bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic Insights into the Epigenetic Modulation of Turnip Mosaic Virus Evolution inArabidopsis thaliana
Authors: Olmo-Uceda María J. , Ambrós Silvia , Corrêa Régis L. , Elena Santiago F. 
Published: June 2024

AbstractPlant-virus interaction models propose that a virus’s ability to infect a host genotype depends on the compatibility between virulence and resistance genes. Recently, we conducted an evolution experiment in which lineages of turnip mosaic virus (TuMV) were passaged inArabidopsis thalianagenotypes carrying mutations in components of the DNA methylation and the histone demethylation epigenetic pathways. All evolved lineages increased infectivity, virulence and viral load in a host genotype-dependent manner. To better understand the underlying reasons for these evolved relationships, we delved into the transcriptomic responses of mutant and WT plant genotypes in mock conditions and infected with either the ancestral or evolved viruses. Such a comparison allowed us to classify every gene into nine basic expression profiles. Regarding the targets of viral adaptation, our analyses allowed the identification of common viral targets as well as host genotype-specific genes and categories of biological processes. As expected, immune response-related genes were found to be altered upon infection. However, we also noticed the pervasive over-representation of other functional groups, suggesting that viral adaptation was not solely driven by the level of expression of plant resistance genes. In addition, a significant association between the presence of transposable elements within or upstream the differentially expressed genes was observed. Finally, integration of transcriptomic data into a virus-host protein-protein interaction network highlighted the most impactful interactions. These findings shed extra light on the complex dynamics between plants and viruses, indicating that viral infectivity depends on various factors beyond just the plant’s resistance genes.
Vaccine-elicited and naturally elicited antibodies differ in their recognition of the HIV-1 fusion peptide
Authors: Reveiz Mateo , Xu Kai , Lee Myungjin , Wang Shuishu , Olia Adam S. , Harris Darcy R. , Liu Kevin , Liu Tracy , Schaub Andrew J. , Stephens Tyler , Wang Yiran , Zhang Baoshan , Huang Rick , Tsybovsky Yaroslav , Kwong Peter D. , Rawi Reda 
Published: June 2024

ABSTRACTBroadly neutralizing antibodies have been proposed as templates for HIV-vaccine design, but it has been unclear how similar vaccine-elicited antibodies are to their naturally elicited templates. To provide insight, here we compare the recognition of naturally elicited and vaccine-elicited antibodies targeting the HIV-1-fusion peptide, which comprises envelope (Env) residues 512-526, with the most common sequence being AVGIGAVFLGFLGAA. Naturally elicited antibodies bound peptides with negative-charge substitutions around residues 517-520 substantially better than the most common sequence, despite these substitutions rarely appearing in HIV; by contrast, vaccine-elicited antibodies were less tolerant of sequence variation, with no substitution of residues 512-516 showing increased binding. Molecular dynamics analysis and cryo-EM structure of the naturally elicited ACS202 antibody in complex with HIV-Env trimer with A517E suggested enhanced binding to result from electrostatic interactions with positively charged antibody residues. Overall, vaccine-elicited antibodies appeared to be more fully optimized to bind the most common fusion peptide sequence.HIGHLIGHTSPeptide substitution scan reveals naturally elicited antibodies against fusion peptide (FP) can bind select non-canonical FP sequences with high affinity.Peptide substitution scan data for FP antibodies correlates significantly with their differential selection indicating variation in binding relates to neutralization tolerance.Structure and energetic analysis of naturally elicited ACS202 with HIV-Env trimer reveals basis for improved recognition of A517E mutant.Atomic level interactions from MD simulation analysis corroborate trends observed with peptide substitutions.verall, peptide substitution scans reveal vaccine-elicited antibodies against FP to be less permissive to FP-sequence variability than naturally elicited antibodies.
Noradrenergic tuning of arousal is coupled to coordinated movements
Authors: Li Li , Rana Akshay N. , Li Esther M. , Travis Myesa O. , Bruchas Michael R. 
Published: June 2024

AbstractMatching arousal level to the motor activity of an animal is important for efficiently allocating cognitive resources and metabolic supply in response to behavioral demands, but how the brain coordinates changes in arousal and wakefulness in response to motor activity remains an unclear phenomenon. We hypothesized that the locus coeruleus (LC), as the primary source of cortical norepinephrine (NE) and promoter of cortical and sympathetic arousal, is well-positioned to mediate movement-arousal coupling. Here, using a combination of physiological recordings, fiber photometry, optogenetics, and behavioral tracking, we show that the LCNEactivation is tightly coupled to the return of organized movements during waking from an anesthetized state. Moreover, in an awake animal, movement initiations are coupled to LCNEactivation, while movement arrests, to LCNEdeactivation. We also report that LCNEactivity covaries with the depth of anesthesia and that LCNEphotoactivation leads to sympathetic activation, consistent with its role in mediating increased arousal. Together, these studies reveal a more nuanced, modulatory role that LCNEplays in coordinating movement and arousal.
Dissociation of novel open loop from ventral putamen to motor areas from classic closed loop in humans II: task-based function
Authors: Dundon Neil M. , Rizor Elizabeth , Stasiak Joanne , Wang Jingyi , Sabugo Kiana , Villaneuva Christina , Barandon Parker , Bostan Andreea C. , Lapate Regina C. , Grafton Scott T. 
Published: June 2024

AbstractHumans ubiquitously increase the speed of their movements when motivated by incentives (i.e., capturing reward or avoiding loss). The complex interplay between incentivization and motor output is pertinent for unpacking the functional profiles of different circuits that link the basal ganglia with motor cortical areas. Here, we analyzed the functional profile of nodes forming two circuits involving putamen and motor cortical areas: the traditional “closed-loop circuit” (CLC) from sensorimotor dorsal putamen (PUTd) and a putative “open-loop circuit” (OLC) from ventral putamen (PUTv). Establishing differential function between CLC and OLC is particularly relevant for therapeutic approaches to Parkinson’s disease, where OLC function is hypothesized to be relatively spared by the disease process. In a large sample fMRI study, 68 healthy controls executed speeded reaches with a joystick under different levels of incentivization to accurately hit precision targets. We dissociated effects of “incentive per se” (i.e., changes in brain activity when an upcoming movement obtains a reward or avoids a loss) from “RT effects” (i.e., brain activity that directly scales with adjustments to movement initiation time). Incentive per se was observed across sites in both CLC and OLC. However, RT effects were primarily in nodes of the OLC and motor sites, consistent with the hypothesized anatomy and function of OLC. Our findings additionally suggest valence might mediate when incentives recruit OLC to more prominent control of motor behavior.
Increased Netrin downstream of overactive Hedgehog signaling disrupts optic fissure formation
Authors: Lusk Sarah , LaPotin Sarah , Presnell Jason S. , Kwan Kristen M. 
Published: June 2024

AbstractBackgroundUveal coloboma, a developmental eye defect, is caused by failed development of the optic fissure, a ventral structure in the optic stalk and cup where axons exit the eye and vasculature enters. The Hedgehog (Hh) signaling pathway regulates optic fissure development: loss-of-function mutations in the Hh receptorptch2produce overactive Hh signaling and can result in coloboma. We previously proposed a model where overactive Hh signaling disrupts optic fissure formation by upregulating transcriptional targets acting both cell- and non-cell-autonomously. Here, we examine the Netrin family of secreted ligands as candidate Hh target genes.ResultsWe find multiple Netrin ligands upregulated in the zebrafishptch2mutant during optic fissure development. Using a gain-of-function approach to overexpress Netrin in a spatiotemporally specific manner, we find thatnetrin1aornetrin1boverexpression is sufficient to cause coloboma and disrupt wild-type optic fissure formation. We used loss-of-function alleles, CRISPR/Cas9 mutagenesis, and morpholino knockdown to test if loss of Netrin can rescue coloboma in theptch2mutant: loss ofnetringenes does not rescue theptch2mutant phenotype.ConclusionThese results suggest that Netrin is sufficient but not required to disrupt optic fissure formation downstream of overactive Hh signaling in theptch2mutant.Key FindingsOveractive Hedgehog signaling in theptch2mutant causes increased netrin expressionSpatiotemporally specific overexpression of netrin1a and netrin1b can cause colobomaSpatiotemporally specific overexpression of netrin1a can disrupt optic fissure and stalk formation as well as optic stalk cell morphology, similar to theptch2mutantLoss of netrin ligands in theptch2mutant does not rescue the phenotype
TransfoRNA: Navigating the Uncertainties of Small RNA Annotation with an Adaptive Machine Learning Strategy
Authors: Taha Yasser , Jehn Julia , Kahraman Mustafa , Frank Maurice , Heuvelman Marco , Horos Rastislav , Yau Christopher , Steinkraus Bruno , Sikosek Tobias 
Published: June 2024

ABSTRACTSmall RNAs hold crucial biological information and have immense diagnostic and therapeutic value. While many established annotation tools focus on microRNAs, there are myriads of other small RNAs that are currently underutilized. These small RNAs can be difficult to annotate, as ground truth is limited and well-established mapping and mismatch rules are lacking.TransfoRNA is a machine learning framework based on Transformers that explores an alternative strategy. It uses common annotation tools to generate a small seed of high-confidence training labels, while then expanding upon those labels iteratively. TransfoRNA learns sequence-specific representations of all RNAs to construct a similarity network which can be interrogated as new RNAs are annotated, allowing to rank RNAs based on their familiarity. While models can be flexibly trained on any RNA dataset, we here present a version trained on TCGA (The Cancer Genome Atlas) small RNA sequences and demonstrate its ability to add annotation confidence to an unrelated dataset, where 21% of previously unannotated RNAs could be annotated. Relative to its training data, TransfoRNA could boost high-confidence annotations in TCGA by ∼50% while providing transparent explanations even for low-confidence ones. It could learn to annotate 97% of isomiRs from just single examples and confidently identify new members of other familiar classes with high accuracy, while reliably rejecting false RNAs.All source code is available athttps://github.com/gitHBDX/TransfoRNAand can be executed at Code Ocean (https://codeocean.com/capsule/5415298/). An interactive website is available atwww.transforna.com.GRAPHICAL ABSTRACT
The Proton Resonance Enhancement for CEST imaging and Shift Exchange (PRECISE) family of RF pulse shapes for Chemical Exchange Saturation Transfer MRI
Authors: Mohanta Zinia , Stabinska Julia , Gilad Assaf A. , Barker Peter B. , McMahon Michael T. 
Published: June 2024

AbstractPurposeTo optimize a 100 msec pulse for producing CEST MRI contrast and evaluate in mice.MethodsA gradient ascent algorithm was employed to generate a family of 100 point, 100 msec pulses for use in CEST pulse trains (‘PRECISE’). Gradient ascent optimizations were performed for exchange rates (kca) = 500 s−1, 1,500 s−1, 2,500 s−1, 3,500 s−1and 4,500 s−1and offsets (Δω) = 9.6, 7.8, 4.2 and 2.0 ppm. 7 PRECISE pulse shapes were tested on an 11.7 T scanner using a phantom containing three representative CEST agents with peak saturation B1= 4 μT. The pulse producing the most contrast in phantoms was then evaluated for CEST MRI pH mapping of the kidneys in healthy mice after iopamidol administration.ResultsThe most promising pulse in terms of contrast performance across all three phantoms was the 9.6 ppm, 2500 s−1optimized pulse with ∼2.7 x improvement over Gaussian and ∼1.3x’s over Fermi pulses. This pulse also displayed a large improvement in contrast over the Gaussian pulse after administration of iopamidol in live mice.ConclusionA new 100 msec pulse was developed based on gradient ascent optimizations which produced better contrast compared to standard Gaussian and Fermi pulses in phantoms. This shape also showed a substantial improvement for CEST MRI pH mapping in live mice over the Gaussian shape and appears promising for a wide range of CEST applications.
Changes in miRNA secondary structure can predict mutations associated with cancer and other diseases
Authors: Novev Javor K. , E. Ahnert Sebastian 
Published: June 2024

AbstractMicroRNAs (miRNAs) are ubiquitous short RNAs regulating gene expression in many organisms, including humans. How the secondary structure (SS) of a mature miRNA affects its regulatory function remains an open question. Here we investigate this question through computational SS predictions of miRNA point mutants. We explore the mutational neighborhoods of miRNAs with association to human diseases, including cancer. We focus on possible SS changes independent of target-site complementarity, by leaving the seed region unchanged. We formulate metrics of the SS differences between such mutants and their wild types (WTs), and test whether these metrics predict disease association by comparing our results with the miRNASNP-v3 database. We find that disease-related mutants tend to have a higher probability of being fully unfolded than their WT; this and other SS-related measures are statistically significant at the database level. With the same approach, we identify a subset of individual miRNAs for which SS changes are most likely to predict disease-related mutations. These are hsa-miR-1269b, hsa-miR-4537, hsa-miR-4477b, hsa-miR-4641, and hsa-miR-6821-3p. In addition, we show that there are pairs of known miRNA WTs differing only by disease-related point mutations outside the seed region and exhibit very different SS. These pairs include hsa-miR-1269a—hsa-miR-1269b, and hsa-miR-3689a-3p—hsa-miR-3689b-3p.
Drosophila melanogasterToll-9 elicits antiviral immunity againstDrosophilaC virus
Authors: Chauhan Manish , Martinak Peter E. , Hollenberg Benjamin M. , Goodman Alan G. 
Published: June 2024

ABSTRACTThe Toll pathway plays a pivotal role in innate immune responses against pathogens. The evolutionary conserved pathogen recognition receptors (PRRs), including Toll like receptors (TLRs), play a crucial role in recognition of pathogen associated molecular patterns (PAMPs). TheDrosophilagenome encodes nine Toll receptors that are orthologous to mammalian TLRs. While mammalian TLRs directly recognize PAMPs, mostDrosophilaTolls recognize the proteolytically cleaved ligand Spätzle to activate downstream signaling cascades. In this study, we demonstrated that Toll-9 is crucial for antiviral immunity againstDrosophilaC virus (DCV), a natural pathogen ofDrosophila. A transposable element insertion in theToll-9gene renders the flies more susceptible to DCV. The stable expression of Toll-9 in S2 cells confers resistance against DCV infection by upregulation of the RNAi pathway. Toll-9 promotes the dephosphorylation of AKT, resulting in the induction of antiviral RNAi genes to inhibit DCV replication. Toll-9 localizes to the endosome where it binds dsRNA, suggesting its role to detect viral dsRNA. Toll-9 also induces apoptosis during DCV infection, contributing to its antiviral role. Together, this work identifies the role of Toll-9 in antiviral immunity against DCV infection through its ability to bind dsRNA and induce AKT-mediated RNAi antiviral immunity.IMPORTANCEInsects rely on innate immunity and RNA interference (RNAi) to combat viral infections. Our study underscores the pivotal role ofDrosophilaToll-9 in antiviral immunity, aligning with findings inBombyx mori, where Toll-9 activation upregulates the RNAi componentDicer2. We demonstrate thatDrosophilaToll-9 functions as a pattern recognition receptor (PRR) for double-stranded RNA (dsRNA) duringDrosophila Cvirus (DCV) infection, akin to mammalian TLRs. Toll-9 activation leads to the upregulation of key RNAi components,Dicer2andArgonaute2, and dephosphorylation of AKT triggers apoptosis via induction of proapoptotic genesHidandReaper. This study also reveals that Toll-9 localizes in endosomal compartments where it interacts with dsRNA. These insights enhance our understanding ofDrosophilainnate immune mechanisms, reflecting the evolutionary conservation of immune responses across diverse species and providing impetus for further research into the conserved roles of TLRs across the animal kingdom.
A Habitat Selection Multiverse Reveals Largely Consistent Results Despite a Multitude of Analysis Options
Authors: Marshall Benjamin Michael , Duthie Alexander Bradley 
Published: June 2024

AbstractResearchers are intrinsically part of the research process. While we may strive for objectivity, there are always judgement calls required during research. When you ask ten researchers to answer the same question with the same dataset, you will likely receive ten different answers. This variation in answers has been linked to several disciplines’ replication crises. Here, we explore whether answers from movement ecology, specifically habitat selection, vary as a result of differing analytical choices. We conducted a multiverse analysis on around 400 synthetic animal movement datasets, exploring a multitude of analysis pathways to determine habitat selection, resulting in approximately half a million unique estimates of selection. By using simulated virtual animals with a known preference, we were able to show which decisions during analysis could lead to more variable estimates of habitat selection. The multiverse revealed that data quantity (i.e., tracking frequency and duration) was more important to obtaining consistent answers than any analysis choice. Overall, the pattern of estimates shows the majority of analysis pathways provide similar final results, particularly for modern analysis methods. The pattern reflects findings from other disciplines, indicating that while movement ecology is not immune to issues of non-replicability stemming from researcher choice, it is also not at any greater risk than other disciplines.
RSG-YOLO: Detection of rice seed germination rate based on enhanced YOLOv8 and multi-scale attention feature fusion
Authors: Li Huikang , Liu Longbao , Li Qi , Liao Juan , Liu Lu , Zhang Yujun , Tang Qixing , Rao Yuan , Gao Yanwei 
Published: June 2024

ABSTRACTThe lack of obvious difference between germinated seeds and non-germinated seeds will cause the low accuracy of detecting rice seed germination rate, remains a challenging issue in the field. In view of this, a new model named Rice Seed Germination-YOLO (RSG-YOLO) is proposed in this paper. This model initially incorporates CSPDenseNet to streamline computational processes while preserving accuracy. Furthermore, the BRA, a dynamic and sparse attention mechanism is integrated to highlight critical features while minimizing redundancy. The third advancement is the employment of a structured feature fusion network, based on GFPN, aiming to reconfigure the original Neck component of YOLOv8, thus enabling efficient feature fusion across varying levels. An additional detection head is introduced, improving detection performance through the integration of variable anchor box scales and the optimization of regression losses. This paper also explores the influence of various attention mechanisms, feature fusion techniques, and detection head architectures on the precision of rice seed germination rate detection. Experimental results indicate that RSG-YOLO achieves a mAP50of 0.981, marking a 4% enhancement over the mAP50of YOLOv8 and setting a new benchmark on the RiceSeedGermination dataset for the detection of rice seed germination rate.
Factors influencing the adoption of health education for Schistosomiasis control in Luangwa, Zambia
Authors: Chinoya Rabecca , Zulu Professor Joseph , Halwiindi Dr Hikabansa , Silumbwe Mr Adam , Maritim Ms Patricia 
Published: June 2024

AbstractImplementation of health education with mass drug administration is advised so as to induce better decision among various populations through uptake of the health messages. However, this disease remains a problem in Luangwa despite implementation of health education. The study was thus conducted to assess the factors influencing the adoption of health education for schistosomiasis control in Luangwa district of Zambia. It was specifically aimed at assessing the scope of health education and strategies being employed in delivery of health education for schistosomiasis in Luangwa. Additionally, it explored the barriers and facilitators in delivering health education for schistosomiasis in Luangwa and finally revealed perceptions of key stakeholders towards health education messages for schistosomiasis in Luangwa.This case study qualitatively explored various factors influencing adoption of health education in Luangwa district. Three Key Informant Interviews, six In-depth Interviews and eight Focus Group Discussions were performed with implementers, health educators and recipients of the health education respectively. The recipients of the health education included school going children, members of the community and mothers who attended under-five clinic sessions.The Factors that were seen to facilitate acceptability of health education include adaptability of health education, community engagement, use of locally acceptable venues to deliver health education, use of teaching aids and learning from others. On the other hand, factors that inhibited acceptability of health education were poor road network, unreached areas, beliefs and myths surrounding bilharzia, the fishing cultural orientation, inadequate income and human resources, busy work schedules and poor access to clean water.The framework used in the study was found to reveal critical aspects of Health education adoption in Luangwa district. However, there still exists a need to conduct further research as well as focus on improving the structural characteristics as are illustrated in this study.
MargheRita: an R package for LC-MS/MS SWATH metabolomics data analysis and confident metabolite identification based on a spectral library of reference standards
Authors: Mosca Ettore , Ulaszewska Marynka , Alavikakhki Zahrasadat , Bellini Edoardo Niccolò , Mannella Valeria , Frigerio Gianfranco , Drago Denise , Andolfo Annapaola 
Published: June 2024

Short Structured AbstractUntargeted metabolomics by mass spectrometry technologies generates huge numbers of metabolite signals, requiring computational analyses for post-acquisition processing and databases for metabolite identification. Web-based data processing solutions frequently include only a part of the entire workflow thus requiring the use of different platforms. The R package “margheRita” enhances fragment matching accuracy and addresses the complete workflow for metabolomic profiling in untargeted studies based on liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS), especially in the case of data-independent acquisition, where all MS/MS spectra are acquired with high quantitative accuracy.Availability and Implementationsource code and documentation are available athttps://github.com/emosca-cnr/margheRita.Contactettore.mosca@itb.cnr.it,andolfo.annapaola@hsr.it