bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structurally Constrained Effective Brain Connectivity
Authors: Crimi Alessandro , Dodero Luca , Sambataro Fabio , Murino Vittorio , Sona Diego 
Published: April 2018

The relationship between structure and function is of interest in many research fields involving the study of complex biological processes. In neuroscience in particular, the fusion of structural and functional data can help understanding the underlying principles of the operational networks in the brain. To address this issue, this paper proposes a constrained autoregressive model leading to a representation of “effective” connectivity that can be used to better understand how the structure modulates the function. Or simply, it can be used to find novel biomarkers characterizing groups of subjects. In practice, an initial structural connectivity representation is re-weighted to explain the functional co-activations. This is obtained by minimizing the reconstruction error of an autoregressive model constrained by the structural connectivity prior. The model has been designed to also include indirect connections, allowing to split direct and indirect components in the functional connectivity, and it can be used with raw and deconvoluted BOLD signal.The derived representation of dependencies was compared to the well known dynamic causal model, giving results closer to known ground-truth. Further evaluation of the proposed effective network was performed on two typical tasks. In a first experiment the direct functional dependencies were tested on a community detection problem, where the brain was partitioned using the effective networks across multiple subjects. In a second experiment the model was validated in a case-control task, which aimed at differentiating healthy subjects from individuals with autism spectrum disorder. Results showed that using effective connectivity leads to clusters better describing the functional interactions in the community detection task, while maintaining the original structural organization, and obtaining a better discrimination in the case-control classification task.HighlightsA method to combine structural and functional connectivity by using autoregressive model is proposed.The autoregressive model is constrained by structural connectivity defining coefficients for Granger causality.The usefulness of the generated effective connections is tested on simulations, ground-truth default mode network experiments, a classification and clustering task.The method can be used for direct and indirect connections, and with raw and deconvoluted BOLD signal.
Cerebellar nuclei neurons dictate cortical growth through developmental scaling of presynaptic Purkinje cells
Authors: Willett Ryan T. , Wojcinski Alexandre , Bayin N. Sumru , Lao Zhimin , Stephen Daniel , Dauber-Decker Katherine L. , Wu Zhuhao , Tessier-Lavigne Marc , Saito Hiromitsu , Suzuki Noboru , Joyner Alexandra L. 
Published: April 2018

AbstractEfficient function of neural systems requires the production of specific cell types in the correct proportions. Here we report that reduction of the earliest born neurons of the cerebellum, excitatory cerebellar nuclei neurons (eCN), results in a subsequent reduction in growth of the cerebellar cortex due to an accompanying loss of their presynaptic target Purkinje cells. Conditional knockout of the homeobox genesEn1andEn2(En1/2) in the rhombic lip-derived eCN and granule cell precursors leads to embryonic loss of a subset of medial eCN and cell non-autonomous and location specific loss of Purkinje cells, with subsequent proportional scaling down of cortex growth. We propose that subsets of eCN dictate the survival of their specific Purkinje cell partners, and in turn sonic hedgehog secreted by Purkinje cells scales the expansion of granule cells and interneurons to produce functional local circuits and the proper folded morphology of the cerebellum.
Physical activity predicts population-level age-related differences in frontal white matter
Authors: Strömmer Juho M. , Davis Simon W. , Henson Richard N. , Tyler Lorraine K. ,   Cam-CAN, Campbell Karen L. 
Published: April 2018

AbstractPhysical activity has positive effects on brain health and cognitive function throughout the lifespan. Thus far, few studies have examined the effects of physical activity on white matter (WM) microstructure and psychomotor speed within the same, population-based sample (critical if conclusions are to extend to the wider population). Here, using diffusion tensor imaging and a simple reaction time task within a relatively large population-derived sample (N = 399; 18–87 years) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), we demonstrate that physical activity mediates the effect of age on white matter integrity, measured with fractional anisotropy. Higher self-reported daily physical activity was associated with greater preservation of WM in several frontal tracts, including the genu of corpus callosum, uncinate fasciculus, external capsule and anterior limb of the internal capsule. We also show that the age-related slowing is mediated by WM integrity in the genu. Our findings contribute to a growing body of work suggesting that a physically active lifestyle may protect against age-related structural disconnection and slowing.
N-1-naphthylphthalamic acid stimulates tomato hypocotyl elongation, elevates ethylene levels and alters metabolic homeostasis
Authors: Nongmaithem Sapana , Devulapalli Sameera , Sreelakshmi Yellamaraju , Sharma Rameshwar 
Published: April 2018

One sentence summaryN-1-naphthylphthalamic acid (NPA) treatment stimulates tomato hypocotyl elongation likely by elevating ethylene emission and lowering indole-3-butyric acid levels in the seedlings.AbstractIn higher plants, phytohormone indole-3-acetic acid is characteristically transported from the apex towards the base of the plant, termed as polar auxin transport (PAT). Among the inhibitors blocking PAT, N-1-naphthylphthalamic acid (NPA) that targets ABCB transporters is most commonly used. NPA-treated light-grown Arabidopsis seedlings show severe inhibition of hypocotyl and root elongation. In light-grown tomato seedlings, NPA inhibited root growth, but contrary to Arabidopsis stimulated hypocotyl elongation. The NPA-stimulation of hypocotyl elongation was milder in blue, red, and far-red light-grown seedlings. The NPA-treatment stimulated emission of ethylene from the seedlings. The scrubbing of ethylene by mercuric perchlorate reduced NPA-stimulated hypocotyl elongation. NPA action on hypocotyl elongation was antagonized by 1-methylcyclopropene, an inhibitor of ethylene action. NPA-treated seedlings had reduced levels of indole-3-butyric acid and higher levels of zeatin in the shoots. NPA did not alter indole-3-acetic levels in shoots. The analysis of metabolic networks indicated that NPA-treatment induced moderate shifts in the networks compared to exogenous ethylene that induced a drastic shift in metabolic networks. Our results indicate that in addition to ethylene, NPA-stimulated hypocotyl elongation in tomato may also involve zeatin and indole-3-butyric acid. Our results indicate that NPA-mediated physiological responses may vary in a species-specific fashion.
Causal gene regulatory network inference using enhancer activity as a causal anchor
Authors: Vipin Deepti , Wang Lingfei , Devailly Guillaume , Michoel Tom , Joshi Anagha 
Published: May 2018

AbstractMotivationTranscription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data has been widely used to infer the cellular regulatory networks, the methods mainly infer correlations rather than causality. We propose that a causal inference framework successfully used for eQTL data can be extended to infer causal regulatory networks using enhancers as causal anchors and enhancer RNA expression as a readout of enhancer activity.ResultsWe developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM consortium. Predicted causal targets of transcription factors (TFs) in mouse embryonic stem cells, macrophages and erythroblastic leukemia overlapped significantly with experimentally validated targets from ChIP-seq and perturbation data. We further improved the model by taking into account that some TFs might act in a quantitative, dosage-dependent manner, whereas others might act predominantly in a binary on/off fashion. We predicted TF targets from concerted variation of eRNA and TF and target promoter expression levels within a single cell type as well as across multiple cell types. Importantly, TFs with high-confidence predictions were largely different between these two analyses, demonstrating that variability within a cell type is highly relevant for target prediction of cell type specific factors. Finally, we generated a compendium of high-confidence TF targets across diverse human cell and tissue types.AvailabilityMethods have been implemented in the Findr software, available at https://github.com/lingfeiwang/findrContactTom.Michoel@roslin.ed.ac.uk, Anagha.Joshi@roslin.ed.ac.uk
HOPS: a quantitative score reveals pervasive horizontal pleiotropy in human genetic variation is driven by extreme polygenicity of human traits and diseases
Authors: Jordan Daniel M. , Verbanck Marie , Do Ron 
Published: April 2018

AbstractHorizontal pleiotropy, where one variant has independent effects on multiple traits, is important for our understanding of the genetic architecture of human phenotypes. We develop a method to quantify horizontal pleiotropy using genome-wide association summary statistics and apply it to 372 heritable phenotypes measured in 361,194 UK Biobank individuals. Horizontal pleiotropy is pervasive throughout the human genome, prominent among highly polygenic phenotypes, and enriched in active regulatory regions. Our results highlight the central role horizontal pleiotropy plays in the genetic architecture of human phenotypes. The HOrizontal Pleiotropy Score (HOPS) method is available on Github at https://github.com/rondolab/HOPS.
The utility of Saw-scaled viper,Echis pyramidum, and Kenyan sand boa,Eryx colubrinusas bioindicator of heavy metals bioaccumulation in relation to DPTA soil extract and biological consequences
Authors: Sleem Doha M. M. , Kadry Mohamed A. M. , Mohallal Eman M. E. , Marie Mohamed A. S. 
Published: April 2018

AbstractThe present investigation was conducted to compare between the ecotoxocological effects of Ca, Mg, Fe, Cu, Zn, Co, Mo, Mn, B, Al, Sr, Pb, Ni, Cd and Cr on the saw-scaled viper,Echis pyramidum (E. p.)and the Kenyan sand boa,Eryx colubrinus(E.c.) inhabiting Gabal El-Nagar and Kahk Qibliyyah respectively in El-Faiyum desert, Egypt. Accumulation varied significantly among the liver, kidney and muscle. The relationship between concentrations of heavy metals in snakes and those in the soil from the collected sites was established by analyzing metal DPTA in soil. Bioaccumulation factor is calculated to estimate the degree of toxicity within the tissues. Morphometric analysis was recorded. All body morphometric measurements were higher inE. p. than inE. c.. Body, liver, gonad, kidney and heart weight, HSI, GSI, RBCs count, Hb content, PCV, MCV, MCH, MCHC, plasma glucose, total lipids and total proteins showed a significant increase inE. p. Histopathological examination showed damage and alterations of liver, kidney and testes sections. The tissues ofE. c. were more destructed than those ofE. p..
Reconstitution of immune cell interactions in free-standing membranes
Authors: Jenkins Edward , Santos Ana Mafalda , Felce James H. , Hatherley Deborah , Dustin Michael L. , Davis Simon J. , Eggeling Christian , Sezgin Erdinc 
Published: April 2018

AbstractThe spatiotemporal regulation of signalling proteins at the contacts formed between immune cells and their targets determines how and when immune responses begin and end. It is important, therefore, to be able to elucidate molecular processes occurring at these interfaces. However, the detailed investigation of each component’s contribution to the formation and regulation of the contact is hampered by the complexity of cellular composition and architecture. Moreover, the transient nature of these interactions creates additional challenges, especially for using advanced imaging technology. One approach to circumventing these problems is to establishin vitrosystems that faithfully mimic immune cell interactions, incorporating complexity that can be ‘dialled-in’ as needed. Here, we present anin vitrosystem making use of synthetic vesicles that mimic important aspects of immune cell surfaces. Using this system, we begin to investigate the spatial distribution of signalling molecules (receptors, kinases and phosphatases) and the intracellular rearrangements that accompany the initiation of signalling in T cells. The model system presented here is expected to be widely applicable.Summary StatementImmune cell-cell interactions are reconstituted in free-standing vesicles wherein spatiotemporal aspects of immune synapse formation can be investigated.
Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging
Authors: Kirshenbaum Greer S. , Robson Victoria K. , Shansky Rebecca M. , Savage Lisa M. , Leonardo E. David , Dranovsky Alex 
Published: April 2018

SummaryAdult neurogenesis is impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in a progressing decline in hippocampal acetylcholine and the slow emergence of profound working memory deficits. These deficits were accompanied by compensatory rewiring of cholinergic dentate gyrus inputs such that ventrally projecting neurons were recruited by the dorsal projection. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal circuit across the lifespan. It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.
Changes in the gut microbiota and fermentation products associated with enhanced longevity in acarbose-treated mice
Authors: Smith Byron J , Miller Richard A , Ericsson Aaron C , Harrison David C , Strong Randy , Schmidt Thomas M 
Published: April 2018

AbstractBackgroundTreatment with theα-glucosidase inhibitor acarbose increases median lifespan by approximately 20% in male mice and 5% in females. This longevity extension differs from dietary restriction based on a number of features, including the relatively small effects on weight and the sex-specificity of the lifespan effect. By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites.ResultsMicrobial communities and the concentrations of SCFAs in the feces of mice treated with acarbose were notably different from those of control mice. At all three study sites, the bloom of a single bacterial taxon was the most obvious response to acarbose treatment. The blooming populations were classified to the largely unculturedBacteroidalesfamilyMuribaculaceaeand were the same taxonomic unit at two of the three sites. Total SCFA concentrations in feces were increased in treated mice, with increased butyrate and propionate in particular. Across all samples,Muribaculaceaeabundance was strongly correlated with propionate and community composition was an important predictor of SCFA concentrations. Cox proportional hazards regression showed that the fecal concentrations of acetate, butyrate, and propionate were, together, predictive of mouse longevity even while controlling for sex, site, and acarbose.ConclusionWe have demonstrated a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose. Treatment modulated the taxonomic composition and fermentation products of the gut microbiome, while the site-dependence of the microbiota illustrates the challenges facing reproducibility and interpretation in microbiome studies. These results motivate future studies exploring manipulation of the gut microbial community and its fermentation products for increased longevity, and to test a causal role of SCFAs in the observed effects of acarbose.
Connectomics of the zebrafish’s lateral-line neuromast reveals wiring and miswiring in a simple microcircuit
Authors: Dow Eliot , Jacobo Adrian , Hossain Sajjad , Siletti Kimberly , Hudspeth A. J. 
Published: April 2018

AbstractThe lateral-line neuromast of the zebrafish displays a restricted, consistent pattern of innervation that facilitates the comparison of microcircuits across individuals, developmental stages, and genotypes. We used serial blockface scanning electron microscopy to determine from multiple specimens the neuromast connectome, or comprehensive set of connections between hair cells and afferent and efferent nerve fibers. This analysis delineated a complex but consistent wiring pattern with three striking characteristics: each nerve terminal is highly specific in receiving innervation from hair cells of a single directional sensitivity; the innervation is redundant; and the terminals manifest a hierarchy of dominance. Mutation of the canonical planar-cell-polarity genevangl2, which decouples the asymmetric phenotypes of sibling hair-cell pairs, results in randomly positioned, randomly oriented sibling cells that nonetheless retain specific wiring. Because larvae that overexpress Notch exhibit uniformly oriented, uniformly innervating hair-cell siblings, wiring specificity is mediated by the Notch signaling pathway.
The impact of a governmental cash transfer programme on tuberculosis cure rate in Brazil: A quasi-experimental approach
Authors: Carter Daniel J. , Daniel Rhian , Torrens Ana W. , Sanchez Mauro N. , Maciel Ethel L. N. , Bartholomay Patricia , Barreira Draurio C. , Rasella Davide , Barreto Maurício L. , Rodrigues Laura C. , Boccia Delia 
Published: April 2018

AbstractBackgroundSocial vulnerability is strongly associated with tuberculosis (TB) indicators like cure rate. By addressing key social determinants, social protection policies such as Brazil’s Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in TB control. Evidence is consolidating around a positive effect of social protection on TB outcomes, however methodological limitations prevent strong conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB cure rate.Methods & FindingsThe data source was Brazil’s TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. Propensity scores (PSs) were estimated from a complete-case logistic regression using covariates from this linked dataset, informed by a directed acyclic graph. Control patients were matched to exposed patients on the PS and the average effect of treatment on the treated (ATT) was estimated as the difference in TB cure rate between matched groups (n = 2167). The ATT was estimated as 10·58 (95% CIs: 4·39, 16·77). This suggests that 10·58% of the TB patients receiving BFP who were cured would not have been cured had they not received BFP. The direction of this effect was robust to sensitivity analyses performed and the PS matching broadly improved balance, although missing data limited the sample size.ConclusionsThis work is the first quasi-experimental evaluation of social protection in wide-scale practice on TB outcomes. It demonstrates a positive effect of conditional cash transfers on TB cure rate consistent with existing work, suggesting changes to policy and future research on increasing access to social protection for TB patients who remain uncovered by the programme.
Histone deacetylase HDA19 affects cortical cell fate by interacting with SCARECROW in the Arabidopsis root
Authors: Chen WQ , Drapek C , Li DX , Xu ZH , Benfey PN , Bai SN 
Published: May 2018

Abstract/SummaryThe Arabidopsis root epidermis is a simple model for investigating cell fate specification and pattern formation. In addition to regulatory networks consisting of transcription factors, histone deacetylases are also involved in the cellular patterning process. Here we report HDA19 affects the root epidermal cellular pattern through regulation of cortical cell fate by interacting with SCARECROW. This work reveals two new components in cortical cell specification and uncovers a new facet of SCR function.
The role of universities for the change of a network structure in the regional business ecosystem
Authors: Kim Changone , Park Sang-Hyeok , Seol Byung-Moon 
Published: May 2018

Purpose
This paper aims to focus on the changing role of universities in university–industry collaboration (UIC) for enriching the regional business ecosystem network. For this, the authors analyze “Business Clinic Day,” (BCD) a specific UIC program which provides a consulting service for firms, small- and medium-sized enterprises (SMEs) having a specific problem, by a group of facilitators. It includes consultants such as chief executive officers (CEOs), professors and heads of regional public or private service providers. This study illustrates that various types of networks are formed between consultants and problem-owners by facilitation of university after the program.

Design/methodology/approach
This study has analyzed with social network analysis how the business network was changed from clinic day program. Furthermore, the networks surrounding SMEs are extended to the other people connected to them. This means that the business network of SMEs had been diversified via the facilitation of “BCD” provided as UIC program.

Findings
Local SMEs have difficulties in enhancing their competitiveness in the market both in terms of internal resources and networks with external organizations. Thus, universities need to promote university–industry collaboration programs to enable SMEs to strengthen their competitiveness by building networks in local business ecosystems.

Originality/value
This study throws new highlights on the facilitator role of a university as a network promoter, in addition to the partner as a technology provider, in the regional business ecosystem.