bluuebunny/crossref_metadata_2025_split huggingface dataset:
Individual variability in functional connectivity architecture of the mouse brain
Authors: Bergmann Eyal , Gofman Xenia , Kavushansky Alexandra , Kahn Itamar 
Published: March 2020

AbstractThe functional organization of brain networks can be estimated using fMRI by examining the coherence of spontaneous fluctuations in the fMRI signal, a method known as resting-state functional connectivity MRI. Previous studies in humans reported that such functional networks are dominated by stable group and individual factors, demonstrating that fMRI is suited to measuring subject-specific characteristics, and suggesting the utility of such precision fMRI approach in personalized medicine. However, mechanistic investigations to the sources of individual variability in health and disease are limited in humans and thus require animal models. Here, we used repeated-measurement resting-state fMRI in awake mice to quantify the contribution of individual variation to the functional architecture of the mouse cortex. Comparing the organization of functional networks across the group, we found dominant common organizational principles. The data also revealed stable individual features, which create a unique fingerprint that allow identification of individual mice from the group. Examining the distribution of individual variation across the mouse cortex, we found it is homogeneously distributed in both sensory and association networks. Finally, connectome-based predictive modeling of motor behavior in the rotarod task revealed that individual variation in functional connectivity explained behavioral variability. Collectively, these results show that mouse functional networks are characterized by individual variations suggesting that individual variation characterizes the mammalian cortex in general, and not only the primate cortex. These findings lay the foundation for future mechanistic investigations of individual brain organization and pre-clinical studies of brain disorders in the context of personalized medicine.
Self-paced treadmills do not allow for valid observation of linear and non-linear gait variability outcomes in patients with Parkinson’s disease
Authors: Rohafza Maryam , Soangra Rahul , Smith Jo Armour , Ignasiak Niklas König 
Published: March 2020

AbstractBackgroundDue to the imposed constant belt speed, motorized treadmills are known to change linear and non-linear gait variability outcomes. This is particularly true of patients with Parkinson’s disease where the treadmill can act as an external pacemaker. Therefore, the use of treadmills is generally not recommended when quantifying gait variability. Self-paced treadmills allow for updating the belt speed relative to the walking speed of the subject and might, therefore, be a useful tool for the collection of long consecutive walking trials, necessary for gait variability observations.Research questionTo validate gait variability measures collected on a self-paced treadmill as compared to overground walking.MethodsThirteen healthy subjects and thirteen patients with Parkinson’s disease performed 5 – 8 minute long walking trials: overground, on a treadmill at a constant speed, as well as in three different self-paced treadmill modes. Stride times and stride lengths were recorded using a validated IMU-system and variability was quantified using the coefficient of variation, sample entropy, and detrended fluctuation analysis. Overground and treadmill trials were compared using Pearson’s correlation coefficient, method error, and Bland and Altman analysis.ResultsFor healthy subjects, the self-paced treadmill resulted in increased correlation coefficients of 0.57 – 0.74 as compared to a constant speed treadmill. Correlation coefficients for stride length variability between overground and treadmill walking were not significant. For patients, generally, large errors of 33-40% of stride time variability were observed between overground and treadmill walking. Stride length variability is most similar at a constant belt speed and shows errors of 14-39%.SignificanceDespite an improvement of temporal gait variability validity in the self-paced mode for healthy subjects, the large systematic and random errors between overground and self-paced treadmill walking prohibit meaningful gait variability observations in patients with Parkinson’s disease using self-paced treadmills.
Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice
Authors: Daharsh Lance , Ramer-Tait Amanda E. , Li Qingsheng 
Published: March 2020

AbstractBackgroundWhile the translatability of gut microbiome studies utilizing animal models to humans has proven difficult, studying the gut microbiome directly in humans is also challenging due to the existence of many confounding variables. Therefore, we utilized double humanized mice, which have both an engrafted stable human-like gut microbiome and functional human immune system. With this model, we were able to determine the in vivo impact of HIV-1 infection or a high-fat diet (HFD) on gut human microbiome composition, and its relationship with human immune cell activation and systemic inflammation.ResultsSurgery was performed on NSG mice to create humanized bone-marrow, liver, thymus mice (hu-mice). In order to create double hu-mice, the hu-mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and subsequently transplanted with human fecal material from healthy human donors. We characterized 262 fecal samples from hu-mice, double hu-mice, and human fecal donors to determine the impact of HIV-1 infection or HFD on the gut microbiome and systemic immune activation and inflammation. We found that HIV-1 infection altered the human-like gut microbiome of double hu-mice, which was associated with decreased human CD4 T cells and increased systemic inflammation and immune activation. Further, using a HFD we induced gut microbial dysbiosis in double hu-mice which corresponded with increased systemic immune activation and inflammation.ConclusionsHere, we describe the changes in the human gut microbiome and human immune system due to HIV-1 infection or HFD using our double hu-mice model. HIV-1 infection led to changes in the composition of the human-like gut microbiome that was associated with human CD4 T cell loss and high levels of inflammation and immune activation. The HFD quickly changed the composition of the gut microbiome and led to systemic immune activation and inflammation. We further identified a subset of gut bacteria in HIV-1 infected and HFD fed double hu-mice that was closely associated with systemic inflammation and immune activation. This study demonstrated how double humanized mice can be used to study the complex in vivo interactions of the gut microbiome and human immune system in the context of both disease and diet.
Excessive visual crowding effects in developmental dyscalculia
Authors: Castaldi Elisa , Turi Marco , Gassama Sahawanatou , Piazza Manuela , Eger Evelyn 
Published: March 2020

AbstractVisual crowding refers to the inability to identify objects when surrounded by other similar items. Crowding-like mechanisms are thought to play a key role in numerical perception by determining the sensory mechanisms through which ensembles are perceived. Enhanced visual crowding might hence prevent the normal development of a system involved in segregating and perceiving discrete numbers of items and ultimately the acquisition of more abstract numerical skills. Here, we investigated whether excessive crowding occurs in developmental dyscalculia (DD), a neurodevelopmental disorder characterized by difficulty in learning the most basic numerical and arithmetical concepts, and whether it is found independently of associated major reading and attentional difficulties. We measured spatial crowding in two groups of adult individuals with DD and control subjects. In separate experiments, participants were asked to discriminate the orientation of a Gabor patch either in isolation or under spatial crowding. Orientation discrimination thresholds were comparable across groups when stimuli were shown in isolation, yet they were much higher for the DD group with respect to the control group when the target was crowded by closely neighbouring flanking gratings. The difficulty in discriminating orientation (as reflected by the combination of accuracy and reaction times) in the DD compared to the control group persisted over several larger target flanker distances. Finally, we found that the degree of such spatial crowding correlated with impairments in mathematical abilities even when controlling for visual attention and reading skills. These results suggest that excessive crowding effects might be a characteristic of DD, independent of other associated neurodevelopmental disorders.Bullet pointsPeople with DD have difficulty learning about numbers and arithmetics.Perception of non-symbolic number seems to be modulated by visual crowding.Can stronger than normal crowding effects contribute to the origin of DD?We measured crowding with orientation discrimination tasks using Gabor gratings.Abnormal crowding characterizes DD independently of other developmental deficits.
Loss of α7 nicotinic acetylcholine receptors in GABAergic interneurons causes sex-dependent impairments in postnatal neurogenesis and cognitive and social behavior
Authors: Nacer Samir A. , Otto Simone , Letsinger Ayland C. , DeFilipp Jemma Strauss , Nikolova Viktoriya D. , Riddick Natallia V. , Stevanovic Korey D. , Cushman Jesse D. , Yakel Jerrel L. 
Published: March 2020

AbstractNeural stem cells within the subgranular zone of the dentate gyrus (DG) generate new neurons that form the granule cell layer during embryonic development and continue to generate new neurons throughout life. The maturation process of newly generated granule cells is modulated by nicotinic acetylcholine receptors (nAChRs), which have been shown to play a role in cell survival, signal modulation, dendritic integration, and memory formation. Disrupted nAChR signaling has been implicated in neuropsychiatric and neurodegenerative disorders, potentially via alterations in DG neurogenesis. GABAergic interneurons are known to express nAChRs, particularly the α7 subunit, and have been shown to shape development, integration, and circuit reorganization of DG granule cells. Therefore, we examined the effects of conditional deletion of α7 nAChRs in GABAergic interneurons on measures of postnatal neurogenesis and behavioral outcomes. Loss of α7 nAChRs resulted in a decrease of postnatal granule cells, as indicated by reduced GFAP+ cells in the DG, specifically in male mice, as well as sex-dependent changes in several behaviors, including social recognition, object investigation, and spatial learning. Overall, these findings suggest α7 nAChRs expressed in GABAergic interneurons play an important role in regulating postnatal neurogenesis and behavior in a sex-dependent manner. This provides important insight into the mechanisms by which cholinergic dysfunction contributes to the cognitive and behavioral changes associated with neurodevelopmental and neurodegenerative disorders.
A RNA-seq characterization of the porcine sperm microbiome
Authors: Gòdia M. , Ramayo-Caldas Y. , Zingaretti L. M. , López S. , Rodriguez-Gil J. E. , Yeste M. , Sánchez A. , Clop A. 
Published: March 2020

SummaryThe microbiome plays a key role in homeostasis and health and it has been also linked to fertility and semen quality in several animal species including swine. Despite the more than likely importance of sperm bacteria on the boar’s reproductive ability and the dissemination of pathogens and antimicrobial resistance genes, a high throughput characterization of the swine sperm microbiome remains undone. The current study aimed at profiling the boar sperm bacterial population and its relationship with seven semen quality traits.We carried RNA-seq on 40 ejaculates and we found that it contains a broad population of bacteria. The most abundant phyla wereProteobacteria(39.1%),Firmicutes(27.5%),Actinobacteria(14.9%) andBacteroidetes(5.7%). The predominant species contaminated sperm after ejaculation from soil, faeces and water sources (Bacillus megaterium,Brachybacterium faecium,Bacillus coagulans). Some potential pathogens were also found but at relatively low levels (Escherichia coli,Clostridioides difficile,Clostridium perfringens,Clostridium botulinumandMycobacterium tuberculosis). We also identified 3 potential antibiotic resistant genes fromE. coliagainst chloramphenicol,Neisseria meningitidisagainst spectinomycin andStaphylococcus aureusagainst linezolid. None of these genes were highly abundant. Finally, we classified the ejaculates into categories according to their bacterial features and semen quality parameters and identified two categories that significantly differed for 5 semen quality traits and 13 bacterial features including the generaAcinetobacter,StenotrophomonasandRhodobacter. Our results show that boar semen contains a rich microbiome with potential pathogens and antibiotic resistance genes which may affect its reproductive performance.
LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate
Authors: Jin Run , Klasfeld Samantha , Garcia Meilin Fernandez , Xiao Jun , Han Soon-Ki , Konkol Adam , Zhu Yang , Wagner Doris 
Published: March 2020

ABSTRACTMaster transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet no bonafide pioneer transcription factor has - been identified in this kingdom. Here we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factorAPETALA1(AP1), is a pioneer transcription factor. In vitro, LFY binds in a sequence-specific manner and with high affinity to the endogenousAP1target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, includingAP1,where it co-occupies DNA with histones. Moreover, the LFY DNA contact helix shares defining properties with those of strong nucleosome binding pioneer factors. At theAP1locus, LFY unlocks chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later and require activity of additional, non-pioneer transcription, factors. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between plant and animal pioneer transcription factors. Further analyses aimed at elucidating the defining characteristics of pioneer transcription factors will allow harnessing these for enhanced cell fate reprogramming.
Industrial Waste based Bio-manufacturing of Synthetic Tandem Repeat Protein Fibers
Authors: Mazeed Tarek El-Sayed , Jung Huihun , Kikuchi Yusuke , Allen Benjamin D. , Wood David W. , Demirel Melik C. 
Published: March 2020

AbstractProtein-based fibers are lightweight, biodegradable, have excellent moisture and temperature regulation, and exceptional mechanical properties, but they are limited in production capacity. Biosynthetic protein-based fibers have the potential to overcome these concerns, but large-scale production with high yield (>1g/L) and purity (>%80), as well as low cost (<$50/kg), must be achieved. Here we developed an optimized expression and purification method for biosynthetic tandem repeat proteins, that are inspired from squid ring tooth (SRT) protein using three wetwaste feedstock, corn steep liquor, molasses, and soybean extract. SRT is composed of a highly stiff, naturally occurring bioplastic and these properties arise from the molecular architecture of the constituant proteins, which are segmented co-polymers with alternating semicrystalline and amorphous domains similar to silk. We have developed protocols to use liquid industrial and agricultural waste as feedstock for SRT production, which has the potential to divert waste streams into useful products. We also show that our biosynthetic protein powder, produced at 1 g/L yield and greater than 80% purity, can be manufactured into fibers using conventional split film or wet-spinning approaches.
Potential Functions of Histone H3.3K56 Acetylation in Mammals
Authors: Fang Lei , Chen Danqi , Zhang Jingzi , Li Hongjie , Bradford Beatrix , Jin Chunyuan 
Published: March 2020

AbstractH3K56 acetylation (H3K56Ac) was first identified in yeast and has recently been reported to play important roles in maintaining genomic stability, chromatin assembly, DNA replication, cell cycle progression and DNA repair. Although H3.1K56Ac has been relatively well studied, the function of H3.3K56Ac remains mostly unknown in mammals. In this study, we used H3.3K56Q and H3.3K56R mutants to study the possible function of H3.3K56 acetylation. The K-to-Q substitution mimics a constitutively acetylated lysine, while the K-to-R replacement mimics a constitutively unmodified lysine. We report that cell lines harboring mutation of H3.3K56R exhibit dramatic morphology changes and cell death. Using Tet-Off inducible system, we show an increased population of polyploid/aneuploid cells and a decreased cell viability in H3.3K56R mutant cells. In consistence with these results, H3.3K56R mutant compromised H3.3 incorporation into several pericentric and centric heterochromatin regions we tested. Moreover, mass spectrometry analysis coupled with label free quantification reveal that biological processes regulated by the H3.3-associating proteins, whose interaction with H3.3 is markedly increased by H3.3K56Q mutation but decreased by H3.3K56Q mutation, include sister chromatid cohesion, mitotic nuclear division, and mitotic nuclear envelope disassembly. These results suggest that H3.3K56 acetylation is crucial for chromosome segregation and cell division in mammals.
Molecular determinants of SR-B1-dependentPlasmodiumsporozoite entry into hepatocytic cells
Authors: Langlois Anne-Claire , Manzoni Giulia , Vincensini Laetitia , Coppée Romain , Marinach Carine , Guérin Maryse , Huby Thierry , Carrière Véronique , Cosset François-Loïc , Dreux Marlène , Rubinstein Eric , Silvie Olivier 
Published: March 2020

ABSTRACTSporozoite forms of the malaria parasitePlasmodiumare transmitted by mosquitoes and first infect the liver for an initial round of replication before parasite proliferation in the blood. The molecular mechanisms involved during sporozoite invasion of hepatocytes remain poorly understood. Two receptors of the Hepatitis C virus (HCV), the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1), play an important role during the entry ofPlasmodiumsporozoites into hepatocytic cells. In contrast to HCV entry, which requires both CD81 and SR-B1 together with additional host factors, CD81 and SR-B1 operate independently during malaria liver infection. Sporozoites from human-infectingP. falciparumandP. vivaxrely respectively on CD81 or SR-B1. Rodent-infectingP. bergheican use SR-B1 to infect host cells as an alternative pathway to CD81, providing a tractable model to investigate the role of SR-B1 duringPlasmodiumliver infection. Here we show that mouse SR-B1 is less functional as compared to human SR-B1 duringP. bergheiinfection. We took advantage of this functional difference to investigate the structural determinants of SR-B1 required for infection. Using a structure-guided strategy and chimeric mouse/human SR-B1 constructs, we could map the functional region of human SR-B1 within apical loops, suggesting that this region of the protein may play a crucial role for interaction of sporozoite ligands with host cells and thus the very first step ofPlasmodiuminfection.IMPORTANCEMalaria is caused byPlasmodiumparasites and remains one of the deadliest parasitic diseases worldwide. The parasite is transmitted by a blood feeding mosquito and first invades the liver for an initial, obligatory and silent round of replication. The liver infection is an attractive target for antimalarial vaccine strategies, however the molecular mechanisms of parasite invasion of hepatocytes remain to be fully elucidated. Two hepatocyte surface proteins are known to be important for parasite entry into hepatocytes, the tetraspanin CD81 and the scavenger receptor class B type 1 (SR-B1). These receptors constitute independent gateways depending on thePlasmodiumspecies. Here, we identified the structural determinants of SR-B1, an important hepatocyte entry factor for human-infectingP. vivax. This study paves the way toward a better characterization of the molecular interactions underlying the crucial early stages of infection, a pre-requisite for the development of novel malaria vaccine strategies.
Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis
Authors: Shami Adrienne Niederriter , Zheng Xianing , Munyoki Sarah K. , Ma Qianyi , Manske Gabriel L. , Green Christopher D. , Sukhwani Meena , Orwig Kyle E. , Li Jun Z. , Hammoud Saher Sue 
Published: March 2020

SummarySpermatogenesis is a highly regulated process that produces sperm to transmit genetic information to the next generation. Although extensively studied in mice, our current understanding of primate spermatogenesis is limited to populations defined by state-specific markers defined from rodent data. As between-species differences have been reported in the process duration and cellular differentiation hierarchy, it remains unclear how molecular markers and cell states are conserved or have diverged from mice to man. To address this challenge, we employ single-cell RNA-sequencing to identify transcriptional signatures of major germ and somatic cell-types of the testes in human, macaque and mice. This approach reveals differences in expression throughout spermatogenesis, including the stem/progenitor pool of spermatogonia, classical markers of differentiation, potential regulators of meiosis, the kinetics of RNA turnover during spermatid differentiation, and germ cell-soma communication. These datasets provide a rich foundation for future targeted mechanistic studies of primate germ cell development andin vitrogametogenesis.