bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Research to Roach Traps: Practical Considerations for a Home-Based Asthma Program
Authors: Talis Natalie , Lewis Nathaniel , Doraiswamy Prakash , Wu Zhiyong , Boakye Brittney 
Published: April 2024

Context:
Home-based asthma interventions have a significant evidence base as an effective means to address moderate and severe breathing concerns triggered by home conditions. However, the literature lacks logistical and staffing considerations necessary to successfully implement such a program at a governmental level. This practice report and process evaluation outlines practical details and lessons learned during a healthy homes pilot, and how they were addressed in the design of a permanent program.

Objective:
To inform the creation of a permanent home-based asthma intervention at the Alexandria Health Department (AHD) (City of Alexandria, Virginia) and understand the tools and resources necessary for success.

Intervention:
Participating households received a health and environmental assessment, followed by cleaning supplies, relevant education, and referrals to partners for services. AHD staff tracked challenges and insights at each step of the intervention. At the end of the pilot, staff worked with the community to identify solutions and design a permanent program.

Conclusions:
Although the pilot model was constructed based on existing case studies, technical assistance from national experts, and guidance documents, the team still experienced challenges around recruitment, staff support, home visit implementation, and impact evaluation. While pilots and existing literature can be instructive for identifying issues, work with residents and partners to develop a uniquely tailored community program was essential for practical success.

Implications on Policy and Practice:
Health departments developing new initiatives should consider both the staff and participant experience throughout the creation of administrative and programmatic processes. Testing out draft versions of these processes and materials using internal and external focus groups can identify potential bottlenecks and solutions upfront.
Home Visiting in California During the First Two Years of the COVID-19 Pandemic: A Repeated Cross-Sectional Study of Low-Income Pregnant and Parenting Caregivers
Authors: Franck Linda S. , Mehra Renee , Remy Linda , Rienks Jennifer 
Published: April 2024

Context:
Prior to the COVID-19 pandemic, home visiting services for low-income children and families were provided almost entirely in person. Little is known about clients’ experience of home visiting provided virtually by video or phone instead of, or in addition to, in-person home visiting.

Objective:
To explore the views of clients in the California Work Opportunity and Responsibility to Kids (CalWORKs) Home Visiting Program (HVP) across California during the first 2 years of the pandemic.

Setting:
Forty counties in California.

Participants:
CalWORKs HVP clients, currently enrolled or who left the program in the 6 months prior to each survey.

Main Outcome Measures:
Clients’ ratings of participation in and experiences with the CalWORKs HVP services, as well as unmet needs.

Results:
We collected 1617 surveys from clients across 3 survey rounds. Pandemic-related restrictions resulted in decreased frequency of home visits and a shift from in person to primarily virtual visits. As in-person home visit frequency decreased, there were significant declines in clients’ level of agreement that they learned child development skills (P = .04), received parenting services (P = .015) or activities (P < .001), or received infant and child nutrition services (P = .003). There were no declines in level of agreement that the CalWORKs HVP improved the quality of life of clients and their children.

Discussion:
Clients consistently rated the CalWORKs HVP as positively contributing to their and their children’s well-being, regardless of the shift from in person to virtual visits. Clients’ participation in some program components decreased over the evaluation. However, it is unknown if clients received fewer referrals, were hesitant to pursue the referrals, or if fewer services were available. Continued research is needed to evaluate the merits and disadvantages of virtual visits as in-person home visits resume postpandemic.
Transcriptome Analysis Reveals Long-Term Somatic Memory of Stress in The Woody Perennial Crop, GrapevineVitis Viniferacv. Cabernet Sauvignon
Authors: Tan Jia W. , Tesfamicael Kiflu , Hu Yikang , Shinde Harshraj , Edwards Everard J. , Tricker Penny , Lopez Carlos Marcelino Rodriguez 
Published: April 2024

SummaryPlants can generate a molecular memory of stress resulting in primed plants that are more resilient to subsequent stresses occurring days to weeks after the priming event. Whether such a priming effect is maintained over longer periods, and after winter dormancy in perennial plants, is less studied. Here, we used whole transcriptome and methylome sequencing of grapevine plants over two growing seasons to characterize grapevines’ response to combined drought and heat stress in naïve and primed plants. Our results showed changes in expression of genes associated with epigenetic modifications during stress and after stress removal, suggesting the establishment of epigenetic memory of stress. Primed plants had a small number of differentially expressed genes associated with stress response one year after the priming event even in the absence of second stress and presented a stronger transcriptional response than naïve plants when re-exposed to stress. Methylome analysis revealed an increase in DNA methylation in primed vines under combined stress, and that methylation patterns were less variable among plants under stress than control plants. We did not observe any correlation between DNA methylation and gene transcription, suggesting that stress-induced expression changes were, at least partially, independent of DNA methylation, with posttranscriptional regulation and histone modifications more likely candidates in the establishment of epigenetic memory. Additionally, we characterized stress responsive genes based on their transcriptional profile and function and propose a new comprehensive and intuitive classification model for stress memory genes in perennials.
Lgr5+ intestinal stem cells are required for organoid survival after genotoxic injury
Authors: Lee Joseph , Gleizes Antoine , Takaesu Felipe , Webster Sarah F , Hailstock Taylor , Barker Nick , Gracz Adam D 
Published: April 2024

ABSTRACTProgenitors and mature cells can maintain the intestinal epithelium by dedifferentiation and facultative intestinal stem cell (fISC) function when active ISCs (aISCs) are lost to damage. Here, we sought to model fISC activation in intestinal organoids with doxorubicin (DXR), a chemotherapeutic known to ablateLgr5+ aISCsin vivo. We identified low and high doses of DXR compatible with long-term organoid survival. Similar fISC gene activation was observed between organoids treated with low vs high DXR, despite significantly decreased survival at the higher dose. aISCs exhibit dose-dependent loss after DXR but survive at doses compatible with organoid survival. We ablated residual aISCs after DXR using aLgr52A-DTRallele and observed that aISC survival of the initial genotoxic insult is required for organoid survival following DXR. These results suggest that while typical fISC genes are activated by DXR injury in organoids, functional stemness remains dependent on the aISC pool. Our data establish a reproducible model of DXR injury in intestinal organoids and reveal differences inin vitroresponses to an establishedin vivodamage modality.
On use of tertiary structure characters in hidden Markov models for protein fold prediction
Authors: Malik Ashar J. , Puente-Lelievre Caroline , Matzke Nicholas , Ascher David B. 
Published: April 2024

AbstractWhile advances in protein structure prediction have opened up insights into arcane proteins, weak sequence homology makes functional characterisation challenging. To overcome this challenge, we use structure-based hidden Markov models of groupings in SCOP, CATH and ECOD to predict folds in proteins and thereby infer function. Conservation of structure and ability of hidden Markov models to detect remote signals make this a powerful resource for complete characterisation of arcane proteins.
Comprehensive evaluation and prediction of editing outcomes for near-PAMless adenine and cytosine base editors
Authors: Zhou Xiaoyu , Gao Jingjing , Luo Liheng , Huang Changcai , Wu Jiayu , Wang Xiaoyue 
Published: April 2024

SummaryBase editors enable the direct conversion of target bases without inducing double-strand breaks, showing great potential for disease modeling and gene therapy. Yet, their applicability has been constrained by the necessity for specific protospacer adjacent motif (PAM). We generated four versions of near-PAMless base editors and systematically evaluated their editing patterns and efficiencies using an sgRNA-target library of 45,747 sequences. Near-PAMless base editors significantly expanded the targeting scope, with both PAM and target flanking sequences as determinants for editing outcomes. We developed BEguider, a deep learning model to accurately predict editing results for near-PAMless base editors. We also provided experimentally measured editing outcomes of 20,541 ClinVar sites, demonstrating that variants previously inaccessible by NGG PAM base editors can now be precisely generated or corrected. We have made our predictive tool and data available online to facilitate development and application of near-PAMless base editors in both research and clinical settings.
The Class III peroxidase OsPrx20 is a key regulator of stress response and growth in rice
Authors: Shen Tao , Wang Qingwen , Chen Dan , Ju Huining , Yan Runjiao , Xu Fengjuan , Fu Donghuan , Bu Xiaona , Zhang Huan , Hu Jiexiong , Zhang Zhengguang , Ni Lan , Jiang Mingyi 
Published: April 2024

AbstractIn plants, reactive oxygen species maintain strictly low intracellular levels that is prerequisite for their function as second messengers. However, abiotic and biotic stresses are also long-term processes, requiring rapid scavenging of excess intracellular ROS. Plant Class III peroxidases, as multifunctional enzymes, are core enzymes in regulating intracellular ROS homeostasis and are key to regulating the complicated signaling network. Here, we found a rice Class III peroxidase OsPrx20 maintains intracellular ROS homeostasis in different conditions. OsPrx20 is a target of Ca2+/calmodulin-dependent protein kinase (OsDMI3) and phosphorylates its Thr-244 site by OsDMI3. Overexpression ofOsPrx20enhances osmotic stress tolerance but reduces blast resistance, while lack ofOsPrx20is opposite, suggesting OsPrx20 positively regulates osmotic stress tolerance but negatively regulates blast resistance in rice. Meanwhile, overexpression ofOsPrx20enlarges spike size and grain fullness, whereas lack ofOsPrx20leads to dwarfism and smaller spike. In ABA signaling, OsPrx20 Thr-244 phosphorylation is specifically dependent on OsDMI3 to reduce the sensitivity of ABA to seed germination and root growth and to enhance osmotic stress tolerance without affecting spike and grain development. Our study reveals an essential regulatory mechanism that directly activates OsPrx20 in ABA signaling, highlighting the multi-functionality of OsPrx20 in different biological processes.
Emergentemm4group AStreptococcusevidences a survival strategy during interaction with immune effector cells
Authors: Odo Chioma M. , Vega Luis A , Mukherjee Piyali , DebRoy Sruti , Flores Anthony R. , Shelburne Samuel A. 
Published: April 2024

ABSTRACTThe major gram-positive pathogen group AStreptococcus(GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence amongstemm4GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. Through the creation and analysis of isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic anhydrase was responsible for the defectivein vitrogrowth observed in the emergent strains. We also identified that the emergent strains survived better inside macrophages and killed macrophages at lower rates relative to the historic strains. Via creation of isogenic mutant strains, we linked the emergent strain “survival” phenotype to the downregulation of the SLO encoding gene and upregulation of themsrABoperon which encodes proteins involved in defense against extracellular oxidative stress. Our findings are in accord with recent surveillance studies which found high ratio of mucosal (i.e., pharyngeal) relative to invasive infections amongstemm4GAS. Inasmuch as ever-increasing virulence is unlikely to be evolutionary advantageous for a microbial pathogen, our data furthers understanding of the well described oscillating patterns of virulent GAS infections by demonstrating mechanisms by which emergent strains adapt a “survival” strategy to outcompete previously circulating isolates.
The G1/S transition in mammalian stem cellsin vivois autonomously regulated by cell size
Authors: Xie Shicong , Zhang Shuyuan , de Medeiros Gustavo , Liberali Prisca , Skotheim Jan M. 
Published: April 2024

AbstractCell growth and division must be coordinated to maintain a stable cell size, but how this coordination is implemented in multicellular tissues remains unclear. In unicellular eukaryotes, autonomous cell size control mechanisms couple cell growth and division with little extracellular input. However, in multicellular tissues we do not know if autonomous cell size control mechanisms operate the same way or whether cell growth and cell cycle progression are separately controlled by cell-extrinsic signals. Here, we address this question by tracking single epidermal stem cells growing in adult mice. We find that a cell-autonomous size control mechanism, dependent on the RB pathway, sets the timing of S phase entry based on the cell’s current size. Cell-extrinsic variations in the cellular microenvironment affect cell growth rates but not this autonomous coupling. Our work reassesses long-standing models of cell cycle regulation within complex metazoan tissues and identifies cell-autonomous size control as a critical mechanism regulating cell divisionsin vivoand thereby a major contributor to stem cell heterogeneity.
Photochromic reversion enables long-term tracking of single molecules in living plants
Authors: von Arx Michelle , Xhelilaj Kaltra , Schulz Philip , zur Oven-Krockhaus Sven , Gronnier Julien 
Published: April 2024

AbstractSingle-molecule imaging promises the observation of individual molecules at work in living cells1,2. In plants, however, the tracking of single molecules is generally limited to mere hundred milliseconds3–5, making it virtually impossible to observe live dynamic cellular events with molecular resolution. Here, we introduce photochromic reversion which uses the reversion of EOS fluorescent protein’s dark state upon blue light illumination6, thereby stabilizing the fluorescent state of single molecules and extending single-molecule tracking in single particle tracking photoactivated localization microscopy (spt-PALM) experiments. Utilizing photochromic reversion, we tracked single molecules over micrometre distances for seconds. We captured transient spatial arrest events of plasma membrane proteins indicative of the observation of dynamic cellular events under physiological conditions. Finally, we implemented an analysis pipeline leveraging machine learning-based diffusional fingerprinting to automatically detect and quantify spatial arrestment, allowing precise kinetic measurements of molecular events at the nanoscale. We envision that photochromic reversion will constitute a pivotal instrument to decipher fundamental principles underlying membrane dynamics and function in plants.
Coupling of cell growth modulation to asymmetric division and cell cycle regulation inCaulobacter crescentus
Authors: Glenn Skye , Lin Wei-Hsiang , Papagiannakis Alexandros , Kato Setsu , Jacobs-Wagner Christine 
Published: April 2024

AbstractIn proliferating bacteria, growth rate is often assumed to be similar between daughter cells. However, most of our knowledge of cell growth derives from studies on symmetrically dividing bacteria. In many α-proteobacteria, asymmetric division is a normal part of the life cycle, with each division producing daughter cells with different sizes and fates. Here, we demonstrate that the functionally distinct swarmer and stalked daughter cells produced by the model α-proteobacteriumCaulobacter crescentushave different average growth rates despite sharing an identical genome and environment. The discrepancy in growth rate is due to a growth slowdown during the cell cycle stage preceding DNA replication (the G1 phase), which is predominantly associated with swarmer cell functionality. We also provide evidence that the second messenger (p)ppGpp extends the timing of the G1/swarmer cell stage by slowing growth specifically during the beginning of the cell cycle. Our data further show that cells factor the amount and rate of their growth to control the G1/S transition, allowing them to adjust the time they spend with ecologically important G1-specific traits.Significance statementBacterial growth rate modulation is generally associated with changes in genetic make-up or environmental condition. This study demonstrates that the rate of cell growth can also vary between daughter cells and across cell cycle stages under invariant and unstressed environmental conditions. This is illustrated by the asymmetrically dividing α-proteobacteriumCaulobacter crescentus, which, at each division, produces two functionally distinct daughter cells that differ in average growth rate. This growth rate difference arises from a G1 phase-specific growth slowdown mediated, in part, by the (p)ppGpp alarmone. Altogether, this study showcases the coupling of cell growth modulation to asymmetric division and cell cycle regulation, which may have implications for other α-proteobacteria given their cell cycle similarities withC. crescentus.
IAPP Marks Mono-hormonal Stem-cell Derived β Cells that Maintain Stable Insulin Productionin vitroandin vivo
Authors: Davis Jeffrey C. , Ryaboshapkina Maria , Kenty Jennifer H. , Eser Pınar Ö. , Menon Suraj , Tyrberg Björn , Melton Douglas A. 
Published: April 2024

AbstractIslet transplantation for treatment of diabetes is limited by availability of donor islets and requirements for immunosuppression. Stem cell-derived islets might circumvent these issues. SC-islets effectively control glucose metabolism post transplantation, but do not yet achieve full functionin vitrowith current published differentiation protocols. We aimed to identify markers of mature subpopulations of SC-β cells by studying transcriptional changes associated within vivomaturation of SC-β cells using RNA-seq and co-expression network analysis. The β cell-specific hormone islet amyloid polypeptide (IAPP) emerged as the top candidate to be such a marker. IAPP+cells had more mature β cell gene expression and higher cellular insulin content than IAPP-cellsin vitro. IAPP+INS+cells were more stable in long-term culture than IAPP-INS+cells and retained insulin expression after transplantation into mice. Finally, we conducted a small molecule screen to identify compounds that enhance IAPP expression. Aconitine up-regulated IAPP and could help to optimize differentiation protocols.HighlightsIAPP expressionin vitromarks a mono-hormonal subpopulation of SC-β cells excluding endocrine hormones other than insulinOnly INS+IAPP+cells maintain stableINSexpressionin vitroup to 100 days after differentiationThe small molecule aconitine accelerates IAPP expression in SC-β cellsin vitro
Glia-derived secretory fatty acid binding protein Obp44a regulates lipid storage and efflux in the developingDrosophilabrain
Authors: Yin Jun , Chen Hsueh-Ling , Grigsby-Brown Anna , He Yi , Cotten Myriam L. , Short Jacob , Dermady Aidan , Lei Jingce , Gibbs Mary , Cheng Ethan S. , Zhang Dean , Long Caixia , Xu Lele , Zhong Tiffany , Abzalimov Rinat , Haider Mariam , Sun Rong , He Ye , Zhou Qiangjun , Tjandra Nico , Yuan Quan 
Published: April 2024

AbstractGlia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins fromDrosophilaCNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.
Accurate estimation of intraspecific microbial gene content variation in metagenomic data with MIDAS v3 and StrainPGC
Authors: Smith Byron J. , Zhao Chunyu , Dubinkina Veronika , Jin Xiaofan , Zahavi Liron , Shoer Saar , Moltzau-Anderson Jacqueline , Segal Eran , Pollard Katherine S. 
Published: April 2024

AbstractMetagenomics has greatly expanded our understanding of the human gut microbiome by revealing a vast diversity of bacterial species within and across individuals. Even within a single species, different strains can have highly divergent gene content, affecting traits such as antibiotic resistance, metabolism, and virulence. Methods that harness metagenomic data to resolve strain-level differences in functional potential are crucial for understanding the causes and consequences of this intraspecific diversity. The enormous size of pangenome references, strain mixing within samples, and inconsistent sequencing depth present challenges for existing tools that analyze samples one at a time. To address this gap, we updated the MIDAS pangenome profiler, now released as version 3, and developed StrainPGC, an approach to strain-specific gene content estimation that combines strain tracking and correlations across multiple samples. We validate our integrated analysis using a complex synthetic community of strains from the human gut and find that StrainPGC outperforms existing approaches. Analyzing a large, publicly available metagenome collection from inflammatory bowel disease patients and healthy controls, we catalog the functional repertoires of thousands of strains across hundreds of species, capturing extensive diversity missing from reference databases. Finally, we apply StrainPGC to metagenomes from a clinical trial of fecal microbiota transplantation for the treatment of ulcerative colitis. We identify twoEscherichia colistrains from two different donors that are both frequently transmitted to patients, but have notable differences in functional potential. StrainPGC and MIDAS v3 together enable precise, intraspecific pangenomic investigations using large collections of metagenomic data without microbial isolation or de novo assembly.