bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide dysregulation of histone acetylation in the Parkinson’s disease brain
Authors: Toker Lilah , Tran Gia T , Sundaresan Janani , Tysnes Ole-Bjørn , Alves Guido , Haugarvoll Kristoffer , Nido Gonzalo S , Dölle Christian , Tzoulis Charalampos 
Published: September 2019

AbstractParkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement of epigenetics in the pathophysiology of PD is mostly unaccounted for. We conducted a histone acetylome-wide association study in PD, using brain tissue from two independent cohorts of cases and controls. Immunoblotting revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. Chromatin immunoprecipitation sequencing (ChIP-seq) further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon, with a strong predilection for genes implicated in the disease, includingSNCA, PARK7, PRKNandMAPT. Integration of the ChIP-seq with transcriptomic data revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Our findings strongly suggest that dysregulation of histone acetylation plays an important role in the pathophysiology of PD and identify novel epigenetic signatures associated with the disease.
Functionally overlapping variants control TB susceptibility in Collaborative Cross mice
Authors: Smith Clare M. , Proulx Megan K. , Lai Rocky , Kiritsy Michael C. , Bell Timothy A , Hock Pablo , Pardo-Manuel de Villena Fernando , Ferris Martin T. , Baker Richard E. , Behar Samuel M. , Sassetti Christopher M. 
Published: September 2019

AbstractHost genetics plays an important role in determining the outcome ofMycobacterium tuberculosis(Mtb) infection. We previously found that Collaborative Cross mouse strains differ in their susceptibility to Mtb, and that the CC042/GeniUnc (CC042) strain suffered from a rapidly progressive disease and failed to produce the protective cytokine, IFNγ, in the lung. Here, we used parallel genetic and immunological approaches to investigate the basis of CC042 susceptibility. Using a population derived from a CC001/Unc (CC001) × CC042 intercross, we mapped four QTL underlying Tuberculosis ImmunoPhenotypes (Tip1-4). These included 2 major effect QTL on Chromosome 7 (Tip1andTip2) that were associated with bacterial burden.Tip2, along withTip3(Chromosome 15) andTip4(Chromosome 16) also correlated with IFNγproduction following infection, whereasTip1appeared to control an IFNγ-independent mechanism of bacterial control. Further immunological characterization revealed that CC042 animals recruited relatively few antigen-specific T cells to the lung and these T cells failed to express the Integrin alpha L (αL; i.e., CD11a), which contributes to T cell activation and migration. These defects could be explained by a CC042 private variant in theItgalgene, which encodes CD11a, and is found within theTip2interval. This 15bp deletion leads to aberrant mRNA splicing and is predicted to result in a truncated protein product. TheItgalCC042genotype was associated with all measured disease traits, indicating that this variant is a major determinant of susceptibility in CC042. The combined effect of functionally distinctTipvariants likely explains the profound susceptibility of CC042 and highlights the multigenic nature of TB control in the Collaborative Cross.Importance statementThe variable outcome ofMycobacterium tuberculosisinfection observed natural populations is difficult to model in genetically homogenous small animal models. The newly-developed Collaborative Cross (CC) represents a reproducible panel of genetically-diverse mice that display a broad range of phenotypic responses to infection. We explored the genetic basis of this variation, focusing on a CC line that is highly susceptible toM. tuberculosisinfection. This study identified multiple quantitative trait loci associated with bacterial control and cytokine production, including one that is caused by a novel loss-of-function mutation in theItgalgene that is necessary for T cell recruitment to the infected lung. These studies verify the multigenic control of mycobacterial disease in the CC panel, identify genetic loci controlling diverse aspects of pathogenesis, and highlight the utility of the CC resource.
A phased, diploid assembly of the Cascade hop (Humulus lupulus) genome reveals patterns of selection and haplotype variation
Authors: Padgitt-Cobb Lillian K. , Kingan Sarah B. , Wells Jackson , Elser Justin , Kronmiller Brent , Moore Daniel , Concepcion Gregory , Peluso Paul , Rank David , Jaiswal Pankaj , Henning John , Hendrix David A. 
Published: September 2019

AbstractHop (Humulus lupulus L. var Lupulus) is a diploid, dioecious plant with a history of cultivation spanning more than one thousand years. Hop cones are valued for their use in brewing, and around the world, hop has been used in traditional medicine to treat a variety of ailments. Efforts to determine how biochemical pathways responsible for desirable traits are regulated have been challenged by the large, repetitive, and heterozygous genome of hop. We present the first report of a haplotype-phased assembly of a large plant genome. Our assembly and annotation of the Cascade cultivar genome is the most extensive to date. PacBio long-read sequences from hop were assembled with FALCON and phased with FALCON-Unzip. Using the diploid assembly to assess haplotype variation, we discovered genes under positive selection enriched for stress-response, growth, and flowering functions. Comparative analysis of haplotypes provides insight into large-scale structural variation and the selective pressures that have driven hop evolution. Previous studies estimated repeat content at around 60%. With improved resolution of long terminal retrotransposons (LTRs) due to long-read sequencing, we found that hop is nearly 78% repetitive. Our quantification of repeat content provides context for the size of the hop genome, and supports the hypothesis of whole genome duplication (WGD), rather than expansion due to LTRs. With our more complete assembly, we have identified a homolog of cannabidiolic acid synthase (CBDAS) that is expressed in multiple tissues. The approaches we developed to analyze a phased, diploid assembly serve to deepen our understanding of the genomic landscape of hop and may have broader applicability to the study of other large, complex genomes.
Evolution of NLR resistance genes with non-canonical N-terminal domains in wild tomato species
Authors: Seong Kyungyong , Seo Eunyoung , Li Meng , Staskawicz Brian 
Published: September 2019

AbstractBackgroundNucleotide-binding and leucine-rich repeat immune receptors (NLRs) are an important component of plant immunity that provides resistance against diverse pathogens. NLRs often exist as large gene families, the members of which display diverse multi-domain architectures (MDAs) and evolve through various mechanisms of duplications and selections.ResultsWe conducted resistance gene enrichment sequencing (RenSeq) with single-molecule real time (SMRT) sequencing of PacBio for 18 accessions in Solanaceae including 15 wild tomatoes. We demonstrate what was previously known as Solanaceae Domain (SD) not only is more diverse in structure and function but also far anciently originated from the most recent common ancestor (MRCA) between Asterids and Amaranthaceae. In tomato, NLRs with the extended N-terminus displayed distinct patterns of evolution based on phylogenetic clades by proliferation, continuous elongation and domain losses.ConclusionsOur study provides high quality gene models of NLRs that can serve as resources for future studies for crop engineering and elucidates greater evolutionary dynamics of the extended NLRs than previously assumed.
Impact of economic crises on offspring health and the developmental origins of health and disease concept
Authors: Sdona Emmanouela , Briana Despina D. , Malamitsi‐Puchner Ariadne 
Published: September 2019

AbstractThere is emerging evidence that economic crises may impact long‐term health. Furthermore, adversity experienced by women and their offspring might be transmitted to next generations. The Developmental Origins of Health and Disease (DOHaD) approach emphasises the importance of early life events for the state of health and risk for disease later in life. In this review, we discuss current evidence on the possible impact of economic crises on offspring health through the DOHaD framework and highlight the importance of critical periods of development for future disease risk. Therefore, successful interventions should prioritise strategies that address early life risk factors.
A “landscapes of power” framework for historical political ecology: The production of cultural hegemony in Araucanía‐Wallmapu
Authors: Escalona Ulloa Miguel , Barton Jonathan R. 
Published: September 2019

The region of Araucania, since its incorporation into the Republic of Chile, has been subject to significant territorial transformations. The Chilean State, supported by economic elites, the political class, and intellectuals have all contributed to the discursive positioning of, and the creation of artefacts in, this regional space. These devices for mobilising power have enabled an appropriation of nature – through natural resource exploitation – and an appropriation of land rights through property titles. The occupation of Araucania from the end of the 19th century was achieved principally through the artefacts of larger settlement consolidation, the railway network, and the building of roads. These were designed and imposed from Santiago through political and administrative channels based on an internal colonialism logic. Conflicts with indigenous Mapuche in Wallmapu (the Mapudungun name for their territory) arose as a consequence of asymmetries of power and this appropriation of space, including expulsion from their land, deforestation, increasing poverty due to restricted access to traditional resources, and epistemic violence through specific constructions of development and the subalterning of indigenous “others.” This historical political ecology not only reveals the expanding frontiers of extractivism and processes of accumulation in favour of national political and economic elites, but more importantly shows how the construction of cultural landscapes became a device for exercising power and justifying appropriation in pursuit of modernity, progress, and development. These landscapes of power evolved over time as different demands were placed on this territory: first as a wheat bowl, and second as forestry plantation. A “landscapes of power” framework is presented in order to work through these constructions of landscape, building on phenomenological and dwelling perspectives in order to focus on the role of cultural hegemony and power relations.
The influence of halokinesis on prograding clinoforms: Insights from the Tiddlybanken Basin, Norwegian Barents Sea
Authors: Rojo Luis Alberto , Marín Dora , Cardozo Nestor , Escalona Alejandro , Koyi Hemin 
Published: September 2019

AbstractAlthough the trajectory and geometry of clinoforms in different types of basins have been described in many studies, few studies discuss the influence of halokinesis on clinoforms in salt‐related basins. In this study, we analyse the Lower Cretaceous clinoforms in the Tiddlybanken Basin, Norwegian Barents Sea to evaluate the impact of salt mobilization on the geometry and trajectory of clinoforms as well as its implications on sediment partitioning. To accomplish this objective, we use a multidisciplinary approach consisting of seismic and well‐interpretation, 3D structural restoration, and forward stratigraphic modelling. The results show that salt mobilization affects prograding clinoforms by: (a) causing lateral variations in progradation rates, resulting in complex palaeogeography, (b) increasing slope angles, which affect the equilibrium of the clinoform profile and can trigger slope‐readjustment processes and (c) producing lateral and temporal variations in accommodation space, leading to different clinoform trajectories, stacking patterns and reservoir distribution along the basin. Forward stratigraphic modelling shows that in salt‐related basins and other tectonically active basins, the isolated use of conventional methods for clinoform analysis might lead to potential interpretation pitfalls such as misinterpretation of trajectories and overestimation of foreset angles, which can have negative consequences for exploration models.
The Sound of Grasp Affordances: Influence of Grasp‐Related Size of Categorized Objects on Vocalization
Authors: Vainio Lari , Vainio Martti , Lipsanen Jari , Ellis Rob 
Published: September 2019

AbstractPrevious research shows that simultaneously executed grasp and vocalization responses are faster when the precision grip is performed with the vowel [i] and the power grip is performed with the vowel [ɑ]. Research also shows that observing an object that is graspable with a precision or power grip can activate the grip congruent with the object. Given the connection between vowel articulation and grasping, this study explores whether grasp‐related size of observed objects can influence not only grasp responses but also vowel pronunciation. The participants had to categorize small and large objects into natural and manufactured categories by pronouncing the vowel [i] or [ɑ]. As predicted, [i] was produced faster when the object's grasp‐related size was congruent with the precision grip while [ɑ] was produced faster when the size was congruent with the power grip (Experiment 1). The effect was not, however, observed when the participants were presented with large objects that are not typically grasped by the power grip (Experiment 2). This study demonstrates that vowel production is systematically influenced by grasp‐related size of a viewed object, supporting the account that sensory‐motor processes related to grasp planning and representing grasp‐related properties of viewed objects interact with articulation processes. The paper discusses these findings in the context of size–sound symbolism, suggesting that mechanisms that transform size‐grasp affordances into corresponding grasp‐ and articulation‐related motor programs might provide a neural basis for size‐sound phenomena that links small objects with closed‐front vowels and large objects with open‐back vowels.
Prevalence of somatic and germline mutations of Fumarate hydratase in uterine leiomyomas from young patients
Authors: Liu Chengbao , Dillon Jessica , Beavis Anna L , Liu Yuehua , Lombardo Kara , Fader Amanda N , Hung Chien‐Fu , Wu Tzyy‐Choou , Vang Russell , Garcia Jairo E , Xing Deyin 
Published: September 2019

AimsHereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome is caused by germline mutations in the Fumarate hydratase (FH) gene. In young women, the syndrome often presents with symptomatic uterine leiomyomas, leading to myomectomy or hysterectomy. In this study, we aimed to investigate the incidence and mutational profiles of FH‐negative leiomyomas from young patients, thus allowing for early identification and triage of syndromic patients for surveillance.Methods and resultsWe evaluated 153 cases of uterine leiomyomas from women aged up to 30 years for loss of FH expression by tissue microarray (TMA)‐based immunohistochemical staining. Mutational analysis of tumours with loss of FH was carried out by polymerase chain reaction (PCR) amplification of 10 exons within the FH gene and subsequent Sanger sequencing. The status of promoter methylation was assessed by bisulphite sequencing. Loss of FH protein expression was detected in seven (4.6%) of 153 tested uterine leiomyomas from young patients. All FH‐negative leiomyomas displayed staghorn vasculature and fibrillary/neurophil‐like cytoplasm. We found that six (86%) of seven FH‐negative tumours detected by immunohistochemistry harboured FH mutations, 50% of which contained germline mutations. In particular, the germline mutational rate in FH gene was 2.0% (three of 153 cases). Bisulphite sequencing analysis failed to detect promoter methylation in any of the seven tumours.ConclusionOur study showed a relatively high rate of FH germline mutation in FH‐negative uterine leiomyomas from patients aged up to 30 years. While genetic mutations confer protein expression loss, epigenetic regulation of the FH gene appears to be unrelated to this phenotype.
Effect of dopant precursors on the optical properties of rare‐earths doped oxyfluoride glass‐ceramics
Authors: Gorni Giulio , Serrano Aida , Bravo David , Castro German R. , Balda Rolindes , Fernández Joaquín , Durán Alicia , Pascual María J. 
Published: September 2019

AbstractThe crystallization of fluoride nanocrystals (NCs) in chemically and mechanically stable aluminosilicate glasses has shown interesting optical properties even for small crystal fractions (10‐15 wt%). When rare‐earth (RE) ions are used as dopants, crystal‐like features can be reproduced and an increase in the emission and/or energy transfer processes, with respect to the starting glasses, is observed. A crucial point for these materials is the study of the local surrounding of RE ions and their incorporation in the NCs. In fact, the effective concentration in the NCs can be much higher than the nominal concentration, up to one order of magnitude or even higher. The knowledge of RE ions incorporation in the NCs permits choosing proper doping levels to optimize both linear and nonlinear optical properties. In this work, transparent oxyfluoride glass‐ceramics with LaF3 NCs, doped with Nd3+ and Er3+ using oxide and fluoride precursors, were prepared using the melt‐quenching method and controlled crystallization. The local surrounding of the RE ions was studied using X‐ray absorption spectroscopy, electron paramagnetic resonance and photoluminiscence. The results show that most RE ions are already in a fluorine‐rich amorphous environment even in the initial glass. The crystallization process provokes the RE ion redistribution and incorporation in the fluoride NCs. The different RE precursors, used as oxides or fluorides, have an influence on the incorporation of the RE in the NCs and, as a consequence, on the final optical properties.
Loss of insulin‐like growth factor‐1 signaling in astrocytes disrupts glutamate handling
Authors: Prabhu Disha , Khan Sariya M. , Blackburn Katherine , Marshall Jessica P. , Ashpole Nicole M. 
Published: September 2019

AbstractInsulin‐like Growth Factor‐1 (IGF‐1) has been studied extensively for its ability to promote neuronal growth and excitability. Declining levels of IGF‐1 have been correlated with impaired learning and memory as well as an increased risk of neurodegenerative diseases. While neuronal regulation by IGF‐1 is well understood, the role of IGF‐1 in influencing astrocyte function requires further exploration. Astrocytes regulate many aspects of the brain microenvironment, including controlling glutamate‐glutamine cycling, which ultimately supports neuronal metabolism, neurotransmission, and protection from over stimulation. In this study, we examined whether IGF‐1 acts through its cognate receptor, IGFR, to alter astrocytic glutamate handling. We utilized both small molecule IGFR inhibitors and Cre‐driven genetic approaches to reduce IGFR in vivo and in cultured rodent astrocytes. When IGFR was knocked out of primary astrocytes derived from igfrf/f mice using AAV5‐CMV‐Cre, significant reductions in glutamate uptake were observed. Similarly, inhibition of IGFR with picropodophyllotoxin for 2 h, as well as 24 h, reduced glutamate uptake in vitro. Mechanistically, short‐term inhibition of IGFR resulted in a significant decrease in glutamate transporter availability on the cell surface, as assessed by biotinylation. Long‐term inhibition of IGFR led to significant reductions in mRNA expression of glutamate transport machinery, as assessed with qPCR. Reduced glutamate transporter mRNA was also observed in the brains of astrocyte‐specific IGFR‐deficient mice, three to four months after knock‐out was induced with tamoxifen. Interestingly, long‐term IGF‐1 inhibition also resulted in an increase in adenosine triphosphate‐stimulated glutamate release, though no change in adenosine triphosphate‐stimulated calcium flux was observed nor were any changes in purinergic receptor protein expression. Together, these data suggest that reduced IGF‐1 signaling will favor an accumulation of extrasynaptic glutamate, which may contribute to neurodegeneration in disease states where IGF‐1 levels are low.
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Cover Image for this issue: doi: 10.1111/jnc.14534.
Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats
Authors: Rana Sabhya , Sieck Gary C. , Mantilla Carlos B. 
Published: September 2019

AbstractThe diaphragm muscle comprises various types of motor units that are recruited in an orderly fashion governed by the intrinsic electrophysiological properties (membrane capacitance as a function of somal surface area) of phrenic motor neurons (PhMNs). Glutamate is the main excitatory neurotransmitter at PhMNs and acts primarily via fast acting AMPA and N‐methyl‐D‐aspartic acid (NMDA) receptors. Differences in receptor expression may also contribute to motor unit recruitment order. We used single cell, multiplex fluorescence in situ hybridization to determine glutamatergic receptor mRNA expression across PhMNs based on their somal surface area. In adult male and female rats (n = 9) PhMNs were retrogradely labeled for analyses (n = 453 neurons). Differences in the total number and density of mRNA transcripts were evident across PhMNs grouped into tertiles according to somal surface area. A ~ 25% higher density of AMPA (Gria2) and NMDA (Grin1) mRNA expression was evident in PhMNs in the lower tertile compared to the upper tertile. These smaller PhMNs likely comprise type S motor units that are recruited first to accomplish lower force, ventilatory behaviors. In contrast, larger PhMNs with lower volume densities of AMPA and NMDA mRNA expression presumably comprise type FInt and FF motor units that are recruited during higher force, expulsive behaviors. Furthermore, there was a significantly higher cytosolic NMDA mRNA expression in small PhMNs suggesting a more important role for NMDA‐mediated glutamatergic neurotransmission at smaller PhMNs. These results are consistent with the observed order of motor unit recruitment and suggest a role for glutamatergic receptors in support of this orderly recruitment.
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Cover Image for this issue: doi: 10.1111/jnc.14747.