bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasion and spread of the neotropical leafhopperCurtara insularis(Hemiptera: Cicadellidae) in Africa and North America and the role of high-altitude windborne migration in invasive insects
Authors: Nartey Rita , Chamorro Lourdes , Buffington Matt , Afrane Yaw A. , Mohammed Abdul R. , Owusu-Asenso Christopher M. , Akosah-Brempong Gabriel , Pambit Zong Cosmos Manwovor-Anbon , Hendrix Solomon V. , Dao Adama , Yaro Alpha S. , Diallo Moussa , Sanogo Zana L. , Djibril Samake , Halbert Susan E. , Bamou Roland , Nance Catherine E. , Bartlett Charles R. , Reynolds Don R. , Chapman Jason W. , Obiri-Danso Kwasi , Lehmann Tovi 
Published: May 2024

AbstractInvasive insects threaten ecosystem stability, public health, and food security. Documenting newly invasive species and understanding how they reach into new territories, establish populations, and interact with other species remain vitally important. Here, we report on the invasion of the South American leafhopper,Curtara insularisinto Africa, where it has established populations in Ghana, encroaching inland at least 350 km off the coast. Importantly, 80% of the specimens collected were intercepted between 160 and 190 m above ground. Further, the fraction of this species among all insects collected was also higher at altitude, demonstrating its propensity to engage in high-altitude windborne dispersal. Its aerial densities at altitude translate into millions of migrants/km over a year, representing massive propagule pressure. Given the predominant south-westerly winds, these sightings suggest an introduction ofC. insularisinto at least one of the Gulf of Guinea ports. To assess the contribution of windborne dispersal to its spread in a new territory, we examine records ofC. insularisrange-expansion in the USA. Reported first in 2004 from central Florida, it reached north Florida (Panhandle) by 2008-2011 and subsequently spread across the southeastern and south-central US. Its expansion fits a “diffusion-like” process with 200—300 km long “annual displacement steps”—a pattern consistent with autonomous dispersal rather than vehicular transport. Most “steps” are consistent with common wind trajectories from the nearest documented population, assuming 2—8 hours of wind-assisted flight at altitude.Curtara insularishas been intercepted at US ports and on trucks. Thus, it uses multiple dispersal modalities, yet its rapid overland spread is better explained by its massive propagule pressure linked with its high-altitude windborne dispersal. We propose that high-altitude windborne dispersal is common yet under-appreciated in invasive insect species.
Mining the UniProtKB/Swiss-Prot database for antimicrobial peptides
Authors: Li Chenkai , Sutherland Darcy , Salehi Ali , Richter Amelia , Lin Diana , Aninta Sambina Islam , Ebrahimikondori Hossein , Yanai Anat , Coombe Lauren , Warren René L. , Kotkoff Monica , Hoang Linda M.N. , Helbing Caren C. , Birol Inanc 
Published: May 2024

AbstractThe ever-growing global health threat of antibiotic resistance is compelling researchers to explore alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) are emerging as a promising solution to fill this need. Naturally occurring AMPs are produced by all forms of life as part of the innate immune system. High-throughput bioinformatics tools have enabled fast and large-scale discovery of AMPs from genomic, transcriptomic, and proteomic resources of selected organisms. Public protein sequence databases, comprising over 200 million records and growing, serve as comprehensive compendia of sequences from a broad range of source organisms. Yet, large-scalein silicoprobing of those databases for novel AMPs has never been reported. In the present study, we propose an AMP mining workflow to predict novel AMPs from the UniProtKB/Swiss-Prot database using the AMP prediction tool, AMPlify, as its discovery engine. Using this workflow, we identified 8,008 novel putative AMPs from all eukaryotic sequences in the database. Focusing on the practical use of AMPs as suitable antimicrobial agents with applications in the poultry industry, we prioritized 40 of those AMPs based on their similarities to known chicken AMPs in predicted structures. In our tests, 13 out of the 38 successfully synthesized peptides showed antimicrobial activity againstEscherichia coliand/orStaphylococcus aureus.
Identification of potential inflammation markers for outgrowth of cow’s milk allergy
Authors: Hendrickx Diana M , Long Mengyichen ,   PRESTO study team, Wopereis Harm , van der Molen Renate G , Belzer Clara 
Published: May 2024

ABSTRACTIntroductionImmunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) is an immune-mediated reaction to cow’s milk (CM). Non-IgE-mediated CMA resolves in most children in the first years of life, whereas IgE-mediated CMA outgrowth is often later or not at all. The exact mechanisms underlying resolution of IgE-mediated CMA are not fully understood.MethodsWe aim to gain insight in the immunological mechanisms underlying resolution of IgE-mediated CMA by analyzing unique saliva samples of allergic infants using the Olink® Target 96 Inflammation panel. Twenty-four children who outgrew their CMA after 12 months were compared to 15 with persistent CMA.ResultsPersistent CMA was accompanied by an increase in interleukin-15 receptor subunit alpha in the first 6 months, followed by a decrease, hinting towards an initial increased T cell response. At the same time caspase-8 was increased and interleukin-7 was decreased in persistent CMA. For CMA resolution, we found elevated levels of delta and notch-like epidermal growth factor-related receptor. Furthermore, adenosine deaminase (ADA) increased significantly between 0 and 12 months in resolved CMA, but not in persistent CMA. KEGG pathway analysis suggests mainly the TNF signaling pathway to be important in the resolution of CM allergy.ConclusionOlink® Target 96 Inflammation panel analysis of saliva samples can reveal potential immunological markers and mechanisms involved in CMA resolution.
On forensic likelihood ratios from low-coverage sequencing
Authors: Ouerghi Feriel , Krane Dan E. , Edge Michael D. 
Published: May 2024

AbstractAdvances in sequencing technology are allowing forensic scientists to access genetic information from increasingly challenging samples. A recently published computational approach,IBDGem, analyzes sequencing reads, including from low-coverage samples, in order to arrive at likelihood ratios for human identification. Here, we show that likelihood ratios produced byIBDGemare best interpreted as testing a null hypothesis different from the traditional one used in a forensic genetics context. In particular, rather than testing the hypothesis that the sample comes from a person unrelated to the person of interest,IBDGemtests the hypothesis that the sample comes from an individual who is included in the reference database used to run the method. This null hypothesis is not generally of forensic interest, because the defense hypothesis is not typically that the evidence comes from an individual included in a reference database. Moreover, the computed likelihood ratios can be much larger than likelihood ratios computed for the standard forensic null hypothesis, often by many orders of magnitude, thus potentially creating an impression of stronger evidence for identity than is warranted. We lay out this result and illustrate it with examples, giving suggestions for directions that might lead to likelihood ratios that test the typical defense hypothesis.
Overlapping coactivator function is required for transcriptional activation by theCandida glabrataPdr1 transcription factor
Authors: Conway Thomas P. , Simonicova Lucia , Moye-Rowley W. Scott 
Published: May 2024

AbstractAzole resistance in the pathogenic yeastCandida glabratais a serious clinical complication and increasing in frequency. The majority of resistant organisms have been found to contain a substitution mutation in the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. These mutations typically lead to this factor driving high, constitutive expression of target genes like the ATP-binding cassette transporter-encoding geneCDR1. Overexpression of Cdr1 is required for the observed elevated fluconazole resistance exhibited by strains containing one of these hyperactivePDR1alleles. While the identity of hyperactivePDR1alleles has been extensively documented, the mechanisms underlying how these gain-of-function (GOF) forms of Pdr1 lead to elevated target gene transcription are not well understood. We have used a tandem affinity purification (TAP)-tagged form of Pdr1 to identify coactivator proteins that biochemically purify with the wild-type and two different GOF forms of Pdr1. Three coactivator proteins were found to associate with Pdr1: the SWI/SNF complex Snf2 chromatin remodeling protein and two different components of the SAGA complex, Spt7 and Ngg1. We found that deletion mutants lacking eitherSNF2orSPT7exhibited growth defects, even in the absence of fluconazole challenge. To overcome these issues, we employed a conditional degradation system to acutely deplete these coactivators and determined that loss of either coactivator complex, SWI/SNF or SAGA, caused defects in Pdr1-dependent transcription. A double degron strain that could be depleted for both SWI/SNF and SAGA exhibited a profound defect inPDR1autoregulation, revealing that these complexes work together to ensure high level Pdr1-dependent gene transcription.
Cell-specific nanoengineering strategy disrupts tolerogenic signaling from myeloid-derived suppressor cells to invigorate antitumor immunity in pancreatic cancer
Authors: Deshpande Nilesh U. , Bianchi Anna , Amirian Haleh , De Castro Silva Iago , Rafie Christine I. , Surnar Bapurao , Rajkumar Karthik , Ogobuiro Ifeanyichukwu C. , Patel Manan , Mehra Siddharth , Nagathihalli Nagaraj S. , Merchant Nipun B. , Dhar Shanta , Datta Jashodeep 
Published: May 2024

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is characterized by intratumoral abundance of neutrophilic/polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) which inhibit T-cell function through JAK2/STAT3-regulated arginase activity. To overcome limitations of systemic inhibition of PMN-MDSCs in cancer-bearing patients—i.e., neutropenia and compensatory myelopoietic adaptations—we develop a nanoengineering strategy to target cell-specific signaling exclusively in PMN-MDSCs without provoking neutropenia. We conjugate a chemically modified small-molecule inhibitor of MDSC-surface receptor CXCR2 (AZD5069) with polyethylene glycol (PEG) and chemically graft AZD5069-PEG constructs onto amphiphilic polysaccharide derivatives to engineer CXCR2-homing nanoparticles (CXCR2-NP). Cy5.5 dye-loaded CXCR2-NP showed near-exclusive uptake in PMN-MDSCs compared with PDAC tumor-cells, cancer-associated fibroblasts, and macrophages. Encapsulation of JAK2/STAT3i Ruxolitinib (CXCR2-NPRuxo) resulted in more durable attenuation in STAT3-regulated arginase activity from PMN-MDSCs and induction of cytolytic T-cell activity vs. free Ruxolitinibin-vitroandin-vivo. Cell-specific delivery of payloads via CXCR2-homing immunonanoparticles represents a novel strategy to disrupt MDSC-mediated immunosuppression and invigorate antitumor immunity in PDAC.
Evolutionary trajectories of resistant mutants during sub-MIC antibiotic exposure
Authors: Warsi Omar M. 
Published: May 2024

ABSTRACTThe emergence of antibiotic resistance is one of the most important examples of contemporary evolution. Selection for resistance can occur over a wide concentration range, both above and below the minimum inhibitory concentration (MIC) of the antibiotic. In a majority of cases, resistance mutations confer fitness costs and several studies have shown the importance of these costs for the emergence, ascendance and maintenance of resistance in a population. Importantly, these costs can often be ameliorated by compensatory mutations and rate and efficiency of compensation is a key parameter in determining the evolutionary success of a costly resistance mutation. Despite this knowledge, we still have a limited understanding of how resistance evolution (to increase resistance) and compensatory evolution (to reduce fitness costs) interact during growth in presence of low, sub-MIC, antibiotic concentrations. To examine the impact of these two processes, we carried out evolution experiments at sub-MIC levels of streptomycin using twoE. colimutants (with loss of function mutations in theselBandubiHgenes, respectively) that show low-level streptomycin resistance, and have different fitness costs. For both mutants, evolution at sub-MIC levels enriched for mutations that increased resistance, but selection for compensatory mutations was also common over the course of the experiment. Our study highlights that costly low-level resistant mutants adapt to sub-MIC antibiotic exposure by either increasing resistance, reducing cost or both and that this evolution can result in the maintenance of these mutants in the population.
diaTracer enables spectrum-centric analysis of diaPASEF proteomics data
Authors: Li Kai , Teo Guo Ci , Yang Kevin L. , Yu Fengchao , Nesvizhskii Alexey I. 
Published: May 2024

AbstractData-independent acquisition (DIA) has become a widely used strategy for peptide and protein quantification in mass spectrometry-based proteomics studies. The integration of ion mobility separation into DIA analysis, such as the diaPASEF technology available on Bruker’s timsTOF platform, further improves the quantification accuracy and protein depth achievable using DIA. We introduce diaTracer, a new spectrum-centric computational tool optimized for diaPASEF data. diaTracer performs three-dimensional (m/z, retention time, ion mobility) peak tracing and feature detection to generate precursor-resolved “pseudo-MS/MS” spectra, facilitating direct (“spectral-library free”) peptide identification and quantification from diaPASEF data. diaTracer is available as a stand-alone tool and is fully integrated into the widely used FragPipe computational platform. We demonstrate the performance of diaTracer and FragPipe using diaPASEF data from triple-negative breast cancer (TNBC), cerebrospinal fluid (CSF), and plasma samples, data from phosphoproteomics and HLA immunopeptidomics experiments, and low-input data from a spatial proteomics study. We also show that diaTracer enables unrestricted identification of post-translational modifications from diaPASEF data using open/mass-offset searches.
Suppression of autophagy induces senescence in the heart
Authors: Zhai Peiyong , Sung Eun-Ah , Shiheido-Watanabe Yuka , Takayama Koichiro , Tian Yimin , Sadoshima Junichi 
Published: May 2024

AbstractAging is a critical risk factor for heart disease, including ischemic heart disease and heart failure. Cellular senescence, characterized by DNA damage, resistance to apoptosis and the senescence-associated secretory phenotype (SASP), occurs in many cell types, including cardiomyocytes. Senescence precipitates the aging process in surrounding cells and the organ through paracrine mechanisms. Generalized autophagy, which degrades cytosolic materials in a non-selective manner, is decreased during aging in the heart. This decrease causes deterioration of cellular quality control mechanisms, facilitates aging and negatively affects lifespan in animals, including mice. Although suppression of generalized autophagy could promote senescence, it remains unclear whether the suppression of autophagy directly stimulates senescence in cardiomyocytes, which, in turn, promotes myocardial dysfunction in the heart. We addressed this question using mouse models with a loss of autophagy function.Suppression of general autophagy in cardiac-specificAtg7knockout (Atg7cKO) mice caused accumulation of senescent cardiomyocytes. Induction of senescence via downregulation ofAtg7was also observed in chimericAtg7cardiac-specific KO mice and cultured cardiomyocytesin vitro, suggesting that the effect of autophagy suppression upon induction of senescence is cell autonomous. ABT-263, a senolytic agent, reduced the number of senescent myocytes and improved cardiac function inAtg7cKO mice. Suppression of autophagy and induction of senescence were also observed in doxorubicin-treated hearts, where activation of autophagy alleviated senescence in cardiomyocytes and cardiac dysfunction. These results suggest that suppression of general autophagy directly induces senescence in cardiomyocytes, which in turn promotes cardiac dysfunction.
Multiwell-based G0-PCC assay for radiation biodosimetry
Authors: Royba Ekaterina , Shuryak Igor , Ponnaiya Brian , Repin Mikhail , Pampou Sergey , Karan Charles , Turner Helen , Garty Guy , Brenner David J. 
Published: May 2024

AbstractIn cytogenetic biodosimetry, assessing radiation exposure typically requires over 48 hours for cells to reach mitosis, significantly delaying the administration of crucial radiation countermeasures needed within the first 24 hours post-exposure. To improve medical response times, we incorporated the G0-Premature Chromosome Condensation (G0-PCC) technique with the Rapid Automated Biodosimetry Tool-II (RABiT-II), creating a faster alternative for large-scale radiation emergencies. Our findings revealed that using a lower concentration of Calyculin A (Cal A) than recommended effectively increased the yield of highly-condensed G0-PCC cells (hPCC). However, integrating recombinant CDK1/Cyclin B kinase, vital for chromosome condensation, proved challenging due to the properties of these proteins affecting interactions with cellular membranes. Interestingly, Cal A alone was capable of inducing chromosome compaction in some G0 cells even in the absence of mitotic kinases, although these chromosomes displayed atypical morphologies. This suggests that Cal A mechanism for compacting G0 chromatin may differ from condensation driven by mitotic kinases. Additionally, we observed a correlation between radiation dose and extent of hPCC chromosome fragmentation, which allowed us to automate radiation damage quantification using a Convolutional Neural Network (CNN). Our method can address the need for a same-day cytogenetic biodosimetry test in radiation emergency situations.
Deep learning-based cytoskeleton segmentation for accurate high-throughput measurement of cytoskeleton density
Authors: Horiuchi Ryota , Kamimura Asuka , Hanaki Yuga , Matsumoto Hikari , Ueda Minako , Higaki Takumi 
Published: May 2024

AbstractMicroscopic analyses of cytoskeleton organization are crucial for understanding various cellular activities, including cell proliferation and environmental responses in plants. Traditionally, assessments of cytoskeleton dynamics have been qualitative, relying on microscopy-assisted visual inspection. However, the transition to quantitative digital microscopy has introduced new technical challenges, with segmentation of cytoskeleton structures proving particularly demanding. In this study, we examined the utility of a deep learning-based segmentation method for accurate quantitative evaluation of cytoskeleton organization using confocal microscopic images of the cortical microtubules in tobacco BY-2 cells. The results showed that, although conventional methods sufficed for measurement of cytoskeleton angles and parallelness, the deep learning-based method significantly improved the accuracy of density measurements. To assess the versatility of the method, we extended our analysis to physiologically significant models in the context of changes in cytoskeleton density, namelyArabidopsis thalianaguard cells and zygotes. The deep learning-based method successfully improved the accuracy of cytoskeleton density measurements for quantitative evaluations of physiological changes in both stomatal movement in guard cells and intracellular polarization in elongating zygotes, confirming its utility in these applications. The results demonstrate the effectiveness of deep learning-based segmentation in providing precise and high-throughput measurements of cytoskeleton density, and has the potential to automate and expedite analyses of large-scale image datasets.
Conceptual framework of episodic disability in the context of Long COVID: Findings from a community-engaged international qualitative study
Authors: O’Brien Kelly K. , Brown Darren A. , McDuff Kiera , St. Clair-Sullivan Natalie , Carusone Soo Chan , Thomson Catherine , McCorkell Lisa , Wei Hannah , Goulding Susie , O’Hara Margaret , Roche Niamh , Stokes Ruth , Kelly Mary , Cheung Angela M. , Erlandson Kristine M. , Harding Richard , Vera Jaime H. , Bergin Colm , Robinson Larry , Avery Lisa , Bannan Ciaran , Torres Brittany , O’Donovan Imelda , Malli Nisa , Solomon Patricia 
Published: May 2024

AbstractBackgroundIncreasing numbers of adults are living with the health-related consequences of Long COVID. The Episodic Disability Framework (EDF), derived from perspectives of adults living with HIV, characterizes the multidimensional and episodic nature of health-related challenges (disability) experienced by an individual. Our aim was to determine the applicability of the Episodic Disability Framework to conceptualize the health-related challenges experienced among adults living with Long COVID.MethodsWe conducted a community-engaged qualitative descriptive study involving online semi-structured interviews. We recruited adults who self-identified as living with Long COVID via collaborator community organizations in Canada, Ireland, United Kingdom, and United States. We purposively recruited for diversity in age, gender identity, ethnicity, sexual orientation, and time since initial COVID-19 infection. We used a semi-structured interview guide informed by the EDF to explore experiences of disability living with Long COVID, specifically health-related challenges and how challenges were experienced over time. We conducted a group-based content analysis.ResultsOf the 40 participants, the median age was 39 years; and the majority were white (73%), women (63%), living with Long COVID for ≥1 year (83%). Consistent with the Episodic Disability Framework, disability was described as multidimensional and episodic, characterized by unpredictable periods of health and illness. Experiences of disability were consistent with the three main components of the Framework: A) dimensions of disability (physical, cognitive, mental-emotional health challenges, difficulties with day-to-day activities, challenges to social inclusion, uncertainty); B) contextual factors, extrinsic (social support; accessibility of environment and health services; stigma and epistemic injustice) and intrinsic (living strategies; personal attributes) that exacerbate or alleviate dimensions of disability; and C) triggers that initiate episodes of disability.ConclusionsThe Episodic Disability Framework provides a way to conceptualize disability the multidimensional and episodic nature of disability experienced by adults living with Long COVID. The Framework provides guidance for future measurement of disability, and health and rehabilitation approaches to enhance practice, research, and policy in Long COVID.