bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Seasonal Importation and Random Genetic Drift on Selection for Drug-Resistant Genotypes ofPlasmodium falciparumin High Transmission Settings
Authors: Zupko Robert J. , Servadio Joseph L. , Nguyen Tran Dang , Tran Thu Nguyen-Anh , Tran Kien Trung , Somé Anyirékun Fabrice , Boni Maciej F. 
Published: October 2023

AbstractHistoricallyPlasmodium falciparumhas followed a pattern of drug resistance first appearing in low transmission settings before spreading to high transmission settings. Several features of low-transmission regions are hypothesized as explanations: higher chance of symptoms and treatment seeking, better treatment access, less within-host competition among clones, and lower rates of recombination. Here, we test whether importation of drug-resistant parasites is more likely to lead to successful emergence and establishment in low-transmission or high-transmission periods of the same epidemiological setting, using a spatial, individual-based stochastic model of malaria and drug-resistance evolution calibrated for Burkina Faso. Upon controlling for the timing of importation of drug-resistant genotypes and examination of key model variables, we found that drug-resistant genotypes imported during the low transmission season were, (1) more susceptible to stochastic extinction due to the action of random genetic drift, and (2) more likely to lead to establishment of drug resistance when parasites are able to survive early stochastic loss due to drift. This implies that rare importation events are more likely to lead to establishment if they occur during a high-transmission season, but that constant importation (e.g., neighboring countries with high levels of resistance) may produce a greater risk during low-transmission periods.
Dissociable causal roles of dorsolateral prefrontal cortex and primary motor cortex as a function of motor skill expertise
Authors: Nguyen Quynh N. , Michon Katherine J. , Lee Taraz G. 
Published: October 2023

AbstractEstablished models of motor skill learning posit that early stages of learning are dominated by an attentionally demanding, effortful mode of control supported by associative corticostriatal circuits involving the dorsolateral prefrontal cortex (DLPFC). As expertise develops, automatic and “effortless” performance coincides with a transition to a reliance on sensorimotor circuits that include primary motor cortex (M1). However, the dynamics of how control evolves during the transition from novice to expert are currently unclear. This lack of clarity is due, in part, to the fact that most motor learning studies comprise a limited number of training sessions and rely on correlative techniques such as neuroimaging. Here, we train human participants on a discrete motor sequencing task over the course of six weeks, followed by an assessment of the causal roles of DLPFC and M1 at varying levels of expertise. We use repetitive transcranial magnetic stimulation to transiently disrupt activity in these regions immediately prior to performance in separate sessions. Our results confirm the dissociable importance of DLPFC and M1 as expertise develops. DLPFC stimulation leads to larger behavioral deficits for novice skills than expert skills, while M1 stimulation leads to relatively larger deficits as expertise develops. However, our results also reveal that prefrontal disruption causes performance deficits at all levels of expertise. These findings challenge existing models and indicate an evolving rather than a strictly diminishing role for DLPFC throughout learning.Significance StatementMotor skills involve the sequential chaining of individual actions. For example, playing the piano involves learning to rapidly transition to from one finger press to another. Human neuroimaging studies have shown that primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) support novice motor sequencing skills, but activity in both regions declines over training. This has been interpreted as increased efficiency in M1 and yet a reduction in the involvement of DLPFC as expertise develops. We causally test this assumption by using non-invasive brain stimulation to transiently disrupt cortical activity following extended skill training. Although we confirm dissociable contributions of DLPFC and M1 as expertise develops, we show that both regions are necessary for performance regardless of skill level.
Quantitative imaging of three-dimensional fiber orientation in the human brain via two illumination angles using polarization-sensitive optical coherence tomography
Authors: Liu Chao J. , Ammon William , Jones Robert J. , Nolan Jackson C. , Gong Dayang , Maffei Chiara , Edlow Brian L. , Augustinack Jean C. , Magnain Caroline , Yendiki Anastasia , Villiger Martin , Fischl Bruce , Wang Hui 
Published: October 2023

AbstractThe accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) provide important tools to directly quantify fiber orientation at micrometer resolution. However, brain imaging based on the optic axis by PS-OCT so far has been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work, we present a novel method to obtain the 3D fiber orientation in full angular space with only two illumination angles. We measure the optic axis orientation and the apparent birefringence by PS-OCT from a normal and a 15 deg tilted illumination, and then apply a computational method yielding the 3D optic axis orientation and true birefringence. We verify that our method accurately recovers a large range of through-plane orientations from -85 deg to 85 deg with a high angular precision. We further present 3D fiber orientation maps of entire coronal sections of human cerebrum and brainstem with 10 μm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that further development of our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain and other complex fibrous tissues at microscopic level.
Gene-specific reactivation of X-linked genes upon Xist loss is linked to the chromatin states in extraembryonic endoderm and epiblast stem cells
Authors: Arava M , Majumdar S , Sowjanya LS , Naik HC , Baro R , Gayen S 
Published: October 2023

AbstractIn eutherian mammals, X-chromosome dosage between sexes is balanced through the inactivation of one of the two X-chromosomes in female cells. In mouse, X-inactivation initiates at ∼4-8 cell stages of embryogenesis, where paternal-X undergoes imprinted X-inactivation. Subsequently, it switches to random X-inactivation in post-iplantation epiblast. The initiation of XCI is orchestrated by Xist. However, the role of Xist in the maintenance of X-chromosome inactivation remains underexplored. Here, we have explored the role of Xist in the maintenance of X-inactivation in extraembryonic endoderm stem cells (XEN) and epiblast stem cells (EpiSC), which undergo imprinted and random form of X-inactivation respectively. We show that removal of Xist leads to the partial reactivation of inactive-X chromosome. Intriguingly, many reactivated genes were found to be common between XEN and EpiSC, indicating these genes require Xist to maintain their silent state irrespective of the lineages or forms of X-inactivation. Notably, despite Xist ablation and the subsequent removal of DNA methylation, several X-linked genes remained resistant to reactivation, indicating the involvement of other factors in maintaining the silencing of these genes. On the other hand, we show that genes on the inactive-X with low levels of H3K9me3 and high levels of H3K27me3 are more susceptible to reactivation upon the loss of Xist. Interestingly, active-X homolog of the reactivated genes was found to be enriched with H3K4me3 and H3K27ac. Taken together, our study sheds light on the role of chromatin states in the reactivation of X-linked genes following the loss of Xist in XEN and EpiSC.
Critical reproductive behaviors in Scaled Quail and Northern Bobwhite are affected by thermal variability and mean temperature
Authors: Kirkpatrick William , Sauer Erin , Carroll Rachel , Cohen Jeremy , Davis Craig , Fuhlendorf Samuel , DuRant Sarah 
Published: October 2023

AbstractAnimals can respond differently to shifting thermal variability versus thermal averages, both of which are changing due to climate warming. How these thermal variables affect parental care behaviors can reveal the ability of parents to modify their behaviors to meet the competing demands of their offspring’s thermal needs and self-maintenance, which becomes critical in suboptimal thermal conditions. Further, the time frame used to examine the interplay between temperature and behavioral shifts (e.g., seasonal patterns in care vs. drivers of individual care decisions) can provide different information about the plasticity of parental care behavior. We investigated the relationship between thermal means, thermal variability, and incubation behaviors across multiple timescales in Scaled Quail and Northern Bobwhite. Both species decreased off-bout length during periods of high thermal variability, a novel finding among studies of avian parental behavior. Further relationships between thermal endpoints (mean vs. variation) and behavior differed depending on the temporal scale. For instance, total daily time spent off the nest was not influenced by daily average temperature, yet individual off-bout duration increased with increasing average temperature in the two hours prior to the off-bout. These results provide evidence that thermal-behavioral relationships differ across scales and likely represent a bird’s ability to modify their incubation strategy to rapidly respond to the immediate thermal environment (altering individual off-bout length based on temperature) to meet self-maintenance needs while resulting in a similar outcome for their nest (total daily off-bout time). However, longer off-bout durations during high temperature events can come with reproductive costs, sometimes resulting in acute offspring mortality when eggs or chicks experience lethal temperatures.
High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics
Authors: Sept Corriene E. , Tak Y. Esther , Cerda-Smith Christian G. , Hutchinson Haley M. , Goel Viraat , Blanchette Marco , Bhakta Mital S. , Hansen Anders S. , Joung J. Keith , Johnstone Sarah , Eyler Christine E. , Aryee Martin J. 
Published: October 2023

AbstractDNA looping is vital for establishing many enhancer-promoter interactions. While CTCF is known to anchor many cohesin-mediated loops, the looped chromatin fiber appears to predominantly exist in a poorly characterized actively extruding state. To better characterize extruding chromatin loop structures, we used CTCF MNase HiChIP data to determine both CTCF binding at high resolution and 3D contact information. Here we presentFactorFinder, a tool that identifies CTCF binding sites at near base-pair resolution. We leverage this substantial advance in resolution to determine that the fully extruded (CTCF-CTCF) state is rare genome-wide with locus-specific variation from ~1-10%. We further investigate the impact of chromatin state on loop extrusion dynamics, and find that active enhancers and RNA Pol II impede cohesin extrusion, facilitating an enrichment of enhancer-promoter contacts in the partially extruded loop state. We propose a model of topological regulation whereby the transient, partially extruded states play active roles in transcription.
Genomic epidemiology and antifungal-resistant characterization ofCandida auris, Colombia, 2016-2021
Authors: Misas Elizabeth , Escandon Patricia L. , Gade Lalitha , Caceres Diego H. , Hurst Steve , Le Ngoc , Min Brian , Lyman Meghan , Duarte Carolina , Chow Nancy A. 
Published: October 2023

ABSTRACTSince 2016 in Colombia, ongoing transmission ofCandida aurishas been reported in multiple cities. Here, we provide an updated description ofC. aurisgenomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates fromC. auriscases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences fromC. auriscases were described in a phylogenetic analysis.AllC. auriscases were of clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N=166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these 85% (N=22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N=38) were resistant to amphotericin B.Mutations in theERG11andTAC1Bgenes were identified in fluconazole-resistant isolates, and two amino acid substitutions in PSK76257-(FLO8) and PSK74852 genes were associated with higher minimum inhibitory concentration values for amphotericin B. This work may help identify mechanisms conferring azole and amphotericin B resistance inC. auris.Overall,C. auriscases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades ofC. aurisinto Colombia.IMPORTANCECandida aurisis an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission ofC. aurisand provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this tracking genomic variation provide information about the evolvingC. aurisburden that could help guide public health strategies to controlC. aurisspread.
Structural characterization of SLYM - a 4thmeningeal membrane
Authors: Plá Virginia , Bitsika Styliani , Giannetto Michael , Ladron-de-Guevara Antonio , Gahn-Martinez Daniel , Mori Yuki , Nedergaard Maiken , Møllgård Kjeld 
Published: October 2023

AbstractTraditionally, the meninges are described as 3 distinct layers, dura, arachnoid and pia. Yet, the classification of the connective meningeal membranes surrounding the brain is based on postmortem macroscopic examination. Ultrastructural and single cell transcriptome analyses have documented that the 3 meningeal layers can be subdivided into several distinct layers based on cellular characteristics. We here re-examined the existence of a 4thmeningeal membrane,SubarachnoidLymphatic-likeMembrane or SLYM in Prox1-eGFP reporter mice. Imaging of freshly resected whole brains showed that SLYM covers the entire brain and brain stem and forms a roof shielding the subarachnoid cerebrospinal fluid (CSF)-filled cisterns and the pia-adjacent vasculature. Thus, SLYM is strategically positioned to facilitate periarterial influx of freshly produced CSF and thereby support unidirectional glymphatic CSF transport. Histological analysis showed that, in spinal cord and parts of dorsal cortex, SLYM fused with the arachnoid barrier layer, while in the basal brain stem typically formed a 1-3 cell layered membrane subdividing the subarachnoid space into two compartments. However, great care should be taken when interpreting the organization of the delicate leptomeningeal membranes in tissue sections. We show that hyperosmotic fixatives dehydrate the tissue with the risk of shrinkage and dislocation of these fragile membranes in postmortem preparations.
Zbtb11 interacts with Otx2 and patterns the anterior neuroectoderm inXenopus
Authors: Satou-Kobayashi Yumeko , Takahashi Shuji , Haramoto Yoshikazu , Asashima Makoto , Taira Masanori 
Published: October 2023

AbstractThezinc finger and BTB domain-containing 11gene (zbtb11) is expressed in theXenopusanterior neuroectoderm, but the molecular nature of the Zbtb11 protein during embryonic development remains to be elucidated. Here, we show the role of Zbtb11 in anterior patterning of the neuroectoderm and the cooperative action with the transcription factor Otx2. Both overexpression and knockdown ofzbtb11caused similar phenotypes: expanded expression of the posterior genegbx2in the neural plate, and later microcephaly with reduced eyes, suggesting that a proper level ofzbtb11expression is necessary for normal patterning of the neuroectoderm, including eye formation. Co-immunoprecipitation assays showed that Zbtb11 formed a complex with itself and with a phosphomimetic and repressive form of Otx2, suggesting that Zbtb11 forms a dimer or oligomer and interacts with Otx2 in a phosphorylation-dependent manner. Reporter analysis further showed that Zbtb11 enhanced the activity of the phosphomimetic Otx2 to repress a silencer element of the posterior genemeis3. These data suggest that Zbtb11 coordinates with phosphorylated Otx2 to specify the anterior neuroectoderm by repressing posterior genes.
Representational drift in barrel cortex is receptive field dependent
Authors: Alisha Ahmed , Bettina Voelcker , Simon Peron 
Published: October 2023

SUMMARYCortical populations often exhibit changes in activity even when behavior is stable. How behavioral stability is maintained in the face of such ‘representational drift’ remains unclear. One possibility is that some neurons are stable despite broader instability. We examine whisker touch responses in superficial layers of primary vibrissal somatosensory cortex (vS1) over several weeks in mice stably performing an object detection task with two whiskers. While the number of touch neurons remained constant, individual neurons changed with time. Touch-responsive neurons with broad receptive fields were more stable than narrowly tuned neurons. Transitions between functional types were non-random: before becoming broadly tuned neurons, unresponsive neurons first pass through a period of narrower tuning. Broadly tuned neurons with higher pairwise correlations to other touch neurons were more stable than neurons with lower correlations. Thus, a small population of broadly tuned and synchronously active touch neurons exhibit elevated stability and may be particularly important for downstream readout.
Conversion of mouse-derived hybridomas to Tasmanian devil recombinant IgG antibodies
Authors: Slyp Bailey , Darby Jocelyn M. , Flies Andrew S. 
Published: October 2023

ABSTRACTThe hybridoma method for production of monoclonal antibodies has been a cornerstone of biomedical research for several decades. Here we convert the monoclonal antibody sequence from mouse-derived hybridomas into a “devilised” recombinant antibody with devil IgG heavy chain and IgK light chain. The chimeric recombinant antibody can be used in functional assays, immunotherapy, and to improve understanding of antibodies and Fc receptors in Tasmanian devils. The process can be readily modified for other species.
Bioactive coatings on 3D printed scaffolds for bone regeneration: Translation fromin vitrotoin vivomodels and the impact of material properties and growth factor concentration
Authors: Marshall Karen. M. , Wojciechowski Jonathan P. , Jayawarna Vineetha , Hasan Abshar , Echalier Cécile , Øvrebø Øystein , Yang Tao , Kanczler Janos M. , Mata Alvaro , Salmeron-Sanchez Manuel , Stevens Molly M. , Oreffo Richard O. C. 
Published: October 2023

AbstractBone tissue engineering is a rapidly advancing field that seeks to develop new functional bone tissue, harnessing materials for application in bone defects which may fail to heal without intervention, as seen in critical-sized bone defects. The material properties must be developed, tailored and optimised as the environment progresses, through increasing animal size and complexity, of the target bone defect site. This study has examined the potential of a poly(caprolactone) trimethacrylate (PCL-TMA) 3D-printable scaffold with select bioactive coatings to function as a scaffold to augment bone formation. Three bioactive coatings were examined, i) elastin-like protein (ELP), ii) poly (ethyl acrylate) (PEA), fibronectin (FN) and bone morphogenetic protein-2 (BMP-2) applied sequentially (PEA/FN/BMP-2) and iii) both ELP and PEA/FN/BMP-2 coatings applied concurrently. The PCL-TMA scaffold construct was observed to be a robust scaffold material and the bioactive coatings applied were found to be biocompatible, with a significant osteogenic response from human skeletal cell populations observedin vitro. The PCL-TMA scaffold and bioactive coatings supported angiogenesis and displayed excellent biocompatibility following evaluation on the chorioallantoic membrane (CAM) assay. Biocompatibility was confirmed, however, no significant bone formation was detected, following examination of heterotopic bone formation in the murine subcutaneous implantation model, whereas extensive mineralisation was observed in the positive control material of collagen sponge with BMP-2. The absence of bone formation on the PCL-TMA scaffolds,in vivo, was potentially a consequence of the method of action of the applied coatings, the surface area of the scaffold construct for BMP-2 binding and the necessity of an appropriatein vivoenvironment to facilitate skeletal cell ingress, warranting future examination in an orthotopic bone defect model of bone tissue repair. The current studies demonstrate the development of a range of innovative scaffold constructs within vitroefficacy and clearly illustrate the importance of an appropriatein vivoenvironment to validatein vitrofunctionality prior to scale up and preclinical application.