bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delineation of the First Human Mendelian Disorder of the DNA Demethylation Machinery: TET3 Deficiency
Authors: Beck David B. , Petracovici Ana , He Chongsheng , Moore Hannah W. , Louie Raymond J. , Ansar Muhammad , Douzgou Sofia , Sithambaram Sivagamy , Cottrell Trudie , Santos-Cortez Regie Lyn P. , Prijoles Eloise J. , Bend Renee , Keren Boris , Mignot Cyril , Nougues Marie-Christine , Õunap Katrin , Reimand Tiia , Pajusalu Sander , Zahid Muhammad , Nadeem Saqib Muhammad Arif , Buratti Julien , Seaby Eleanor G , McWalter Kirsty , Telegrafi Aida , Baldridge Dustin , Shinawi Marwan , Leal Suzanne M. , Schaefer G. Bradley , Stevenson Roger E. , Banka Siddharth , Bonasio Roberto , Fahrner Jill A. 
Published: July 2019

ABSTRACTGermline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate epigenetic inheritance via histone post-translational modifications and DNA methylation. Cytosine methylation of DNA (5mC) is the quintessential epigenetic mark, yet no human Mendelian disorder of DNA demethylation has been delineated. Here, we describe in detail the first Mendelian disorder caused by disruption of DNA demethylation. TET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans. Here we identify and characterize 11 cases of human TET3 deficiency in 8 families with the common phenotypic features of intellectual disability/global developmental delay, hypotonia, autistic traits, movement disorders, growth abnormalities, and facial dysmorphism. Mono-allelic frameshift and nonsense variants in TET3 occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues with all but one occurring within the catalytic domain and most displaying hypomorphic function in a catalytic activity assay. TET3 deficiency shows substantial phenotypic overlap with other Mendelian disorders of the epigenetic machinery, including intellectual disability and growth abnormalities, underscoring shared disease mechanisms.
Systematic revision and redefinition of the genus Scirrotherium Edmund and Theodor, 1997 (Cingulata, Pampatheriidae): Implications for the origin of pampatheriids and the evolution of the South American lineage including Holmesina
Authors: Jiménez-Lara Kevin 
Published: July 2019

AbstractThe intrageneric relationships of the pampatheriid genus Scirrotherium and its affinities with supposedly related genera, i.e., Kraglievichia and Holmesina, are revised through parsimony phylogenetic analyses and new comparative morphological descriptions. For this work, unpublished material of pampatheriids (numerous osteoderms, one partial skull and a few postcranial bones) from Neogene formations of Colombia was analyzed. The results show that Scirrotherium is paraphyletic if we include all its referred species, i.e., Scirrotherium hondaensis, S. carinatum and S. antelucanus. The species S. carinatum is closer to Kraglievichia paranensis than to S. hondaensis or S. antelucanus, therefore the new name K. carinatum comb. nov. is proposed. The relationship among S. hondaensis and S. antelucanus could not be resolved, so these species should be designated in aphyly. In spite of failing to recover S. hondaensis and S. antelucanus as one single clade, here is preferred to maintain the generic name Scirrotherium in both species based on diagnostic evidence. New emended diagnoses for Scirrotherium, S. hondaensis and Kraglievichia are provided. The genus Holmesina was found to be monophyletic and positioned as the sister clade of Scirrotherium + Kraglievichia. The evolutionary and biogeographic implications of the new phylogeny and taxonomic re-arrangements are discussed. A possible geographic origin of the family Pampatheriidae and Scirrotherium in low latitudes of South America as early as Early Miocene times is claimed. The South American ancestor or sister taxon of Holmesina is predicted to be morphologically more similar to Scirrotherium than to Kraglievichia.
Categorical representation from sound and sight in the ventral occipito-temporal cortex of sighted and blind
Authors: Mattioni Stefania , Rezk Mohamed , Battal Ceren , Bottini Roberto , Cuculiza Mendoza Karen E. , Oosterhof Nikolaas N. , Collignon Olivier 
Published: July 2019

AbstractIs vision necessary for the development of the categorical organization of the Ventral Occipito-Temporal Cortex (VOTC)? We used fMRI to characterize VOTC responses to eight categories presented acoustically in sighted and early blind individuals, and visually in a separate sighted group. We observed that VOTC reliably encodes sound categories in sighted and blind people using a representational structure and connectivity partially similar to the one found in vision. Sound categories were, however, more reliably encoded in the blind than the sighted group, using a representational format closer to the one found in vision. Crucially, VOTC in blind represents the categorical membership of sounds rather than their acoustic features. Our results suggest that sounds trigger categorical responses in the VOTC of congenitally blind and sighted people that partially match the topography and functional profile of the visual response, despite qualitative nuances in the categorical organization of VOTC between modalities and groups.
The negative adipogenesis regulator DLK1 is transcriptionally regulated by TIS7 (IFRD1) and translationally by its orthologue SKMc15 (IFRD2)
Authors: Vietor Ilja , Cikes Domagoj , Piironen Kati , Vasakou Theodora , Heimdörfer David , Gstir Ronald , Erlacher Matthias David , Tancevski Ivan , Eller Philipp , Demetz Egon , Hess Michael , Kuhn Volker , Degenhart Gerald , Rozman Jan , Klingenspor Martin , Hrabe de Angelis Martin , Valovka Taras , Huber Lukas A. 
Published: July 2019

AbstractDelta-like homolog 1 (DLK1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Here we identify two independent regulatory mechanisms, transcriptional and translational, by which TIS7 (IFRD1) and its orthologue SKMc15 (IFRD2) regulate DLK1 levels. Mice deficient in both TIS7 and SKMc15 (dKO) had severely reduced adipose tissue and were resistant to high fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation was significantly up regulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk-1 inhibited the expression of adipogenesis regulators PPARγ and C/EBPα, and fatty acid transporter CD36. Although both, TIS7 and SKMc15, contributed to this phenotype, they utilized two different mechanisms. TIS7 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk-1. On the other hand, here we provide distinctive experimental evidence that SKMc15 acts as a general translational inhibitor significantly affecting DLK-1 protein levels. Our study provides data describing novel mechanisms of DLK1 regulation in adipocyte differentiation involving TIS7 and SKMc15.SYNOPSISThis study uncovered that IFRD1 (TIS7) and its orthologue IFRD2 (SKMc15) are two essential regulators of adipogenesis. These proteins are highly similar on the sequence level, yet they regulate adipocyte differentiation using different but complementary mechanisms. Our main findings are:IFRD1 (TIS7) and IFRD2 (SKMc15) knockout mice are resistant against diet-induced obesityIFRD1 (TIS7) and IFRD2 (SKMc15) are critical for proper nutritional fat uptake and adipogenesisIFRD1 (TIS7) controls adipogenesis via Wnt/β-catenin-dependent transcriptional regulation of adipocyte-specific genesIFRD2 (SKMc15) regulates adipocyte-specific genes acting as a novel general translational inhibitor
Detecting genotype-population interaction effects by ancestry principal components
Authors: Yu Chenglong , Ni Guiyan , van der Werf Julius , Lee S. Hong 
Published: July 2019

ABSTRACTHeterogeneity in the phenotypic mean and variance across populations is often observed for complex traits. One way to understand heterogeneous phenotypes lies in uncovering heterogeneity in genetic effects. Previous studies on genetic heterogeneity across populations were typically based on discrete groups of population stratified by different countries or cohorts, which ignored the difference of population characteristics for the individuals within each group and resulted in loss of information. Here we introduce a novel concept of genotype-by-population (G×P) interaction where population is defined by the first and second ancestry principal components (PCs), which are less likely to be confounded with country/cohort-specific factors. We applied a reaction norm model fitting each of 70 complex traits with significant SNP-heritability and the PCs as covariates to examine G×P interactions across diverse populations including white British and other white Europeans from the UK Biobank (N = 22,229). Our results demonstrated a significant population genetic heterogeneity for behavioural traits such as age first had sexual intercourse and qualifications. Our approach may shed light on the latent genetic architecture of complex traits that underlies the modulation of genetic effects across different populations.
Mitochondrial dysfunction impairs human neuronal development and reduces neuronal network activity and synchronicity
Authors: Klein Gunnewiek T.M. , Van Hugte E. J. H. , Frega M. , Guardia G. Solé , Foreman K.B. , Panneman D. , Mossink B. , Linda K. , Keller J.M. , Schubert D. , Cassiman D. , Morava E. , Rodenburg R. , Perales-Clemente E. , Nelson T.J. , Kasri N. Nadif , Kozicz T. 
Published: July 2019

SummaryEpilepsy, intellectual and cortical sensory deficits and psychiatric manifestations are among the most frequent manifestations of mitochondrial diseases. Yet, how mitochondrial dysfunction affects neural structure and function remains largely elusive. This is mostly due to the lack of a properin vitrotranslational neuronal model system(s) with impaired energy metabolism. Leveraging the induced pluripotent stem cell technology, from a cohort of patients with the common pathogenic m.3243A>G variant of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), we differentiated excitatory cortical neurons (iNeurons) with normal (low heteroplasmy) and impaired (high heteroplasmy) mitochondrial function on an isogenic nuclear DNA background. iNeurons with high levels of heteroplasmy exhibited mitochondrial dysfunction, delayed neural maturation, reduced dendritic complexity and fewer functional excitatory synapses. Micro-electrode array recordings of neuronal networks with high heteroplasmy displayed reduced network activity and decreased synchronous network bursting. The impaired neural energy metabolism of iNeurons compromising the structural and functional integrity of neurons and neural networks, could be the primary driver of increased susceptibility to neuropsychiatric manifestations of mitochondrial disease.
Importance of Matrix-dimensionality in Regulating the Bone Marrow Hematopoietic Cells Pool
Authors: Zhang P. , Zhang C. , Han J. , Gao J. , Zhao W. , Yang H. 
Published: July 2019

AbstractIn bone marrow, hematopoietic stem cells (HSCs) and multiple hematopoietic progenitor cells (HPCs) cooperate to differentiate and replenish blood and immune cells. It has long been recognized bone marrow niche parameters interact with hematopoietic stem and progenitor cells (HSPCs) and additional work is required to study niche physical signals controlling cell behavior. Here we presented that important biophysical signals, stiffness and dimensionality, regulating expansion of bone marrow HSPCs. Mice bone marrow derived progenitor cells were cultured in collagen I hydrogel in vitro. We found stiffer 3D matrix promoted the expansion of lineage negative (Lin−) progenitor cells and Lin−Sca-1+c-kit+ (LSK) HSPCs compared to softer hydrogel. Compared with cells cultured in 2D environment, 3D embedded construct had significant advantage on HSPCs expansion, accompanied by increases on myeloid and lymphoid lineage fractions. Bright changes on gene expression were subsequently discovered. According to these data, we concluded that culture matrix dimensionality is an important factor to regulate the behavior of subpopulations in hematopoietic cell pool, which should be considered in attempts to illuminate HSCs fate decision in vitro.Statement of SignificanceWe would like to submit the enclosed manuscript entitled "Importance of Niche-dimensionality in Regulating the Bone Marrow Hematopoietic Cells Pool", which we wish to be considered for publication in Biophysical Journal. Studies about the interaction between HSCs and factors provided by their microenvironment is largely focus on pure perspective of biology. But biophysical factors affecting HSC fate and behavior needs to be further explore. Herein we found ex vivo culture dimensionality affected HSPC expansion. Cell surface marker detection and mRNA expression analysis predicted the changes on myeloid and lymphoid lineage fractions. We hope niche physical signals which we identified will be considered to design HSC biomimetic niches in clinical applications. And we believe that our study will make it interesting to general readers. We deeply appreciate your consideration of our manuscript, and we look forward to receiving comments from the reviewers.
NGO accountability: retrospective and prospective academic contributions
Authors: Agyemang Gloria , O’Dwyer Brendan , Unerman Jeffrey 
Published: July 2019

PurposeThe purpose of this paper is to offer a retrospective and prospective analysis of the themes explored in the 2006Accounting, Auditing and Accountability Journalspecial issue on non-governmental organisation (NGO) accountability.Design/methodology/approachThe paper is a reflective review essay.FindingsThe paper outlines how a number of themes in the 2006 special issue addressing downward accountability, hierarchical accountability and management control have been subsequently developed in a selection of papers from the accounting literature. The development of these themes leads to several suggestions for future research in NGO accountability.Originality/valueThe paper offers a systematic, original perspective on recent developments in certain areas of the field of NGO accountability.
Telecommunication access business model options in Maluku and Papua, the less-favored business regions in Indonesia
Authors: Oktarini Lydia , Kawano Hirotaka 
Published: July 2019

Purpose
This paper aims to provide feasible business model options that benefit all stakeholders; the government, the investor and especially the inhabitants in Maluku and Papua, the less-favored business regions in Indonesia.

Design/methodology/approach
Three feasible business model options result from ICT for development literature, current role of the government, other models and investment scheme review, statistical analysis, technology analysis and investment simulations.

Findings
This paper proposes three different feasible business model options. The infrastructure subsidy model, which combines 20 per cent private investment and 80 per cent government subsidy, is the most feasible business model based on investment simulations. This model which combines 20 per cent private investment and 80 per cent government subsidy provides stronger determination of Indonesian Government for serving rural and remote people. The revenue subsidy and the mixed project subsidy are alternative models that may provide more attractive schemes from the standpoint of investors.

Research limitations/implications
However, current paper has limitation which is subject to enhance for better analysis in future research such as implementation of the in-depth assessment of risk management system to deal with all exposed risks.

Practical implications
This paper provides that setting up a complete telecommunication access infrastructures in eastern Indonesia is feasible under new proposed models.

Social implications
The new proposed models provide stronger determination of Indonesian Government for serving rural and remote people and minimizing the digital divide in eastern area.

Originality/value
Under the new proposed models, the role and capacity of the government is adjusted. The government should dominate and be less dependent on private investment. Also, the government should shift from triggering service penetration into developing a complete infrastructure set up.
Incentive structures in multi-partner project teams
Authors: Han Jiaojie , Rapoport Amnon , Fong Patrick S.W. 
Published: July 2019

Purpose
The purpose of this paper is to investigate the impact of incentive contracts in multi-partner project teams (MPPTs) on the agents’ effort expenditure and project performance, analyze how the agents allocate their efforts between production and cooperation and offer suggestions for project managers on how to design incentive contracts.

Design/methodology/approach
The paper proposes a model of MPPT in which agents are inequity-averse and their effort expenditures are exogenously bounded. An extensive numerical example is presented in online Appendix 2 to illustrate the theoretical results.

Findings
The paper suggests that if the potential benefit of the agents’ cooperation in MPPT is high or if both agents exhibit inequity aversion and the efforts’ marginal costs are low, then group-based incentive contracts outperform individual-based incentive contracts. It also shows that the impact of the incentive contract on the agents’ effort expenditure and project team performance is correlated with several critical project attributes.

Originality/value
Fulfilling a need to study the design of incentive structures in MPPTs, the paper complements the existing literature in three ways. First, in contrast to single-partner project teams, it considers projects with multiple partners where cooperation between them enhances the project outcome. Second, rather than focusing on individual production problems, it considers multi-task projects with constrained efforts that must be allocated between production and cooperation. Third, it analyzes the effects of changes in the project attributes, incentive intensities and information transparency on the effectiveness of the contract.
Impact of heat generation/absorption on the unsteady magnetohydrodynamic stagnation point flow and heat transfer of nanofluids
Authors: Jusoh Rahimah , Nazar Roslinda , Pop Ioan 
Published: July 2019

Purpose
The purpose of this study is to describe the unsteady three-dimensional magnetohydrodynamic stagnation point flow of nanofluids with heat generation/absorption.

Design/methodology/approach
The comprehensive numerical simulations in this study accommodate a physical insight into the heat transfer and flow problem. The use of finite difference method through the bvp4c function in Matlab provides the numerical results and graphical illustrations for the heat transfer rate and shear stress.

Findings
Dual solutions are discovered in this study. Thus, stability analysis is implemented and the first solution complies the stability behavior. Silver nanoparticles dominate the highest thermal conductivity. Accretion of the rate of heat transfer is obtained with an increment in the magnitude of heat absorption, suction parameter and nanoparticle volume fraction. A stronger magnetic field and larger unsteadiness parameter contribute to the increase of the surface shear stress.

Practical implications
Many practical fluid mechanics problems involve the time-dependent element. Practically, an unsteady flow of nanofluid can be implemented in the micro-manufacturing, periodic heat exchanges process, nano drug delivery system and nuclear reactors.

Originality/value
In spite of numerous studies on the unsteady flow, none of the researchers combined the effect of heat generation/absorption and magnetic field in the nanofluid model. The behavior of the flow and heat transfer have been analyzed thoroughly with the variations in the unsteadiness parameter, heat source/sink and nanoparticle volume fraction. Moreover, the discovery of dual solutions in this model strengthens the novelty of this study. Subsequently, the implementation of stability analysis leads to a remarkable revelation where the first solution is found to be stable.
Drop-out in programming courses – prediction and prevention
Authors: Hawlitschek Anja , Köppen Veit , Dietrich André , Zug Sebastian 
Published: July 2019

Purpose
An ideal learning analytics tool for programming exercises performs the role of a lecturer who monitors the code development, provides customized support and identifies students at risk to drop out. But a reliable prediction and prevention of drop-out is difficult, due to the huge problem space in programming tasks and variety of solutions and programming strategies. The purpose of this paper is to tackle this problem by, first, identifying activity patterns that indicate students at risk; and, second, finding reasons behind specific activity pattern, for identification of instructional interventions that prevent drop-out.

Design/methodology/approach
The authors combine two investigation strategies: first, learning analytic techniques (decision trees) are applied on features gathered from students, while completing programming exercises, in order to classify predictors for drop-outs. Second, the authors determine cognitive, motivational and demographic learner characteristics based on a questionnaire. Finally, both parts are related with a correlation analysis.

Findings
It was possible to identify generic variables that could predict early and later drop-outs. For students who drop out early, the most relevant variable is the delay time between availability of the assignment and the first login. The correlation analysis indicates a relation with prior programming experience in years and job occupation per week. For students who drop out later in the course, the number of errors within the first assignment is the most relevant predictor, which correlates with prior programming skills.

Originality/value
The findings indicate a relation between activity patterns and learner characteristics. Based on the results, the authors deduce instructional interventions to support students and to prevent drop-outs.
Management styles in a project environment: evidence from software industry in Oman
Authors: Chaudhry Muhammad Saqib , Raziq Muhammad Mustafa , Saeed Abubakr , Sajjad Aymen , Borini Felipe Mendes 
Published: July 2019

Purpose
The purpose of this paper is to examine the management styles adopted by project managers in the software industry in Oman.

Design/methodology/approach
A sample of 208 project management professionals is drawn from the Omani software industry. Data analysis is based on factor analysis and analysis of variance techniques.

Findings
The results suggest that project managers in the Omani software industry mainly adopt three management styles: people oriented, task oriented and organization oriented. Furthermore, the management styles of project managers are affected by their experience and age, and the organizational structure.

Originality/value
The paper contributes to the literature by examining management styles adopted by managers in a temporary organization environment from an under-researched context, Oman.