bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-lying zeros of elliptic curve L-functions: Beyond the Ratios Conjecture
Authors: FIORILLI DANIEL , PARKS JAMES , SÖDERGREN ANDERS 
Published: January 2016

AbstractWe study the low-lying zeros of L-functions attached to quadratic twists of a given elliptic curve E defined over $\mathbb{Q}$. We are primarily interested in the family of all twists coprime to the conductor of E and compute a very precise expression for the corresponding 1-level density. In particular, for test functions whose Fourier transforms have sufficiently restricted support, we are able to compute the 1-level density up to an error term that is significantly sharper than the square-root error term predicted by the L-functions Ratios Conjecture.
No Place Like Home? Surveillance and What Home Means in Old Age
Authors: Mortenson W. Ben , Sixsmith Andrew , Beringer Robert 
Published: January 2016

RÉSUMÉLes technologies de surveillance nouvelles, telles que celles inclus dans le logement avec assistance ambiante—les capteurs environnementaux portés sur le corps, les interfaces intelligentes, et les réseaux de communication—sont en cours d'élaboration afin d'améliorer la sécurité et la sûreté des personnes âgées qui sont à risque, mais des questions éthiques ont été soulevées quant à dans quelle mesure ils compromettraient les droits et la vie privée des personnes à surveiller. L'étude qualitative que nous avons mené a été conçu pour nous aider à comprendre les façons dont ces technologies de surveillance nouvelles seraient influencer les expériences quotidiennes des individus de leur maison. Les participants ont estimé que de nouvelles formes de surveillance auraient une influence sur leur sentiment de sécurité, de l'autonomie et de la confiance en soi, et modifieraient leurs perceptions chez soi. Les résultats soulignent la nécessité d'améliorer notre compréhension de la façon dont le logement assisté ambiant affectera la vie des personnes à surveiller.
Changes in Synapsin Levels in the MillipedeGymnostreptus olivaceusSchubart, 1944 Exposed to Different Concentrations of Deltamethrin
Authors: Francisco Annelise , Nunes Pablo H. , Nocelli Roberta C. F. , Fontanetti Carmem S. 
Published: January 2016

AbstractMillipedes are ecologically important soil organisms and may also be an economically threatening species in rural and urban areas when population outbreaks occur. In order to control infestations commercial formulations of deltamethrin have been commonly applied, even though there are few studies about the effects of such insecticide on millipedes. This paper describes the effects of this insecticide on millipedes showing neurotoxic effects assessed by synapsin labeling and confocal microscopy. Deltamethrin concentrations related to the DL50of the active ingredient and a field concentration were applied topically in the diplopodGymnostreptus olivaceusto evaluate the behavior, mortality rate, and synapsin levels in the brain 12, 24, and 48h after contact with deltamethin. The insecticide caused mortality at the higher concentrations employed, in which no change was observed in neurotransmission in the survivors. In contrast, at field concentrations, deltamethrin did not cause any deaths, but triggered significant changes in synapsin levels. The results obtained form the synapsin labeling provide several interpretations suggesting that the isolated application of this tool must be associated with additional tools in order to evaluate biologically induced effects of deltamethrin in an accurate way. In addition, the feasibility of chemical control of millipedes with deltamethrin is questioned.
Repetitive magnetic stimulation induces plasticity of inhibitory synapses
Authors: Lenz Maximilian , Galanis Christos , Müller-Dahlhaus Florian , Opitz Alexander , Wierenga Corette J. , Szabó Gábor , Ziemann Ulf , Deller Thomas , Funke Klaus , Vlachos Andreas 
Published: January 2016

AbstractRepetitive transcranial magnetic stimulation (rTMS) is used as a therapeutic tool in neurology and psychiatry. While repetitive magnetic stimulation (rMS) has been shown to induce plasticity of excitatory synapses, it is unclear whether rMS can also modify structural and functional properties of inhibitory inputs. Here we employed 10-Hz rMS of entorhinohippocampal slice cultures to study plasticity of inhibitory neurotransmission on CA1 pyramidal neurons. Our experiments reveal a rMS-induced reduction in GABAergic synaptic strength (2–4 h after stimulation), which is Ca2+-dependent and accompanied by the remodelling of postsynaptic gephyrin scaffolds. Furthermore, we present evidence that 10-Hz rMS predominantly acts on dendritic, but not somatic inhibition. Consistent with this finding, a reduction in clustered gephyrin is detected in CA1 stratum radiatum of rTMS-treated anaesthetized mice. These results disclose that rTMS induces coordinated Ca2+-dependent structural and functional changes of specific inhibitory postsynapses on principal neurons.
Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1–Mad2
Authors: Zhou Haining , Wang Tianning , Zheng Tao , Teng Junlin , Chen Jianguo 
Published: January 2016

AbstractThe spindle assembly checkpoint (SAC) arrests cells in mitosis by sensing unattached kinetochores, until all chromosomes are bi-oriented by spindle microtubules. Kinetochore accumulation of the SAC component Mad1–Mad2 is crucial for SAC activation. However, the mechanism by which Mad1–Mad2 accumulation at kinetochores is regulated is not clear. Here we find that Cep57 is localized to kinetochores in human cells, and binds to Mis12, a KMN (KNL1/Mis12 complex/Ndc80 complex) network component. Cep57 also interacts with Mad1, and depletion of Cep57 results in decreased kinetochore localization of Mad1–Mad2, reduced SAC signalling and increased chromosome segregation errors. We also show that the microtubule-binding activity of Cep57 is involved in the timely removal of Mad1 from kinetochores. Thus, these findings reveal that the KMN network-binding protein Cep57 is a mitotic kinetochore component, and demonstrate the functional connection between the KMN network and the SAC.
Superactivation of AMPA receptors by auxiliary proteins
Authors: Carbone Anna L. , Plested Andrew J. R. 
Published: January 2016

AbstractGlutamate receptors form complexes in the brain with auxiliary proteins, which control their activity during fast synaptic transmission through a seemingly bewildering array of effects. Here we devise a way to isolate the activation of complexes using polyamines, which enables us to show that transmembrane AMPA receptor regulatory proteins (TARPs) exert their effects principally on the channel opening reaction. A thermodynamic argument suggests that because TARPs promote channel opening, receptor activation promotes AMPAR-TARP complexes into a superactive state with high open probability. A simple model based on this idea predicts all known effects of TARPs on AMPA receptor function. This model also predicts unexpected phenomena including massive potentiation in the absence of desensitization and supramaximal recovery that we subsequently detected in electrophysiological recordings. This transient positive feedback mechanism has implications for information processing in the brain, because it should allow activity-dependent facilitation of excitatory synaptic transmission through a postsynaptic mechanism.
Haematopoietic ESL-1 enables stem cell proliferation in the bone marrow by limiting TGFβ availability
Authors: Leiva Magdalena , Quintana Juan A. , Ligos José M. , Hidalgo Andrés 
Published: January 2016

AbstractThe life-long maintenance of haematopoietic stem and progenitor cells (HSPCs) critically relies on environmental signals produced by cells that constitute the haematopoietic niche. Here we report a cell-intrinsic mechanism whereby haematopoietic cells limit proliferation within the bone marrow, and show that this pathway is repressed by E-selectin ligand 1 (ESL-1). Mice deficient in ESL-1 display aberrant HSPC quiescence, expansion of the immature pool and reduction in niche size. Remarkably, the traits were transplantable and dominant when mutant and wild-type precursors coexisted in the same environment, but were independent of E-selectin, the vascular receptor for ESL-1. Instead, quiescence is generated by unrestrained production of the cytokine TGFβ by mutant HSPC, and in vivo or in vitro blockade of the cytokine completely restores the homeostatic properties of the haematopoietic niche. These findings reveal that haematopoietic cells, including the more primitive compartment, can actively shape their own environment.
Protein-targeted corona phase molecular recognition
Authors: Bisker Gili , Dong Juyao , Park Hoyoung D. , Iverson Nicole M. , Ahn Jiyoung , Nelson Justin T. , Landry Markita P. , Kruss Sebastian , Strano Michael S. 
Published: January 2016

AbstractCorona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated by the quenching kinetics. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications.
Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells
Authors: Klawitter Sabine , Fuchs Nina V. , Upton Kyle R. , Muñoz-Lopez Martin , Shukla Ruchi , Wang Jichang , Garcia-Cañadas Marta , Lopez-Ruiz Cesar , Gerhardt Daniel J. , Sebe Attila , Grabundzija Ivana , Merkert Sylvia , Gerdes Patricia , Pulgarin J. Andres , Bock Anja , Held Ulrike , Witthuhn Anett , Haase Alexandra , Sarkadi Balázs , Löwer Johannes , Wolvetang Ernst J. , Martin Ulrich , Ivics Zoltán , Izsvák Zsuzsanna , Garcia-Perez Jose L. , Faulkner Geoffrey J. , Schumann Gerald G. 
Published: January 2016

AbstractHuman induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.
Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways
Authors: Kawakami Eiryo , Singh Vivek K , Matsubara Kazuko , Ishii Takashi , Matsuoka Yukiko , Hase Takeshi , Kulkarni Priya , Siddiqui Kenaz , Kodilkar Janhavi , Danve Nitisha , Subramanian Indhupriya , Katoh Manami , Shimizu-Yoshida Yuki , Ghosh Samik , Jere Abhay , Kitano Hiroaki 
Published: January 2016

AbstractCellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems.
Hippocampal Transcriptome Profile of Persistent Memory Rescue in a Mouse Model of THRA1 Mutation-Mediated Resistance to Thyroid Hormone
Authors: Wang Yiqiao , Fisahn André , Sinha Indranil , Nguyen Dinh Phong , Sterzenbach Ulrich , Lallemend Francois , Hadjab Saїda 
Published: January 2016

AbstractHypothyroidism due to THRA1 (gene coding for thyroid hormone receptor α1) mutation-mediated Resistance to Thyroid Hormone (RTH) has been recently reported in human and is associated with memory deficits similar to those found in a mouse model for Thra1 mutation mediated RTH (Thra1+/m mice). Here, we show that a short-term treatment of Thra1+/m mice with GABAA receptor antagonist pentylenetetrazol (PTZ) completely and durably rescues their memory performance. In the CA1 region of the hippocampus, improvement of memory is associated with increased in long-term potentiation (LTP) and an augmentation of density of dendritic spines (DDS) onto the apical dendrites of pyramidal cells reflecting an increase in the local excitatory drive. Unbiased gene profiling analysis of hippocampi of treated Thra1+/+ and Thra1+/m mice were performed two weeks and three months post treatment and identified co-expression modules that include differentially expressed genes related with and predicting higher memory, LTP and DDS in the hippocampi of PTZ-treated animals. We observed that PTZ treatment changed similar sets of genes in both Thra1+/+ and Thra1+/m mice, which are known to be involved in memory consolidation and neurotransmission dynamics and could participate in the persistent effects of PTZ on memory recovery.
Hierarchical ZnO Nanowires-loaded Sb-doped SnO2-ZnO Micrograting Pattern via Direct Imprinting-assisted Hydrothermal Growth and Its Selective Detection of Acetone Molecules
Authors: Choi Hak-Jong , Choi Seon-Jin , Choo Soyoung , Kim Il-Doo , Lee Heon 
Published: January 2016

AbstractWe propose a novel synthetic route by combining imprinting transfer of a Sb-doped SnO2 (ATO)-ZnO composite micrograting pattern (MP), i.e., microstrip lines, on a sensor substrate and subsequent hydrothermal growth of ZnO nanowires (NWs) for producing a hierarchical ZnO NW-loaded ATO-ZnO MP as an improved chemo-resistive sensing layer. Here, ATO-ZnO MP structure with 3-μm line width, 9-μm pitch and 6-μm height was fabricated by direct transfer of mixed ATO and ZnO nanoparticle (NP)-dispersed resists, which are pre-patterned on a polydimethylsiloxane (PDMS) mold. ZnO NWs with an average diameter of less than 50 nm and a height of 250 nm were quasi-vertically grown on the ATO-ZnO MP, leading to markedly enhanced surface area and heterojunction composites between each ATO NP, ZnO NP and ZnO NW. A ZnO NW-loaded MP sensor with a relative ratio of 1:9 between ATO and ZnO (1:9 ATO-ZnO), exhibited highly sensitive and selective acetone sensing performance with 2.84-fold higher response (Rair/Rgas = 12.8) compared to that (Rair/Rgas = 4.5) of pristine 1:9 ATO-ZnO MP sensor at 5 ppm. Our results demonstrate the processing advantages of direct imprinting-assisted hydrothermal growth for large-scale homogeneous coating of hierarchical oxide layers, particularly for applications in highly sensitive and selective chemical sensors.
Identification of novel genes and pathways in carotid atheroma using integrated bioinformatic methods
Authors: Nai Wenqing , Threapleton Diane , Lu Jingbo , Zhang Kewei , Wu Hongyuan , Fu You , Wang Yuanyuan , Ou Zejin , Shan Lanlan , Ding Yan , Yu Yanlin , Dai Meng 
Published: January 2016

AbstractAtherosclerosis is the primary cause of cardiovascular events and its molecular mechanism urgently needs to be clarified. In our study, atheromatous plaques (ATH) and macroscopically intact tissue (MIT) sampled from 32 patients were compared and an integrated series of bioinformatic microarray analyses were used to identify altered genes and pathways. Our work showed 816 genes were differentially expressed between ATH and MIT, including 443 that were up-regulated and 373 that were down-regulated in ATH tissues. GO functional-enrichment analysis for differentially expressed genes (DEGs) indicated that genes related to the “immune response” and “muscle contraction” were altered in ATHs. KEGG pathway-enrichment analysis showed that up-regulated DEGs were significantly enriched in the “FcεRI-mediated signaling pathway”, while down-regulated genes were significantly enriched in the “transforming growth factor-β signaling pathway”. Protein-protein interaction network and module analysis demonstrated that VAV1, SYK, LYN and PTPN6 may play critical roles in the network. Additionally, similar observations were seen in a validation study where SYK, LYN and PTPN6 were markedly elevated in ATH. All in all, identification of these genes and pathways not only provides new insights into the pathogenesis of atherosclerosis, but may also aid in the development of prognostic and therapeutic biomarkers for advanced atheroma.
New insights into functional regulation in MS-based drug profiling
Authors: Carvalho Ana Sofia , Molina Henrik , Matthiesen Rune 
Published: January 2016

AbstractWe present a novel data analysis strategy which combined with subcellular fractionation and liquid chromatography–mass spectrometry (LC-MS) based proteomics provides a simple and effective workflow for global drug profiling. Five subcellular fractions were obtained by differential centrifugation followed by high resolution LC-MS and complete functional regulation analysis. The methodology combines functional regulation and enrichment analysis into a single visual summary. The workflow enables improved insight into perturbations caused by drugs. We provide a statistical argument to demonstrate that even crude subcellular fractions leads to improved functional characterization. We demonstrate this data analysis strategy on data obtained in a MS-based global drug profiling study. However, this strategy can also be performed on other types of large scale biological data.
Efficacy and safety of dulaglutide in patients with type 2 diabetes: a meta-analysis and systematic review
Authors: Zhang Lin , Zhang Mei , Zhang Yuwei , Tong Nanwei 
Published: January 2016

AbstractA meta-analysis was conducted to assess the clinical efficacy and safety of dulaglutide in patients with type 2 diabetes mellitus (T2DM). Medline, Embase, Cochrane Library and www. clinicaltrials. gov (up to February 15th, 2015) were searched. Randomized controlled trials comparing dulaglutide to other drugs for T2DM were collected. Twelve RCTs were included and the overall bias was low. As the monotherapy, compared with control (placebo, metformin and liraglutide), dulaglutide resulted in a significant reduction in HbA1c (WMD, −0.68%; 95% CI, −0.95 to −0.40), FPG (WMD, −0.90 mmol/L; 95% CI, −1.28 to −0.52), a similar risk of hypoglycemia (7.8% vs. 10.6%), less body weight loss (WMD, 0.51 kg; 95% CI, 0.27 to 0.75). As an add-on intervention with oral antihyperglycemic medication (OAM) and insulin, compared with control (placebo, sitagliptin, exenatide, liraglutide and glargine), dulaglutide lowered HbA1c (WMD, −0.51%; 95% CI, −0.68 to −0.35) and body weight significantly (WMD, −1.30 kg, 95% CI, −1.85 to −1.02) notably and elicited a similar reduction in FPG (WMD, −0.19 mmol/L; 95% CI, −1.20 to 0.82), an similar incidence of hypoglycemia (24.5% vs. 24.5%). This meta-analysis revealed the use of dulaglutide as a monotherapy or an add-on to OAM and lispro appeared to be effective and safe for adults with T2DM.
A new physical mapping approach refines the sex-determining gene positions on the Silene latifolia Y-chromosome
Authors: Kazama Yusuke , Ishii Kotaro , Aonuma Wataru , Ikeda Tokihiro , Kawamoto Hiroki , Koizumi Ayako , Filatov Dmitry A. , Chibalina Margarita , Bergero Roberta , Charlesworth Deborah , Abe Tomoko , Kawano Shigeyuki 
Published: January 2016

AbstractSex chromosomes are particularly interesting regions of the genome for both molecular genetics and evolutionary studies; yet, for most species, we lack basic information, such as the gene order along the chromosome. Because they lack recombination, Y-linked genes cannot be mapped genetically, leaving physical mapping as the only option for establishing the extent of synteny and homology with the X chromosome. Here, we developed a novel and general method for deletion mapping of non-recombining regions by solving “the travelling salesman problem” and evaluate its accuracy using simulated datasets. Unlike the existing radiation hybrid approach, this method allows us to combine deletion mutants from different experiments and sources. We applied our method to a set of newly generated deletion mutants in the dioecious plant Silene latifolia and refined the locations of the sex-determining loci on its Y chromosome map.
High level of depressive symptoms as a barrier to reach an ideal cardiovascular health. The Paris Prospective Study III
Authors: Gaye B. , Prugger C. , Perier M. C. , Thomas F. , Plichart M. , Guibout C. , Lemogne C. , Pannier B. , Boutouyrie P. , Jouven X. , Empana J. P. 
Published: January 2016

AbstractWe hypothesized that depression might represent a barrier to reach an ideal cardiovascular health (CVH) as estimated by the 7-item tool proposed by the American Heart Association. Between 2008 and 2012, 9,417 subjects 50–75 years of age were examined in a large health center and enrolled in the Paris Prospective Study III (PPS3). Participants with 0–2, 3–4 and 5–7 health metrics at the ideal level were categorized as having poor, intermediate and ideal CVH, respectively. Participants with a score ≥7 on the 13-item Questionnaire of Depression 2nd version, Abridged or who were on antidepressants were referred as having high level of depressive symptoms (HLDS). The mean age of the 9417 study participants was 59.57 (SD 6.28) years and 61.16% were males. A total of 9.55% had HLDS. Poor, intermediate and ideal CVH was present in 40.38%, 49.52% and 10.10% of the participants. In multivariate polytomous logistic regression analysis, HLDS was inversely associated with ideal CVH (odds ratio = 0.70; 95% CI: 0.55;0.90). This was driven by an association with the behavioural component of the CVH. Participants with HLDS had a substantial reduced chance of reaching an ideal CVH.