bluuebunny/crossref_metadata_2025 huggingface dataset:
Low-lying zeros of elliptic curve L-functions: Beyond the Ratios Conjecture
Authors: FIORILLI DANIEL , PARKS JAMES , SÖDERGREN ANDERS
Published: January 2016

We 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

Les 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

Millipedes 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.
Enabling Lab-in-Gap Transmission Electron Microscopy at Atomic Resolution
Authors: Zhang Xiao Feng
Published: January 2016

Abstract: Hitachi Lab-in-Gap transmission electron microscopy (TEM) technologies are introduced. The term Lab-in-Gap refers to a special function that allows in situ and in operando TEM studies of materials in gas or liquid environments while stimulations, such as thermal or electrical fields, are applied to the specimen sitting in the pole piece gap in a TEM system. Physical or chemical process can be activated and imaged in real time using TEM or other imaging modes. The new generation environmental TEM platform with large pole piece gap and advanced aberration correctors opens wide possibilities for integrating multiple stimuli sources as well as large-area, sub-Å resolution live imaging for dynamic structural changes.
Studying the nonlinear performance of an amplifying reflectarray antenna
Authors: Aryanian Iman , Abdipour Abdolali , Moradi Gholamreza
Published: January 2016

In this paper, significance of studying the nonlinear performance of amplifying reflectarray antenna is clarified by showing nonlinear behavior of the unit cell. Furthermore, the procedure for nonlinear analysis of amplifying reflectarray antenna is described and nonlinear analysis is verified by ADS software simulation. Moreover, a typical amplifying reflectarray antenna is designed considering the nonlinear behavior. Nonlinear analysis of the active aperture-coupled patch unit cell is performed using harmonic balance method considering nonlinear model of the amplifier. Then, the effect of nonlinear element in radiation pattern of the antenna is studied. Passive unit cell is simulated using full-wave analysis method considering infinite array approach, and scattering parameters of the unit cell is obtained. Next, these scattering parameters are transformed to admittance parameters and used in obtaining nonlinear response and harmonic distortion of the unit cell containing amplifier. Obtained results show up to 3.4 dB error in predicting pattern of the antenna with linear modeling of the active element.
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

Repetitive 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

The 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

Glutamate 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

The 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

Corona 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

Human 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.
Correction: Corrigendum: Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa
Authors: St. Laurent Brandyce , Miller Becky , Burton Timothy A. , Amaratunga Chanaki , Men Sary , Sovannaroth Siv , Fay Michael P. , Miotto Olivo , Gwadz Robert W. , Anderson Jennifer M. , Fairhurst Rick M.
Published: January 2016

Nature Communications 6: Article number: 8614 (2015); Published: 20 October 2015; Updated: 8 January 2016. In the first paragraph of the Results section in this Article, the An. gambiae G3 line is incorrectly stated to have been artificially selected for permissiveness to infection by multiple P. falciparum strains.
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

Cellular 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

Hypothyroidism 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

We 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

Atherosclerosis 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

We 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

A 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

Sex 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

We 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.
Gene targets of mouse miR-709: regulation of distinct pools
Authors: Surendran Sneha , Jideonwo Victoria N. , Merchun Chris , Ahn Miwon , Murray John , Ryan Jennifer , Dunn Kenneth W. , Kota Janaiah , Morral Núria
Published: January 2016

MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 is an abundant miRNA expressed ubiquitously. Through transcriptome analysis, we have identified targets of miR-709 in hepatocytes. miR-709 represses genes implicated in cytoskeleton organization, extracellular matrix attachment and fatty acid metabolism. Remarkably, none of the previously identified targets in non-hepatic tissues are silenced by miR-709 in hepatocytes, even though several of these genes are abundantly expressed in liver. In addition, miR-709 is upregulated in hepatocellular carcinoma, suggesting it participates in the genetic reprogramming that takes place during cell division, when cytoskeleton remodeling requires substantial changes in gene expression. In summary, the present study shows that miR-709 does not repress the same pool of genes in separate cell types. These results underscore the need for validating gene targets in every tissue a miRNA is expressed.
Adapting to Adaptations: Behavioural Strategies that are Robust to Mutations and Other Organisational-Transformations
Authors: Egbert Matthew D. , Pérez-Mercader Juan
Published: January 2016

Genetic mutations, infection by parasites or symbionts and other events can transform the way that an organism’s internal state changes in response to a given environment. We use a minimalistic computational model to support an argument that by behaving “interoceptively,” i.e. responding to internal state rather than to the environment, organisms can be robust to these organisational-transformations. We suggest that the robustness of interoceptive behaviour is due, in part, to the asymmetrical relationship between an organism and its environment, where the latter more substantially influences the former than vice versa. This relationship means that interoceptive behaviour can respond to the environment, the internal state and the interaction between the two, while exteroceptive behaviour can only respond to the environment. We discuss the possibilities that (i) interoceptive behaviour may play an important role of facilitating adaptive evolution (especially in the early evolution of primitive life) and (ii) interoceptive mechanisms could prove useful in efforts to create more robust synthetic life-forms.
PKN3 is the major regulator of angiogenesis and tumor metastasis in mice
Authors: Mukai Hideyuki , Muramatsu Aiko , Mashud Rana , Kubouchi Koji , Tsujimoto Sho , Hongu Tsunaki , Kanaho Yasunori , Tsubaki Masanobu , Nishida Shozo , Shioi Go , Danno Sally , Mehruba Mona , Satoh Ryosuke , Sugiura Reiko
Published: January 2016

PKN, a conserved family member related to PKC, was the first protein kinase identified as a target of the small GTPase Rho. PKN is involved in various functions including cytoskeletal arrangement and cell adhesion. Furthermore, the enrichment of PKN3 mRNA in some cancer cell lines as well as its requirement in malignant prostate cell growth suggested its involvement in oncogenesis. Despite intensive research efforts, physiological as well as pathological roles of PKN3in vivoremain elusive. Here, we generated mice with a targeted deletion of PKN3. The PKN3 knockout (KO) mice are viable and develop normally. However, the absence of PKN3 had an impact on angiogenesis as evidenced by marked suppressions of micro-vessel sprouting inex vivoaortic ring assay andin vivocorneal pocket assay. Furthermore, the PKN3 KO mice exhibited an impaired lung metastasis of melanoma cells when administered from the tail vein. Importantly, PKN3 knock-down by small interfering RNA (siRNA) induced a glycosylation defect of cell-surface glycoproteins, including ICAM-1, integrin β1 and integrin α5 in HUVECs. Our data provide the firstin vivogenetic demonstration that PKN3 plays critical roles in angiogenesis and tumor metastasis and that defective maturation of cell surface glycoproteins might underlie these phenotypes.
17beta-estradiol counteracts neuropathic pain: a behavioural, immunohistochemical and proteomic investigation on sex-related differences in mice
Authors: Vacca Valentina , Marinelli Sara , Pieroni Luisa , Urbani Andrea , Luvisetto Siro , Pavone Flaminia
Published: January 2016

Sex differences play a role in pain sensitivity, efficacy of analgesic drugs and prevalence of neuropathic pain, even if the underlying mechanisms are far from being understood. We demonstrate that male and female mice react differently to structural and functional changes induced by sciatic nerve ligature, used as model of neuropathic pain. Male mice show a gradual decrease of allodynia and a complete recovery while, in females, allodynia and gliosis are still present four months after neuropathy induction. Administration of 17β-estradiol is able to significantly attenuate this difference, reducing allodynia and inducing a complete recovery also in female mice. Parallel to pain attenuation, 17β-estradiol treated-mice show a functional improvement of the injured limb, a faster regenerative process of the peripheral nerve and a decreased neuropathy-induced gliosis. These results indicate beneficial effects of 17β-estradiol on neuropathic pain and neuronal regeneration and focuses on the importance of considering gonadal hormones also in clinical studies.
Inner membrane fusion mediates spatial distribution of axonal mitochondria
Authors: Yu Yiyi , Lee Hao-Chih , Chen Kuan-Chieh , Suhan Joseph , Qiu Minhua , Ba Qinle , Yang Ge
Published: January 2016

In eukaryotic cells, mitochondria form a dynamic interconnected network to respond to changing needs at different subcellular locations. A fundamental yet unanswered question regarding this network is whether and if so how, local fusion and fission of individual mitochondria affect their global distribution. To address this question, we developed high-resolution computational image analysis techniques to examine the relations between mitochondrial fusion/fission and spatial distribution within the axon of Drosophila larval neurons. We found that stationary and moving mitochondria underwent fusion and fission regularly but followed different spatial distribution patterns and exhibited different morphology. Disruption of inner membrane fusion by knockdown of dOpa1, Drosophila Optic Atrophy 1, not only increased the spatial density of stationary and moving mitochondria but also changed their spatial distributions and morphology differentially. Knockdown of dOpa1 also impaired axonal transport of mitochondria. But the changed spatial distributions of mitochondria resulted primarily from disruption of inner membrane fusion because knockdown of Milton, a mitochondrial kinesin-1 adapter, caused similar transport velocity impairment but different spatial distributions. Together, our data reveals that stationary mitochondria within the axon interconnect with moving mitochondria through fusion and fission and that local inner membrane fusion between individual mitochondria mediates their global distribution.
Anaerobic decomposition of humic substances by Clostridium from the deep subsurface
Authors: Ueno Akio , Shimizu Satoru , Tamamura Shuji , Okuyama Hidetoshi , Naganuma Takeshi , Kaneko Katsuhiko
Published: January 2016

Decomposition of humic substances (HSs) is a slow and cryptic but non-negligible component of carbon cycling in sediments. Aerobic decomposition of HSs by microorganisms in the surface environment has been well documented; however, the mechanism of anaerobic microbial decomposition of HSs is not completely understood. Moreover, no microorganisms capable of anaerobic decomposition of HSs have been isolated. Here, we report the anaerobic decomposition of humic acids (HAs) by the anaerobic bacterium Clostridium sp. HSAI-1 isolated from the deep terrestrial subsurface. The use of 14C-labelled polycatechol as an HA analogue demonstrated that the bacterium decomposed this substance up to 7.4% over 14 days. The decomposition of commercial and natural HAs by the bacterium yielded lower molecular mass fractions, as determined using high-performance size-exclusion chromatography. Fourier transform infrared spectroscopy revealed the removal of carboxyl groups and polysaccharide-related substances, as well as the generation of aliphatic components, amide and aromatic groups. Therefore, our results suggest that Clostridium sp. HSAI-1 anaerobically decomposes and transforms HSs. This study improves our understanding of the anaerobic decomposition of HSs in the hidden carbon cycling in the Earth’s subsurface.
High glucose enhances progression of cholangiocarcinoma cells via STAT3 activation
Authors: Saengboonmee Charupong , Seubwai Wunchana , Pairojkul Chawalit , Wongkham Sopit
Published: January 2016

Epidemiological studies have indicated diabetes mellitus (DM) as a risk of cholangiocarcinoma (CCA), however, the effects and mechanisms of high glucose on progression of CCA remain unclear. This study reports for the first time of the enhancing effects of high glucose on aggressive phenotypes of CCA cells via STAT3 activation. CCA cells cultured in high glucose media exerted significantly higher rates of cell proliferation, adhesion, migration and invasion than those cultured in normal glucose. The phosphokinase array revealed STAT3 as the dominant signal activated in response to high glucose. Increased nuclear STAT3, p-STAT3 and its downstream target proteins, cyclin D1, vimentin and MMP2, were shown to be underling mechanisms of high glucose stimulation. The link of high glucose and STAT3 activation was confirmed in tumor tissues from CCA patients with DM that exhibited higher STAT3 activation than those without DM. Moreover, the levels of STAT3 activation were correlated with the levels of blood glucose. Finally, decreasing the level of glucose or using a STAT3 inhibitor could reduce the effects of high glucose. These findings suggest that controlling blood glucose or using a STAT3 inhibitor as an alternative approach may improve the therapeutic outcome of CCA patients with DM.
CPUY201112, a novel synthetic small-molecule compound and inhibitor of heat shock protein Hsp90, induces p53-mediated apoptosis in MCF-7 cells
Authors: Xu Xiao-Li , Bao Qi-chao , Jia Jian-Min , Liu Fang , Guo Xiao-Ke , Zhang Ming-ye , Wei Jin-lian , Lu Meng-chen , Xu Li-li , Zhang Xiao-Jin , You Qi-Dong , Sun Hao-Peng
Published: January 2016

Heat-shock protein 90 (Hsp90) is highly expressed in many tumor cells and is associated with the maintenance of malignant phenotypes. Targeting Hsp90 has had therapeutic success in both solid and hematological malignancies, which has inspired more studies to identify new Hsp90 inhibitors with improved clinical efficacy. Using a fragment-based approach and subsequent structural optimization guided by medicinal chemistry principles, we identified the novel compound CPUY201112 as a potent Hsp90 inhibitor. It binds to the ATP-binding pocket of Hsp90 with a kinetic dissociation (Kd) constant of 27 ± 2.3 nM. It also exhibits potent in vitro antiproliferative effects in a range of solid tumor cells. In MCF-7 cells with high Hsp90 expression, CPUY201112 induces the degradation of Hsp90 client proteins including HER-2, Akt and c-RAF. We prove that treating MCF-7 cells with CPUY201112 results in cell cycle arrest and apoptosis through the wild-type (wt) p53 pathway. CPUY201112 also synergizes with Nutlin-3a to induce cancer cell apoptosis. CPUY201112 significantly inhibited the growth of MCF-7 xenografts in nude mice without apparent body weight loss. These results demonstrate that CPUY201112 is a novel Hsp90 inhibitor with potential use in treating wild-type p53 related cancers.
Tomato yellow leaf curl virus (TYLCV-IL): a seed-transmissible geminivirus in tomatoes
Authors: Kil Eui-Joon , Kim Sunhoo , Lee Ye-Ji , Byun Hee-Seong , Park Jungho , Seo Haneul , Kim Chang-Seok , Shim Jae-Kyoung , Lee Jung-Hwan , Kim Ji-Kwang , Lee Kyeong-Yeoll , Choi Hong-Soo , Lee Sukchan
Published: January 2016

Tomato yellow leaf curl virus (TYLCV) is one of the most well-known tomato-infecting begomoviruses and transmitted by Bemisia tabaci. Seed transmission has previously been reported for some RNA viruses, but TYLCV has not previously been described as a seed-borne virus. In 2013 and 2014, without whitefly-mediated transmission, TYLCV was detected in young tomato plants germinated from fallen fruits produced from TYLCV-infected tomato plants in the previous cultivation season. In addition, TYLCV-Israel (TYLCV-IL) was also detected in seeds and their seedlings of TYLCV-infected tomato plants that were infected by both viruliferous whitefly-mediated transmission and agro-inoculation. The seed infectivity was 20–100%, respectively and the average transmission rate to seedlings was also 84.62% and 80.77%, respectively. TYLCV-tolerant tomatoes also produced TYLCV-infected seeds, but the amount of viral genome was less than seen in TYLCV-susceptible tomato plants. When tomato plants germinated from TYLCV-infected seeds, non-viruliferous whiteflies and healthy tomato plants were placed in an insect cage together, TYLCV was detected from whiteflies as well as receiver tomato plants six weeks later. Taken together, TYLCV-IL can be transmitted via seeds and tomato plants germinated from TYLCV-infected seeds can be an inoculum source of TYLCV. This is the first report about TYLCV seed transmission in tomato.
Frustration of Negative Capacitance in Al2O3/BaTiO3 Bilayer Structure
Authors: Kim Yu Jin , Park Min Hyuk , Lee Young Hwan , Kim Han Joon , Jeon Woojin , Moon Taehwan , Do Kim Keum , Jeong Doo Seok , Yamada Hiroyuki , Hwang Cheol Seong
Published: January 2016

Enhancement of capacitance by negative capacitance (NC) effect in a dielectric/ferroelectric (DE/FE) stacked film is gaining a greater interest. While the previous theory on NC effect was based on the Landau-Ginzburg-Devonshire theory, this work adopted a modified formalism to incorporate the depolarization effect to describe the energy of the general DE/FE system. The model predicted that the SrTiO3/BaTiO3 system will show a capacitance boost effect. It was also predicted that the 5 nm-thick Al2O3/150 nm-thick BaTiO3 system shows the capacitance boost effect with no FE-like hysteresis behavior, which was inconsistent with the experimental results; the amorphous-Al2O3/epitaxial-BaTiO3 system showed a typical FE-like hysteresis loop in the polarization – voltage test. This was due to the involvement of the trapped charges at the DE/FE interface, originating from the very high field across the thin Al2O3 layer when the BaTiO3 layer played a role as the NC layer. Therefore, the NC effect in the Al2O3/BaTiO3 system was frustrated by the involvement of reversible interface charge; the highly stored charge by the NC effect of the BaTiO3 during the charging period could not be retrieved during the discharging process because integral part of the polarization charge was retained within the system as a remanent polarization.
Association between the DOCK7, PCSK9 and GALNT2 Gene Polymorphisms and Serum Lipid levels
Authors: Guo Tao , Yin Rui-Xing , Huang Feng , Yao Li-Mei , Lin Wei-Xiong , Pan Shang-Ling
Published: January 2016

This study was to determine the association between several single nucleotide polymorphisms (SNPs) in the dedicator of cytokinesis 7 (DOCK7), proprotein convertase subtilisin/kexin type 9 (PCSK9) and polypeptide N-acetylgalactosaminyltransferase 2 (GALNT2) and serum lipid levels. Genotyping of 9 SNPs was performed in 881 Jing subjects and 988 Han participants. Allele and genotype frequencies of the detected SNPs were different between the two populations. Several SNPs were associated with triglyceride (TG, rs10889332, rs615563, rs7552841, rs1997947, rs2760537, rs4846913 and rs11122316), high-density lipoprotein (HDL) cholesterol (rs1997947), low-density lipoprotein (LDL) cholesterol (rs1168013 and rs7552841), apolipoprotein (Apo) A1 (rs1997947), ApoB (rs10889332 and rs7552841) and ApoA1/ApoB ratio (rs7552841) in Jing minority; and with TG (rs10889332, rs615563, rs7552841, rs11206517, rs1997947, rs4846913 and rs11122316), HDL cholesterol (rs11206517 and rs4846913), LDL cholesterol (rs1168013), ApoA1 (rs11206517 and rs4846913), ApoB (rs7552841) and ApoA1/ApoB ratio (rs4846913) in Han nationality. Strong linkage disequilibria were noted among the SNPs. The commonest haplotype was G-C-G-C-T-G-C-C-G (>10%). The frequencies of C-C-G-C-T-G-T-C-G, G-C-A-C-T-G-C-C-G, G-C-G-C-T-A-C-C-A, G-C-G-C-T-G-C-C-A, G-C-G-C-T-G-T-C-A haplotypes were different between the two populations. Haplotypes could explain much more serum lipid variation than any single SNP alone especially for TG. Differences in lipid profiles between the two populations might partially attribute to these SNPs and their haplotypes.
The Impact of Dietary Energy Intake Early in Life on the Colonic Microbiota of Adult Mice
Authors: Xu Jinyu , Galley Jeffrey D. , Bailey Michael T. , Thomas-Ahner Jennifer M. , Clinton Steven K. , Olivo-Marston Susan E.
Published: January 2016

The complex and dynamic interactions between diet, gut microbiota (GM) structure and function and colon carcinogenesis are only beginning to be elucidated. We examined the colonic microbiota and aberrant crypt foci (ACF) in C57BL/6N female mice fed various dietary interventions (control, energy restricted and high-fat) provided during two phases (initiation and progression) of azoxymethane (AOM)-induced early colon carcinogenesis. During progression (wks. 22–60), a high-fat diet enhanced ACF formation compared to a control or energy restricted diet. In contrast, energy restriction during initiation phase (wks. 3–21) enhanced ACF burden at 60 weeks, regardless of the diet in progression phase. Alterations in GM structure during the initiation phase diet were partially maintained after changing diets during the progression phase. However, diet during the progression phase had major effects on the mucosal GM. Energy restriction in the progression phase increased Firmicutes and reduced Bacteroidetes compared to a high-fat diet, regardless of initiation phase diet, suggesting that diet may have both transient effects as well as a lasting impact on GM composition. Integration of early life and adult dietary impacts on the colonic microbial structure and function with host molecular processes involved in colon carcinogenesis will be key to defining preventive strategies.
Surfactants for Bubble Removal against Buoyancy
Authors: Raza Md. Qaisar , Kumar Nirbhay , Raj Rishi
Published: January 2016

The common phenomenon of buoyancy-induced vapor bubble lift-off from a heated surface is of importance to many areas of science and technology. In the absence of buoyancy in zero gravity of space, non-departing bubbles coalesce to form a big dry patch on the heated surface and heat transfer deteriorates despite the high latent heat of vaporization of water. The situation is worse on an inverted heater in earth gravity where both buoyancy and surface tension act upwards to oppose bubble removal. Here we report a robust passive technique which uses surfactants found in common soaps and detergents to avoid coalescence and remove bubbles downwards, away from an inverted heater. A force balance model is developed to demonstrate that the force of repulsion resulting from the interaction of surfactants adsorbed at the neighboring liquid-vapor interfaces of the thin liquid film contained between bubbles is strong enough to overcome buoyancy and surface tension. Bubble removal frequencies in excess of ten Hz resulted in more than twofold enhancement in heat transfer in comparison to pure water. We believe that this novel bubble removal mechanism opens up opportunities for designing boiling-based systems for space applications.
A straw-housed paper-based colorimetric antibody–antigen sensor
Authors: Chan Soo Khim , Lim Theam Soon
Published: January 2016

A simple and low cost paper-based ELISA sensor was developed by modifying the cellulose paper with chitosan and glutaraldehyde. The sensor incubation and wash was carried out using a straw for further convenience.
Electrochemical behavior of isofraxidin at an electrodeposition reduced graphene oxide electrode and its analytical application
Authors: Wu Junjun , Wang Lu , Xie Zhengkun , Zou Lina , Ye Baoxian
Published: January 2016

A highly sensitive voltammetric sensor ERGO/GCE was constructed and used for sensitive detection of isofraxidin. Then the electrochemical behavior of isofraxidin was carefully investigated for the first time and a possible reaction mechanism was proposed.
Pyridine–copper(ii) formates for the generation of high conductivity copper films at low temperatures
Authors: Paquet C. , Lacelle T. , Deore B. , Kell A. J. , Liu X. , Korobkov I. , Malenfant P. R. L.
Published: January 2016

Pyridine derivatives coordinated to copper(ii) formates are shown to have lower decomposition temperatures than the alkylamine analogues.
Shape-controlled synthesis of three-dimensional triangular bismuth microstructures and sensing of H2O2
Authors: Das Ashis , Sangaranarayanan M. V.
Published: January 2016

The electrodeposition of triangular microstructures of Bi on indium tin oxide surfaces is carried out by optimizing the potentials, precursor concentrations and deposition times.