bluuebunny/crossref_metadata_2025_split huggingface dataset:
TFAP2 transcription factors are regulators of lipid droplet biogenesis
Authors: Scott Cameron C , Vossio Stefania , Rougemont Jacques , Gruenberg Jean 
Published: March 2018

AbstractHow trafficking pathways and organelle abundance adapt in response to metabolic and physiological changes is still mysterious, although a few transcriptional regulators of organellar biogenesis have been identified in recent years. We previously found that the Wnt signaling directly controls lipid droplet formation, linking the cell storage capacity to the established functions of Wnt in development and differentiation. In the present paper, we report that Wnt-induced lipid droplet biogenesis does not depend on the canonical TCF/LEF transcription factors. Instead, we find that TFAP2 family members mediate the pro-lipid droplet signal induced by Wnt3a, leading to the notion that the TFAP2 transcription factor may function as a “master” regulator of lipid droplet biogenesis.
Histone H3 T11 phosphorylation by Sch9 and CK2 regulates lifespan by controlling the nutritional stress response
Authors: Oh Seunghee , Suganuma Tamaki , Gogol Madelaine M. , Workman Jerry L. 
Published: March 2018

AbstractUpon nutritional stress, the metabolic status of cells is changed by nutrient signaling pathways to ensure survival. Altered metabolism by nutrient signaling pathways has been suggested to influence cellular lifespan. However, it remains unclear how chromatin regulation is involved in this process. Here, we found that histone H3 threonine 11 phosphorylation (H3pT11) functions as a marker for nutritional stress and aging. Sch9 and CK2 kinases cooperatively regulate H3pT11 under stress conditions. Importantly, H3pT11 defective mutants prolonged chronological lifespan by altering nutritional stress responses. Thus, the phosphorylation of H3T11 by Sch9 and CK2 engages a nutritional stress response to chromatin in the regulation of lifespan.
Contrasting patterns of coding and flanking region evolution in mammalian keratin associated protein-1 genes
Authors: Zhou Huitong , Visnovska Tina , Gong Hua , Schmeier Sebastian , Hickford Jon , Ganley Austen R.D. 
Published: March 2018

AbstractDNA repeats are common elements in eukaryotic genomes, and their multi-copy nature provides the opportunity for genetic exchange. This exchange can produce altered evolutionary patterns, including concerted evolution where within genome repeat copies are more similar to each other than to orthologous repeats in related species. Here we investigated the genetic architecture of the keratin-associated protein (KAP) gene family,KRTAP1. This family encodes proteins that are important components of hair and wool in mammals, and the genes are present in tandem copies. Comparison ofKRTAP1gene repeats from species across the mammalian phylogeny shows strongly contrasting evolutionary patterns between the coding regions, which have a concerted evolution pattern, and the flanking regions, which have a normal, radiating pattern of evolution. This dichotomy in evolutionary pattern transitions abruptly at the start and stop codons, and we show it is not the result of purifying selection acting to maintain species-specific protein sequences, nor of codon adaptation or reverse transcription ofKRTAP1-nmRNA. Instead, the results are consistent with short-tract gene conversion events coupled with selection for these events in the coding region driving the contrasting evolutionary patterns found in theKRTAP1repeats. Our work shows the power that repeat recombination has to complement selection and finely tune the sequences of repetitive genes. Interplay between selection and recombination may be a more common mechanism than currently appreciated for achieving specific adaptive outcomes in the many eukaryotic multi-gene families, and our work argues for greater emphasis on exploring the sequence structures of these families.
Temporal Control of Transcription by Zelda in living Drosophila embryos
Authors: Dufourt Jeremy , Trullo Antonio , Hunter Jennifer , Fernandez Carola , Lazaro Jorge , Dejean Matthieu , Morales Lucas , Schulz Katharine N , Favard Cyril , Harrison Melissa M , Radulescu Ovidiu , Lagha Mounia 
Published: March 2018

Abstract/introPioneer factors have the exquisite ability to engage their target sites at nucleosomal DNA, which leads to a local remodeling of chromatin and the establishment of a transcriptional competence. However, the direct impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains elusive. In Drosophila embryos, the maternally deposited activator Zelda (Zld) exhibits key pioneer factor properties and indeed regulates the awakening of the zygotic genome. The analysis of thousands of endogenous Zld bound regions in various genetic contexts, as well as the study of isolated synthetic enhancers with static approaches, led to the proposal that Zld could act as a quantitative developmental timer. Here we employ quantitative live imaging methods and mathematical modeling to directly test the effect of Zld on temporal coordination in gene activation and on mitotic memory. Using an automatic tracking software, we quantified the timing of activation in hundreds of nuclei and their progeny in Drosophila embryos. We demonstrate that increasing the number of Zld binding sites accelerates the kinetics of transcriptional activation regardless of their past transcriptional state. In spite of its known pioneering activities, we show that Zld is not a mitotic bookmarker and is neither necessary nor sufficient to foster mitotic memory. Fluorescent recovery after photo-bleaching and fluorescent correlation spectroscopy experiments reveal that, Zld is highly dynamic and exhibits transient binding to chromatin. We propose that Zld low binding rates could be compensated for by local accumulation of Zld in nuclear microenvironments in vivo, thus allowing rapid and coordinated gene activation.
EREFinder: Genome-wide detection of estrogen response elements
Authors: Anderson Andrew P. , Jones Adam G. 
Published: March 2018

AbstractMotivationEstrogen response elements (EREs) are specific DNA sequences to which ligand-bound estrogen receptors (ERs) physically bind, allowing them to act as transcription factors for target genes. Locating EREs and ER responsive regions is therefore a potentially important component of the study of estrogen-regulated pathways.ResultsWe tested and demonstrated the ability of EREFinder, a novel algorithm we developed, to locate regions of ER-binding across the human genome and show that these regions designated by the program occur more frequently near estrogen responsive genes. EREFinder can handle large input files, has settings to allow for broad and narrow searches, and provides the full output to allow for greater data manipulation. These features facilitate a wide range of hypothesis testing for researchers and make EREFinder an excellent tool to aid in estrogen-related research.Availability and ImplementationSource code and binaries freely available for download at https://github.com/JonesLabIdaho/EREfinder, implemented in C++ and supported on Linux and MS Windows.Contactaanderson@bio.tamu.eduSupplemental MaterialsR scripts can be found at https://github.com/JonesLabIdaho/EREfinder
QTL mapping of natural variation reveals that the developmental regulatorbrunoreduces tolerance toP-element transposition in theDrosophilafemale germline
Authors: Kelleher Erin S. , Jaweria Jaweria , Akoma Uchechukwu , Ortega Lily , Tang Wenpei 
Published: March 2018

ABSTRACTTransposable elements (TEs) are obligate genetic parasites that propagate in host genomes by replicating in germline nuclei, thereby ensuring transmission to offspring. This selfish replication not only produces deleterious mutations---in extreme cases, TE mobilization induces genotoxic stress that prohibits the production of viable gametes. Host genomes could reduce these fitness effects in two ways: resistance and tolerance. Resistance to TE propagation is enacted by germline specific small-RNA-mediated silencing pathways, such as the piRNA pathway, and is studied extensively. However, it remains entirely unknown whether host genomes may also evolve tolerance, by desensitizing gametogenesis to the harmful effects of TEs. In part, the absence of research on tolerance reflects a lack of opportunity, as small-RNA-mediated silencing evolves rapidly after a new TE invades, thereby masking existing variation in tolerance.We have exploited the recent the historical invasion of theDrosophila melanogastergenome byP-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed byP-elements disrupts oogenesis, and in extreme cases leads to atrophied ovaries that completely lack germline cells. By performing QTL-mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing ofP-elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis toP-element transposition. We localized the most significant QTL to a small 230 Kb euchromatic region, with the LOD peak occurring in theBrunolocus, which codes for a critical and well-studied developmental regulator of oogenesis. We further demonstrate that multiplebrunoloss-of-function alleles are strong dominant suppressors of ovarian atrophy, allowing for the development of mature egg-chambers in the face ofP-element activity. Genetic and cytological analyses suggest thatbrunotolerance is explained by enhanced retention of germline stem cells in dysgenic ovaries, which are typically lost due to DNA damage. Our observations reveal segregating variation in TE tolerance for the first time, and implicate gametogenic regulators as a source of tolerant variants in natural populations.
Avian thermoregulation in the heat: is evaporative cooling more economical in nocturnal birds?
Authors: O’Connor Ryan S. , Smit Ben , Talbot William A. , Gerson Alexander R. , Brigham R. Mark , Wolf Blair O. , McKechnie Andrew E. 
Published: March 2018

AbstractEvaporative cooling is a prerequisite for avian occupancy of hot, arid environments, and is the only avenue of heat dissipation when air temperatures (Ta) exceed body temperature (Tb). Whereas diurnal birds can potentially rehydrate throughout the day, nocturnal species typically forgo drinking between sunrise and sunset. We hypothesized that nocturnal birds have evolved reduced rates of evaporative water loss (EWL) and more economical evaporative cooling mechanisms than those of diurnal species that permit them to tolerate extended periods of intense heat without becoming lethally dehydrated. We used phylogenetically-informed regressions to compare EWL and evaporative cooling efficiency (ratio of evaporative heat loss [EHL] and metabolic heat production [MHP]; EHL/MHP) among nocturnal and diurnal birds at high Ta. We analyzed variation in three response variables: 1) slope of EWL at Tabetween 40 and 46°C, 2) EWL at Ta= 46°C, and 3) EHL/MHP at Ta= 46°C. Nocturnality emerged as a weak, negative predictor, with nocturnal species having slightly shallower slopes and reduced EWL compared to diurnal species of similar mass. In contrast, nocturnal activity was positively correlated with EHL/MHP, indicating a greater capacity for evaporative cooling in nocturnal birds. However, our analysis also revealed conspicuous differences among nocturnal taxa. Caprimulgids and Australian-owlet nightjars had shallower slopes and reduced EWL compared to similarly-sized diurnal species, whereas owls had EWL rates comparable to diurnal species. Consequently, our results did not unequivocally demonstrate more economical cooling among nocturnal birds. Owls predominately select refugia with cooler microclimates, but the more frequent and intense heat waves forecast for the 21stcentury may increase microclimate temperatures and the necessity for active heat dissipation, potentially increasing owls’ vulnerability to dehydration and hyperthermia.
A preliminary evaluation of metacognitive beliefs in high functioning children with autism spectrum disorder
Authors: Campbell Breeanna , Curran Michelle , Inkpen Raymond , Katsikitis Mary , Kannis-Dymand Lee 
Published: March 2018

Purpose
Metacognitive beliefs and processes have been found to perpetuate anxiety and depression in youth and adults. However, the presence of metacognitive beliefs in children with autism spectrum disorder is somewhat unclear and has received limited research attention to date. The purpose of this paper is to explore metacognitive beliefs in children with autism and associations with anxiety and depression.

Design/methodology/approach
In total, 23 high functioning participants (17 male and 6 female) between the ages of 8 and 12 (M=10.38) diagnosed on the autism spectrum completed the study. Participants completed the Revised Children’s Scale of Anxiety and Depression and the Metacognitions Questionnaire for Children.

Findings
Correlation analyses revealed that positive and negative metacognitive beliefs were found, as hypothesised, to be prevalent in this sample.

Originality/value
Despite methodological limitations, this is one of the first research evaluations to provide evidence for metacognitive beliefs in high functioning children with autism and comorbid anxiety or low mood.
A pilot study on combining risperidone and pivotal response treatment on communication difficulties in children with autism spectrum disorder
Authors: Rezaei Mohammad , Moradi AliReza , Tehrani-Doost Mehdi , Hassanabadi HamidReza , Khosrowabadi Reza 
Published: March 2018

Purpose
The purpose of this paper is to investigate the effects of combined risperidone (RIS) and pivotal response treatment (PRT) in children with autism spectrum disorder (ASD).

Design/methodology/approach
In all, 34 children diagnosed with ASD (mean age of 12.36 years) were randomly divided into two groups: an RIS treatment group (n=18) and an RIS plus PRT (n=16). Communication skills were evaluated with the child communication checklist (CCC).

Findings
Total score of the CCC was increased in both groups after three months compared with the score prior to treatment. The total score of the CCC was significantly higher in the combined treatment group than in the RIS group.

Originality/value
Treatment with RIS combined with PRT may result in a better outcome in communication skill for children with autism than RIS training alone.
Best practice relief supply for emergency services in a developed economy
Authors: Wilson Mark M.J. , Tatham Peter , Payne John , L’Hermitte Cécile , Shapland Michael 
Published: March 2018

Purpose
The purpose of this paper is to discuss the challenges inherent in planning and responding to disaster events in a multi-agency context where numerous governmental and non-governmental actors and agencies are involved in the planning and response phases. In particular, the authors examine a situation where a lead agency has recently been delegated the responsibility for emergency relief logistics and how it might determine and implement best practice.

Design/methodology/approach
Adopting an iterative inductive approach, the authors gather data and insights from academic literature, emergency management policies, frameworks and documents and exploratory in-depth interviews with 12 key informants who have considerable experience with the challenges of logistic preparation and response to disasters in a developed country context. The data and context are limited to developed counties, especially the state of Queensland, Australia.

Findings
The authors discuss the challenge of achieving coordinated supply chain management where mandated/lead response agencies are required to meet stakeholder and local community expectations and outcomes. From these findings, the authors offer 11 practical recommendations to assist the delivery of best practice in emergency logistics.

Originality/value
Humanitarian logistics is usually examined from a low/middle-income country perspective, yet an efficient and effective disaster response is no less important for developed economies. In this respect, the authors offer a fresh examination of the challenges of delivering best practice for emergency logistics in order to achieve expected community outcomes.
Dynamic truck and trailer routing problem for last mile distribution in disaster response
Authors: Maghfiroh Meilinda F.N. , Hanaoka Shinya 
Published: March 2018

Purpose
The purpose of this paper is to investigate the application of the dynamic vehicle routing problem for last mile distribution during disaster response. The authors explore a model that involves limited heterogeneous vehicles, multiple trips, locations with different accessibilities, uncertain demands, and anticipating new locations that are expected to build responsive last mile distribution systems.

Design/methodology/approach
The modified simulated annealing algorithm with variable neighborhood search for local search is used to solve the last mile distribution model based on the criterion of total travel time. A dynamic simulator that accommodates new requests from demand nodes and a sample average estimator was added to the framework to deal with the stochastic and dynamicity of the problem.

Findings
This study illustrates some practical complexities in last mile distribution during disaster response and shows the benefits of flexible vehicle routing by considering stochastic and dynamic situations.

Research limitations/implications
This study only focuses day-to-day distribution on road/land transportation for distribution, and additional transportation modes need to be considered further.

Practical implications
The proposed model offers operational insights for government disaster agencies by highlighting the dynamic model concept for supporting relief distribution decisions. The result suggests that different characteristics and complexities of affected areas might require different distribution strategies.

Originality/value
This study modifies the concept of the truck and trailer routing problem to model locations with different accessibilities while anticipating the information gap for demand size and locations. The results show the importance of flexible distribution systems during a disaster for minimizing the disaster risks.
The British Press and the 1918 Reform Act
Authors: Bingham Adrian 
Published: March 2018

AbstractThis essay provides the first comprehensive study of the British press's reporting of, and discussions about, the electoral reform proposals that became the Representation of the People Act 1918. It shows that, in responding enthusiastically to calls for substantial constitutional change, newspapers from across the ideological spectrum revealed a deep disillusionment with partisan politics and party machines, and imagined a re‐energised democracy that would rise to the complex tasks of post‐war reconstruction. Female voters were to have a significant role in this more inclusive political system, and even long‐standing opponents of women's suffrage chose this moment publicly to alter their position – although by repeatedly framing enfranchisement as an outcome of service to the nation, the language of democratic rights was sometimes blurred. Many newspapers also argued for proportional representation (PR) to create a fairer, less cynical and less strictly‐managed type of politics. These debates marked an important moment in the redefinition of British democracy, and they would have a lasting influence on post‐war political culture. After 1918, the press generally defended this new democracy, even if some commentators expressed anxieties that certain voters lacked the capacity or inclination properly to exercise their political responsibilities. Set against the political turbulence across Europe, and the inevitable disquiet generated by economic dislocation and mass unemployment, it is the resilience of democracy in Britain, rather than its weakness, that is notable. In these difficult times, the press played a crucial role in legitimising and stabilising the parliamentary system and celebrating a more inclusive politics.
Kernel excess mass test for multimodality
Authors: Lee Seonmi , Jang Woncheol , Park Byeong U. 
Published: March 2018

SummaryIn this paper we propose a new statistical procedure for testing the multimodality of an underlying distribution. Peter Hall developed an innovative idea of calibrating the null distribution for the excess mass test statistic using the empirical distribution function. We find that the qualitative characteristics of a smooth underlying distribution function on the number of modes is barely preserved in the excess mass functional by the non‐smooth empirical distribution function. Instead of the empirical distribution function, we propose to use a kernel distribution function estimator. We derive the limiting distribution of the resulting test statistic under strong unimodality, based on which we apply the calibration idea to the proposed test statistic to obtain a cut‐off value. Our numerical study suggests that the calibrated kernel excess mass test has greater power than other existing methods. We also illustrate the use of the proposed method in a case study in astronomy which supports an assumption on a physical property of minor planets in the solar system.
Greedy forward regression for variable screening
Authors: Cheng Ming‐Yen , Feng Sanying , Li Gaorong , Lian Heng 
Published: March 2018

SummaryIn the ultra‐high dimensional setting, two popular variable screening methods with the desirable sure screening property are sure independence screening (SIS) and forward regression (FR). Both are classical variable screening methods, and recently have attracted greater attention under high‐dimensional data analysis. We consider a new and simple screening method that incorporates multiple predictors at each step of forward regression, with decisions on which variables to incorporate based on the same criterion. If only one step is carried out, the new procedure reduces to SIS. Thus it can be regarded as a generalisation and unification of FR and SIS. More importantly, it preserves the sure screening property and has computational complexity similar to FR at each step, yet it can discover the relevant covariates in fewer steps. Thus it reduces the computational burden of FR drastically while retaining the advantages of the latter over SIS. Furthermore, we show that it can find all the true variables if the number of steps taken is the same as the correct model size, which is a new theoretical result even for the original FR. An extensive simulation study and application to two real data examples demonstrate excellent performance of the proposed method.