bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the earlyDrosophila melanogasterembryo
Authors: Stadler Michael R. , Haines Jenna E. , Eisen Michael B. 
Published: June 2017

AbstractEvidence has emerged in recent years linking insulators and the proteins that bind them to the higher order structure of animal chromatin, but the precise nature of this relationship and the manner by which insulators influence chromatin structure have remained elusive. Here we present high-resolution genome-wide chromatin conformation capture (Hi-C) data from earlyDrosophila melanogasterembryos that allow us to map three-dimensional interactions to 500 base pairs. We observe a complex, nested pattern of regions of chromatin self-association, and use a combination of computational and manual annotation to identify boundaries between these topological associated domains (TADs). We demonstrate that, when mapped at high resolution, boundaries resemble classical insulators: short (500 - 1000 bp) genomic regions that are sensitive to DNase digestion and strongly bound by known insulator proteins. Strikingly, we show that for regions where the banding pattern of polytene chromosomes has been mapped to genomic position at comparably high resolution, there is a perfect correspondence between polytene banding and our chromatin conformation maps, with boundary insulators forming the interband regions that separate compacted bands that correspond to TADs. We propose that this precise, high-resolution relationship between insulators and TADs on the one hand and polytene bands and interbands on the other extends across the genome, and suggest a model in which the decompaction of insulator regions drives the organization of interphase chromosomes by creating stable physical separation between adjacent domains.
A functional role for the epigenetic regulator ING1 in activity-induced gene expression in primary cortical neurons
Authors: Leighton Laura J. , Zhao Qiongyi , Li Xiang , Dai Chuanyang , Marshall Paul R. , Liu Sha , Wang Yi , Zajaczkowski Esmi L. , Khandelwal Nitin , Kumar Arvind , Bredy Timothy W. , Wei Wei 
Published: June 2017

AbstractEpigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of Inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin,Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) ofPpp3r1depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.Author contributionsL.J.L., Q.Z., T.W.B and W.W. designed the experiments. N.K., A.K., X.L., C.D., S.L. and W.W. designed and assembled shRNA constructs. L.J.L., W.W., X.L., C.D., P.R.M., E.Z., and S.L. conducted experiments. Q.Z. and Y.W. analysed ChIP-seq data. L.J.L., Q.Z., and W.W. wrote the paper. All authors reviewed and edited the manuscript.Conflicts of interestNone.
Oxytocin gene networks in the human brain: A gene expression and large-scale fMRI meta-analysis study
Authors: Quintana Daniel S. , Rokicki Jaroslav , van der Meer Dennis , Alnæs Dag , Kaufmann Tobias , Palomera Aldo Córdova , Dieset Ingrid , Andreassen Ole A. , Westlye Lars T. 
Published: June 2017

AbstractOxytocin is a neuropeptide involved in animal and human reproductive and social behavior, with implications for a range of psychiatric disorders. However, the therapeutic potential of oxytocin in mental health care suggested by animal research has not been successfully translated into clinical practice. This may be partly due to a poor understanding of the expression and distribution of the oxytocin signaling pathway in the human brain, and its complex interactions with other biological systems. Among the genes involved in the oxytocin signaling pathway, three genes have been frequently implicated in human social behavior:OXT(structural gene for oxytocin),OXTR(oxytocin receptor), andCD38(central oxytocin secretion). We characterized the distribution ofOXT, OXTR,andCD38mRNA across the brain, identified putative gene pathway interactions by comparing gene expression patterns across 20737 genes, and assessed associations between gene expression patterns and mental states via large-scale fMRI metaanalysis. In line with the animal literature, expression of the three selected oxytocin pathway genes was increased in central, temporal, and olfactory regions. Across the brain, there was high co-expression with several dopaminergic and muscarinic acetylcholine genes, reflecting an anatomical basis for critical gene pathway interactions. Finally, fMRI meta-analysis revealed that the oxytocin pathway gene maps correspond with motivation and emotion processing.
Beyond Consensus: Embracing Heterogeneity in Curated Neuroimaging Meta-Analysis
Authors: Ngo Gia H. , Eickhoff Simon B. , Nguyen Minh , Sevinc Gunes , Fox Peter T. , Spreng R. Nathan , Thomas Yeo B.T. 
Published: June 2017

AbstractCoordinate-based meta-analysis can provide important insights into mind-brain relationships. A popular approach for curated small-scale meta-analysis is activation likelihood estimation (ALE), which identifies brain regions consistently activated across a selected set of experiments, such as within a functional domain or mental disorder. ALE can also be utilized in meta-analytic co-activation modeling (MACM) to identify brain regions consistently co-activated with a seed region. Therefore, ALE aims to find consensus across experiments, treating heterogeneity across experiments as noise. However, heterogeneity within an ALE analysis of a functional domain might indicate the presence of functional sub-domains. Similarly, heterogeneity within a MACM analysis might indicate the involvement of a seed region in multiple co-activation patterns that are dependent on task contexts. Here, we demonstrate the use of the author-topic model to automatically determine if heterogeneities within ALE-type meta-analyses can be robustly explained by a small number of latent patterns. In the first application, the author-topic modeling of experiments involving self-generated thought (N = 179) revealed cognitive components fractionating the default network. In the second application, the author-topic model revealed that the left inferior frontal junction (IFJ) participated in multiple task-dependent co-activation patterns (N = 323). Furthermore, the author-topic model estimates compared favorably with spatial independent component analysis in both simulation and real data. Overall, the results suggest that the author-topic model is a flexible tool for exploring heterogeneity in ALE-type meta-analyses that might arise from functional sub-domains, mental disorder subtypes or task-dependent co-activation patterns. Code for this study is publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/meta-analysis/Ngo2019_AuthorTopic).
tDCS changes in motor excitability are specific to orientation of current flow
Authors: Rawiji Vishal , Ciocca Matteo , Zacharia André , Soares David , Truong Dennis , Bikson Marom , Rothwell John , Bestmann Sven 
Published: June 2017

AbstractMeasurements and models of current flow in the brain during transcranial Direct Current Stimulation (tDCS) indicate stimulation of regions in-between electrodes. Moreover, the cephalic cortex result in local fluctuations in current flow intensity and direction, and animal studies suggest current flow direction relative to cortical columns determines response to tDCS. Here we test this idea by measuring changes in cortico-spinal excitability by Transcranial Magnetic Stimulation Motor Evoked Potentials (TMS-MEP), following tDCS applied with electrodes aligned orthogonal (across) or parallel to M1 in the central sulcus. Current flow models predicted that the orthogonal electrode montage produces consistently oriented current across the hand region of M1 that flows along cortical columns, while the parallel electrode montage produces none-uniform current directions across the M1 cortical surface. We find that orthogonal, but not parallel, orientated tDCS modulates TMS-MEPs. We also show modulation is sensitive to the orientation of the TMS coil (PA or AP), which is through to select different afferent pathways to M1. Our results are consistent with tDCS producing directionally specific neuromodulation in brain regions in-between electrodes, but shows nuanced changes in excitability that are presumably current direction relative to column and axon pathway specific. We suggest that the direction of current flow through cortical target regions should be considered for targeting and dose-control of tDCS.HighlightsDirection of current flow is important for tDCS after-effects.tDCS modulates excitability between two electrodes.tDCS differentially modulates PA and AP inputs into M1.AbbreviationsPApostero-anteriorAPantero-posteriorMLmedio-lateraltDCStranscranial direct current stimulationMEPmotor evoked potentialM1primary motor cortexTMStranscranial magnetic stimulation;AP-TMS-MEPsmotor evoked potentials elicited with anterior-posterior directed TMS;PA-TMS-MEPsmotor evoked potentials elicited with posterior-anterior directed TMSFundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors
Authors: Olson William , Abdus-Saboor Ishmail , Cui Lian , Burdge Justin , Raabe Tobias , Ma Minghong , Luo Wenqin 
Published: June 2017

AbstractThe human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying the ‘pain fovea’, we sparsely traced non-peptidergic nociceptors across the body using a newly generatedMrgprDCreERT2mouse line. We found that mouse plantar paw skin also has a low density of MrgprD+neurites, and individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the magnification of plantar paw regions to contribute to the ‘pain fovea’.
Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells
Authors: Gonçalves Emanuel , Sciacovelli Marco , Costa Ana S. H. , Isaac Johnson Timothy , Machado Daniel , Frezza Christian , Saez-Rodriguez Julio 
Published: June 2017

AbstractDeregulated signal transduction pathways and energy metabolism are hallmarks of cancer and both play a fundamental role in the process of tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes. We identified previously reported functionally relevant phosphosites and potentially novel regulatory residues in enzymes of the central carbon metabolism. In particular, we show that pyruvate dehydrogenase (PDHA1) enzymatic activity is inhibited by increased phosphorylation in FH-deficient cells. Our work provides a novel approach to investigate how post-translational modifications of enzymes regulate metabolism and could have important implications for understanding the metabolic transformation of FH-deficient cancers.
Real estate management: incentives for effort
Authors: Palm Peter 
Published: June 2017

PurposeThe aim of this paper is to examine how the real estate owner (decision maker) can ensure that the preferred tasks are prioritised. In particular, the incentives to ensure motivation to perform to accomplish the strategic goals of the decision maker are investigated.Design/methodology/approachThis research is based on an interview study of 19 firm representatives, 6 decision makers and 13 management representatives, all from the Swedish commercial real estate sector.FindingsThe study concludes that the real estate management organisation in the outsourced management setting is governed by the contract, in detail constituting work tasks, and in the in-house management setting, there is freedom with responsibilities instead of regulations.Research limitations/implicationsThe research in this paper is limited to Swedish commercial real estate sector.Practical implicationsThe insight in the paper regarding how decision makers create incentives for the real estate management organisation in the different organisational settings can provide inspiration to design incentives for effort.Originality/valueIt provides an insight regarding how the industry, depending on organisation setting, prioritise different work tasks and how incentives are created to enable effort.
The right to walk in cities, a comparative review of Macau, Lisbon and Las Vegas
Authors: Balsas Carlos J.L. 
Published: June 2017

Purpose
The purpose of this paper is to analyze walking activity and recent efforts at augmenting walkability conditions in the cities of Macau, Lisbon and Las Vegas.

Design/methodology/approach
The methodology consisted mostly of in-loco observations, pedestrian counts and extensive reviews of the literature, city plans and regulations.

Findings
The findings include the need to properly design, maintain and retrofit pedestrian facilities, while reducing safety conflicts among street users as well as the establishment and the nurturing of a culture of walking.

Research limitations/implications
A fivefold international walkability research agenda with implications for other cities around the world is established: the value and the need for comparative studies and best practices; the need for urban design interventions; the cultivation of attractiveness and aesthetics; the implementation of safety, construction and maintenance criteria; and responsible funding programs.

Practical implications
This paper has twofold implications for stakeholders with direct responsibilities in the design, planning, building and maintenance of streets and public spaces, and for those who simply use those places at their own discretion.

Social implications
A succinct set of recommendations include the need to augment endogeneity, the need to make cities for people and not for automobiles and commitment to resolving pedestrian safety concerns.

Originality/value
This paper discusses the factors affecting street vibrancy from both a stakeholder’s and a user’s perspective. The fundamental and inalienable right to walk is analyzed using the WPPFUS framework (walking levels, purposes, primacy of walking, facilities, unique features and safety concerns).
Why the youth are so eager for university education? Evidence from Iran’s labor market
Authors: K. Haddad GholamReza , Habibi Nader 
Published: June 2017

Purpose
The purpose of this paper is to estimate the wage difference between overeducated and adequately educated workers in a sample of semi-skilled and low-skill occupations in Iran’s labor market. The objective is to see if overeducated employees in these occupations enjoy higher wages in comparison to their adequately educated co-workers.

Design/methodology/approach
The authors use the propensity score matching (PSM) model to estimate the wage difference between overeducated and adequately educated workers in a sample of semi-skilled and low-skill occupations in Iran’s labor market. The PSM method allows the authors to prevent selection bias by comparing each group of overeducated workers with a matched group of adequately educated workers with similar socio-economic characteristics.

Findings
The results show that in Iran’s labor market, the overeducated workers enjoy a wage premium in the range of 10-25 percent for their excess education when they have to work in semi- or low-skill occupations. While this relative advantage has gradually declined for private sector employees over the period 2001-2013, it has remained stable for public sector jobs. The result is attributable to the fact that salary and benefits for public sector employees are directly linked to education attainment and their work experience. The findings show that the relative wage advantage of overeducation is larger for the younger employees with ten or fewer years of experience who have more education than older workers. Overall these findings offer an explanation for the strong desire of Iranian youth for university education. If a university graduate finds a job that matches her/his specialization she/he will enjoy a higher salary than a high school graduate. If she/he has to accept a semi-skilled or low-skill job for which she/he is overeducated, she/he still enjoys a wage premium over her/his co-workers who are not overeducated.

Originality/value
The analysis makes three unique contributions: first, the authors use a unique and detailed micro-data for an economy (Iran) in which the public sector dominates the private sector. The authors investigate the hypothesis for private and public sectors separately. Second, the authors divide the sample of workers into market newcomers and experienced workers. The authors analyze the impact of overeducations on each group separately. Third, the authors use the treatment effect of being overeducated on the individual’s monthly wage by the PSM. The advantage of the PSM method is that it eliminates the selection bias in the wage effect of overeducation, whereas the traditional regression-based techniques may result in this type of bias.
External debt among HIPCs in Africa: accounting and panel VAR analysis of some determinants
Authors: Mensah David , Aboagye Anthony Q.Q. , Abor Joshua Y. , Kyereboah-Coleman Anthony 
Published: June 2017

Purpose
The management of external debt among highly indebted poor countries (HIPCs) in Africa still remains a challenge despite numerous packages and attempts to ameliorate the consequences of such odious debt. The purpose of this paper is to establish the factors that contribute to the growth rate of external debt and how these factors respond to shocks to external debt growth rate in Africa.

Design/methodology/approach
Data were obtained from 24 African countries and analyzed using a panel vector autoregression estimation methodology.

Findings
The study found that external debt growth rates respond positively to unit shock or changes in government investment spending, consumption spending, and domestic borrowings over a long period of time. In the medium term, external debt growth rates respond negatively to shocks in tax revenue, inflation, and output growth rates. The paper also provides empirical support that external debt may be consumed rather than invested among HIPCs in Africa.

Research limitations/implications
The findings of this paper are limited to only HIPCs in Africa.

Practical implications
This study has some few debilitating implications for external debt management among HIPCs in Africa. First, the paper suggests that debt repayment may be a problem. This is largely because external debt is consumed rather than invested. External debt sustainability needs a holistic approach in less developed countries. The findings place much emphasis on improvements in gross domestic product and tax revenues as the principal routes out of the debt doldrums. However, this option must be exploited with great caution as there is ample evidence that these poor countries increase their external borrowing capacities with improvements in economic outlook.

Originality/value
This paper fills a research gap that identifies specific components of government deficit budgets that may be contributing to the growth rate of external debts among HIPCs.
FDI and incumbent R&D behavior: evidence from Indian manufacturing sector
Authors: Khachoo Qayoom , Sharma Ruchi 
Published: June 2017

PurposeThe study is an attempt to analyze the impact of foreign direct investment (FDI) on research and development (R&D) behavior of incumbent firms’, both domestic and foreign, operating in Indian manufacturing sector. FDI inflows into the host country escalates the level of competition compelling domestic as well as existing foreign firms to adjust their spending on R&D. The purpose of this paper is to propose that response of domestic and existing foreign firms to the FDI entry vary, with domestic firms increasing their spending on R&D whereas foreign firms reducing it.Design/methodology/approachUsing a rich firm level data set from Indian manufacturing for the period 2000-2012, the study utilizes Heckman’s two- step estimation strategy to estimate the impact of FDI entry on R&D behavior of incumbents.FindingsFDI entry significantly increases the tendency of domestic and foreign firms to invest in R&D; however, the impact on R&D intensity for both domestic and foreign firms appears to be minimal.Originality/valueThe study contributes to the existing literature on two fronts. One, unlike other studies, it examines the impact of FDI entry not only on R&D behavior of domestic firms but also on the R&D behavior of existing foreign firms. Second, it addresses the problem of selection bias that has been largely ignored by majority of empirical studies on R&D.
TORC1‐mediated sensing of chaperone activity alters glucose metabolism and extends lifespan
Authors: Perić Matea , Lovrić Anita , Šarić Ana , Musa Marina , Bou Dib Peter , Rudan Marina , Nikolić Andrea , Sobočanec Sandra , Mikecin Ana‐Matea , Dennerlein Sven , Milošević Ira , Vlahoviček Kristian , Raimundo Nuno , Kriško Anita 
Published: June 2017

SummaryProtein quality control mechanisms, required for normal cellular functioning, encompass multiple functions related to protein production and maintenance. However, the existence of communication between proteostasis and metabolic networks and its underlying mechanisms remain elusive. Here, we report that enhanced chaperone activity and consequent improved proteostasis are sensed by TORC1 via the activity of Hsp82. Chaperone enrichment decreases the level of Hsp82, which deactivates TORC1 and leads to activation of Snf1/AMPK, regardless of glucose availability. This mechanism culminates in the extension of yeast replicative lifespan (RLS) that is fully reliant on both TORC1 deactivation and Snf1/AMPK activation. Specifically, we identify oxygen consumption increase as the downstream effect of Snf1 activation responsible for the entire RLS extension. Our results set a novel paradigm for the role of proteostasis in aging: modulation of the misfolded protein level can affect cellular metabolic features as well as mitochondrial activity and consequently modify lifespan. The described mechanism is expected to open new avenues for research of aging and age‐related diseases.