bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodular biosensors reveal a novel platform for activation of G proteins by growth factor receptors
Authors: Midde Krishna K. , Aznar Nicolas , Laederich Melanie B. , Ma Gary S. , Kunkel Maya T. , Newton Alexandra C. , Ghosh Pradipta 
Published: February 2015

Significance
Long-held tenets in the field of signal transduction are that G proteins are activated exclusively by G protein-coupled receptors and that growth factor receptor tyrosine kinases (RTKs) do not have the wherewithal to do the same. In this work we created fluorescent biosensors derived from the multimodular signal transducer Gα-interacting vesicle-associated protein (GIV), an unusual protein that binds RTKs and activates G proteins, and used them in FRET and bimolecular fluorescent complementation assays to visualize RTK–GIV–G protein signaling complexes directly in single living cells. These studies not only provide evidence that GIV serves as a platform for transactivation of G proteins by growth factor RTKs but also illuminate the spatial and temporal dynamics of such noncanonical G protein signaling.
Epigenetic control of intestinal barrier function and inflammation in zebrafish
Authors: Marjoram Lindsay , Alvers Ashley , Deerhake M. Elizabeth , Bagwell Jennifer , Mankiewicz Jamie , Cocchiaro Jordan L. , Beerman Rebecca W. , Willer Jason , Sumigray Kaelyn D. , Katsanis Nicholas , Tobin David M. , Rawls John F. , Goll Mary G. , Bagnat Michel 
Published: February 2015

Significance
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are intestinal disorders of poorly understood origin and are associated with significant morbidity and mortality. A crucial factor associated with IBD onset is the presence of elevated levels of the proinflammatory cytokine tumor necrosis factor (TNF) in the intestine, signified by the use of anti-TNF therapy to treat patients with Crohn’s disease. Despite its pathogenic relevance, the mechanisms regulating TNF expression and IBD onset remain largely unknown. Here, we show that loss of epigenetic regulation results in the induction of TNF in the intestinal epithelium, leading to a loss of intestinal barrier function and inflammation. Our results suggest that mutations in genes controlling epigenetic regulators can lead to IBD onset.
Sugar-based amphiphilic nanoparticles arrest atherosclerosis in vivo
Authors: Lewis Daniel R. , Petersen Latrisha K. , York Adam W. , Zablocki Kyle R. , Joseph Laurie B. , Kholodovych Vladyslav , Prud’homme Robert K. , Uhrich Kathryn E. , Moghe Prabhas V. 
Published: February 2015

Significance
Lipid-rich plaques in major blood vessels recruit macrophages that further exacerbate the lipid burden and risk of heart attacks or stroke. A local approach to prevent plaque growth has yet to be successfully deployed. In this study, we examine how synthetic ligands counteract macrophage atherogenesis and de-escalate plaque burden. Using a library of sugar-based amphiphilic core-shell layered nanoparticles, we demonstrate the design principles necessary to prevent oxidized lipid uptake and suppress scavenger receptor expression in macrophages, switching them to an “atheroprotective” phenotype. When administered in vivo, nanoparticles were retained at atherosclerotic lesions, where they mitigated cholesterol clefts, inflammation, and artery occlusion. Thus, synthetic nanomedicines could be used to potentially treat acute coronary syndrome, a major unmet need in cardiovascular diseases.
ATF3 mediates inhibitory effects of ethanol on hepatic gluconeogenesis
Authors: Tsai Wen-Wei , Matsumura Shigenobu , Liu Weiyi , Phillips Naomi G. , Sonntag Tim , Hao Ergeng , Lee Soon , Hai Tsonwin , Montminy Marc 
Published: February 2015

Significance
Insulin resistance is a major risk factor for the development of diabetes. Associated increases in hepatic glucose production contribute to this process by promoting compensatory increases in insulin secretion that eventually lead to islet failure. This study characterizes the role of ATF3, a transcriptional repressor of the basic region-leucine zipper (bZIP) family, in mediating the hypoglycemic effects of acute alcohol consumption through the down-regulation of gluconeogenic genes. Based on the ability of ATF3 to displace CREB and its coactivator CRTC2 from CREB-binding sites on gluconeogenic genes, we imagine that small molecules with similar activity may provide therapeutic benefits to individuals with type II diabetes.
Cell stress increases ATP release in NLRP3 inflammasome-mediated autoinflammatory diseases, resulting in cytokine imbalance
Authors: Carta Sonia , Penco Federica , Lavieri Rosa , Martini Alberto , Dinarello Charles Anthony , Gattorno Marco , Rubartelli Anna 
Published: February 2015

Significance
Single amino acid mutations in NLRP3 in patients with cryopyrin-associated periodic syndromes (CAPS) lead to oversecretion of IL-1β, resulting in severe inflammatory manifestations. How this occurs is unclear. We show here that cellular stress in blood monocytes contributes to CAPS pathophysiology, allowing copious release of ATP in response to minute concentrations of inflammatory stimuli. As a consequence, the released ATP enhances NLRP3-mediated secretion of IL-1β and IL-18 by activating P2X purinoceptor 7. Later, CAPS cells undergo oxidative stress, which impairs secretion of the anti-inflammatory IL-1 receptor antagonist, worsening the clinical picture. Antioxidants rescue the reduced production of the antagonist. Blocking extracellular ATP and improving stress tolerance may represent novel therapeutic strategies in autoinflammatory diseases.
Rare variants in neuronal excitability genes influence risk for bipolar disorder
Authors: Ament Seth A. , Szelinger Szabolcs , Glusman Gustavo , Ashworth Justin , Hou Liping , Akula Nirmala , Shekhtman Tatyana , Badner Judith A. , Brunkow Mary E. , Mauldin Denise E. , Stittrich Anna-Barbara , Rouleau Katherine , Detera-Wadleigh Sevilla D. , Nurnberger John I. , Edenberg Howard J. , Gershon Elliot S. , Schork Nicholas ,   The Bipolar Genome Study, Price Nathan D. , Gelinas Richard , Hood Leroy , Craig David , McMahon Francis J. , Kelsoe John R. , Roach Jared C. , Kelsoe John R. , Greenwood Tiffany A. , Nievergelt Caroline M. , Shilling Paul D. , Shekhtman Tatyana , Roach Jared C. , Ament Seth A. , Hood Leroy , Nurnberger John I. , Edenberg Howard J. , Foroud Tatiana , Koller Daniel L. , Gershon Elliot S. , Badner Judith A. , Liu Chunyu , Scheftner William A. , Lawson William B. , Coryell William , Potash James B. , Rice John , Byerley William , McMahon Francis J. , Hou Liping , Berrettini Wade H. , Zandi Peter P. , McInnis Melvin G. , Craig David W. , Szelinger Szabolcs , Schulze Thomas G. , Schork Nicholas J. , Quarless Danjuma 
Published: February 2015

Significance
Bipolar disorder (BD) is a common, severe, and recurrent psychiatric disorder with no known cure and substantial morbidity and mortality. Heritable causes contribute up to 80% of the lifetime risk for BD. Common genetic variation explains ∼25% of this heritable risk. Rare genetic variants may explain additional risk. We identified contributions of rare variants to BD by sequencing the genomes of 200 individuals from 41 families with BD. The two main findings of this study were as follows: rare risk variants for BD were enriched in genes and pathways that regulate diverse aspects of neuronal excitability; and most of these risk variants were noncoding with predicted regulatory functions. These results highlight specific hypotheses for future research and potential therapeutic targets.
Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK
Authors: Sagiv-Barfi Idit , Kohrt Holbrook E. K. , Czerwinski Debra K. , Ng Patrick P. , Chang Betty Y. , Levy Ronald 
Published: February 2015

Significance
Antibodies that block the negative signals between PD1-Ligand on tumor cells and PD-1 on T cells are effective therapies against several types of cancer. Ibrutinib, a covalent inhibitor of BTK is an approved therapy for B-cell leukemia and lymphoma. But ibrutinib also inactivates ITK, an enzyme required for certain subsets of T lymphocytes (Th2 T cells). We found that the combination of anti–PD-L1 antibodies and ibrutinib led to impressive therapeutic effects not only in animal models of lymphoma but, surprisingly, also in models of breast cancer and colon cancer. Based on these preclinical results, we suggest that the combination of PD-1/PD-L1 blockade and ibrutinib be tested broadly in patients with lymphoma and also in other hematologic malignancies and solid tumors.
Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis
Authors: Shen Yiguo , Ge Woo-Ping , Li Yulong , Hirano Arisa , Lee Hsien-Yang , Rohlmann Astrid , Missler Markus , Tsien Richard W. , Jan Lily Yeh , Fu Ying-Hui , Ptáček Louis J. 
Published: February 2015

Significance
Paroxysmal nonkinesigenic dyskinesia (PNKD) is an autosomal dominant episodic movement disorder precipitated by coffee, alcohol, and stress. Here, we show that PNKD interacts with synaptic active zone proteins Rab3-interacting molecule (RIM)1 and RIM2, localizes to synapses, and modulates neurotransmitter release. PNKD knockout mice have impaired synaptic transmission and short-term plasticity.
Myoblast differentiation of human mesenchymal stem cells on graphene oxide and electrospun graphene oxide–polymer composite fibrous meshes: importance of graphene oxide conductivity and dielectric constant on their biocompatibility
Authors: Chaudhuri Biswadeep , Bhadra Debabrata , Moroni Lorenzo , Pramanik Krishna 
Published: February 2015

Abstract
Recently graphene and graphene based composites are emerging as better materials to fabricate scaffolds. Addition of graphene oxide (GO) nanoplatelets (GOnPs) in bioactive polymers was found to enhance its conductivity (σ) and, dielectric permittivity (ϵ) along with biocompatibility. In this paper, human cord blood derived mesenchymal stem cells (CB-hMSCs) were differentiated to skeletal muscle cells (hSkMCs) on spin coated thin GO sheets composed of GOnPs and on electrospun fibrous meshes of GO–PCL (poly-caprolactone) composite. Both substrates exhibited excellent myoblast differentiations and promoted self-alignedmyotubesformation similar to natural orientation. σ, ϵ, microstructural and vibration spectroscopic studies were carried out for the characterizations of GO sheet and the composite scaffolds. Significantly enhanced values of both σ and ϵ of the GO–PCL composite were considered to provide favourable cues for the formation of superior multinucleated myotubes on the electrospun meshes compared to those on thin GO sheets. The present results demonstrated that both substrates might be used as potential candidates for CB-hMSCs differentiation and proliferation for human skeletal muscle tissue regeneration.
The rare two-dimensional materials with Dirac cones
Authors: Wang Jinying , Deng Shibin , Liu Zhongfan , Liu Zhirong 
Published: February 2015

Abstract
Inspired by the great development of graphene, more and more research has been conducted to seek new two-dimensional (2D) materials with Dirac cones. Although 2D Dirac materials possess many novel properties and physics, they are rare compared with the numerous 2D materials. To provide explanation for the rarity of 2D Dirac materials as well as clues in searching for new Dirac systems, here we review the recent theoretical aspects of various 2D Dirac materials, including graphene, silicene, germanene, graphynes, several boron and carbon sheets, transition-metal oxides (VO2)n/(TiO2)m and (CrO2)n/(TiO2)m, organic and organometallic crystals, so-MoS2, and artificial lattices (electron gases and ultracold atoms). Their structural and electronic properties are summarized. We also investigate how Dirac points emerge, move, and merge in these systems. The von Neumann–Wigner theorem is used to explain the scarcity of Dirac cones in 2D systems, which leads to rigorous requirements on the symmetry, parameters, Fermi level, and band overlap of materials to achieve Dirac cones. Connections between existence of Dirac cones and the structural features are also discussed.
Different DNA repair pathways are required following excision and integration of the DNA cut & paste transposonpiggyBatinSaccharomyces cerevisiae
Authors: She Weifeng , Cambouris Courtney Busch , Craig Nancy L. 
Published: February 2015

AbstractThe movement of transposable elements from place to place in a genome requires both element-encoded and host-encoded factors. In DNA cut & paste transposition, the element-encoded transposase performs the DNA breakage and joining reactions that excise the element from the donor site and integrate it into the new insertion site. Host factors can influence many aspects of transposition. Notably, host DNA repair factors mediate the regeneration of intact duplex DNA necessary after transposase action by repairing the double strand break in the broken donor backbone, from which the transposon has excised, and repairing the single strand gaps that flank the newly inserted transposon. We have exploited the ability of the mammalian transposonpiggyBat, a member of thepiggyBacsuperfamily, to transpose inSaccharomyces cerevisiaeand used the yeast single gene deletion collection to screen for genes encoding host factors involved inpiggyBattransposition.piggyBactransposition is distinguished by the fact thatpiggyBacelements insert into TTAA target sites and also that the donor backbone is restored to its pre-transposon sequence after transposon excision, that is, excision is precise. We have found that repair of the broken donor backbone requires the non-homologous end-joining repair pathway (NHEJ). By contrast, NHEJ is not required for DNA repair at the new insertion site. Thus multiple DNA repair pathways are required forpiggyBactransposition.
Flaw or discovery? Calculating exact p-values for genome-wide association studies in inbred populations
Authors: Shen Xia 
Published: February 2015

ABSTRACTMotivation:Genome-wide association studies have been conducted in inbred populations where the sample size is small. The ordinary association p-values and multiple testing correction therefore become questionable, as the detected genetic effect may or may not be due to chance, depending on the minor allele frequency distribution across the genome. Instead of permutation testing, marker-specific false positive rate can be analytically calculated in inbred populations without heterozygotes.Results:Solutions of exact p-values for genome-wide association studies in inbred populations were derived and implemented. An example is presented to illustrate that the marker-specific experiment-wise p-value varies as the genome-wide minor allele frequency distribution changes. A simulation using realArabidopsis thalianagenome indicates that the use of exact p-values improves detection power and reduces inflation due to population structure. An analysis of a defense-related case-control phenotype using the exact p-values revealed the causal locus, where markers with higher MAFs had smaller p-values than the top variants with lower MAFs in ordinary genome-wide association analysis.Availability and Implementation:Project URL:https://r-forge.r-project.org/projects/statomics/. The R packagep.exact:https://r-forge.r-project.org/R/?group_id=2030.Contact:xia.shen@ki.se
Genome-Wide Characterization ofcis-Acting DNA Targets Reveals the Transcriptional Regulatory Framework ofOpaque2in Maize
Authors: Li Chaobin , Qiao Zhenyi , Qi Weiwei , Wang Qian , Yuan Yue , Yang Xi , Tang Yuanping , Mei Bing , Lv Yuanda , Zhao Han , Xiao Han , Song Rentao 
Published: February 2015

AbstractOpaque2 (O2) is a transcription factor that plays important roles during maize endosperm development. Mutation of the O2 gene improves the nutritional value of maize seeds but also confers pleiotropic effects that result in reduced agronomic quality. To reveal the transcriptional regulatory framework of O2, we studied the transcriptome of o2 mutants using RNA sequencing (RNA-Seq) and determined O2 DNA binding targets using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq). The RNA-Seq analysis revealed 1605 differentially expressed genes (DEGs) and 383 differentially expressed long, noncoding RNAs. The DEGs cover a wide range of functions related to nutrient reservoir activity, nitrogen metabolism, stress resistance, etc. ChIP-Seq analysis detected 1686 O2 DNA binding sites distributed over 1143 genes. Overlay of the RNA-Seq and ChIP-Seq results revealed 35 O2-modulated target genes. We identified four O2 binding motifs; among them, TGACGTGG appears to be the most conserved and strongest. We confirmed that, except for the 16- and 18-kD zeins, O2 directly regulates expression of all other zeins. O2 directly regulates two transcription factors, genes linked to carbon and amino acid metabolism and abiotic stress resistance. We built a hierarchical regulatory model for O2 that provides an understanding of its pleiotropic biological effects.
The present state of entrepreneurship ecosystems in selected countries in Africa
Authors: Sheriff Michael , Muffatto Moreno 
Published: February 2015

Purpose– Entrepreneurship ecosystems could be useful road maps for the formulation of entrepreneurship policies for countries in Africa. The twenty-first century economic development agenda lay a lot of emphasis on the pivotal role that entrepreneurship plays in the growth of economies, job creation and poverty alleviation especially in Africa. But without the right entrepreneurial ecosystems to enhance the formulation of pertinent entrepreneurship policies, achieving entrepreneurial economic growth will be difficult. The existing frameworks for the development of entrepreneurship ecosystems are based on research that has been conducted elsewhere. The paper aims to discuss these issues.Design/methodology/approach– Entrepreneurship research in Africa has rarely focused in understanding and evaluating the entrepreneurship ecosystems. In this paper, we have attempted to examine the present state of the entrepreneurship ecosystems in four countries (Botswana, Egypt, Ghana and Uganda) in Africa. Despite the fact that extant literature on the concept is limited, it has been reviewed to provide a picture of entrepreneurship ecosystems. Relevant national and international documents were also examined to evaluate the present state of entrepreneurship ecosystems in these countries.Findings– The findings from each of the countries though they depict a static situation, justify the proposition that entrepreneurs are omnipresent, it is only the entrepreneurship environment that accounts for the differences in entrepreneurial economic growth and the cross-countries comparisons shows the dissimilarities in national entrepreneurship environments.Research limitations/implications– In conclusion, a broad process to develop entrepreneurship ecosystems initiatives is suggested alongside the crucial roles that governments and other stakeholders should play which implies that a National Entrepreneurship Mission might be necessary.Originality/value– Multiple case studies that have compared entrepreneurship ecosystems of countries in Africa are very rare. This study though explorative, is one of the first. The findings and conclusions could be useful for a detailed study to map out pertinent and self sustaining entrepreneurship ecosystems that are necessary for the formulation of entrepreneurship policies.
Female entrepreneurship and growth in Cameroon
Authors: Okah-Efogo Françoise , Timba Gaëlle Tatiana 
Published: February 2015

Purpose
– The purpose of this paper is to supplement the literature on the effect of female entrepreneurship on economic growth by bringing new evidence for the case of SMEs owned by women in Cameroon.

Design/methodology/approach
– Effects of female entrepreneurship on Cameroonian economic growth are analyzed through a simple statistical analysis.

Findings
– Our results reveal that there is a growing female entrepreneurship in Cameroon, localized in many different sectors of activity. Moreover, these SMEs are opportunity entrepreneurship which contributes to economic growth by considerably reducing unemployment particularly for women, generating revenues for government and enhancing human capital skills.

Research limitations/implications
– The study suggests an investment in SMEs owned by women and an investment in education and skills of those women in order to positively affect economic growth.

Originality/value
– Many studies have focussed their attention on the relationship between SMEs and economic growth, but few attempted to evaluate the theoretical assumptions in case studies and in a gender perspective.
Commentary on Abrahamson and Rubin (2012) “Discourse structure differences in lay and professional health communication”, Journal of Documentation, Vol. 68 No. 6, pp. 826-851
Authors: Urquhart Christine , Urquhart Alexander H. 
Published: February 2015

Purpose
– The purpose of this paper is to criticise the paper by Jennie A. Abrahamson and Victoria L. Rubin (2012) “Discourse structure differences in lay and professional health communication”, Journal of Documentation, Vol. 68 No. 6, pp. 826-851.

Design/methodology/approach
– The author reviewed the antecedents of Rhetorical Structure Theory (RST) in discourse analysis, and paid close attention to the differences between the original formulation of RST, later formulations of the RST model and the application of RST in this paper. The author also reviewed the literature on physician-patient communication, and patient-patient support to contextualise the findings of Abrahamson and Rubin.

Findings
– The paper shows evidence of over-simplification of RST since its initial formulation. Next, the Motivation relationship in the original Mann/Thompson formulation of RST appears problematic. This makes the authors’ RST findings that patient-patient (or consumer-consumer) information sharing appear to be more effective than physician-consumer information sharing rather tenuous. An important additional flaw is that there was only one physician participant in this study. A practical limitation to the study is that physicians mostly interact face-to-face with patients and use of consumer advice web sites may not fit well with the current practice of medicine.

Research limitations/implications
– The author had limited examples in the paper to examine how the authors had categorised the binary unit relationships.

Originality/value
– RST is promising for discourse analysis of information advice web sites but simplifications in its application can lead to unwarranted claims.
MC 2.0: testing an apparel co-design experience model
Authors: Wu Juanjuan , Kang Ju-Young M. , Damminga Cara , Kim Hye-Young , Johnson Kim K P 
Published: February 2015

Purpose
– The purpose of this paper is to test an online apparel co-design experience model and to investigate six determinants (perceived ease of use, perceived usefulness, enjoyment, level of personalization, social presence, and attitude towards the co-designed product) of online apparel co-design experience and effects on behavioural intention.

Design/methodology/approach
– Female college students (n=265) were surveyed after an actual online apparel co-design experience in a computer lab and interactions with other users wherever such arenas were provided. structural equation modelling was used for data analysis.

Findings
– The findings revealed that subjects’ apparel co-design experience was positively affected by enjoyment, attitude towards the co-designed product, perceived ease of use, and social presence. And behavioural intention towards the mass customization sites was positively affected by subjects’ attitude towards the co-design experience, subjective norm, and enjoyment.

Originality/value
– The research makes a unique theoretical contribution by conceptualizing MC 2.0 (MC sites that provide arenas for user interaction) and by incorporating and confirming the significance of both “enjoyment” and “social presence” variables as predictors of online apparel co-design experience.