bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet, psychosocial stress, and Alzheimer’s disease-related neuroanatomy in female nonhuman primates
Authors: Frye Brett M. , Craft Suzanne , Register Thomas C. , Andrews Rachel N. , Appt Susan E. , Vitolins Mara Z. , Uberseder Beth , Silverstein-Metzler Marnie G. , Chen Haiying , Whitlow Christopher T. , Kim Jeongchul , Barcus Richard A. , Lockhart Samuel N. , Hoscheidt Siobhan , Say Brandon M. , Corbitt Sarah E. , Shively Carol A. 
Published: September 2020

ABSTRACTINTRODUCTIONAssociations between diet, psychosocial stress, and neurodegenerative disease, including Alzheimer’s disease (AD), have been reported, but causal relationships are difficult to determine in human studies.METHODSWe used structural magnetic resonance imaging in a well-validated nonhuman primate model of AD-like neuropathology to examine the longitudinal effects of diet (Mediterranean versus Western) and social subordination stress on brain anatomy, including global volumes, cortical thicknesses and volumes, and twenty individual regions of interest (ROIs).RESULTSWestern diet resulted in greater cortical thicknesses, total brain volumes and gray matter, and diminished cerebrospinal fluid and white matter volumes. Socially stressed subordinates had smaller whole brain volumes but larger ROIs relevant to AD than dominants.DISCUSSIONThe observation of increased size of AD-related brain areas is consistent with similar reports of mid-life volume increases predicting increased AD risk later in life. While the biological mechanisms underlying the findings require future investigation, these observations suggest that Western diet and psychosocial stress instigate pathologic changes that increase risk of AD-associated neuropathologies, whereas Mediterranean diet may protect the brain.RESEARCH IN CONTEXTSystematic review: The authors reviewed the literature with PubMed and Google Scholar and found a number of publications which are cited that suggest that AD pathogenesis begins well before the onset of symptoms.Interpretation: Our findings support the hypothesis that Western diet and psychosocial stress may instigate neuroinflammatory responses that increase risk of later developing AD-like neuropathologies, whereas the structural stasis in the Mediterranean diet group may represent a resilient phenotype.Future directions: The manuscript serves as a critical first step in describing risk and resilient phenotypes during middle age in a nonhuman primate model of AD-like neuropathology. This report lays the groundwork for ongoing efforts to determine whether neuroinflammatory profiles differed across diet and stress groups. Future studies should aim to understand the temporal emergence of functional disparities associated with the changes in brain structure observed here.HIGHLIGHTSGlobal brain volumes changed in response to Western, but not Mediterranean, diet.Western diet increased cortical thickness in multiple regions relevant to AD.Mediterranean diet did not alter cortical thicknesses relevant to AD.Brain regions associated with AD risk differed between low and high stress monkeys.Psychosocial stress may modulate the effects of diet on the brain.
Pair bonding slows epigenetic aging and alters methylation in brains of prairie voles
Authors: Sailer Lindsay L. , Haghani Amin , Zoller Joseph A. , Li Caesar Z. , Ophir Alexander G. , Horvath Steve 
Published: September 2020

ABSTRACTThe quality of romantic relationships can be predictive of health consequences related to aging. DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how pair bonding impacts aging. Prairie voles (Microtus ochrogaster) have emerged as a model to study social attachment among adult pairs. Here we describe DNA methylation-based estimators of age for prairie voles based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for voles was trained on 3 tissue sources (ear, liver, and samples of brain tissue from within the pair bonding circuit). A novel dual species human-vole clock accurately measured relative age defined as the ratio of chronological age to maximum age. According to the human-vole clock of relative age, sexually inexperienced voles exhibit accelerated epigenetic aging in brain tissue (p= 0.02) when compared to pair bonded animals of the same chronological age. Epigenome wide association studies identified CpGs in four genes that were strongly associated with pair bonding across the three tissue types (brain, ear, and liver):Hnrnph1, Fancl, Fam13b, andFzd1. Further, four CpGs (near theBmp4exon,Eif4g23 prime UTR,Robo1exon, andNfat5intron) exhibited a convergent methylation change between pair bonding and aging. This study describes highly accurate DNA methylation-based estimators of age in prairie voles and provides evidence that pair bonding status modulates the methylome.
Glioma stem cells invasive phenotype at optimal stiffness is driven by MGAT5 dependent mechanosensing
Authors: Marhuenda Emilie , Fabre Christine , Zhang Cunjie , Martin-Fernandez Martà , Iskratsch Thomas , Saleh Ali , Bauchet Luc , Cambedouzou Julien , Hugnot Jean-Philippe , Duffau Hugues , Dennis James W. , Cornu David , Bakalara Norbert 
Published: September 2020

AbstractGlioblastomas stem-like cells (GSCs) by invading the brain parenchyma escape resection and radiotherapy. GSC invasion is associated with altered N-glycosylation pattern of integrins and other transmembrane proteins resulting in changed mechanosensing but details are elusive. Because the tumour microenvironment has an increased stiffness we studied the interaction between matrix stiffness, N-glycosylation and GSC migration. To mimic the fibrillar microenvironments, we designed 3D-ex-polyacrylonitrile nanofibers scaffolds (NFS) with adjustable stiffnesses by loading multiwall carbon nanotubes (MWCNT). We found that migration of GSCs was maximum at 166 kPa. Migration rate was correlated with cell shape, expression of focal adhesion (FA), Epithelial to Mesenchymal Transition (EMT) proteins and (β1,6) branched N-glycan binding, galectin-3. Mutation of MGAT5 in GSC inhibited N-glycans (β1–6) branching, suppressed the stiffness dependence of FA and EMT protein expression as well as migration on 166kPa NFS; underpinning the role of multibranched N-glycans as a critical regulator of mechanotransduction by GSC.Significance StatementDuring pathological processes in which cell migration is involved, cells undergo important functional changes in protein glycosylation and are responsive to environmental mechanical modifications. We addressed the question of the glycosylation role in mechanotransduction regulation of glioma stem cells. We created a bio-inspired 3D nanofiber scaffold (NFS) loaded with multiwall carbon nanotubes to obtain NFS of adjustable stiffness in physiological and pathological ranges. We highlighted and described a mechanism of fine mechanotransduction leading to a nonlinear migration response regarding to 3D microenvironment stiffness values. We show the importance to develop mechano-pharmacology as new therapeutic target by demonstrating the relationship existing between environmental stiffness and multibranched N-glycans catalysed by the MGAT5 enzyme to optimize directed migration.
Aneuploidy-driven genome instability triggers resistance to chemotherapy
Authors: Ippolito Marica Rosaria , Martis Valentino , Hong Christy , Wardenaar René , Zerbib Johanna , Spierings Diana C.J. , Ben-David Uri , Foijer Floris , Santaguida Stefano 
Published: September 2020

AbstractMitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage, together with mutational burden, might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven genome instability and chemoresistance and might explain why some chemotherapies fail to succeed.
Prenatal Methadone Exposure Disrupts Behavioral Development and Alters Motor Neuron Intrinsic Properties and Local Circuitry
Authors: Grecco Gregory G. , Mork Briana , Huang Jui Yen , Metzger Corinne E. , Haggerty David L. , Reeves Kaitlin C. , Gao Yong , Hoffman Hunter , Katner Simon N. , Masters Andrea R. , Morris Cameron W. , Newell Erin A. , Engleman Eric A. , Baucum Anthony J. , Kim Jieun , Yamamoto Bryan K. , Allen Matthew R. , Wu Yu-Chien , Lu Hui-Chen , Sheets Patrick L. , Atwood Brady K. 
Published: September 2020

ABSTRACTDespite the rising prevalence of methadone treatment in pregnant women with opioid use disorder, the effects of methadone on neurobehavioral development remain unclear. We developed a translational mouse model of prenatal methadone exposure (PME) that resembles the typical pattern of opioid use by pregnant women who first use oxycodone then switch to methadone maintenance pharmacotherapy, and subsequently become pregnant while maintained on methadone. We investigated the effects of PME on physical development, sensorimotor behavior, and motor neuron properties using a multidisciplinary approach of physical, biochemical, and behavioral assessments along with brain slice electrophysiology and in vivo magnetic resonance imaging. PME produced substantial impairments in offspring physical growth, activity in an open field, and sensorimotor milestone acquisition which were associated with alterations in motor neuron functioning and connectivity. The present study adds to the limited work examining PME by providing a comprehensive, translationally relevant characterization of how PME disrupts offspring development.
Evolution of the canonical sex chromosomes of the guppy and its relatives
Authors: Kirkpatrick M. , Sardell J.M. , Pinto B. J. , Dixon G. , Peichel C. L. , Schartl M. 
Published: September 2020

AbstractThe sex chromosomes of the guppy,Poecilia reticulata, and its close relatives are of particular interest: they are much younger than the highly degenerate sex chromosomes of model systems such as mammals andDrosophila melanogaster, and they carry many of the genes responsible for the males’ dramatic coloration. Over the last decade, several studies have analyzed these sex chromosomes using a variety of approaches including sequencing genomes and transcriptomes, cytology, and linkage mapping. Conflicting conclusions have emerged, in particular concerning the history of the sex chromosomes and the evolution of suppressed recombination between the X and Y. Here we address these controversies by reviewing the evidence and reanalyzing data. We find no support for a nonrecombining sex determining region (SDR) or evolutionary strata inP. reticulata. Further, we find that the evidence most strongly support the hypothesis that the SDRs ofP. pictaandP. wingeievolved independently after those lineages diverged. We identify possible causes of conflicting results in previous studies and suggest best practices going forward.
The role of pregnancy-specific glycoproteins on trophoblast motility in three-dimensional gelatin hydrogels
Authors: Zambuto Samantha G. , Rattila Shemona , Dveksler Gabriela , Harley Brendan A.C. 
Published: September 2020

SUMMARYTrophoblast invasion is a complex biological process necessary for establishment of pregnancy; however, much remains unknown regarding what signaling factors coordinate the extent of invasion. Pregnancy-specific glycoproteins (PSGs) are some of the most abundant circulating trophoblastic proteins in maternal blood during human pregnancy, with maternal serum concentrations rising to as high as 200-400 μg/mL at term. Here, we employ three-dimensional (3D) trophoblast motility assays consisting of trophoblast spheroids encapsulated in 3D gelatin hydrogels to quantify trophoblast outgrowth area, viability, and cytotoxicity in the presence of PSG1 and PSG9 as well as epidermal growth factor and Nodal. We show PSG9 reduces trophoblast motility whereas PSG1 increases motility. Further, we assess bulk nascent protein production by encapsulated spheroids to highlight the potential of this approach to assess trophoblast response (motility, remodeling) to soluble factors and extracellular matrix cues. Such models provide an important platform to develop a deeper understanding of early pregnancy.Graphical Abstract
Effects of species traits and ecosystem characteristics on species detection by eDNA metabarcoding in lake fish communities
Authors: Doi Hideyuki , Matsuoka Shunsuke , Matsuzaki Shin-ichiro S. , Nagano Mariko , Sato Hirotoshi , Yamanaka Hiroki , Matsuhashi Saeko , Yamamoto Satoshi , Minamoto Toshifumi , Araki Hitoshi , Ikeda Kousuke , Kato Atsuko , Kumei Kouichi , Maki Nobutaka , Mitsuzuka Takashi , Takahara Teruhiko , Toki Kimihito , Ueda Natsuki , Watanabe Takeshi , Yamazoe Kanji , Miya Masaki 
Published: September 2020

AbstractAlthough environmental DNA (eDNA) metabarcoding is acknowledged to be an exceptionally useful and powerful tool for monitoring surveys, it has limited applicability, particularly for nationwide surveys. To evaluate the performance of eDNA metabarcoding in broad-scale monitoring, we examined the effects of species ecological/biological traits and ecosystem characteristics on species detection rates and the consequences for community analysis. We conducted eDNA metabarcoding on fish communities in 18 Japanese lakes on a country-wide scale. By comparing species records, we found that certain species traits, including body size, body shape, saltwater tolerance, and habitat preferences, influenced eDNA detection. We also found that the proportion of species detected decreased significantly with an increase in lake surface area, owing to an ecosystem-size effect on species detection. We conclude that species traits, including habitat preferences and body size, and ecosystem size should be taken into consideration when assessing the performance of eDNA metabarcoding in broad-scale monitoring.
Controlled Release of Anti-inflammatory and Pro-angiogenic Factors from Macroporous Scaffolds
Authors: Liang Jia-Pu , Accolla Robert P. , Jiang Kaiyuan , Li Ying , Stabler Cherie L. 
Published: September 2020

AbstractThe simultaneous local delivery of anti-inflammatory and pro-angiogenic agents via biomaterial scaffolds presents a promising method for improving the engraftment of tissue-engineered implants while avoiding potentially detrimental systemic delivery. In this study, PDMS microbeads were loaded with either anti-inflammatory dexamethasone (Dex) or pro-angiogenic 17β-estradiol (E2) and subsequently integrated into a single macroporous scaffold to create a controlled, dual drug-delivery platform. Compared to a standard monolithic drug dispersion scaffold, macroporous scaffolds containing drug-loaded microbeads exhibited reduced initial burst release and increased the durability of drug release for both agents. Incubation of scaffolds with LPS-stimulated M1 macrophages found that Dex suppressed the production of pro-inflammatory and pro-angiogenic factors, when compared to drug-free control scaffolds; however, the co-incubation of macrophages with Dex and E2 scaffolds restored their pro-angiogenic features. Following implantation, Dex-loaded microbead scaffolds (Dex-µBS) suppressed host cell infiltration and integration, when compared to controls. In contrast, the co-delivery of dexamethasone with estrogen from the microbead scaffold (Dex/E2-µBS) dampened overall host cell infiltration but restored graft vascularization. These results demonstrate the utility of a microbead scaffold approach for the controlled, tailored, and local release of multiple drugs from an open framework implant. It further highlights the complementary impacts of local Dex and E2 delivery to direct the healthy integration of implants, which has broad applications to the field of tissue engineering and regenerative medicine.
MogR is a ubiquitous transcriptional repressor affecting motility, biofilm formation and virulence inBacillus thuringiensis
Authors: Smith Veronika , Josefsen Malin , Lindbäck Toril , Hegna Ida K. , Finke Sarah , Tourasse Nicolas J. , Nielsen-LeRoux Christina , Økstad Ole Andreas , Fagerlund Annette 
Published: September 2020

AbstractFlagellar motility is considered an important virulence factor in different pathogenic bacteria. InListeria monocytogenesthe transcriptional repressor MogR regulates motility in a temperature-dependent manner, directly repressing flagellar- and chemotaxis genes. The only other bacteria known to carry amogRhomolog are members of theBacillus cereusgroup, which includes motile species such asB. cereusandBacillus thuringiensisas well as the non-motile speciesBacillus anthracis, Bacillus mycoidesandBacillus pseudomycoides. Furthermore, the main motility locus inB. cereusgroup bacteria, carrying the genes for flagellar synthesis, appears to be more closely related toL. monocytogenesthan toBacillus subtilis,which belongs to a separate phylogenetic group of Bacilli and does not carry amogRortholog. Here, we show that inB. thuringiensis, MogR overexpression results in non-motile cells devoid of flagella. Global gene expression profiling showed that 110 genes were differentially regulated by MogR overexpression, including flagellar motility genes, but also genes associated with virulence, stress response and biofilm lifestyle. Accordingly, phenotypic assays showed that MogR also affects cytotoxicity and biofilm formation inB. thuringiensis. Overexpression of a MogR variant mutated in two amino acids within the putative DNA binding domain restored phenotypes to those of an empty vector control. In accordance, introduction of these mutations resulted in complete loss in MogR binding to its candidate flagellar locus target sitein vitro. In contrast toL. monocytogenes, MogR appears to be regulated in a growth-phase dependent and temperature-independent manner inB. thuringiensis407. Interestingly,mogRwas found to be conserved also in non-motileB. cereusgroup species such asB. mycoidesandB. pseudomycoides, which both carry major gene deletions in the flagellar motility locus and where inB. pseudomycoides mogRis the only gene retained. Furthermore,mogRis expressed in non-motileB. anthracis. Altogether this provides indications of an expanded set of functions for MogR inB. cereusgroup species, beyond motility regulation. In conclusion, MogR constitutes a novelB. thuringiensispleiotropic transcriptional regulator, acting as a repressor of motility genes, and affecting the expression of a variety of additional genes involved in biofilm formation and virulence.
Reconstructing the history and biological consequences of a plant invasion on the Galápagos islands
Authors: Gibson Matthew J.S. , de Lourdes Torres María , Brandvain Yaniv , Moyle Leonie C. 
Published: September 2020

AbstractThe introduction of non-native species into new habitats is one of the foremost risks to global biodiversity. Here, we evaluate a recent invasion of wild tomato (Solanum pimpinellifolium) onto the Galápagos islands from a population genomic perspective, using a large panel of novel collections from the archipelago as well as historical accessions from mainland Ecuador and Peru. We infer a recent invasion ofS. pimpinellifoliumon the islands, largely the result of a single event from central Ecuador which, despite its recency, has rapidly spread onto several islands in the Galápagos. By reconstructing patterns of local ancestry throughout the genomes of invasive plants, we uncover evidence for recent hybridization and introgression betweenS. pimpinellifoliumand the closely related endemic speciesSolanum cheesmaniae. Two large introgressed regions overlap with known fruit color loci involved in carotenoid biosynthesis. Instead of red fruits, admixed individuals with endemic haplotypes at these loci have orange fruit colors that are typically characteristic of the endemic species. We therefore infer that introgression explains the observed trait convergence. Moreover, we infer roles for two independent loci in driving this pattern, and a likely history of selection favoring the repeated phenotypic transition from red to orange fruits. Together, our data reconstruct a complex history of invasion, expansion, and gene flow among wild tomatoes on the Galápagos islands. These findings provide critical data on the evolutionary importance of hybridization during colonization and its role in influencing conservation outcomes.Significance StatementThe isolation and unique diversity of the Galápagos Islands provide numerous natural experiments that have enriched our understanding of evolutionary biology. Here we use population genomic sequencing to reconstruct the timing, path, and consequences of a biological invasion by wild tomato onto the Galápagos. We infer that invasive populations originated from a recent human-mediated migration event from central Ecuador. Our data also indicate that invasive populations are hybridizing with endemic populations, and that this has led to some invasive individuals adopting both fruit color genes and the fruit color characteristic of the endemic island species. Our results demonstrate how hybridization can shape patterns of trait evolution over very short time scales, and characterize genetic factors underlying invasive success.
Regulation of retinal neurogenesis by somatostatin signaling
Authors: Weir Kurt , Kim Dong Won , Blackshaw Seth 
Published: September 2020

AbstractNeuropeptides have been reported to regulate progenitor proliferation and neurogenesis in the central nervous system. However, these studies have typically been conducted using pharmacological agents inex vivopreparations, andin vivoevidence for their developmental function is generally lacking. Recent scRNA-Seq studies have identified multiple neuropeptides and their receptors as being selectively expressed in neurogenic progenitors of the embryonic mouse and human retina. This includes Sstr2, whose ligand somatostatin is transiently expressed by immature retinal ganglion cells. By analyzing retinal explants treated with selective ligands that target these receptors, we found that Sstr2-dependent somatostatin signaling induces a dose-dependent inhibition of photoreceptor generation while increasing the relative fraction of primary progenitor cells. These effects were confirmed by scRNA-Seq analysis of retinal explants and abolished inSstr2-deficient retinas. Although no changes in the relative fraction of primary progenitors or photoreceptor precursors were observed inSstr2-deficient retinasin vivo, scRNA-Seq analysis demonstrated accelerated differentiation of neurogenic progenitors. We conclude that Sstr2 signaling may act to negatively regulate retinal neurogenesis in combination with other retinal ganglion cell-derived secreted factors such as Shh, althoughin vivoSstr2 is dispensable for normal retinal development.