bluuebunny/crossref_metadata_2025_split huggingface dataset:
Range ofIxodes laguri, a nidicolous tick that parasitizes critically endangered rodents, with details on its western distribution limit in Austria
Authors: Rubel Franz 
Published: February 2024

AbstractThe nidicolous tickIxodes laguriis a nest-dwelling parasite of small mammals that mainly infest rodents of the families Cricetidae, Gliridae, Muridae and Sciuridae. There is no proven vectorial role forI. laguri, although it is suggested that it is a vector ofFrancisella tularensis. In this study, a first map depicting the entire geographical distribution ofI. laguribased on geo-referenced locations is presented. For this purpose, a digital data set of 141 georeferenced locations from 16 countries was compiled. Particular attention is paid to the description of the westernmost record ofI. laguriin the city of Vienna, Austria. There,I. laguriis specifically associated with its main hosts, the critically endangered European hamster (Cricetus cricetus) and the European ground squirrel (Spermophilus citellus). These two host species have also been mapped in the present paper to estimate the potential distribution ofI. laguriin the Vienna metropolitan region. The range ofI. laguriextends between 16–108° E and 38–54° N, i.e. from Vienna in the east of Austria to Ulaanbaatar, the capital of Mongolia. In contrast to tick species that are expanding their range and are also becoming more abundant as a result of global warming,I. lagurihas become increasingly rare through-out its range. However,I. laguriis not threatened by climate change, but by anthropogenic influences on its hosts and their habitats, which are typically open grasslands and steppes. Rural habitats are threatened by the intensification of agriculture and semi-urban habitats are increasingly being destroyed by urban development.
PiggyBac Transposase Mediated Inducible Trophoblast-specific Knockdown of Mechanistic Target of Rapamycin in Mice Decreases Placental Nutrient Transport and Inhibits Fetal Growth
Authors: Rosario Fredrick J , Urschitz Johann , Razavy Haide , Elston Marlee , Theresa Powell L , Jansson Thomas 
Published: February 2024

AbstractAbnormal fetal growth is associated with perinatal complications and adult disease. The placental mechanistic target of rapamycin (mTOR) signaling activity is positively correlated to placental nutrient transport and fetal growth. However, if this association represents a mechanistic link, it remains unknown. We hypothesized that trophoblast-specific mTOR knockdown in late pregnant mice decreases placental nutrient transport and inhibits fetal growth. PiggyBac Transposase-Enhanced Pronuclear Injection was performed to generate transgenic mice containing a trophoblast-specific Cyp19I.1 promoter-driven, doxycycline-inducible luciferase reporter transgene with aMtorshRNAmir sequence in its 3’ untranslated region (UTR). We induced mTOR knockdown by administration of doxycycline starting at E14.5. Dams were euthanized at E 17.5, and trophoblast-specific gene targeting was confirmed. Placental mTOR protein expression was reduced by ∼68% in these animals, which was associated with a marked inhibition of mTORC1 and mTORC2 signaling activity. Moreover, we observed a decreased expression of System A amino acid transporter isoform SNAT2 and the System L amino acid transporter isoform LAT1 in isolated trophoblast plasma membranes and lower fetal but not placental weight. Inhibition of trophoblast mTOR signaling in late pregnancy is mechanistically linked to decreased placental nutrient transport and reduced fetal growth. Modulating placental mTOR signaling may represent a novel intervention in pregnancies with abnormal fetal growth.
Random walks with spatial and temporal resets may underlie searching movements in ants
Authors: Lecheval Valentin , Robinson Elva J.H. , Mann Richard P. 
Published: February 2024

AbstractMany ant species are central place foragers, living in a nest and exploiting the surrounding environment. It is however unclear how their exploration behaviour relates to the emerging exploited area. Ants provide a great opportunity to study the emergence of foraging range from individual movements, given the potentially large number of scouting workers involved. Here, we introduce a random walk model with stochastic resetting to depict the movements of searching ants. Stochastic resetting refers to spatially reset at random times the position of agents to a given location, here the nest of searching ants. We investigate the effect of a range of resetting mechanisms by changing how the probability of returning to the nest depends on the duration of unsuccessful foraging trips. We compare the macroscopic predictions of our model to laboratory and field data. We find that the probability for searching ants to return to their nest decreases as the number of foraging trips increases, resulting in scouts going further away from the nest as the number of foraging trips increases. Our findings highlight the importance of resetting random walk models to depict the movements of central place foragers and nurtures novel questions regarding the searching behaviour of ants.
Dose-response functional and transcriptomic effects of follicle-stimulating hormone onex vivomouse folliculogenesis
Authors: Zhan Tingjie , Zhang Jiyang , Zhang Ying , Zhao Qingshi , Chemerinski Anat , Douglas Nataki C. , Zhang Qiang , Xiao Shuo 
Published: February 2024

AbstractThe gonadotropin-dependent phase of ovarian folliculogenesis primarily requires follicle-stimulating hormone (FSH) to support one or multiple antral follicles, dependent on the species, to mature fully, enabling ovarian steroidogenesis, oogenesis, and ovulation to sustain female reproductive cycles and fertility. FSH binds to its membrane receptor in granulosa cells to activate various signal transduction pathways and gene regulatory networks. Poor female reproductive outcomes can result from both FSH insufficiency owing to genetic or non-genetic factors and FSH excess as encountered with ovarian stimulation in assisted reproductive technology (ART), but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in anex vivomouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and the threshold is moderately variable among individual follicles. FSH at subthreshold, threshold, and suprathreshold levels induced distinct expression patterns of follicle maturation-related genes and the follicular transcriptomics. The RNA-seq analysis identified novel genes and signaling pathways that may critically regulate follicle maturation. Suprathreshold FSH resulted in multiple ovarian disorders including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.
Urbanization is associated with reduced genetic diversity in marine fish populations
Authors: Karachaliou Eleana , Schmidt Chloé , de Greef Evelien , Docker Margaret F , Garroway Colin J 
Published: February 2024

AbstractThe economic and ecological benefits of living by the ocean have led many coastal settlements to grow into large densely populated cities. Large coastal cities have had considerable environmental effects on marine ecosystems through resource extraction, waste disposal, and use for transportation. Thus, it is important to understand the consequences of urbanization and human activities on evolutionary processes and biodiversity in marine fishes. Using published population genetic datasets for marine fishes amounting to 75,496 individuals sampled from 73 species at 1143 sample sites throughout the world’s oceans, we evaluated how human population density and a composite measure of cumulative human impacts affected genetic diversity and differentiation. We found that genetic diversity was significantly lower in marine fish populations associated with denser human populations regardless of species and locality. The effects of cumulative human impacts on genetic diversity were less prominent, perhaps due to this measure capturing more spatially varying processes. Urbanization in coastal regions has degraded marine biodiversity in a way that erodes adaptive potential for marine fish populations. This highlights the need to mitigate threats from human activities and focus efforts on sustainable urban planning and resource use to conserve marine biodiversity sustaining coastal fisheries and ecosystems.
Temporal dynamics ofCandida albicansmorphogenesis and gene expression reveals distinctions between in vitro and in vivo filamentation
Authors: Wakade Rohan S. , Wellington Melanie , Krysan Damian J. 
Published: February 2024

AbstractCandida albicansis a common human fungal pathogen that is also a commensal of the oral cavity and gastrointestinal tract.C. albicanspathogenesis is linked to its transition from budding yeast to filamentous morphologies including hyphae and pseudohyphae. The centrality of this virulence trait toC. albicanspathobiology has resulted in extensive characterization a wide range factors associated with filamentation with a strong focus on transcriptional regulation. The vast majority of these experiments have used in vitro conditions to induce the yeast-to-filament transition. Taking advantage of in vivo approaches to quantitatively characterize both morphology and gene expression during filamentation during mammalian infection, we have investigated the dynamics of these two aspects of filamentation in vivo and compared them to in vitro filament induction with “host-like” tissue culture media supplemented with serum at mammalian body temperature. Although filamentation shares many common features in the two conditions, we have found two significant differences. First, alternative carbon metabolism genes are expressed early during in vitro filamentation and late in vivo, suggesting significant differences in glucose availability. Second,C. albicansbegins a hyphae-to-yeast transition after 4hr incubation while we find little evidence of hyphae-to-yeast transition in vivo up to 24hr post infection. We show that the low rate of in vivo hyphae-to-yeast transition is likely due to very low expression ofPES1, a key driver of lateral yeast in vitro, and that heterologous expression ofPES1is sufficient to trigger lateral yeast formation in vivo.ImportanceCandida albicansfilamentation is correlated with virulence and is an intensively studied aspect ofC. albicans biology. The vast majority of studies onC. albicansfilamentation are based on in vitro induction of hyphae and pseudohyphae. Here we used an in vivo filamentation assay and in vivo expression profiling to compare the tempo of morphogenesis and gene expression between in vitro and in vivo filamentation. Although the hyphal gene expression profile is induced rapidly in both conditions, it remains stably expressed over a 12hr time course in vivo while it peaks after 4hr in vitro and is reduced. This reduced hyphal gene expression in vitro correlates with reduced hyphae and increased hyphae-to-yeast transition. In contrast, there is little evidence of evidence of hyphae-to-yeast transition in vivo.
Lung-resident memory B cells maintain allergic IgE responses in the respiratory tract
Authors: Nelson Alexander J. , Tatematsu Bruna K. , Beach Jordan R. , Sojka Dorothy K. , Wu Yee Ling 
Published: February 2024

SUMMARYAllergen-specific IgE is a key mediator of allergic asthma. However, the tissue sites and cell types that support IgE production at the mucosa remained undefined. Here, we reveal that inhaled allergens induce the formation of IgG1+lung-resident memory B cells (MBC) that switch to IgE. Using a mouse reporter for IgE class switch recombination, a requirement for the generation of IgE, we identify lung tissues as a major site of IgE class switching, which is dominated by IgG1+MBCs and supported by IL-4-producing TH2 cells. This is in sharp contrast to what occurs in the draining lymph nodes where germinal center B cells are the IgE-switching population and TFHcells provide IL-4. By single-cell transcriptomic analyses, we reveal potential mechanisms for the formation of lung-resident MBCs. Altogether, this study identifies the origin of allergen-specific IgE in the respiratory tract and explains how local chronic hypersensitivity is maintained in allergic asthma.
Chromatin regulatorKdm6bis required for the establishment and maintenance of neural stem cells in mouse hippocampus
Authors: Gil Eugene , Hong Sung Jun , Wu David , Park Dae Hwi , Delgado Ryan N. , Malatesta Martina , Ahanger Sajad Hamid , Lin Karin , Villeda Saul , Lim Daniel A. 
Published: February 2024

ABSTRACTNeural stem cells (NSCs) in the mouse hippocampal dentate gyrus (DG) – a structure important to learning and memory – generate new neurons postnatally and throughout adult life. However, the regulators that enable this lifelong neurogenesis remain incompletely understood. Here we show that the chromatin regulator KDM6B is required for both the establishment and maintenance of NSCs in the mouse DG. Conditional deletion ofKdm6bin embryonic DG precursors results in an adult hippocampus that is essentially devoid of NSCs, and hippocampal-dependent behaviors are defective.Kdm6b-deletion causes precocious neuronal differentiation, and the NSC population fails to become established in the postnatal DG. Using single cell RNA sequencing (scRNA-seq), we observed thatKdm6b-deletion disrupts the transcriptomic signature of NSC maintenance. Furthermore, deletingKdm6bin adult DG NSCs induces early neuronal differentiation, and the NSC population is not properly maintained. These data illustrate the critical role thatKdm6bplays in adult DG neurogenesis, which may help understand how mutations in this chromatin regulator result in cognitive disorders in human patients.
TFEB controls syncytiotrophoblast differentiation
Authors: Esbin Meagan N. , Dahal Liza , Fan Vinson B. , McKenna Joey , Yin Eric , Darzacq Xavier , Tjian Robert 
Published: February 2024

AbstractDuring human development, a subset of differentiating fetal cells form a temporary organ, the placenta, which invades the uterine wall to support nutrient, oxygen, and waste exchange between the mother and fetus until birth. Most of the human placenta is formed by a syncytial villous structure which arises via cell-cell fusion of underlying fetal trophoblast stem cells. Genetic and functional studies have characterized the membrane protein fusogens, Syncytin-1 and Syncytin-2, that are both necessary and sufficient for human trophoblast cell-cell fusion. However, identification and characterization of upstream transcriptional regulators regulating their expression has been limited. Here, using CRISPR knockout in anin vitrocellular model of syncytiotrophoblast development (BeWo cells), we find that the transcription factor TFEB, mainly known as a regulator of autophagy and lysosomal biogenesis, is required for cell-cell fusion of syncytiotrophoblasts. TFEB translocates to the nucleus, exhibits increased chromatin interactions, and directly binds the Syncytin-1 and Syncytin-2 promoters to control their expression during differentiation. While TFEB appears to play an important role in syncytiotrophoblast differentiation, ablation of TFEB largely does not affect lysosomal gene expression or lysosomal biogenesis in differentiating BeWo cells, suggesting that TFEB plays an alternative role in placental cells.
2-D Neural Geometry Underpins Hierarchical Organization of Sequence in Human Working Memory
Authors: Fan Ying , Wang Muzhi , Ding Nai , Luo Huan 
Published: February 2024

AbstractWorking memory (WM) is constructive in nature. Instead of passively retaining information, WM reorganizes complex sequences into hierarchically embedded chunks to overcome capacity limits and facilitate flexible behavior. To investigate the neural mechanisms underlying hierarchical reorganization in WM, we performed two electroencephalography (EEG) and one magnetoencephalography (MEG) experiments, wherein humans retain in WM a temporal sequence of items, i.e., syllables, which are organized into chunks, i.e., multisyllabic words. We demonstrate that the 1-D sequence is represented by 2-D neural representational geometry in WM arising from parietal-frontal regions, with separate dimensions encoding item position within a chunk and chunk position in the sequence. Critically, this 2-D geometry is observed consistently in different experimental settings, even during tasks discouraging hierarchical reorganization in WM and correlates with WM behavior. Overall, these findings strongly support that complex sequences are reorganized into factorized multi-dimensional neural representational geometry in WM, which also speaks to general structure-based organizational principles given WM’s involvement in many cognitive functions.
Accurate Bayesian phylogenetic point estimation using a tree distribution parameterized by clade probabilities
Authors: Berling Lars , Klawitter Jonathan , Bouckaert Remco , Xie Dong , Gavryushkin Alex , Drummond Alexei J. 
Published: February 2024

AbstractBayesian phylogenetic analysis with MCMC algorithms generates an estimate of the posterior distribution of phylogenetic trees in the form of a sample of phylogenetic trees and related parameters. The high dimensionality and non-Euclidean nature of tree space complicates summarizing the central tendency and variance of the posterior distribution in tree space. Here we introduce a new tractable tree distribution and associated point estimator that can be constructed from a posterior sample of trees. Through simulation studies we show that this point estimator performs at least as well and often better than standard methods of producing Bayesian posterior summary trees. We also show that the method of summary that performs best depends on the sample size and dimensionality of the problem in non-trivial ways.Author summaryOur research introduces novel methods to analyse a set of phylogenetic tree topologies, such as those generated by Bayesian Markov Chain Monte Carlo algorithms. We define a new model for a distribution on trees that is based on observed clade frequencies. We study it together with closely related models that are based on observed clade split frequencies. These distributions are easy to work with and, as we show experimentally, provide excellent estimates of the true posterior distribution. Furthermore, we demonstrate that they enable us to find the tree with the highest posterior probability, which acts as a summary tree or point estimate of the distribution. In simulation studies, we show that the new methods performs as least as well or better than existing methods. Additionally, we highlight that choosing the best method for summarizing sets of trees remains challenging, as it depends on the sample size and complexity of the problem in non-trivial ways. This work has the potential to improve the accuracy of phylogenetic studies.
PreMode predicts mode-of-action of missense variants by deep graph representation learning of protein sequence and structural context
Authors: Zhong Guojie , Zhao Yige , Zhuang Demi , Chung Wendy K , Shen Yufeng 
Published: February 2024

AbstractAccurate prediction of the functional impact of missense variants is important for disease gene discovery, clinical genetic diagnostics, therapeutic strategies, and protein engineering. Previous efforts have focused on predicting a binary pathogenicity classification, but the functional impact of missense variants is multi-dimensional. Pathogenic missense variants in the same gene may act through different modes of action (i.e., gain/loss-of-function) by affecting different aspects of protein function. They may result in distinct clinical conditions that require different treatments. We developed a new method, PreMode, to perform gene-specific mode-of-action predictions. PreMode models effects of coding sequence variants using SE(3)-equivariant graph neural networks on protein sequences and structures. Using the largest-to-date set of missense variants with known modes of action, we showed that PreMode reached state-of-the-art performance in multiple types of mode-of-action predictions by efficient transfer-learning. Additionally, PreMode’s prediction of G/LoF variants in a kinase is consistent with inactive-active conformation transition energy changes. Finally, we show that PreMode enables efficient study design of deep mutational scans and optimization in protein engineering.
Correlation between bioluminescent blinks and swimming behavior in the splitfin flashlight fishAnomalops katoptron
Authors: Jägers Peter , Frischmuth Timo , Herlitze Stefan 
Published: February 2024

AbstractThe light organs of the splitfin flashlight fishAnomalops katoptronare necessary for schooling behavior, to determine nearest neighbor distance, and to feed on zooplankton under dim light conditions. Each behavior is coupled to context-dependent blink frequencies and can be regulated via mechanical occlusion of light organs. During shoaling in the laboratory individuals show moderate blink frequencies around 100 blinks per minute. In this study, we correlated bioluminescent blinks with the spatio-temporal dynamics of swimming profiles in three dimensions, using a stereoscopic, infrared camera system. Groups of flashlight fish showed intermediate levels of polarization and distances to the group centroid. Individuals showed higher swimming speeds and curved swimming profiles during light organ occlusion. The largest changes in swimming direction occurred when darkening the light organs. BeforeA. katoptronexposed light organs again, they adapted a nearly straight movement direction. Light organs create a strong contrast against the background. Therefore, a close combination of light signals and movement is crucial to the behavior ofA. katoptron.
Charting the Cannabis plant chemical space with computational metabolomics
Authors: Myoli Akhona , Choene Mpho , Kappo Abidemi Paul , Madala Ntakadzeni Edwin , van der Hooft Justin J.J. , Tugizimana Fidele 
Published: February 2024

AbstractIntroductionThe chemical classification of Cannabis is typically confined to the cannabinoid content, whilst Cannabis encompasses diverse chemical classes that vary in abundance among all its varieties. Hence, neglecting other chemical classes within Cannabis strains results in a restricted and biased comprehension of elements that may contribute to chemical intricacy and the resultant medicinal qualities of the plant.ObjectivesThus, herein, we report a computational metabolomics study to elucidate the Cannabis metabolic map beyond the cannabinoids.MethodsMass spectrometry-based computational tools were used to mine and evaluate the methanolic leaf and flower extracts of two Cannabis cultivars: Amnesia haze (AMNH) and Royal dutch cheese (RDC).ResultsThe results revealed the presence of different chemical compound classes including cannabinoids, but extending it to flavonoids, polyketides, and phospholipids at varying distributions across the cultivar plant tissues. Therefore, the two cultivars were differentiated based on the overall chemical content of their plant tissues where AMNH was observed to be more dominant in the flavonoid content while RDC was more dominant in the lipid-like molecules. Additionally,in silicomolecular docking studies in combination with biological assay studies indicated the potentially differing anti-cancer properties of the two cultivars resulting from the elucidated chemical profiles.ConclusionThese findings highlight distinctive chemical profiles beyond cannabinoids in Cannabis strains. This novel mapping of the metabolomic landscape of Cannabis provides actionable insights into plant biochemistry and justifies selecting certain varieties for medicinal use.