bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Kiosk Station for the Assessment of Multiple Cognitive Domains and Enrichment of Monkeys
Authors: Womelsdorf Thilo , Thomas Christopher , Neumann Adam , Watson Marcus , Boroujeni Kianoush Banaie , Hassani Seyed A. , Parker Jeremy M. , Hoffman Kari L. 
Published: March 2021

AbstractBackgroundNonhuman primates (NHPs) are self-motivated to perform cognitive tasks on touchscreens in their animal housing setting. To leverage this ability, fully integrated hardware and software solutions are needed, that work within housing and husbandry routines while also spanning cognitive task constructs of the Research Domain Criteria (RDoC).New MethodWe describe a Kiosk Station (KS-1) that provides robust hardware and software solutions for running cognitive tasks in cage-housed NHPs. KS-1 consists of a frame for mounting flexibly on housing cages, a touchscreen animal interface with mounts for receptables, reward pumps and cameras, and a compact computer cabinet with an interface for controlling behavior. Behavioral control is achieved with a unity3D program that is virtual-reality capable, allowing semi-naturalistic visual tasks to assess multiple cognitive domains.ResultsKS-1 is fully integrated into the regular housing routines of monkeys. A single person can operate multiple KS-1s. Monkeys engage with KS-1 at high motivation and cognitive performance levels at high intra-individual consistency.Comparison with Existing MethodsKS-1 is optimized for flexible mounting onto standard apartment cage systems. KS-1 has a robust animal interface with options for gaze/reach monitoring. It has an integrated user interface for controlling multiple cognitive task using a common naturalistic object space designed to enhance task engagement. All custom KS-1 components are open-sourced.ConclusionsKS-1 is a versatile tool for cognitive profiling and enrichment of cage-housed monkeys. It reliably measures multiple cognitive domains which promises to advance our understanding of animal cognition, inter-individual differences and underlying neurobiology in refined, ethologically meaningful behavioral foraging contexts.
Computationally reconstructed interactome ofBradyrhizobium diazoefficiensUSDA110 reveals novel functional modules and protein hubs for symbiotic nitrogen fixation
Authors: Ma Jun-Xiao , Yang Yi , Li Guang , Ma Bin-Guang 
Published: March 2021

AbstractSymbiotic nitrogen fixation is an important part of the nitrogen biogeochemical cycles and the main nitrogen source of the biosphere. As a classical model system for symbiotic nitrogen fixation, rhizobium-legume systems have been studied elaborately for decades. Detailed panorama about the molecular mechanism of the communication and coordination between rhizobia and host plants is becoming clearer. For more systematic insights, there is an increasing demand on new studies integrating multi-omics information. Here we present a comprehensive computational framework, integrating the reconstructed protein interactome ofB. diazoefficiensUSDA110 with its transcriptome and proteome data, to study the complex protein-protein interaction (PPI) network involved in the symbiosis system. We reconstructed the interactome ofB. diazoefficiensUSDA110 by computational approaches. Based on the comparison of interactomes betweenB. diazoefficiensUSDA110 and other rhizobia, we inferred that the slow growth ofB. diazoefficiensUSDA110 may owe to the requirement of more protein modifications and further identified 36 conserved functional PPI modules. Integrated with transcriptome and proteome data, interactomes representing free-living cell and symbiotic nitrogen-fixing (SNF) bacteroid were obtained. Based on the SNF interactome, a core-sub-PPI-network for symbiotic nitrogen fixation was determined and 9 novel functional modules and 11 key protein hubs playing key roles for symbiosis were identified. The reconstructed interactome ofB. diazoefficiensUSDA110 may serve as a valuable reference for studying the mechanism underlying the SNF system of rhizobia and legumes.
Minimal interplay between explicit knowledge, dynamics of learning and temporal expectations in different, complex uni- and multisensory contexts
Authors: Ball Felix , Spuerck Inga , Noesselt Toemme 
Published: March 2021

AbstractWhile temporal expectations (TE) generally improve reactions to temporally predictable events, it remains unknown how temporal rule learning and explicit knowledge about temporal rules contribute to performance improvements and whether any contributions generalise across modalities. Here, participants discriminated the frequency of diverging auditory, visual or audiovisual targets embedded in auditory, visual or audiovisual distractor sequences. Temporal regularities were manipulated run-wise (early vs. late target within sequence). Behavioural performance (accuracy, RT) plus measures from a computational learning model all suggest that temporal rule learning occurred but did not generalise across modalities, that dynamics of learning (size of TE effect across runs) and explicit knowledge have little to no effect on the strength of TE, and that explicit knowledge affects performance – if at all – in a context dependent manner: only under complex task regimes (unknown target modality) might it partially help to resolve response conflict while it is lowering performance in less complex environments..
Combinatorial patterns of gene expression changes contribute to variable expressivity of the developmental delay-associated 16p12.1 deletion
Authors: Jensen Matthew , Tyryshkina Anastasia , Pizzo Lucilla , Smolen Corrine , Das Maitreya , Huber Emily , Krishnan Arjun , Girirajan Santhosh 
Published: March 2021

ABSTRACTBackgroundRecent studies have suggested that individual variants do not sufficiently explain the variable expressivity of phenotypes observed in complex disorders. For example, the 16p12.1 deletion is associated with developmental delay and neuropsychiatric features in affected individuals, but is inherited in >90% of cases from a mildly-affected parent. While children with the deletion are more likely to carry additional “second-hit” variants than their parents, the mechanisms for how these variants contribute to phenotypic variability are unknown.MethodsWe performed detailed clinical assessments, whole-genome sequencing, and RNA sequencing of lymphoblastoid cell lines for 32 individuals in five large families with multiple members carrying the 16p12.1 deletion. We identified contributions of the 16p12.1 deletion and “second-hit” variants towards a range of expression changes in deletion carriers and their family members, including differential expression, outlier expression, alternative splicing, allele-specific expression, and expression-quantitative trait loci analyses.ResultsWe found that the deletion dysregulates multiple autism and brain development genes such asFOXP1,ANK3, andMEF2. Carrier children also showed an average of 5,323 gene expression changes compared with one or both parents, which matched with 33/39 observed developmental phenotypes. We identified significant enrichments for 13/25 classes of “second-hit” variants in genes with expression changes, where 4/25 variant classes were only enriched when inherited from the non-carrier parent, including loss-of-function SNVs and large duplications. In 11 instances, including forZEB2andSYNJ1, gene expression was synergistically altered by both the deletion and inherited “second-hits” in carrier children. Finally, brain-specific interaction network analysis showed strong connectivity between genes carrying “second-hits” and genes with transcriptome alterations in deletion carriers.ConclusionsOur results suggest a potential mechanism for how “second-hit” variants modulate expressivity of complex disorders such as the 16p12.1 deletion through transcriptomic perturbation of gene networks important for early development. Our work further shows that family-based assessments of transcriptome data are highly relevant towards understanding the genetic mechanisms associated with complex disorders.
Spontaneously Hypertensive Rat substrains show differences in premorbid addiction vulnerability traits and cocaine self-administration: Implications for a novel rat reduced complexity cross
Authors: Kantak Kathleen M. , Stots Carissa , Mathieson Elon , Bryant Camron D. 
Published: March 2021

ABSTRACTForward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine vulnerability traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated a number of premorbid addiction vulnerability traits and cocaine self-administration behaviors using a longitudinal within-subjects design. Trait impulsivity and compulsivity were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine abuse liability studied under fixed-ratio and chained schedules of cocaine self-administration. Trait compulsivity correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the chained schedule. Trait compulsivity also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22%-40% of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.HighlightsClosely related SHR substrains have distinct cocaine vulnerability traitsInhibitory control was poorer in SHR/NCrl than SHR/NHsdSHR/NCrl were more sucrose reactive and sensitive to acute cocaine than SHR/NHsdCocaine abuse liability was greater in SHR/NCrl than SHR/NHsdSHR substrains can be used in an RCC to uncover cocaine vulnerability genes & variants
Experimental susceptibility of North American raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) to SARS-CoV-2
Authors: Francisco Raquel , Hernandez Sonia M. , Mead Daniel G. , Adcock Kayla G. , Burke Sydney C. , Nemeth Nicole M. , Yabsley Michael J. 
Published: March 2021

AbstractSkunks and raccoons were intranasally inoculated or indirectly exposed to SARS-CoV-2. Both species are susceptible to infection; however, the lack of, and low quantity of infectious virus shed by raccoons and skunks, respectively, and lack of cage mate transmission in both species, suggest that neither species are competent SARS-CoV-2 reservoirs.Article Summary LineExperimental SARS-CoV-2 inoculation of North American raccoons and striped skunks showed susceptibility to infection, but transient, low-level shedding suggests that neither species is likely to be a competent natural reservoir.
COVID-19 vaccine response in pregnant and lactating women: a cohort study
Authors: Gray Kathryn J. , Bordt Evan A. , Atyeo Caroline , Deriso Elizabeth , Akinwunmi Babatunde , Young Nicola , Baez Aranxta Medina , Shook Lydia L. , Cvrk Dana , James Kaitlyn , De Guzman Rose M. , Brigida Sara , Diouf Khady , Goldfarb Ilona , Bebell Lisa M. , Yonker Lael M. , Fasano Alessio , Rabi Sayed A. , Elovitz Michal A. , Alter Galit , Edlow Andrea G. 
Published: March 2021

ABSTRACTBackgroundPregnant and lactating women were excluded from initial COVID-19 vaccine trials; thus, data to guide vaccine decision-making are lacking. We sought to evaluate the immunogenicity and reactogenicity of COVID-19 mRNA vaccination in pregnant and lactating women.Methods131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, and 16 non-pregnant) were enrolled in a prospective cohort study at two academic medical centers. Titers of SARS-CoV-2 Spike and RBD IgG, IgA and IgM were quantified in participant sera (N=131), umbilical cord sera (N=10), and breastmilk (N=31) at baseline, 2nd vaccine dose, 2-6 weeks post 2nd vaccine, and delivery by Luminex, and confirmed by ELISA. Titers were compared to pregnant women 4-12 weeks from native infection (N=37). Post-vaccination symptoms were assessed. Kruskal-Wallis tests and a mixed effects model, with correction for multiple comparisons, were used to assess differences between groups.ResultsVaccine-induced immune responses were equivalent in pregnant and lactating vs non-pregnant women. All titers were higher than those induced by SARS-CoV-2 infection during pregnancy. Vaccine-generated antibodies were present in all umbilical cord blood and breastmilk samples. SARS-CoV-2 specific IgG, but not IgA, increased in maternal blood and breastmilk with vaccine boost. No differences were noted in reactogenicity across the groups.ConclusionsCOVID-19 mRNA vaccines generated robust humoral immunity in pregnant and lactating women, with immunogenicity and reactogenicity similar to that observed in non-pregnant women. Vaccine-induced immune responses were significantly greater than the response to natural infection. Immune transfer to neonates occurred via placental and breastmilk.
Adaptive evolution ofMoniliophthoraPR-1 proteins towards its pathogenic lifestyle
Authors: Vasconcelos Adrielle A. , José Juliana , Filho Paulo M. Tokimatu , Camargo Antonio P. , Teixeira Paulo J. P. L. , Thomazella Daniela P. T. , do Prado Paula F. V. , Fiorin Gabriel L. , Costa Juliana L. , Figueira Antonio , Carazzolle Marcelo F. , Pereira Gonçalo A. G. , Baroni Renata M. 
Published: March 2021

AbstractMoniliophthora perniciosaandMoniliophthora roreriare hemibiotrophic fungi that harbor a large number of Pathogenesis-Related 1 genes, many of which are induced in the biotrophic interaction withTheobroma cacao.Here, we provide evidence that the evolution of PR-1 inMoniliophthorawas adaptive and potentially related to the emergence of the parasitic lifestyle in this genus. Phylogenetic analysis revealed conserved PR-1 genes, shared by many Agaricales saprotrophic species, that have diversified in new PR-1 genes putatively related to pathogenicity inMoniliophthora, as well as in recent specialization cases within both species. PR-1 families inMoniliophthorawith higher evolutionary rates exhibit induced expression in the biotrophic interaction and positive selection clues, supporting the hypothesis that these proteins accumulated adaptive changes in response to host-pathogen arm race. Furthermore, we show that the highly diversifiedMpPR-1genes are not induced by two phytoalexins, suggesting detoxification might not be their main function as proposed before.
Lung organoids and microplastic fibers: a new exposure model for emerging contaminants
Authors: Winkler Anna , Santo Nadia , Madaschi Laura , Cherubini Alessandro , Rusconi Francesco , Rosso Lorenzo , Tremolada Paolo , Lazzari Lorenza , Bacchetta Renato 
Published: March 2021

AbstractBackgroundThree-dimensional (3D) structured organoids are the most advancedin vitromodels for studying human health effects, but they have been applied only once to evaluate the biological effects associated with microplastic exposure. Fibers from synthetic clothes and fabrics are a major source of airborne microplastics, and their release from dryer machines is still poorly understood.ObjectivesIn this study, we aimed to establish anin vitroorganoid model of human lung epithelial cells to evaluate its suitability for studying the effects of airborne microplastic contamination on humans. Furthermore, we aimed to characterize the microplastic fibers (MPFs) released in the exhaust filter of a household dryer and to test their interactions and inflammatory effects on the established lung organoids.MethodsThe polyester fibers emitted from the drying of synthetic fabrics were collected. Morphological characterization of the fibers released into the air filter was performed by optical microscopy and scanning electron microscopy (SEM)/energy dispersive x-ray spectroscopy (EDS). The organoids were exposed to various MPF concentrations (1, 10, and 50 mg L−1) and analyzed by optical microscopy, SEM, and confocal microscopy. Gene expression analysis of lung-specific genes, inflammatory cytokines, and oxidative stress-related genes was achieved by quantitative reverse transcription–polymerase chain reaction (qRT-PCR).ResultsWe successfully cultured organoids with lung-specific genes. The presence of MPFs did not inhibit organoid growth, but polarized cell growth was observed along the fibers. Moreover, the MPFs did not cause inflammation or oxidative stress. Interestingly, the MPFs were coated with a cellular layer, resulting in the inclusion of fibers in the organoid.DiscussionThis work could have potential long-term implications regarding lung epithelial cells undergoing repair. This preliminary exposure study using human lung organoids could form the basis for further research regarding the toxicological assessment of emerging contaminants such as micro- or nanoplastics.
Genetic inactivation of SARM1 axon degeneration pathway improves outcome trajectory after experimental traumatic brain injury based on pathological, radiological, and functional measures
Authors: Bradshaw Donald V. , Knutsen Andrew K. , Korotcov Alexandru , Sullivan Genevieve M. , Radomski Kryslaine L. , Dardzinski Bernard J. , Zi Xiaomei , McDaniel Dennis P. , Armstrong Regina C. 
Published: March 2021

ABSTRACTTraumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration. TheSarm1gene is a central driver of axon degeneration through a conserved molecular pathway.Sarm1-/- mice with knockout (KO) of theSarm1gene enable genetic proof-of-concept testing ofSarm1inactivation as a therapeutic target. We evaluatedSarm1deletion effects after TBI using a concussive model that causes traumatic axonal injury and progresses to CC atrophy at 10 weeks, indicating post-traumatic neurodegeneration.Sarm1wild-type (WT) mice developed significant CC atrophy that was reduced inSarm1KO mice. Using electron microscopy to quantify individual axons demonstrated thatSarm1KO preserved more intact axons and reduced damaged or demyelinated axons. MRI in live mice identified significantly reduced CC volume after TBI inSarm1WT mice that was attenuated inSarm1KO mice. MR diffusion tensor imaging detected reduced fractional anisotropy in both genotypes while axial diffusivity remained higher inSarm1KO mice. Immunohistochemistry revealed significant attenuation of CC atrophy, myelin loss, and neuroinflammation inSarm1KO mice after TBI. Functionally, TBI resulted in late-stage motor learning and sleep deficits that were ameliorated inSarm1KO mice. Based on these findings,Sarm1inactivation can protect axons and white matter tracts to improve translational outcomes associated with CC atrophy and post-traumatic neurodegeneration.
Single cell analysis of the aging female hypothalamus
Authors: Hajdarovic Kaitlyn H. , Yu Doudou , Hassell Lexi-Amber , Evans Shane , Packer Sarah , Neretti Nicola , Webb Ashley E. 
Published: March 2021

ABSTRACTAlterations in metabolism, sleep patterns, body composition, and hormone status are all key features of aging. The hypothalamus is a well-conserved brain region that controls these homeostatic and survival-related behaviors. Despite the importance of this brain region in healthy aging, little is known about the intrinsic features of hypothalamic aging. Here, we utilize single nuclei RNA-sequencing to assess the transcriptomes of 40,064 hypothalamic nuclei from young and aged female mice. We identify cell type-specific signatures of aging in neurons, astrocytes, and microglia, as well as among the diverse collection of neuronal subtypes in this region. We uncover key changes in cell types critical for metabolic regulation and body composition, as well as in an area of the hypothalamus linked to cognition. In addition, our analysis reveals an unexpected female-specific feature of hypothalamic aging. Specifically, we discover that the master regulator of X-inactivation,Xist, is elevated with age, particularly in hypothalamic neurons. Moreover, using machine learning, we show that levels of X-chromosome genes, andXistitself, are the best predictors of cellular age. Together, this study identifies critical cell-specific changes of the aging hypothalamus in mammals, and uncovers a novel marker of neuronal aging in females.
Discrete dynamic model of the mammalian sperm acrosome reaction: the influence of acrosomal pH and biochemical heterogeneity
Authors: Aldana Andrés , Carneiro Jorge , Martínez-Mekler Gustavo , Darszon Alberto 
Published: March 2021

AbstractThe acrosome reaction (AR) is an exocytotic process essential for mammalian fertilization. It involves diverse biochemical and physiological changes that culminate in the release of the acrosomal content to the extracellular medium as well as a reorganization of the plasma membrane (PM) that allows sperm to interact and fuse with the egg. In spite of many efforts, there are still important pending questions regarding the molecular mechanism regulating the AR. Particularly, the contribution of acrosomal alkalinization to AR triggering in physiological conditions is not well understood. Also, the dependence of the proportion of sperm capable of undergoing AR on the biochemical heterogeneity within a sperm population has not been studied. Here we present a discrete mathematical model for the human sperm AR, based on the biophysical and biochemical interactions among some of the main components of this complex exocytotic process. We show that this model can qualitatively reproduce diverse experimental results, and that it can be used to analyze how acrosomal pH (pHa) and cell heterogeneity regulate AR. Our results confirm that pHaincrease can on its own trigger AR in a subpopulation of sperm, and furthermore, it indicates that this is a necessary step to trigger acrosomal exocytosis through progesterone, a known physiological inducer of AR. Most importantly, we show that the proportion of sperm undergoing AR is directly related to the detailed structure of the population biochemical heterogeneity.