bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus
Authors: Koenig Michelle R. , Razo Elaina , Mitzey Ann , Newman Christina M. , Dudley Dawn M. , Breitbach Meghan E. , Semler Matthew R. , Stewart Laurel M. , Weiler Andrea M. , Rybarczyk Sierra , Bach Kathryn M. , Mohns Mariel S. , Simmons Heather A. , Mejia Andres , Fritsch Michael , Dennis Maria , Teixeira Leandro B. C. , Schotzko Michele L. , Nork T. Michael , Rasmussen Carol A. , Katz Alex , Nair Veena , Hou Jiancheng , Hartman Amy , Hoeve James Ver , Kim Charlene , Schneider Mary L. , Ausderau Karla , Kohn Sarah , Jaeger Anna S. , Aliota Matthew T. , Hayes Jennifer M. , Schultz-Darken Nancy , Eickhoff Jens , Antony Kathleen M. , Noguchi Kevin , Zeng Xiankun , Permar Sallie , Prabhakaran Vivek , Capuano Saverio , Friedrich Thomas C. , Golos Thaddeus G. , O’Connor David H. , Mohr Emma L. 
Published: August 2019

AbstractCongenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.
An essential, kinetoplastid-specific GDP-Fuc: β-D-Gal α-1,2-fucosyltransferase is located in the mitochondrion ofTrypanosoma brucei
Authors: Bandini Giulia , Damerow Sebastian , Güther Maria Lucia Sampaio , Guo Hongjie , Mehlert Angela , Beverley Stephen M. , Ferguson Michael A. J. 
Published: August 2019

ABSTRACTFucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential inTrypanosoma brucei.Here we show that the single identifiableT. bruceifucosyltransferase (TbFUT1) is a GDP-Fuc: β-D-galactose α-1,2-fucosyltransferase with an apparent preference for a Galβ1,3GlcNAcβ1-O-R acceptor motif. Conditional null mutants ofTbFUT1demonstrated that it is essential for both the mammalian-infective bloodstream form and the insect vector-dwelling procyclic form. Unexpectedly, TbFUT1 was localized in the mitochondrion ofT. bruceiand found to be required for mitochondrial function in bloodstream form trypanosomes. Finally, theTbFUT1gene was able to complement aLeishmania majormutant lacking the homologous fucosyltransferase gene (Guo et al., 2021). Together these results suggest that kinetoplastids possess an unusual, conserved and essential mitochondrial fucosyltransferase activity that may have therapeutic potential across trypanosomatids.
A Fyn - specific biosensor reveals localized, pulsatile kinase activity and spatially regulated signaling crosstalk
Authors: Mukherjee Ananya , Singh Randhir , Udayan Sreeram , Biswas Sayan , Pothula Purushotham , Manmadhan Saumya , George Geen , Kumar Shilpa Dilip , Das Ranabir , Rao Balaji M. , Gulyani Akash 
Published: August 2019

AbstractCell behavior is controlled through spatio-temporally localized protein activity. Despite unique and often contradictory roles played by Src-family-kinases (SFKs) in regulating cell physiology, activity patterns of individual SFKs have remained elusive. Here, we report a biosensor for specifically visualizing active conformation of SFK-Fyn in live cells. We deployed combinatorial library screening to isolate a binding-protein (F29) targeting activated Fyn. Nuclear-magnetic-resonance (NMR) analysis provides the structural basis of F29 specificity for Fyn over homologous SFKs. Using F29, we engineered a sensitive, minimally-perturbing fluorescence-resonance-energy-transfer (FRET) biosensor (FynSensor) that reveals cellular Fyn activity to be spatially localized, pulsatile and sensitive to adhesion/integrin signaling. Strikingly, growth factor stimulation further enhanced Fyn activity in pre-activated intracellular zones. However, inhibition of focal-adhesion-kinase activity not only attenuates Fyn activity, but abolishes growth-factor modulation. FynSensorimaging uncovers spatially-organized, sensitized signaling clusters, direct crosstalk between integrin and growth-factor-signaling, and clarifies how compartmentalized Src-kinase activity may drive cell fate.
The effect of population bottleneck size and selective regime on genetic diversity and evolvability in bacteria
Authors: Wein Tanita , Dagan Tal 
Published: August 2019

AbstractPopulation bottlenecks leading to a drastic reduction of the population size are common in the evolutionary dynamics of natural populations; their occurrence is known to have implications for genome evolution due to genetic drift, the consequent reduction in genetic diversity and the rate of adaptation. Nevertheless, an empirical characterization of the effect of population bottleneck size on evolutionary dynamics of bacteria is currently lacking. Here we show that selective conditions have a stronger effect on the evolutionary history of bacteria in comparison to genetic drift following population bottlenecks. We evolvedEscherichia colipopulations under three different population bottlenecks (small, medium, large) in two temperature regimes (37°C and 20°C). We find a high genetic diversity in the large in comparison to the small bottleneck size. Nonetheless, the cold temperature led to reduced genetic diversity in all bottleneck sizes, hence, the temperature has a stronger effect on the genetic diversity in comparison to the bottleneck size. A comparison of the fitness gain among the evolved populations reveals a similar pattern where the temperature has a significant effect on the fitness. Our study demonstrates that population bottlenecks are an important determinant of the evolvability in bacteria; their consequences depend on the selective conditions and are best understood via their effect on the standing genetic variation.
Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into first pharyngeal arch
Authors: Javali Alok , Laxmanan Vairavan , Palakodeti Dasaradhi , Sambasivan Ramkumar 
Published: August 2019

AbstractVertebrate cranial neural crest cells (CNCC) are multipotent. Proximal to the source CNCC form the cranial ganglia. Distally, in the pharyngeal arches, they give rise to the craniofacial skeleton and connective tissues. Fate choices are made as CNCC pattern into distinct destination compartments. In spite of this importance, the mechanism patterning CNCC is poorly defined. Here, we report that a novel β-catenin-controlled switch in the cell arrangement is critical in patterning CNCC. In mouse embryos, at the first pharyngeal arch axial level, membrane β-catenin levels correlate with the extent of cell-cell adhesion and thus, with a collective or a dispersed state of CNCC. Using in vitro human neural crest model and chemical modulators of β-catenin levels, we show a requirement for down-modulating β-catenin for the collective-to-dispersed switch. Similarly, in β-catenin gain of function mutant mouse embryos, CNCC fail to disperse, which may underlie their failure to populate first pharyngeal arch. Thus, we show that β-catenin-mediated regulation of CNCC tissue architecture, a previously underappreciated mechanism, underlies the patterning of CNCC into fate-specific compartments.Summary statementThe report shows a crucial step in cranial neural crest patterning. Neural crest cells invading the pharyngeal arches transition from a collective to a dispersed state. This transition in cell arrangement is dependent on membrane β-catenin levels.
Alcohol Drinking Exacerbates Neural and Behavioral Pathology in the 3xTg-AD Mouse Model of Alzheimer’s Disease
Authors: Hoffman Jessica L. , Faccidomo Sara , Kim Michelle , Taylor Seth M. , Agoglia Abigail E. , May Ashley M. , Smith Evan N. , Wong LC , Hodge Clyde W. 
Published: August 2019

ABSTRACTAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that represents the most common cause of dementia in the United States. Although the link between alcohol use and AD has been studied, preclinical research has potential to elucidate neurobiological mechanisms that underlie this interaction. This study was designed to test the hypothesis that non-dependent alcohol drinking exacerbates the onset and magnitude of AD-like neural and behavioral pathology. We first evaluated the impact of voluntary 24-h, 2-bottle choice home-cage alcohol drinking on the prefrontal cortex and amygdala neuroproteome in C57BL/6J mice and found a striking association between alcohol drinking and AD-like pathology. Bioinformatics identified the AD-associated proteins MAPT (Tau), amyloid beta precursor protein (APP), and presenilin-1 (PSEN-1) as the main modulators of alcohol-sensitive protein networks that included AD-related proteins that regulate energy metabolism (ATP5D, HK1, AK1, PGAM1, CKB), cytoskeletal development (BASP1, CAP1, DPYSL2 [CRMP2], ALDOA, TUBA1A, CFL2, ACTG1), cellular/oxidative stress (HSPA5, HSPA8, ENO1, ENO2), and DNA regulation (PURA, YWHAZ). To address the impact of alcohol drinking on AD, studies were conducted using 3xTg-AD mice that express human MAPT, APP, and PSEN-1 transgenes and develop AD-like brain and behavioral pathology. 3xTg-AD and wildtype mice consumed alcohol or saccharin for 4 months. Behavioral tests were administered during a 1-month alcohol free period. Alcohol intake induced AD-like behavioral pathologies in 3xTg-AD mice including impaired spatial memory in the Morris Water Maze, diminished sensorimotor gating as measured by prepulse inhibition, and exacerbated conditioned fear. Multiplex immunoassay conducted on brain lysates showed that alcohol drinking upregulated primary markers of AD pathology in 3xTg-AD mice: Aβ 42/40 ratio in the lateral entorhinal and prefrontal cortex and total Tau expression in the lateral entorhinal cortex and amygdala at 1-month post alcohol exposure. Immunocytochemistry showed that alcohol use upregulated expression of pTau (Ser199/Ser202) in the hippocampus, which is consistent with late stage AD. According to the NIA-AA Research Framework, these results suggest that alcohol use is associated with Alzheimer’s pathology. Results also showed that alcohol use was associated with a general reduction in Akt/mTOR signaling via several phosphoproteins (IR, IRS1, IGF1R, PTEN, ERK, mTOR, p70S6K, RPS6) in multiple brain regions including hippocampus and entorhinal cortex. Dysregulation of Akt/mTOR phosphoproteins suggests alcohol may target this pathway in AD progression. These results suggest that nondependent alcohol drinking increases the onset and magnitude of AD-like neural and behavioral pathology in 3xTg-AD mice.
Intramolecular regulation of anillin during cytokinesis
Authors: Beaudet Daniel , Pham Nhat , Skaik Noha , Piekny Alisa 
Published: August 2019

ABSTRACTCytokinesis occurs by the ingression of an actomyosin ring that cleaves a cell into two daughters. This process is tightly controlled to avoid aneuploidy, and we previously showed that active Ran coordinates ring positioning with chromatin. Active Ran is high around chromatin, and forms an inverse gradient to cargo-bound importins. We found that the ring component anillin contains an NLS that binds to importin and is required for its function. Anillin contains a RhoA-binding domain (RBD), which we revealed autoinhibits the adjacent NLS-containing C2 domain. Here, we show that active RhoA relieves inhibition of the C2 domain. Furthermore, FRAP experiments show that the NLS regulates anillin’s cortical properties, supporting feedback to the RBD. Indeed, mutations that disrupt the interface between the RBD and C2 domain disrupt anillin’s localization and function. Thus, active RhoA induces a conformational change that increases accessibility to the C2 domain, which is maintained by importin-binding for recruitment to the equatorial cortex.
The influence of substrate concentration on the culturability of heterotrophic soil microbes isolated by high-throughput dilution-to-extinction cultivation
Authors: Bartelme Ryan P. , Custer Joy M. , Dupont Christopher L. , Espinoza Josh L. , Torralba Manolito , Khalili Banafshe , Carini Paul 
Published: August 2019

AbstractThe vast majority of microbes inhabiting oligotrophic shallow subsurface soil environments have not been isolated or studied under controlled laboratory conditions. In part, the challenges associated with isolating shallow subsurface microbes may persist because microbes in deeper soils are adapted to low nutrient availability or quality. Here we use high-throughput dilution-to-extinction culturing to isolate shallow subsurface microbes from a conifer forest in Arizona, USA. We hypothesized that the concentration of heterotrophic substrates in microbiological growth medium would affect which microbial taxa were culturable from these soils. To test this, we diluted extracted cells into one of two custom-designed defined growth media that differed only by a 100-fold difference in the concentration of amino acids and organic carbon. Across both media, we isolated a total of 133 pure cultures, all of which were classified as Actinobacteria or Alphaproteobacteria. The substrate availability dictated which actinobacterial phylotypes were culturable but had no significant effect on the culturability of Alphaproteobacteria. We isolated cultures that were representative of the most abundant phylotype in the soil microbial community (Bradyrhizobiumspp.) and representatives of five of the top 10 most abundantActinobacteriaphylotypes, includingNocardioidesspp.,Mycobacteriumspp., and several other phylogenetically-divergent lineages. Flow cytometry of nucleic acid-stained cells showed that cultures isolated on low-substrate medium had significantly lower nucleic-acid fluorescence than those isolated on high-substrate medium. These results show that dilution-to-extinction is an effective method to isolate abundant soil microbes and the concentration of substrates in culture medium influences the culturability of specific microbial lineages.ImportanceIsolating environmental microbes and studying their physiology under controlled conditions is an essential aspect of understanding their ecology. Subsurface ecosystems are typically nutrient-poor environments that harbor diverse microbial communities—the majority of which are thus far uncultured. In this study, we use modified high-throughput cultivation methods to isolate subsurface soil microbes. We show that a component of whether a microbe is culturable from subsurface soils is the concentration of growth substrates in the culture medium. Our results offer new insight into technical approaches and growth medium design that can be used to access the uncultured diversity of soil microbes.
Mutant GT198 in angiogenesis as a common origin of human prostate and bladder cancers
Authors: Zhang Liyong , Liu Yehai , Cheng Liang , Zhao Chengquan , Ko Lan 
Published: August 2019

ABSTRACTProstate and bladder cancers are common cancers in men. It has been speculated that the high concomitant incidence of the two cancers is due to a potential shared cause underlying both cancers. In this report, we have identified a common cause of human prostate and bladder cancers as the mutant oncoprotein GT198 (PSMC3IP). GT198 is a DNA repair factor and a steroid hormone receptor coactivator. GT198 has been previously shown to be mutated in angiogenic pericyte stem cells in solid tumor microenvironment. GT198 is also a direct protein target of chemo drugs paclitaxel and doxorubicin. Here we show, the GT198 gene is mutated with protein overexpression in tumor stroma of human prostate and bladder cancers. Affected stromal cells include angiogenic blood vessel pericyte stem cells, and vascular smooth muscle cell lineages including myofibroblasts in prostate and smooth muscle cells in bladder. In prostate cancers, GT198+ tumor stromal cells are associated with early stages of cancer with lower Gleason scores. In bladder cancers, the presence of angiogenesis and GT198+ stroma are associated with better progression-free survival in docetaxel-treated patients. Together, our evidence suggests that angiogenic pericyte stem cells are initial lesions producing a mutant stroma carrying GT198 somatic mutations. Subsequently, mutant myofibroblasts promote adenocarcinomas in prostate and mutant smooth muscle cells promote urothelial carcinomas in bladder. Chemo drugs targeting to GT198 is more effective in early stages of cancers with GT198+ stromal cells. This study supports oncoprotein GT198 as a common cause and a drug target in human prostate and bladder cancers.
Leaf anatomy is not correlated to CAM function in a C3+CAM hybrid species,Yucca gloriosa
Authors: Heyduk Karolina , Ray Jeremy N. , Leebens-Mack Jim 
Published: August 2019

AbstractBackground and AimsCAM photosynthesis is often considered to be a complex trait, requiring orchestration of leaf anatomy and physiology for optimal performance. But the observation of trait correlations is based largely on comparisons between C3and strong CAM species, resulting in a lack of understanding as to how such traits evolve and the level of intraspecific variability for CAM and associated traits.MethodsTo understand intraspecific variation for traits underlying CAM and how these traits might assemble over evolutionary time, we conducted detailed time course physiological screens and measured aspects of leaf anatomy in 24 genotypes of a C3+CAM hybrid species,Yucca gloriosa(Asparagaceae). Comparisons were made toY. gloriosasprogenitor species,Y. filamentosa(C3) andY. aloifolia(CAM).Key resultsBased on gas exchange and measurement of leaf acids,Y. gloriosaappears to use both C3and CAM, and varies across genotypes in the degree to which CAM can be upregulated under drought stress. While correlations between leaf anatomy and physiology exist when testing across all threeYuccaspecies, such correlations break down at the species level inY. gloriosa.ConclusionsThe variation in CAM upregulation inY. gloriosais a result of its relatively recent hybrid origin. The lack of trait correlations between anatomy and physiology withinY. gloriosaindicate that the evolution of CAM, at least initially, can proceed through a wide combination of traits, and more favorable combinations are eventually selected for in strong CAM plants.
Early Tetrapodomorph Biogeography: Controlling for Fossil Record Bias in Macroevolutionary Analyses
Authors: Gardner Jacob D. , Surya Kevin , Organ Chris L. 
Published: August 2019

ABSTRACTThe fossil record provides direct empirical data for understanding macroevolutionary patterns and processes. Inherent biases in the fossil record are well known to confound analyses of this data. Sampling bias proxies have been used as covariates in regression models to test for such biases. Proxies, such as formation count, are associated with paleobiodiversity, but are insufficient for explaining species dispersal owing to a lack of geographic context. Here, we develop a sampling bias proxy that incorporates geographic information and test it with a case study on early tetrapodomorph biogeography. We use recently-developed Bayesian phylogeographic models and a new supertree of early tetrapodomorphs to estimate dispersal rates and ancestral habitat locations. We find strong evidence that geographic sampling bias explains supposed radiations in dispersal rate (potential adaptive radiations). Our study highlights the necessity of accounting for geographic sampling bias in macroevolutionary and phylogenetic analyses and provides an approach to test for its effect.
The critical role of mental imagery in human emotion: insights from Aphantasia
Authors: Wicken Marcus , Keogh Rebecca , Pearson Joel 
Published: August 2019

AbstractOne proposed function of imagery is to make thoughts more emotionally evocative through sensory simulations. Here we report a novel test of this theory utilizing a special population with no visual imagery: Aphantasia. After using multi-method verification of aphantasia, we show that this condition, but not the general population, is associated with a flat-line physiological response to frightening written, but not perceptual scenarios, supporting imagery’s critical role in emotion.
Isolation of an archaeon at the prokaryote-eukaryote interface
Authors: Imachi Hiroyuki , Nobu Masaru K. , Nakahara Nozomi , Morono Yuki , Ogawara Miyuki , Takaki Yoshihiro , Takano Yoshinori , Uematsu Katsuyuki , Ikuta Tetsuro , Ito Motoo , Matsui Yohei , Miyazaki Masayuki , Murata Kazuyoshi , Saito Yumi , Sakai Sanae , Song Chihong , Tasumi Eiji , Yamanaka Yuko , Yamaguchi Takashi , Kamagata Yoichi , Tamaki Hideyuki , Takai Ken 
Published: August 2019

AbstractThe origin of eukaryotes remains enigmatic. Current data suggests that eukaryotes may have risen from an archaeal lineage known as “Asgard archaea”. Despite the eukaryote-like genomic features found in these archaea, the evolutionary transition from archaea to eukaryotes remains unclear due to the lack of cultured representatives and corresponding physiological insight. Here we report the decade-long isolation of a Lokiarchaeota-related Asgard archaeon from deep marine sediment. The archaeon, “CandidatusPrometheoarchaeum syntrophicum strain MK-D1”, is an anaerobic, extremely slow-growing, small cocci (∼550 nm), that degrades amino acids through syntrophy. Although eukaryote-like intracellular complexities have been proposed for Asgard archaea, the isolate has no visible organella-like structure.Ca. P. syntrophicum instead displays morphological complexity – unique long, and often, branching protrusions. Based on cultivation and genomics, we propose an “Entangle-Engulf-Enslave (E3) model” for eukaryogenesis through archaea-alphaproteobacteria symbiosis mediated by the physical complexities and metabolic dependency of the hosting archaeon.