bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do African Voters Favor Coethnics? Evidence from a Survey Experiment in Benin
Authors: Adida Claire L. 
Published: April 2015

AbstractCan African politicians play the ethnic card? Ethnicity matters for a host of outcomes in Africa, but debate remains about the extent to which it motivates the African voter. In experimental settings, we know that ethnicity shapes political support for hypothetical candidates. This paper offers an experimental test of the extent to which ethnicity shapes political support for actual, real-world politicians. Relying on Benin’s mixed-ethnicity President, this paper proposes a survey experiment that measures the independent effect of coethnic cues in boosting support across both coethnic groups. The results reveal that coethnic cues work: the same political actor can draw support from two different ethnic groups based solely on subtle ethnic cues.
A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling
Authors: Shimizu Noriaki , Maruyama Takako , Yoshikawa Noritada , Matsumiya Ryo , Ma Yanxia , Ito Naoki , Tasaka Yuki , Kuribara-Souta Akiko , Miyata Keishi , Oike Yuichi , Berger Stefan , Schütz Günther , Takeda Shin’ichi , Tanaka Hirotoshi 
Published: April 2015

AbstractSkeletal muscle has a pleiotropic role in organismal energy metabolism, for example, by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. Here we unravel the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues. Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. We demonstrate that the resulting depletion of plasma alanine serves as a cue to increase plasma levels of fibroblast growth factor 21 (FGF21) and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. We propose that this skeletal muscle-liver-fat signalling axis may serve as a target for the development of therapies against various metabolic diseases, including obesity.
Detection of PHLPP1α/β in Human and Mouse Brain by Different Anti-PHLPP1 Antibodies
Authors: Jackson Travis C. , Bayir Hülya , Ikonomovic Milos D. , Janesko-Feldman Keri , Mi Zaichuan , Gao Tianyan , Jackson Edwin K. , Kochanek Patrick M. 
Published: April 2015

AbstractPleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140–150 kDa) and PHLPP1β (~180–190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145–150 kDa). The other four antibodies detect a non-specific signal at ~150 kDa as evidenced by its abundance in PHLPP1 KO tissues. Results suggest Cosmo antibody is a better reagent to detect PHLPP1α by Western blot. In contrast, we found it unsuitable for immunofluorescence applications in brain. Our findings caution interpretation of the ~150 kDa band detected by some PHLPP1 antibodies in rodent and human tissues. Results also recapitulate the importance of including molecular weight standards in Western blot data to simplify retrospective analysis.
Identification of a novel selective agonist of PPARγ with no promotion of adipogenesis and less inhibition of osteoblastogenesis
Authors: Liu Chang , Feng Tingting , Zhu Ningyu , Liu Peng , Han Xiaowan , Chen Minghua , Wang Xiao , Li Ni , Li Yongzhen , Xu Yanni , Si Shuyi 
Published: April 2015

AbstractNuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) plays an important role in the regulation of glucose homeostasis and lipid metabolism. However, current PPARγ-targeting drugs such as thiazolidinediones (TZDs) are associated with undesirable side effects. We identified a small molecular compound, F12016, as a selective PPARγ agonist by virtual screening, which showed moderate PPARγ agonistic activity and binding ability for PPARγ. F12016 did not activate other PPAR subtypes at 30 μM and selectively modulated PPARγ target gene expression. In diabetic KKAy mice, F12016 had insulin-sensitizing and glucose-lowering properties and suppressed weight gain. In vitro, F12016 effectively increased glucose uptake and blocked cyclin-dependent kinase 5-mediated phosphorylation of PPARγ at Ser273, but slightly triggered adipogenesis and less inhibited osteoblastogenesis than rosiglitazone. Moreover, compared with the full agonist rosiglitazone, F12016 had a distinct group of coregulators and a different predicted binding mode for the PPARγ ligand-binding domain. A site mutation assay confirmed the key epitopes, especially Tyr473 in AF-2. In summary, our study shows that F12016 is a non-TZD, novel selective PPARγ agonist without the classical lipogenic side effects, which may provide a new structural strategy for designing PPARγ ligands with advantages over TZDs.
Association between the CD24 Ala57Val polymorphism and risk for multiple sclerosis and systemic lupus erythematosus: a meta-analysis
Authors: Huang Jian , Yang Yaqi , Liang Zibin , Kang Miaomiao , Kuang Ying , Li Feng 
Published: April 2015

AbstractThe cluster of differentiation 24 (CD24) Ala57Val polymorphism has been implicated as a risk factor for multiple sclerosis (MS) and systemic lupus erythematosus (SLE); however, genetic studies have produced controversial results. A meta-analysis was performed on this topic. We used odds ratio (OR) and 95% confidence interval (95% CI) to investigate the strength of association. Eleven studies from nine publications consisting of 2466 cases and 2650 controls were included. The results suggested that the CD24 Val/Val genotypes were associated with an increased risk of MS in all study subjects and Caucasians (OR = 2.28, 95% CI: 1.68–3.10, Pz < 0.001 and OR = 2.30, 95% CI: 1.66–3.20, Pz < 0.001, respectively). Sensitivity analysis showed that no individual study was found to be significantly biasing the pooled results. Although meta-analysis also suggested an association between the CD24 Val/Val genotypes and SLE risk in Caucasians (OR = 1.71, 95% CI: 1.31–2.24, Pz < 0.001), sensitivity analysis demonstrated that the association was not statistically significant after removing a Spanish study. In conclusion, this meta-analysis suggests that the CD24 Ala57Val polymorphism is associated with an increased risk of MS in Caucasians. However, the available evidence is not sufficient to support an association between the CD24 Ala57Val polymorphism and SLE risk.
Stellungnahme der Taskforce „Neurostimulation bei Schlafapnoe“ zur Stimulation der oberen Atemwege
Authors: Steffen A. , Heiser C. , Herzog M. , Bergler W. , Rothmeier N. , Maurer J. 
Published: April 2015

ZusammenfassungDie Stimulation der oberen Atemwege kann als Sekundärtherapie der mindestens mittelgradigen obstruktiven Schlafapnoe als wirksame Behandlungsmethode betrachtet werden. Die atmungsgesteuerte Stimulation der oberen Atemwege (geschlossener Kreislauf; Fa. Inspire Medical Systems) weist ein hohes Evidenzniveau mit größeren Patientenkollektiven und längeren Nachbeobachtungszeiten auf, sodass die Einschätzung als sichere und effektive Therapiealternative fundiert erfolgen kann. Ob die Ergebnisse der atmungsunabhängigen Stimulation (offener Kreislauf; Fa. ImThera Medical) mit denen der atmungssynchronen vergleichbar sind, kann zum jetzigen Zeitpunkt nicht beurteilt werden. Es ist jedoch zu erwarten, dass eine erste Einschätzung hierzu nach Abschluss der Studie THN#2 möglich sein wird. Zur weiteren Optimierung beider Verfahren und zu Langzeitergebnissen sind weiterführende klinisch-wissenschaftliche Studien mit für die Verfahren jeweils unterschiedlichen Fragestellungen notwendig. Die Arbeitsgruppe Schlafmedizin der DGHNO begleitet die weitere Entwicklung mithilfe einer im Mai 2014 eigens gegründeten Taskforce „Neurostimulation bei Schlafapnoe“.
Unraveling the association between mRNA expressions and mutant phenotypes in a genome-wide assessment of mice
Authors: Liao Ben-Yang , Weng Meng-Pin 
Published: April 2015

Significance
The general perception that mRNA transcription of a gene is regulated by the functional requirements of the cell or tissue has never been systematically tested using genome-wide data. To assess the functional implications of mRNA transcription in mice directly, we analyzed gene expression data and phenotype data of mouse mutants as a proxy of gene function at the tissue level. Our results confirmed the important role transcriptional regulation has in maintaining the gene’s proper spatial and temporal functions. In addition, we found that mutations resulting in phenotypic defects in expressed tissues are more likely to occur in highly transcribed genes, tissue-specific genes, genes expressed during early embryonic stages, or genes with evolutionarily conserved mRNA expression.
Experimental ocean acidification alters the allocation of metabolic energy
Authors: Pan T.-C. Francis , Applebaum Scott L. , Manahan Donal T. 
Published: April 2015

SignificanceAnthropogenic emission of CO2is causing global ocean acidification. For many species, biological responses to acidification often show limited impact at the level of the whole animal. Our integrative studies of whole-organism growth and metabolic rates, rates of protein synthesis and ion transport, enzyme activity, and gene expression show that although the organismal-level impact of acidification on developing sea urchins was minimal, dramatic compensation occurred at the cellular level. Increased rates of synthesis and ion transport resulted in 84% of available energy being allocated to those processes under acidification. Defining the limits of differential energy allocation for the maintenance of critical physiological functions in response to compounding stressors will help provide a mechanistic understanding of resilience potential to environmental change.
RoR2 functions as a noncanonical Wnt receptor that regulates NMDAR-mediated synaptic transmission
Authors: Cerpa Waldo , Latorre-Esteves Elena , Barria Andres 
Published: April 2015

Significance
NMDA receptors (NMDARs) are key components of excitatory synapses. Here we report that Wnt signaling via activation of tyrosine kinase-like orphan receptor 2 can regulate synaptic NMDARs. Understanding what controls number and subunit composition is central to understand neuropathologies associated with dysfunction of synaptic NMDARs, including Alzheimer’s disease and schizophrenia. Our data indicate a previously unidentified role for Wnt signaling in the regulation of established synaptic connections and provides a mechanism for Wnt ligands to modulate basal synaptic transmission, synaptic plasticity, and brain functions acutely.
Response of seafloor ecosystems to abrupt global climate change
Authors: Moffitt Sarah E. , Hill Tessa M. , Roopnarine Peter D. , Kennett James P. 
Published: April 2015

Significance
This investigation presents the first record to our knowledge of the disturbance and recovery of seafloor ecosystem biodiversity in response to abrupt climate change. Ocean sediments have been extensively studied using geochemical and microfaunal (e.g., Foraminifera) analyses; however, these traditional approaches produce limited interpretations of ecological and community-scale responses. We demonstrate here that ocean sediments harbor metazoan fossil material that can be used to reconstruct the response of seafloor biodiversity to global-scale climate events. We show that the last deglaciation, the most recent episode of climate warming, was accompanied by abrupt reorganizations of continental margin seafloor ecosystems through expansions and contractions of the subsurface low-oxygen zones. This archive reveals that global climate change disturbs seafloor ecosystems on continental margins and commits them to millennia of ecological recovery.
Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants
Authors: Belkadi Aziz , Bolze Alexandre , Itan Yuval , Cobat Aurélie , Vincent Quentin B. , Antipenko Alexander , Shang Lei , Boisson Bertrand , Casanova Jean-Laurent , Abel Laurent 
Published: April 2015

Significance
Whole-exome sequencing (WES) is gradually being optimized to identify mutations in increasing proportions of the protein-coding exome, but whole-genome sequencing (WGS) is becoming an attractive alternative. WGS is currently more expensive than WES, but its cost should decrease more rapidly than that of WES. We compared WES and WGS on six unrelated individuals. The distribution of quality parameters for single-nucleotide variants (SNVs) and insertions/deletions (indels) was more uniform for WGS than for WES. The vast majority of SNVs and indels were identified by both techniques, but an estimated 650 high-quality coding SNVs (∼3% of coding variants) were detected by WGS and missed by WES. WGS is therefore slightly more efficient than WES for detecting mutations in the targeted exome.
Amplitude of the actomyosin power stroke depends strongly on the isoform of the myosin essential light chain
Authors: Guhathakurta Piyali , Prochniewicz Ewa , Thomas David D. 
Published: April 2015

Significance
Myosin is an enzyme that uses energy from ATP to exert force on another protein, actin, resulting in muscle contraction. Force is generated in the power stroke, when the actin–myosin complex transitions from a weak-binding structure (ATP bound to myosin) to a strong-binding structure (ADP). We detected the amplitude of the power stroke directly by measuring fluorescence resonance energy transfer from actin to myosin, with high time resolution following excitation with a pulsed laser. We found that the amplitude of the power stroke is strongly dependent on the form of the essential light chain that is bound to myosin. This provides a structural explanation for previous functional observations, with implications for muscle pathophysiology and therapeutic design.
Autoinhibition of MDMX by intramolecular p53 mimicry
Authors: Chen Lihong , Borcherds Wade , Wu Shaofang , Becker Andreas , Schonbrunn Ernst , Daughdrill Gary W. , Chen Jiandong 
Published: April 2015

Significance
MDMX protein is a critical regulator of p53 and a novel drug target. The current generation of MDM2 inhibitors does not inhibit MDMX. Therefore, their therapeutic efficacy will be influenced by poorly characterized MDMX functional status in tumors. Efforts to develop MDMX inhibitors have been largely unsuccessful, indicating gaps in our understanding of the structure and regulation of MDMX. This study provides evidence that MDMX-p53 binding is regulated by an autoinhibitory mechanism that involves intramolecular interaction in MDMX through p53 mimicry. The results suggest a mechanism by which DNA damage signaling inhibits MDMX and activates p53.
Zinc as chaperone-mimicking agent for retardation of amyloid β peptide fibril formation
Authors: Abelein Axel , Gräslund Astrid , Danielsson Jens 
Published: April 2015

Significance
One histologic hallmark of Alzheimer’s disease is the self-assembly of amyloid β peptide (Aβ) into insoluble amyloid aggregates. This aggregation process is strongly dependent on environmental conditions and metal ions, such as zinc, have been shown to modulate Aβ aggregation. To understand the underlying molecular mechanism of how zinc affects fibril formation we analyzed the aggregation kinetics and could conclude that zinc causes a significant reduction in elongation rate (i.e., monomer addition to the fibril ends). We used NMR methods to elucidate the details of zinc binding and we found that the N terminus of Aβ transiently folds around the zinc ion, forming a metastable dynamic complex.
Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction
Authors: Chen Zhiyuan , Hagen Darren E. , Elsik Christine G. , Ji Tieming , Morris Collin James , Moon Laura Emily , Rivera Rocío Melissa 
Published: April 2015

Significance
Large offspring syndrome (LOS) is a fetal overgrowth condition that mimics the human syndrome Beckwith–Wiedemann. These conditions have been observed with higher incidence in offspring conceived with the use of assisted reproductive technologies and are believed to be the result of misregulation of a set of genes that are expressed only from the maternally or paternally inherited chromosomes. These genes are known as imprinted genes. In our study, we demonstrate that the kidney, brain, muscle, and liver of LOS fetuses show misregulation of multiple imprinted genes when compared with controls. Furthermore, we show that the magnitude of overgrowth in LOS fetuses correlates with the number of misregulated imprinted genes. Our results may help create diagnostics for these fetal syndromes.
Amygdala lesions do not compromise the cortical network for false-belief reasoning
Authors: Spunt Robert P. , Elison Jed T. , Dufour Nicholas , Hurlemann René , Saxe Rebecca , Adolphs Ralph 
Published: April 2015

Significance
Humans use a so-called “theory-of-mind” to reason about the beliefs of others. Neuroimaging studies of belief reasoning suggest it activates a specific cortical network. The amygdala is interconnected with this network and plays a fundamental role in social behavior. For the first time, to our knowledge, we test whether amygdala lesions compromise the cortical implementation of theory-of-mind. Two patients with bilateral amygdala lesions performed a belief reasoning test while undergoing functional MRI. Remarkably, both patients showed typical test performance and cortical activity when compared with nearly 500 healthy controls. This result shows that the amygdala is not a necessary part of theory-of-mind function in adulthood and forces a reevaluation of the amygdala’s role in social cognition.
Quantitative analysis of vesicle recycling at the calyx of Held synapse
Authors: Qiu Xufeng , Zhu Qianwen , Sun Jianyuan 
Published: April 2015

Significance
Compared with vesicle exocytosis and endocytosis, relatively little is known about vesicle recycling. Here, we developed a novel methodological approach, potentially applicable to all axosomatic synapses, to quantify the kinetics of vesicle recycling with exquisite signal and temporal resolution. Using this approach combined with electron-microscopic observations, we estimated that ∼80% of synaptic vesicles participate in recycling and provided an explanation to reconcile the discrepancies in previous reports. We kinetically dissected vesicle recycling in the calyceal terminal, defined a new concept of the readily priming pool, and proposed a realistic kinetic model to quantify the basic properties of vesicle recycling. These findings contribute to filling the gap in understanding vesicle recycling, particularly postendocytotic vesicle trafficking.
CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer
Authors: Cheah Ming T. , Chen James Y. , Sahoo Debashis , Contreras-Trujillo Humberto , Volkmer Anne K. , Scheeren Ferenc A. , Volkmer Jens-Peter , Weissman Irving L. 
Published: April 2015

Significance
Our study defines the crucial role of CD14-high bladder cancer (BC) cells in orchestrating multiple hallmarks of cancer in the early stages of BC. Inflammatory factors produced by this subpopulation of tumor cells activate angiogenesis to support establishment and maintenance of an immune-suppressive, inflammatory tumor microenvironment. Additionally, this subpopulation is able to drive tumor growth by producing factors that drive autocrine and paracrine proliferative stimulation. Here we show that a tumor-cell subpopulation establishes a tumor microenvironment orchestrating tumor-promoting inflammation and tumor-cell proliferation. Collectively, this study highlights the need to explore the broader role of CD14-expressing neoplastic cells in other solid tumors. It is noteworthy that CD14 expression is critical for IL6 secretion by these cells. Therefore, therapeutic targeting of CD14 might represent a strategy for treating cancer.
Linked topological colloids in a nematic host
Authors: Martinez Angel , Hermosillo Leonardo , Tasinkevych Mykola , Smalyukh Ivan I. 
Published: April 2015

SignificanceColloidal dispersions are abundant in nature, fundamental science, and technology, with examples ranging from fog and milk to colloidal models of atomic crystals and glasses and colloidal quantum dots used in fabricating the third-generation solar cells. Despite the recent progress in exquisite control of geometric shape and topology of constituent colloidal particles, thus far only single-component colloidal building blocks have been fabricated or found occurring in nature. We develop multicomponent linked colloidal particles lacking connectivity of their surfaces, with each component behaving as a genus-one colloidal particle itself but being topologically linked with the other components within a colloidal building block. We uncover topological property-defining behavior of such colloidal particles when dispersed in a nematic liquid crystal medium.
Large-scale recoding of an arbovirus genome to rebalance its insect versus mammalian preference
Authors: Shen Sam H. , Stauft Charles B. , Gorbatsevych Oleksandr , Song Yutong , Ward Charles B. , Yurovsky Alisa , Mueller Steffen , Futcher Bruce , Wimmer Eckard 
Published: April 2015

Significance
Arboviruses (arthropod-borne viruses), a large group of RNA viruses, replicate in insects that transmit them to mammals, their second host. Insects and mammals have evolved different protein encoding strategies (codon pair bias); hence, arboviruses must delicately balance their encodings between two phyla. Using dengue virus (DENV), the most important human arbovirus pathogen, as a model, we have, by computer design and chemical synthesis, undone this balance in codon pair bias in favor of insects. Recoded DENVs grow well in insect cells but are highly attenuated in mammalian cells and in suckling mice. This unique approach offers a previously unidentified possibility to rapidly develop new vaccine candidates against DENV and perhaps against many different human arboviruses.
Lag threads organize the brain’s intrinsic activity
Authors: Mitra Anish , Snyder Abraham Z. , Blazey Tyler , Raichle Marcus E. 
Published: April 2015

Significance
It is well known that slow intrinsic activity, as measured by resting-state fMRI in a variety of animals including humans, is organized into temporally synchronous networks. The question of whether intrinsic activity contains reproducible temporal sequences has received far less attention. We have previously shown that human resting-state fMRI contains a highly reproducible lag structure. Here, we demonstrate that this lag structure is of high dimensionality and consists of multiple highly reproducible temporal sequences, which we term “lag threads.” Moreover, we demonstrate that the well-known zero-lag temporal correlation structure of intrinsic activity emerges as a consequence of lag structure. Thus, lag threads may represent a fundamental and previously unsuspected level of organization in resting-state activity.