bluuebunny/crossref_metadata_2025_split huggingface dataset:
Music Reveals Medial Prefrontal Cortex Sensitive Period in Childhood
Authors: Gabard-Durnam Laurel J. , Hensch Takao K. , Tottenham Nim 
Published: September 2018

AbstractAn outstanding issue in our understanding of human brain development is whether sensitive periods exist for higher-order processes (e.g., emotion regulation) that depend on the prefrontal cortex. Evidence from rodent models suggests that there is a sensitive period before puberty when acoustic stimuli, like music, shape medial prefrontal cortex (mPFC) responses that regulate affect in the context of acute stress in adulthood. The present study examined whether a homologous sensitive period for the mPFC occurs during human childhood. In the context of acute stress, adult behavioral preferences were observed only for music experienced during childhood, not preschool or adolescent periods. Childhood music increased mPFC activation and modulated connectivity with the amygdala, which was associated with enhanced emotion regulation and lowered autonomic arousal. Moreover, the timing of this sensitive period could be moved by early-life stress. These findings indicate that childhood is a sensitive period for mPFC encoding of regulatory stimuli.Sensitive periods are developmental moments of heightened neuroplasticity when experiences shape brain function and behavior with lasting effects (1). They are fundamental to human cortical ontogeny, and yet, the timing and nature of sensitive periods for human prefrontal cortex functions remain unknown (2–8). In the rodent, Yang and colleagues have shown that the medial prefrontal cortex (mPFC) exhibits a sensitive period during the prepubertal juvenile period, with heightened responsivity to complex auditory stimuli (i.e., music) (9). Specifically, initial exposure to music during the open (juvenile) sensitive period or a pharmacologically re-opened sensitive period in adulthood was followed by that music uniquely producing a behavioral preference in adulthood, increasing mPFC activity, and reducing anxiety-like behavior. This finding and others converging on the same prepubertal period of plasticity in the rodent (9, 10) may have important implications for human development; the complementary prepubertal period in humans (i.e., school-age childhood) also exhibits developmentally-unique mPFC circuitry phenotypes (11–17) that make childhood a strong candidate for a human mPFC sensitive period. Here, we used Billboard music chart data to identify age-specific exposures to pop songs to test whether music shapes human mPFC responses during a childhood sensitive period as in the rodent. To parallel the approach used in the rodent, we examined whether (i) music experienced during childhood uniquely produced a behavioral preference under stress, (ii) childhood music enhanced emotion regulation behaviorally and physiologically, (iii) mPFC activity was enhanced by childhood music, and mPFC circuitry mediated emotion regulation benefits of childhood music, and (iv) whether the timing of this putative sensitive period could be shifted by early adversity.
Extraction-Free Whole Transcriptome Gene Expression Analysis of FFPE Sections and Histology-Directed Subareas of Tissue
Authors: Trejo Christy L , Babić Miloš , Imler Elliot , Gonzalez Migdalia , Bibikov Sergei , Shepard Peter J , VanSteenhouse Harper C , Yeakley Joanne M , Seligmann Bruce E 
Published: September 2018

AbstractWe describe the use of a ligation-based targeted whole transcriptome expression profiling assay, TempO-Seq™, to profile formalin-fixed paraffin-embedded (FFPE) tissue, including H&E stained FFPE tissue, by directly lysing tissue scraped from slides without extracting RNA or converting the RNA to cDNA. The correlation of measured gene expression changes in unfixed and fixed samples using blocks prepared from a pellet of a single cell type was R2 = 0.97, demonstrating that no significant artifacts were introduced by fixation. Fixed and fresh samples prepared in an equivalent manner produced comparable sequencing depth results (+/-20%), with similar %CV (11.5 and 12.7%, respectively), indicating no significant loss of measurable RNA due to fixation. The sensitivity of the TempO-Seq assay was the same whether the tissue section was fixed or not. The assay performance was equivalent for human, mouse, or rat whole transcriptome. The results from 10 mm2 and 2 mm2 areas of tissue obtained from 5 μm thick sections were equivalent, thus demonstrating high sensitivity and ability to profile focal areas of histology within a section. Replicate reproducibility of separate areas of tissue ranged from R2 = 0.83 (lung) to 0.96 (liver) depending on the tissue type, with an average correlation of R2 = 0.90 across nine tissue types. The average %CVs were 16.8% for genes expressed at greater than 200 counts, and 20.3% for genes greater than 50 counts. Tissue specific differences in gene expression were identified and agreed with the literature. There was negligible impact on assay performance using FFPE tissues that had been archived for up to 30 years. Similarly, there was negligible impact of H&E staining, facilitating accurate visualization for scraping and assay of small focal areas of specific histology within a section.
Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age
Authors: Muñoz Maniega Susana , Meijboom Rozanna , Chappell Francesca M. , Valdés Hernández Maria C. , Starr John M. , Bastin Mark E. , Deary Ian J. , Wardlaw Joanna M. 
Published: September 2018

AbstractBrain white matter hyperintensities (WMH), common in older adults, may contribute to cortical disconnection and cognitive dysfunction. The presence of WMH within white matter (WM) tracts indicates underlying microstructural WM changes that may also affect the normal-appearing WM (NAWM) of a tract. We performed an exploratory study using diffusion magnetic resonance imaging of 52 healthy participants from the Lothian Birth Cohort 1936 (age 72.2 ± 0.7 years) selected to include a range of WMH burden, to quantify microstructural changes of tracts intersecting WMH. We reconstructed tracts using automated tractography and identified intersections with WMH. Tissue volumes and water diffusion tensor parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were established for tract-WMH and tract-NAWM. MD and FA were also measured for tract-NAWM at 2 mm incremental distances from the tract-WMH edge, and from the edge of nearby, non-intersecting, WMH. We observed microstructural changes in tract-WMH suggestive of tissue damage. Tract-NAWM also showed a spatial gradient of FA and MD abnormalities, which diminished with distance from the tract-WMH. Nearby WMH lesions, not directly crossed by the tract, also affected tract microstructure with a similar pattern. Additionally, both FA and MD changes in tract-NAWM were predicted by FA and MD changes respectively in tract-WMH. FA was also predicted by tract-WMH overlap volume, whereas MD was better predicted by whole-brain WMH load. These results suggest that tract-NAWM microstructure is affected by the pathological process underlying WMH, when WMH are either within or near to the tract. The changes in NAWM tract tissue may indicate future lesion progression and may play an important role in cognitive ageing.
Translation of upstream open reading frames in a model of neuronal differentiation
Authors: Rodriguez C.M. , Chun S.Y. , Mills R.E. , Tod P.K. 
Published: September 2018

AbstractUpstream open reading frames (uORFs) initiate translation within mRNA 5’ leaders, and have the potential to alter main coding sequence (CDS) translation on transcripts in which they reside. Ribosome profiling (RP) studies suggest that translating ribosomes are pervasive within 5’ leaders across model systems. However, the significance of this observation remains unclear. To explore a role for uORF usage in neuronal differentiation, we performed RP on undifferentiated and differentiated human neuroblastoma cells. Using a spectral coherence algorithm (SPECtre), we identify 4,954 uORFs across 31% of all neuroblastoma transcripts. These uORFs predominantly utilize non-AUG initiation codons and exhibit translational efficiencies (TE) comparable to annotated coding regions. Usage of both AUG initiated uORFs and a conserved and consistently translated subset of non-AUG initiated uORFs correlates with repressed CDS translation. Ribosomal protein transcripts are enriched in uORFs, and select uORFs on such transcripts were validated for expression. With neuronal differentiation, we observed an overall positive correlation between translational shifts in uORF/CDS pairs. However, a subset of transcripts exhibit inverse shifts in translation of uORF/CDS pairs. These uORFs are enriched in AUG initiation sites, non-overlapping, and shorter in length.Cumulatively, CDSs downstream of uORFs characterized by persistent translation show smaller shifts in TE with neuronal differentiation relative to CDSs without a predicted uORF, suggesting that fluctuations in CDS translation are buffered by uORF translation. In sum, this work provides insights into the dynamic relationships and potential regulatory functions of uORF/CDS pairs in a model of neuronal differentiation.
A data-driven approach to the automated mapping of functional brain topographies across species
Authors: Pauli Wolfgang M. 
Published: September 2018

AbstractBehavioral neuroscience has made great strides in developing animal models of human behavior and psychiatric disorders. Animal models allow for the formulation of hypotheses regarding the mechanisms underlying psychiatric disorders, and the opportunity to test these hypotheses using procedures that are too invasive for human participants. However, recent scientific reviews have highlighted the low success rate of translating results from animal models into clinical interventions in humans. A potential roadblock is that bidirectional functional mappings between the human and rodent brain are incomplete. To narrow this gap, we created a framework, Neurobabel, for performing large-scale automated synthesis of human neuroimaging data and behavioral neuroscience data. By leveraging the semantics of how researchers within each field describe their studies, this framework enables region to region mapping of brain regions across species, as well as cross-species mapping of psychological functions. As a proof of concept, we utilize the framework to create a functional cross-species mapping between the amygdala and hippocampus for fear-related and spatial memories, respectively. We then proceed to address two open questions in the field: (1) Do rodents have a dorsolateral prefrontal cortex? (2) Which human brain region corresponds to the rodent prelimbic cortex?
Genes of the Pig, Sus scrofa, reconstructed with EvidentialGene
Authors: Gilbert Donald G. 
Published: September 2018

AbstractThe pig is a well-studied model animal of biomedical and agricultural importance. Genes of this species, Sus scrofa, are known from experiments and predictions, and collected at the NCBI Reference Sequence database section. Gene reconstruction from transcribed gene evidence of RNA-seq now can accurately and completely reproduce the biological gene sets of animals and plants. Such a gene set for the pig is reported here, including human orthologs missing from current NCBI and Ensembl reference pig gene sets, additional alternate transcripts, and other improvements. Methodology for accurate and complete gene set reconstruction from RNA is used: the automated SRA2Genes pipeline of EvidentialGene project.
Tracktor: image-based automated tracking of animal movement and behaviour
Authors: Sridhar Vivek Hari , Roche Dominique G. , Gingins Simon 
Published: September 2018

Abstract1. Automated movement tracking is essential for high-throughput quantitative analyses of the behaviour and kinematics of organisms. Automated tracking also improves replicability by avoiding observer biases and allowing reproducible workflows. However, few automated tracking programs exist that are open access, open source, and capable of tracking unmarked organisms in noisy environments.2. Tracktor is an image-based tracking freeware designed to perform single-object tracking in noisy environments, or multi-object tracking in uniform environments while maintaining individual identities. Tracktor is code-based but requires no coding skills other than the user being able to specify tracking parameters in a designated location, much like in a graphical user interface (GUI). The installation and use of the software is fully detailed in a user manual.3. Through four examples of common tracking problems, we show that Tracktor is able to track a variety of animals in diverse conditions. The main strengths of Tracktor lie in its ability to track single individuals under noisy conditions (e.g. when the object shape is distorted), its robustness to perturbations (e.g. changes in lighting conditions during the experiment), and its capacity to track multiple individuals while maintaining their identities. Additionally, summary statistics and plots allow measuring and visualizing common metrics used in the analysis of animal movement (e.g. cumulative distance, speed, acceleration, activity, time spent in specific areas, distance to neighbour, etc.).4. Tracktor is a versatile, reliable, easy-to-use automated tracking software that is compatible with all operating systems and provides many features not available in other existing freeware. Access Tracktor and the complete user manual here: https://github.com/vivekhsridhar/tracktor
Active control of arousal by a locus coeruleus GABAergic circuit
Authors: Breton-Provencher Vincent , Sur Mriganka 
Published: September 2018

AbstractArousal and novelty responses linked to locus coeruleus noradrenergic (LC-NA) activity affect cognitive performance. However, the mechanisms that control modes of LC-NA activity remain unknown. Here, we reveal a local population of GABAergic neurons (LC-GABA) capable of modulating LC-NA activity and arousal. Monosynaptic retrograde virus tracing shows that inputs to LC-GABA and LC-NA neurons arise from similar regions, though a few regions provide differential inputs to one subtype over the other. Recordings in the LC demonstrate two modes of LC-GABA responses whereby spiking is either correlated or broadly anti-correlated with LC-NA responses, reflecting anatomically similar and functionally coincident inputs, or differential and non-coincident inputs, to LC-NA and LC-GABA neurons. Coincident inputs control the gain of phasic LC-NA mediated novelty responses, while non-coincident inputs, such as from the prefrontal cortex to LC, alter overall levels of LC-NA responses without affecting response gain. These findings demonstrate distinct modes by which an inhibitory LC circuit regulates the gain and tone of arousal in the brain.
Cross-talk between the receptor tyrosine kinases AXL and ERBB3 regulates invadopodia formation in melanoma cells
Authors: Revach Or-Yam , Sandler Oded , Samuels Yardena , Geiger Benjamin 
Published: September 2018

AbstractThe invasive phenotype of metastatic cancer cells is accompanied by the formation of actin-rich invadopodia, which adhere to the extracellular matrix, and degrade it. In this study, we explored the role of the tyrosine kinome in the formation of invadopodia in metastatic melanoma cells. Using a microscopy-based siRNA screen, we identified novel invadopodia regulators, the knock-down of which either suppresses (e.g., TYK2, IGFR1, ERBB3, TYRO3, FES, ALK, PTK7) or enhances invadopodia formation and function (e.g., ABL2, AXL, CSK). Particularly intriguing was the discovery that the receptor tyrosine kinase AXL displays a dual regulatory function, manifested by enhancement of invadopodia function upon knock-down or long-term inhibition, as well as following its over-expression. We show here that this apparent contradiction may be attributed to the capacity of AXL to directly stimulate invadopodia; yet its suppression up-regulates the ERBB3 signaling pathway, which consequently activates core invadopodia regulators, and greatly enhances invadopodia function. Bioinformatic analysis of multiple melanoma cells points to an inverse expression pattern of AXL and ERBB3, with the apparent association of high-AXL melanomas, with high expression of invadopodia components and an invasive phenotype. The relevance of these results to melanoma metastasis in vivo, and to potential anti-invasion therapy, is discussed.
Macaque dorsal premotor cortex exhibits decision-related activity only when specific stimulus-response associations are known
Authors: Wang Megan , Montanède Christéva , Chandrasekaran Chandramouli , Peixoto Diogo , Shenoy Krishna V. , Kalaska John F. 
Published: September 2018

SummaryHow deliberation on sensory cues and action selection interact in decision-related brain areas is still not well understood. Here, monkeys reached to one of two targets, whose colors alternated randomly between trials, by discriminating the dominant color of a checkerboard cue composed of different numbers of squares of the two target colors in different trials. In a “Targets First” task the colored targets appeared first, followed by the checkerboard; in a “Checkerboard First” task, this order was reversed. After both cues appeared in both tasks, responses of dorsal premotor cortex (PMd) neurons covaried with action choices, strength of evidence for action choices, and RTs--- hallmarks of decision-related activity. However, very few neurons were modulated by checkerboard color composition or the color of the chosen target, even in the Checkerboard First task. These findings implicate PMd in the action-selection but not the perceptual components of the decision-making process in these tasks.
Genome-wide selection footprints and deleterious variations in young Asian allotetraploid rapeseed
Authors: Zou Jun , Mao Lingfeng , Qiu Jie , Wang Meng , He Zhesi , Jia Lei , Wu Dongya , Huang Yongji , Chen Meihong , Shen Yifei , Shen Enhui , Li Ruiyuan , Hu Dandan , Wang Kai , Shi Lei , Ye Chuyu , Bancroft Ian , King Graham J , Meng Jinling , Fan Longjiang 
Published: September 2018

SummaryBrassica napus (AACC, 2n=38), is an important oilseed crop grown worldwide. However, little is known about the population evolution of this species, the genomic difference between its major genetic clusters, such as European and Asian rapeseed, and impacts of historical large-sale introgression events in this young tetraploid. In this study, we reported the de novo assembly of the genome sequences of an Asian rapeseed (B. napus), Ningyou 7 and its four progenitors and carried out de novo assembly-based comparison, pedigree and population analysis with other available genomic data from diverse European and Asian cultivars. Our results showed that Asian rapeseed originally derived from European rapeseed, but it had subsequently significantly diverged, with rapid genome differentiation after intensive local breeding selection. The first historical introgression of B. rapa dramatically broadened the allelic pool of Asian B. napus, but decreased their deleterious variations. The secondary historical introgression of European rapeseed (canola-quality) has reshaped Asian rapeseed into two groups, accompanied by an increase in genetic load. This study demonstrates distinctive genomic footprints by recent intra- and inter-species introgression events for local adaptation, and provide novel insights for understanding the rapid genome evolution of a young allopolyploid crop.
Evidence of functional long-range Wnt/Wg in the developingDrosophilawing epithelium
Authors: Chaudhary Varun , Boutros Michael 
Published: September 2018

SUMMARYWnts are secreted proteins that regulate cell fate specification during development of all metazoans. Wnt proteins were proposed to spread over several cell diameters to activate signalling directly at a distance. In theDrosophilawing epithelium, an extracellular gradient of Wingless (Wg, the homolog of Wnt1) was observed extending over several cells away from producing cells. However, it was also recently shown that a membrane-tethered Neurotactin-Wg fusion protein (NRT-Wg) can rescue the loss-of endogenous Wg, leading to proper patterning of the wing. Therefore, whether Wg spreading is required for correct tissue patterning during development remains controversial and the functional range of wild-type Wg is unclear. Here, by capturing secreted Wg on distally located cells we show that the Wg gradient acts directly up to eleven cell distances. Cells located outside the reach of extracellular Wg depend on the Frizzled2 receptor to maintain target gene expression. We find that NRT-Wg is not restricted to the producing cells and propose that it can rescue signalling defects by perdurance in the receiving cells. These results provide insight into the mechanisms by which Wnt proteins mediate patterning of a rapidly growing tissue.
Effects of aging on liver microcirculatory function and sinusoidal phenotype
Authors: Maeso‐Díaz Raquel , Ortega‐Ribera Martí , Fernández‐Iglesias Anabel , Hide Diana , Muñoz Leticia , Hessheimer Amelia J. , Vila Sergi , Francés Rubén , Fondevila Constantino , Albillos Agustín , Peralta Carmen , Bosch Jaime , Tacke Frank , Cogger Victoria C. , Gracia‐Sancho Jordi 
Published: September 2018

AbstractThe socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.
Vitamin D receptor interacts with NLRP3 to restrict the allergic response
Authors: Huang H , Hong J-Y , Wu Y-J , Wang E-Y , Liu Z-Q , Cheng B-H , Mei L , Liu Z-G , Yang P-C , Zheng P-Y 
Published: September 2018

Summary
Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2-biased response. In this study, VDR−/− mice and WT (WT) mice were used. Th2 cell differentiation between VDR−/− mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR−/− mice. The VDR−/−CD4+ T cells were prone to Th2 polarization. VDR−/− mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR−/− mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.