bluuebunny/crossref_metadata_2025_split huggingface dataset:
CAYSS: package for automatic Cytometry Analysis of Yeast Spore Segregation
Authors: Raffoux Xavier , Falque Matthieu 
Published: October 2024

ABSTRACTMeiotic recombination is a powerful source of haplotypic diversity, and thus plays an important role in the dynamics of short-term adaptation. However, high-throughput quantitative measurement of recombination parameters is challenging because of the large size of offspring to be genotyped. One of the most efficient approaches for large-scale recombination measurement is to study the segregation of fluorescent markers in gametes. Applying this to yeast spores by flow cytometry has already been proved to be highly efficient, but manual analyses of density distributions of signal intensities is time-consuming and produces non-perfectly reproducible results. Such analyses are required to identify events corresponding to spores and to assign each of them to a genotypic class depending on their fluorescence intensity. The CAYSS package automatically reproduces the manual process that we’ve been developing to analyze yeast recombination for years, including Maximum-Likelihood estimation of fluorescence extinction (Raffoux et al. 2018a). When comparing the results of manualvsCAYSS automatic analyses of the same cytometry data, recombination rates and interference were on average very similar, with less than 3% differences on average and strong correlations (R2>0.9). In conclusion, as compared to manual analysis, CAYSS allows to save a lot of human time and produces totally reproducible results.The CAYSS software is freely available under GPL license fromhttps://forgemia.inra.fr/gqe-base/cayss/-/releases. The package is also provided as Supplementary Material 1 and a tutorial may be found as Supplementary Material 2.TAKE AWAYThe CAYSS R package measures recombination rate and crossover interference from flow cytometry data of isolated yeast spores segregating for fluorescent markers. The analysis is fully automatic and reproducible. It includes spore identification from FSC and SSC data, genotype determination from fluorescence intensities, and Maximum Likelihood estimation of recombination parameters.
Chromosome-level genome assembly of a doubled haploid brook trout (Salvelinus fontinalis)
Authors: Lecomte Laurie , Ferchaud Anne-Laure , Normandeau Eric , Mérot Claire , Langlois-Parisé Isabelle , Therrien Jean-Christophe , Bérubé Pierre , Djambazian Haig , Nawarathna Pubudu Manoj , Fraser Dylan , Ragoussis Jiannis , Bernatchez Louis 
Published: October 2024

AbstractBrook trout (Salvelinus fontinalis) is a socioeconomically important fish species for fisheries, aquaculture and aquatic conservation. We produced a 2.5 Gb reference assembly by combining Hi-C chromosome conformation capture with high-coverage short- and long-read sequencing of a fully homozygous mitotic gynogenic doubled haploid fish, which facilitates assembly of highly complex salmonid genomes. The assembly has a N50 of 50.98 Mb and 88.9% of the total assembled sequence length is anchored into 42 main chromosomes, of which 63.44% represents repeated contents, including 1,461,010 DNA transposons. 56,058 genes were found with the NCBI annotation pipeline, with 99% of the 3,640 expected conserved orthologs BUSCO genes (actinopterygii_odb10 lineage database). Additionally, we found significant homology within the 42 chromosomes, as expected for this pseudo-tetraploid species, as well as with the sister species lake trout (Salvelinus namaycush) and Atlantic salmon (Salmo salar). This assembly will serve as a reliable genomic resource for brook trout, thus enabling a wider range of reference-based applications to support ongoing research and management decision-making for the species.
Mapping the Microstructure of Human Cerebral Cortex In Vivo with Diffusion MRI
Authors: Sadikov Amir , Choi Hannah , Xiao Jaclyn , Cai Lanya T. , Mukherjee Pratik 
Published: October 2024

AbstractDespite advances in diffusion MRI, which have led to remarkable progress in mapping white matter of the living human brain, the understanding of cerebral cortical microstructure in vivo and its relationship to macrostructure, myeloarchitecture, cytoarchitecture, chemoarchitecture, metabolism, and function lag far behind. We present neuromaps of 21 microstructural metrics derived from diffusion tensor, diffusion kurtosis, mean apparent propagator, and neurite orientation dispersion and density imaging of the young adult cerebral cortex. These 21 metrics are explained by four composite factors that correspond to diffusion kurtosis (intracellular volume fraction/neurite density), isotropic diffusion (free water fraction), heterogenous diffusion (extracellular volume fraction) and diffusion anisotropy (neurite orientation dispersion), respectively. We demonstrate how cortical microstructure follows cytoarchitectural and laminar differentiation, aligns with the macroscale sensory-fugal and sensorimotor-association axes, and contributes to functional brain networks, neural oscillatory dynamics, neurotransmitter receptor/transporter distributions, and cognition and behavior. We show that cortical dMRI metrics are heritable and can better predict participant age and cognition than can cortical thickness or myelination. We find cortical microstructural covariation across individuals to encode functional and structural connectivity as well as gene expression and neurotransmitter similarity. Finally, our exploratory analysis suggests cortical microstructure from diffusion MRI could prove useful in investigating a broad array of neuropsychiatric disorders.
Optimization of methods for rapid and robust generation of cardiomyocyte-specificcrispantsin zebrafish using thecardiodeletersystem
Authors: Keeley Sean , Fernández-Lajarín Miriam , Bergemann David , John Nicolette , Parrott Lily , Andrea Brittany E. , González-Rosa Juan Manuel 
Published: October 2024

ABSTRACTCRISPR/Cas9 has massively accelerated the generation of gene loss-of-function models in zebrafish. However, establishing tissue-specific mutant lines remains a laborious and time-consuming process. Although a few dozen tissue-specific Cas9 zebrafish lines have been developed, the lack of standardization of some key methods, including gRNA delivery, has limited the implementation of these approaches in the zebrafish community. To tackle these limitations, we have established a cardiomyocyte-specific Cas9 line, thecardiodeleter, which efficiently generates biallelic mutations in combination with gene-specific gRNAs. We have also optimized the development of transposon-basedguide shuttlesthat carry gRNAs targeting a gene of interest and permanently label the cells susceptible to becoming mutant. We validated this modular approach by deleting five genes (ect2,tnnt2a,cmlc2,amhc, anderbb2), all resulting in the loss of the corresponding protein or phenocopying established mutants. Additionally, we provide detailed protocols describing how to generateguide shuttles, which will facilitate the dissemination of these techniques in the zebrafish community. Our approach enables the rapid generation of tissue-specificcrispantsand analysis of mosaic phenotypes, bypassing limitations such as embryonic lethality, making it a valuable tool for cell-autonomous studies and genetic screenings.
Capsanthin/Capsorubin Synthase Expression in Tomato Alters Carotenoid Pools, Enhancing Provitamin A and Flavor Volatiles
Authors: Fu Jingwei , Tieman Denise , Rathinasabapathi Bala 
Published: October 2024

AbstractWe conceptualized a tomato biofortification strategy via engineering simultaneous accumulation ofβ-carotene, a provitamin A and pepper-specialized ketocarotenoids, capsanthin, and capsorubin. Capsanthin/capsorubin synthase (CCS) in pepper, an enzyme phylogenetically related to lycopene β-cyclases (LCYB) known forβ-carotene synthesis, was investigated for itsin vivorole in ripening fruit. In pepper, silencing ofCCSvia virus-induced gene silencing reduced the flux from lycopene toβ-carotene (theβ-branch) with significant changes in carotenoid compositions. In a carotenogenic bacterial expression system, pepper CCS was more effective than tomato LCYB1 or LCYB2 in lycopene cyclization toβ-carotene and CCS synthesized capsanthin, but the LCYBs did not. Therefore, we overexpressed pepperCCSin different tomato varieties, including ‘Micro-Tom’ WT, ‘Micro-Tom’ mutant,pyp1-1(H7L)(defective in xanthophyll esterification), and five inbreds and characterized their carotenoid profiles. InCCS-transformed tomato fruit (WT and selected varieties), besides the biosynthesis of capsanthin and capsorubin, total carotenoids,β-carotene, and xanthophyll esters remarkably increased compared to the controls, while such increments were weaker in thepyp1-1(H7L). CCS expression had a positive influence on the flux toward theβ-branch and the storage pool of xanthophyll esters consistent with its dual functions in lycopene cyclization and ketocarotenoid biosynthesis. The data further supported that xanthophyll esters facilitated carotenoid accumulation. While CCS-expression had no significant impact on growth or yield, fruit ofCCS-transformed tomato had greater levels ofβ-carotene-derived flavor volatiles than the controls. Consumption of 37–131-gram ofCCS-derived hybrid fruit meets the provitamin A recommended dietary allowance, indicating greatly improved nutritional value.
The topography of gene tree topology space in a plant genus with a legacy of recent polyploidy and introgression
Authors: Landis Jacob B. , Farmer Andrew D. , Garcia Lucio , McNair Racella , Ruiz Mariana Franco , Liu Qingli , Doyle Jeff J. 
Published: October 2024

AbstractThe eukaryotic genome has been described as a collection of different histories; for any set of taxa one of these histories is the record of cladogenic events that together comprise the species tree. Among the other histories expected to occur are those attributable to deep coalescence/lineage sorting; to biological causes such as introgression and horizontal transfer; or to pseudo-orthology, long branch attraction, and other technical issues. Gene tree topology space is the portion of tree space occupied by the gene trees reconstructed for a particular dataset of sampled genetic loci. Because coalescent theory predicts that the species tree topology will generally be the most frequent among gene trees, a reasonable expectation is that there will be a peak in gene tree topology space at the species tree topology, with secondary peaks present due to trees tracking other histories. Gene tree topology space in the small (∼30 species, including the cultivated soybean) legume genus,Glycineshould not only have signals from the species tree and from lineage sorting, but also from a likely introgression event that created incongruence between the plastid and nuclear genomes. Additionally,Glycineis the product of a relatively recent (<13 million years) whole genome duplication, raising the possibility of pseudo-orthology. We explored this space using a set of 2389 nuclear genes and representative accessions from a 570-taxon concatenation tree, reconstructing gene trees for all nuclear loci and from complete plastid genomes and partial mitochondrial genomes. Species trees (ASTRAL) and maximum likelihood (ML) concatenation trees were congruent for a 61-taxon dataset but were incongruent with organellar genome trees. Gene tree topology space was flat: No topology was represented by more than one gene tree. This was also true for a reduced dataset of 27 taxa; only when the dataset was reduced to six ingroup taxa were multiple gene trees having the species tree topology observed, along with a topology congruent with the chloroplast genome topology, presumably representing nuclear loci introgressed along with the plastome. Clustering failed to identify any regional differentiation of gene tree topology space populated by loci with similar topologies. Pseudo-orthology did not contribute meaningfully to incongruence, in agreement with recent modeling work that minimizes concerns about this phenomenon. Clearly, different genes have different historical signals, but these signals are complex and exist at the level of clades within trees rather than as entire gene trees.
Non-invasive brain stimulation over the Frontopolar Cortex promotes willingness to exert cognitive effort in a foraging-like sequential choice task
Authors: Bogdanov Mario , Bustamante Laura A. , Devine Sean , Sheldon Signy , Otto A. Ross 
Published: October 2024

AbstractIndividuals avoid spending cognitive effort unless expected rewards offset the perceived costs. Recent work employing tasks that provide explicit information about demands and incentives, suggests causal involvement of the Frontopolar Cortex (FPC) in effort-based decision-making. Using transcranial direct current stimulation (tDCS), we examined whether the FPC’s role in motivating effort generalizes to sequential choice problems in which task demand and reward rates vary indirectly and as a function of experience. In a double-blind, within- subject design, 46 participants received anodal (i.e., excitatory) or sham stimulation over the right FPC during an Effort Foraging Task, which required choosing between harvesting patches for successively decreasing resources or traveling to replenished patches by performing a cognitive task with environment-specific difficulty. As expected, participants exited patches later (i.e., displayed lower exit thresholds) when travelling required greater (versus less) effort, indicating increased travel costs in high-effort environments. Under anodal tDCS, the difference in exit thresholds between environments was significantly smaller relative to sham. Finally, individual differences analyses hint that participants with lower self-reported motivation to exert effort exhibited greater travel cost reductions following tDCS. Together, these findings support the theorized causal role of the FPC in motivating cognitively effortful behavior, expand its role to more ecologically valid serial decisions and highlight the potential for tDCS as a tool to increase motivation with potential clinical applications.Significance statementUncovering the neural mechanisms regulating engagement in effortful behavior is crucial, as it will improve our understanding and treatment of conditions characterized by reduced motivation, e.g., apathy and anhedonia. The Frontopolar Cortex (FPC) has been implicated in increasing effort exertion in settings that provide explicit information about effort demand and reward. Using transcranial direct current stimulation (tDCS), we investigated whether the FPC retains its motivating capacity in sequential choice problems that vary effort and reward indirectly. We demonstrate that FPC stimulation decreases cognitive effort-based travel costs in an Effort Foraging Task, indicating a causal and general involvement of the FPC in motivating effortful behavior, highlighting the potential of tDCS as a new avenue for increasing motivation with potential clinical applications.
Restoration of Fbxo7 expression in dopaminergic neurons restores tyrosine hydroxylase in a mouse model of Parkinson’s disease
Authors: Al Rawi Sara , Tyers Pamela , Barker Roger A , Laman Heike 
Published: October 2024

AbstractMutations inFBXO7are linked to an atypical parkinsonism. Conditional knock out (KO) of Fbxo7 in dopaminergic neurons in a mouse model caused a neurodegenerative phenotype, including a significant reduction in striatal TH staining at 6 weeks of age and a significant loss of dopaminergic neurons in the SNpc. To test whether re-expression of Fbxo7 could act as a treatment to prevent or restore TH expression in the striatum in this model, we used a rAAV vector to deliver murine Fbxo7 and a mRuby fluorescent marker to dopaminergic neurons. We found that Fbxo7 expression, both before and after the TH loss, restored its expression in the striatum and nucleus accumbens in the mouse. This study therefore highlights that Fbxo7 is important for the integrity and persistence of the dopaminergic nigrostriatal pathway in the mammalian brain, which could be of relevance to Parkinson’s disease with therapeutic implications.
Early hominin arrival in Southeast Asia triggered the evolution of major human malaria vectors
Authors: Singh Upasana Shyamsunder , Harbach Ralph E. , Hii Jeffery , Chang Moh Seng , Somboon Pradya , Prakash Anil , Sarma Devojit , Broomfield Ben , Morgan Katy , Albert Sandra , Das Aparup , Linton Yvonne-Marie , Carlton Jane M. , Walton Catherine 
Published: October 2024

AbstractUnderstanding the evolution of anthropophily, the preference of mosquitoes to feed on humans, offers insights into current and future human disease transmission. Some species of the Leucosphyrus Group ofAnophelesmosquitoes in Southeast Asia are highly anthropophilic and efficient vectors of human malaria parasites, while others primarily feed on non-human primates and transmit non-human primate malaria parasites. Through phylogenomic analysis of 11 out of 20 recognized species, we studied the biogeography and evolutionary history of anthropophily in this group. Molecular dating and ancestral state reconstruction revealed that anthropophily evolved during the late Pliocene/early Pleistocene in Sundaland, likely in response to early hominins. This finding provides independent non-archaeological evidence supporting the limited fossil record of early hominin colonization in Southeast Asia around 1.8 million years ago.
Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors
Authors: Dreyer Kathleen S. , Donahue Patrick S. , Boucher Jonathan D. , Chambers Katherine M. , Ornelas Marya Y. , Edelstein Hailey I. , Leibowitz Benjamin D. , Zhu Katherine J. , Dray Kate E. , Muldoon Joseph J. , Leonard Joshua N. 
Published: October 2024

ABSTRACTDNA-based hypoxia biosensors conditionally express a gene of interest when a cell is in a state of inadequate oxygen supply, which is a feature of several acute and chronic diseases. These biosensors can be deployed in engineered cells to study or treat disease. Although the central mediators of hypoxia responsiveness have been characterized, the dynamics of this response are generally less understood, and there is no general approach to modulate hypoxia biosensors to tune their performance to meet application-specific needs. To address the need for high-performing hypoxia biosensors, we investigated strategies to enhance biosensor performance by identifying minimal promoter choices and positive feedback circuits that both achieved low background and amplified hypoxia-induced gene expression. To generate insight into the mechanisms by which feedback drives differential performance, we developed an explanatory mathematical model. Our analysis suggests a previously unreported dual regulatory mechanism that was necessary to explain the full set of experimental observations and that provides new insights into regulatory dynamics in chronic hypoxia. This study exemplifies the potential of using synthetic gene circuits to perturb natural systems in a manner that uniquely enables the elucidation of novel facets of natural regulation.
The dynamics of wildVitisspecies in response to climate change facilitate the breeding of grapevine and its rootstocks with climate resilience
Authors: Zhang Mengyan , Xu Xiaodong , Zhang Tianhao , Liu Zhenya , Wang Xingyi , Shi Xiaoya , Peng Wenjing , Wang Xu , Chen Zhuyifu , Zhao Ruoyan , Wang Wenrui , Zhang Yi , Jin Zhongxin , Zhou Yongfeng , Ma Zhiyao 
Published: October 2024

AbstractClimate change poses significant challenges to agricultural suitability and food security due to the limited adaptability of domesticated crops, however, our understanding of their climate adaptability is still limited. In this study, we compare the potential distributional dynamics in response to future climate change between grapevine and its wild relatives (VitisL.) based on ecological niche models (ENMs). We reveal that the annual mean temperature is the primary factor influencing the potential distribution of cultivated grapes (V. viniferaL.). By 2080, under RCP 8.5, suitable areas for wine and table grapes fromV. viniferaare predicted to reduced by 15.04×105km² and 13.26×105km², respectively. The results suggest that grape cultivation, particularly for table grapes, will face serious threats from future climate change. In contrast, seventy percent of wild grapes are well able to withstand future climate conditions. For example, under RCP 8.5, North American wild grapes likeV. rotundifoliaandV. labrusca, as well as East Asian wild grapes such asV. heyneanaandV. davidii, are projected to demonstrate significant adaptability. These wild grapes have the potential to provide rootstocks that could enhance the adaptability of cultivated grapes and serve as invaluable resources for breeding programs aimed at developing new cultivars better suited to withstand the environmental pressures of climate change. Our results not only predict potential suitable distribution areas of wild grapes in the future, but also emphasize the essential impact of these wild genetic resources on grape breeding for promoting adaptation to future climate change.
Understanding Thromboembolus Transport Patterns In The Brain For Stroke In The Presence Of Carotid Artery Stenosis
Authors: Roopnarinesingh Ricardo , Jani Neel D. , Leppert Michelle , Mukherjee Debanjan 
Published: October 2024

AbstractDeciphering the source of an embolism is a common challenge encountered in stroke treatment. Carotid stenosis is a key source of embolic strokes. Carotid interventions can be indicated when a patient has greater than 50% stenosis in the carotid ipsilateral to the cerebral infarction, which is designated as the symptomatic carotid. However, there are often significant number of cases where carotid emboli travel contralaterally leading to ambiguity regarding which carotid is symptomatic. We use a patient-specific computational embolus-hemodynamics interaction model developed in prior works to conduct an in silico experiment spanning 30 heart-to-brain arterial models with differing combinations of bilateral severe and mild stenosis degrees. We used these models to study source-to-destination transport of thromboemboli released from left/right carotid disease sites, and cardiogenic sources. Across all cases considered, thromboemboli from left and right carotid sources showed non-zero contralateral transport. We also found that cardiogenic thromboemboli do not have an altered hemisphere distribution or distinct transport preference dependent on stenosis degree, thus potentially making the underlying etiology more cryptic. In patients with carotid stenosis or chronic occlusion ipsilateral to the area affected by stroke, we have demonstrated that the presence of contralateral stenosis can cause emboli that travel across the Circle of Willis (CoW) which can potentially lead to ambiguity when deciding which carotid is truly symptomatic.