology applications.
Auxin-salicylic acid seesaw regulates the age-dependent balance between plant growth and herbivore defense
Authors: Han Wen-Hao , Zhang Feng-Bin , Ji Shun-Xia , Liang Kai-Lu , Wang Jun-Xia , Fan Xiao-Ping , Liu Shu-Sheng , Wang Xiao-Wei 
Published: October 2024

SUMMARYPlants must fine-tune their needs for growth and defense. According to the Plant Vigor Hypothesis, younger, more vigorous plants tend to be more susceptible to herbivores compared to older, mature plants, yet the molecular mechanisms underlying this dynamic remain elusive. Here, we uncover a hormonal crosstalk framework that orchestrates the age-related balance between plant growth and herbivore defense. We demonstrate that the accumulation of salicylic acid (SA), synthesized byNicotiana benthamianaphenylalanine ammonia-lyase 6 (NbPAL6), dictates insect resistance in adult plants. The expression ofNbPAL6is driven by the key transcription factor, NbMYB42, which is regulated by two interacting auxin response factors, NbARF18La/b. In juvenile plants, higher auxin levels activateNbmiR160c, a microRNA that simultaneously silencesNbARF18La/b, subsequently reducingNbMYB42expression, lowering SA accumulation, and thus weakening herbivore defense. Furthermore, excessive SA accumulation in juvenile plants enhances defense but antagonizes auxin signaling, impairing early growth. Our findings suggest a seesaw-like model that balances growth and herbivore defense depending on the plant’s developmental stage.
A unified framework for hydromechanical signaling: Do plant signals go with the flow?
Authors: Bacheva Vesna , Rockwell Fulton , Salmon Jean-Baptiste , Woodson Jesse , Frank Margaret , Stroock Abraham 
Published: October 2024

AbstractLocal wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distal leaves. The transmission mechanisms of this ubiquitous class of signals remain poorly understood. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes – propagation of pressure changes and transmission of chemical elicitors via mass flows driven by these pressure changes – as potential mechanisms for the initiation and propagation of wound-induced signals. We show that rapid pressure changes in the xylem can transmit mechanical information across the plant, while their coupling with neighboring non-vascular tissue drives swelling and mass flow that can transport chemical elicitors to distal leaves. We confront our model predictions with signaling dynamics measurements in several species, and show that the poroelastic model captures observed mechanical, biochemical, and electrophysiological signals. This framework provides a valuable foundation for assessing mechanisms of signal transmission and for designing future experiments to elucidate factors involved in signal initiation, propagation, and target elicitation.
Unc-51-like Kinase 1 (ULK1) Regulates Bacterial Ubiquitylation and p62 Recruitment during Xenophagic Clearance ofListeria monocytogenes
Authors: Siqueira MS , Farias TSM , Ribeiro RM , Ribeiro JS , Pereira TD , Carneiro LAM , Travassos LH 
Published: October 2024

ABSTRACTAutophagy is an essential cellular homeostatic process, that also serves as an innate immune mechanism against intracellular bacterial pathogens, through a highly selective form of autophagy known as xenophagy. Despite advances in understanding how bacteria are targeted for autophagic degradation, the specific regulatory mechanisms that drive the initial steps and ensure bacterial selection remain incompletely defined. Our study uncovers a pivotal role for Unc-51-like kinase 1 (ULK1) in the xenophagic clearance of the intracellular bacterial pathogenListeria monocytogenes. We observed that ULK1 is essential for the efficient ubiquitylation of bacteria and subsequent recruitment of the autophagic adaptor protein p62 to the bacterial surface. Furthermore, we show that the impact of ULK1 deficiency in these early events - reduction in bacterial ubiquitylation followed by impaired p62 targeting – later result in diminished formation of bacteria-targeted autophagosomes. Notably, phosphorylation of p62 at the S409 residue, which is known to enhance its affinity for ubiquitin, is necessary for its recruitment and effective bacterial clearance, highlighting the regulatory role of ULK1 in this process. These findings unveil a previously unrecognized function of ULK1 in modulating early xenophagy steps, contributing to the autophagic control of intracellular pathogens. Our findings offer new perspectives into the manipulation of ULK1activity for therapeutic interventions against infectious diseases.IMPORTANCEAutophagy is a vital process in eukaryotic cells that enables them to digest intracellular components, helping them respond to various stresses, including starvation, the accumulation of dysfunctional organelles, and infections. While the autophagic flux has been extensively studied over the past few decades, some key mechanisms remain poorly understood. In our research, we aimed to clarify one such mechanism: the way the autophagic machinery specifically targets intracellular bacteria. We identified a novel role for the protein ULK1 in this process, demonstrating that ULK1 is essential for marking bacteria within the cell and recruiting the protein p62. This marking and recruitment of p62 are critical steps for effective bacterial clearance. This underscores the pivotal role of ULK1 in initiating the cellular defense against bacterial infections. Our findings could pave the way for new therapeutic strategies aimed at enhancing the body’s capacity to combat bacterial infections.
Duplex PCR assay to determine sex and mating status ofIxodes scapularis(Acari: Ixodidae), vector of the Lyme disease pathogen
Authors: Ronai Isobel , Frederick Julia C. , Thompson Alec T. , Sharma Prisha , Yabsley Michael J. , Pal Utpal , Extavour Cassandra G. , Glenn Travis C. 
Published: October 2024

ABSTRACTTicks are a major health threat to humans and other animals, through direct damage, toxicoses, and transmission of pathogens. An estimated half a million people are treated annually in the United States of America for Lyme disease, a disease caused by the bite of a black-legged tick (Ixodes scapularisSay) infected with the bacterial pathogenBorrelia burgdorferi. This tick species also transmits another six human-disease causing pathogens, for which vaccines are currently unavailable. WhileI.scapularisare sexually dimorphic at the adult life stage, the DNA sequence differences between male and femaleI.scapularisthat could be used as a sex-specific marker have not yet been established. We determine the sex-specific DNA sequences forI.scapularis(male heterogametic system with XY), using whole-genome resequencing and restriction site-associated DNA sequencing. Then we identify a male-specific marker that we use as the foundation of a molecular sex identification method (duplex PCR) to differentiate the sex of anI.scapularistick. In addition, we provide evidence that this molecular sexing method can establish the mating status of adult females that have been mated and inseminated with male-determining sperm. Our molecular tool allows the characterization of mating and sex-specific biology across development forI.scapularis, a major pathogen vector, which is crucial for a better understanding of their biology and controlling tick populations.
A general model for the seasonal to decadal dynamics of leaf area
Authors: Zhou Boya , Cai Wenjia , Zhu Ziqi , Wang Han , Harrison Sandy P. , Prentice I. Colin 
Published: October 2024

AbstractLeaf phenology, represented at ecosystem scale by the seasonal dynamics of leaf area index (LAI), is a key control on the exchanges of CO2, energy and water between the land and atmosphere. Robust simulation of leaf phenology is thus important for both dynamic global vegetation models (DGVMs) and land-surface representations in climate and Earth System models. There is no general agreement on how leaf phenology should be modelled. However, a recent theoretical advance posits a universal relationship between the time course of “steady-state” gross primary production (GPP) and LAI – that is, the mutually consistent LAI and GPP that would pertain if weather conditions were held constant. This theory embodies the concept that leaves should be displayed when their presence is most beneficial to plants, combined with the reciprocal relationship of LAI and GPP via (a) the Beer’s law dependence of GPP on LAI, and (b) the requirement for GPP to support the allocation of carbon to leaves. Here we develop a global prognostic leaf phenology model, combining this theoretical approach with a parameter-sparse terrestrial GPP model (the P model) that achieves good fit to GPP derived from flux towers in all biomes, and a scheme based on the P model that predicts seasonal maximum LAI as the lesser of an energy-limited rate (maximizing GPP) and a water-limited rate (maximizing the use of available precipitation). The exponential moving average method is used to represent the time lag between leaf allocation and modelled steady-state LAI. The model captures satellite-derived LAI dynamics across biomes at both site and global levels. Since this model outperforms the 15 DGVMs used in the TRENDY project, it could provide a basis for improved representation of leaf-area dynamics in vegetation and climate models.
Global identification of AGO3–RNA interactions inChlamydomonasreveals the small RNA–mediated regulation of nuclear and chloroplast gene expression
Authors: Murakami Suzuna , Takahashi Hiroki , Shimizu Kaede , Yamasaki Tomohito 
Published: October 2024

AbstractMicroRNAs (miRNAs) form complexes with Argonaute (AGO) proteins and bind to mRNAs with complementary sequences to repress their expression. Organisms typically possess several hundred miRNAs regulating diverse biological processes. Although the roles of miRNAs have been well elucidated in multicellular organisms, they remain largely unexplored in unicellular organisms. In the green algaChlamydomonas reinhardtii, the first unicellular organism in which miRNAs were discovered, identifying miRNA target genes remains challenging. Here, we report the high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) to generate global AGO3–RNA interaction maps, identifying 131 mRNAs derived from nuclear genes. We also detected mRNAs from two chloroplast genes, suggesting that AGO3 may also influence chloroplast gene expression. Our findings indicate thatChlamydomonassmall RNAs repress nuclear and chloroplast gene expression. Furthermore, HITS-CLIP analyses are now feasible for any RNA-binding protein inChlamydomonas, offering new opportunities to uncover the functions of RNA-binding proteins of interest.
Impulsivity Facets and Substance Use Involvement: Insights from Genomic Structural Equation Modeling
Authors: Vilar-Ribó Laura , Hatoum Alexander S , Grotzinger Andrew D , Mallard Travis T ,   23andMe Research Team, Elson Sarah , Fontanillas Pierre , Palmer Abraham A , Gustavson Daniel E , Sanchez-Roige Sandra 
Published: October 2024

AbstractBackgroundImpulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear.MethodsWe used genomic structural equation modeling and genome-wide association studies (N=79,729-903,147) based on individuals of European ancestry to examine the latent genetic architecture of impulsivity and substance use behaviors. We included GWAS data from nine impulsivity traits and seven substance use (SU) and SUD traits.ResultsWe found that the SU and SUD factors were strongly genetically inter-correlated (rG=0.77) but their associations with impulsivity factors differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (rG=.0.30-0.50) and SUD (rG=0.37-0.47) factors; sensation seeking was more strongly genetically correlated with the SU factor (rG=0.27 vs.rG=0.10); delay discounting was more strongly genetically correlated with the SUD factor (rG=0.32 vs.rG=0.21); and lack of perseverance was only weakly genetically correlated with the SU factor (rG=0.09). After controlling for the genetic correlation between SU/SUD, we found that lack of premeditation and positive urgency were independently genetically associated with both the SU (β=0.39, β=0.28, respectively) and SUD factors (β=0.28, β=0.19, respectively); sensation seeking and lack of perseverance were independently genetically associated with the SU factor (β=0.46, β=0.19, respectively); and negative urgency and delay discounting were independently genetically associated with the SUD factor (β=0.34, β=0.39, respectively).ConclusionsOur findings show that specific impulsivity facets confer risk for distinct stages of substance use involvement, with potential implications for SUDs prevention and treatment.
Public reporting guidelines for outbreak data: Enabling accountability for effective outbreak response by developing standards for transparency and uniformity
Authors: Grégoire Vanessa , Zhu Alex W. , Brown Catherine M. , Brownstein John S. , Cardo Denise , Cumming Fergus , Danila Richard , Donnelly Christl A. , Duchin Jeffrey S. , Fill Mary-Margaret A. , Fraser Christophe , Fullerton Katie , Funk Sebastian , George Dylan , Hopkins Susan , Kraemer Moritz U.G. , Layton Marcelle , Lessler Justin , Lynfield Ruth , McCaw James M. , McPherson Tristan D. , Moore Zack , Morgan Oliver , Riley Steven , Rosenfeld Roni , Samoff Erika , Schaffner William , Shaffner Julie , Sturm Roberta , Terashita Dawn , Walke Henry , Washington Raynard E. , Rivers Caitlin M. 
Published: October 2024

AbstractCurrently, there are few standards for what essential information about an infectious disease outbreak should be reported to the public and when. The content and timeliness of public reporting (e.g. situation reports) is at the discretion of the jurisdiction overseeing the outbreak response, resulting in a substantial heterogeneity in available information. To address this problem, we undertook a consensus process to develop recommendations for what epidemiological information public health authorities should report to the public during an outbreak, including the administrative level and frequency of reporting. We first assembled a steering committee of nine experts representing federal public health, state public health, academia, and international partners to develop a candidate list of reporting items. We then invited 45 experts, 35 of whom agreed to participate in a Delphi panel. Of those, 25 participated in voting in the first round, 25 participated in voting in the second round, and 25 participated in voting in the third round, demonstrating consistent engagement in the consensus-building process. The final stage of the Delphi process consisted of a hybrid consensus meeting to finalize the voting items. This resulted in a final list of nine reporting items representing the minimum set of information to include in publicly available situation reports: Numbers of new confirmed cases, new hospital admissions, new deaths, cumulative confirmed cases, cumulative hospital admissions, and cumulative deaths, each reported weekly and at Administrative level 1 (typically state or province), and stratified by sex, age group, and race/ethnicity. This minimum reporting standard creates a strong framework and guidance for uniform sharing of outbreak information and promotes consistency of data between jurisdictions to enable prompt and effective response.
Pain Among US Adults Before, During, and After the COVID-19 Pandemic: A Repeated Cross-Sectional Study using the 2019-2023 National Health Interview Survey
Authors: Zajacova Anna , Grol-Prokopczyk Hanna , Nahin Richard L. 
Published: October 2024

ABSTRACTImportanceChronic pain (CP) is a major public health problem in the US. The COVID-19 pandemic led to widespread disruptions in the US and it is important to monitor changes in pain during and after the pandemic.ObjectiveTo determine prevalence of chronic pain (CP) and high-impact chronic pain (HICP) before, during, and after the COVID-19 pandemic and identify potential contributing factors.MethodsWe analyze a nationally representative sample of 88,469 community-dwelling Americans aged 18 and older from three cross-sectional waves of the National Health Interview Survey before (2019), during (2021), and after (2023) the COVID-19 pandemic.Year of interview is the exposure. All regression models control for age and sex; fully controlled models include 19 additional covariates (demographics, socioeconomic status, health behaviors, health conditions, mental health, and health insurance type); analyses also explore the role of long COVID. Outcomes are CP and HICP using measures proposed by the US National Pain Strategy; we also present findings for six site-specific pain measures.ResultsBetween 2019 and 2023, CP and HICP prevalence increased by 18% and 13%, respectively. Specifically, CP prevalence was 20.6% (95%CI: 19.9-21.2%) in 2019, 20.9%(20.3-21.6%) in 2021, and 24.3% (23.7-25.0%) in 2023. HICP prevalence declined from 7.5% (7.1-7.8%) in 2019 to 6.9% (6.6-7.3%) in 2021, before rising sharply to 8.5% (8.1-8.9%) in 2023. The increases occurred in all examined body sites except for tooth/jaw pain, and in all major population groups. Approximately 13% of the increase in CP and HICP was attributable to long COVID.Conclusions and RelevancePain among US adults was high before and during the pandemic but has surged substantially since. In 2023, an unprecedented 60 million Americans had chronic pain and 21 million had high-impact chronic pain.
Extreme weather events and dengue in Southeast Asia: a regionally-representative analysis of 291 locations from 1998 to 2021
Authors: Ith Sophearen , Seposo Xerxes , Phy Vitou , Tantrakarnapa Kraichat , Apostol Geminn Louis C. , Dhewantara Pandji Wibawa , Hod Rozita , Hassan Mohd Rohaizat , Othman Hidayatulfathi , Sahani Mazrura , Lim Jue Tao , Nhung Ha Hong , Tuan Nguyen Hai , Nghia Ngu Duy , Takemura Taichiro , Nouhak Inthavong , Carlos Chua Paul Lester , Cook Alex R , Colón-González Felipe J , Hashizume Masahiro 
Published: October 2024

AbstractBackgroundClimate change, leading to more frequent and intense extreme weather events (EWEs), could significantly impact dengue transmission. However, the associations between EWEs and dengue remains underexplored in the Southeast Asia (SEA) region. We investigated the association between selected EWEs (i.e. heatwaves, extremely wet, and drought conditions) and dengue in the SEA region.Methods and FindingsMonthly dengue case reports were obtained from 291 locations across eight SEA countries between 1998 and 2021. Heatwaves are defined as the monthly total number of days where temperatures exceed the 95th percentile for at least two consecutive days. Droughts and extremely wet conditions are defined by a self-calibrating Palmer Drought Severity Index (scPDSI). We implemented a generalized additive mixed model coupled with a distributed lag non-linear model to estimate the association between each EWE and dengue. Months with fewer than 12 heatwave days increased dengue risk with delayed effect after two months lag, compared with months without any heatwave. Highest dengue risk is at 7 heatwave days (RR=1·28; 95%CI: 1·19,1·38). Compared to normal conditions (i.e. scPDSI=0), drought conditions (i.e. scPDSI=–4) were positively associated with dengue risk (RR=1·85; 95%CI: 1·73,1·99), while extremely wet conditions (i.e. scPDSI=4) have reduced dengue risk (RR=0·89; 95%CI: 0·87,0·91). Although the findings of this study are significant, its limitations arise from the inconsistency of dengue case reporting, which might complicate dengue risk estimation.ConclusionsThis study shows that the delayed effect of heatwaves and drought conditions magnifies the risk of dengue in the SEA region. Our findings offer stakeholders sizeable amount of time to organize and implement public health interventions in minimizing the prospective dengue risk, posed by EWEs in the context of climate change in SEA. Future research may focus on factors associated with dengue risk variations within SEA region to facilitate the development of location-based, tailor-fit mitigation and preventative interventions.
Changing patterns of heart failure in China from 1990 to 2021: a secondary analysis of the Global Burden of Disease study 2021
Authors: Yang Qiwen , Zhuang Rui , Lyu Diyang , Xue Donghua , Niu Chaofeng , Shi Yujie , Li Meng , Zhang Lijing 
Published: October 2024

AbstractBackgroundHeart failure is a leading public health issue in China, with a steadily increasing burden. This study aims to assess the changing patterns of heart failure in China from 1990 to 2021, providing evidence for informed healthcare strategies.MethodsData on prevalence, years lived with disability (YLDs), and their corresponding 95% uncertainty intervals (UI) were obtained from the Global Burden of Disease (GBD) Study 2021. The joinpoint regression model was used to identify both overall and localized trends of heart failure burden, and the age-period-cohort model served to analyze the contributions of age, period, and birth cohort separately. We further utilized the autoregressive integrated moving average (ARIMA) model to predict future trends of heart failure in the next 10 years.ResultsIn 2021, 13099727 (95% UI, 11320895 to 15376467) individuals lived with heart failure and this illness accounted for 1290810 (95% UI, 865894 to 1775731) YLDs in China. The burden of heart failure is more pronounced in males and the elderly, and ischemic heart disease has become the leading cause since 2002. The age-standardized rates of prevalence and YLDs increased at average annual percentage changes of 0.23% (95% CI, 0.20 to 0.26) and 0.25% (95% CI, 0.23 to 0.27) respectively. The curve of local drift showed a downward trend with age. Both the period and cohort rate ratios have increased significantly over the last 30 years. By 2031, the age-standardized rates of prevalence will decrease to 678.69 (95% CI, 640.75 to 716.63), while the age-standardized rates of YLDs will increase to 69.19 (95% CI, 66.95 to 71.43).ConclusionsThe burden of heart failure in China remains concerning. The implementation of comprehensive strategies should be taken into consideration, including strengthening primary healthcare system, enhancing public awareness, and promoting cardiac rehabilitation.Clinical PerspectiveWhat Is New?This is the first study of the Global Burden of Disease (GBD) 2021 that comprehensively analyzes the burden of heart failure in China over the past 30 years.What Are the Clinical Implications?The burden of heart failure in China remains concerning.Comprehensive strategies prioritizing primary healthcare system, public awareness, and cardiac rehabilitation could be effective to mitigate the burden of heart failure.