bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene–Environment Interactions Between Depressive Symptoms and Smoking Quantity
Authors: Keskitalo-Vuokko Kaisu , Korhonen Tellervo , Kaprio Jaakko
Published: May 2016

We investigated genetic and environmental correlations and gene by environment interactions (GxE) between depressive symptoms measured by the Beck Depression Inventory (BDI) and quantity smoked measured by number of cigarettes smoked per day (CPD) using quantitative genetic modeling. The population-based sample consisted of 12,063 twin individuals from the Finnish Twin Cohort Study. Bivariate Cholesky decomposition revealed that the phenotypic correlation (r = 0.09) between BDI and CPD was explained by shared genetic (rg = 0.18) and environmental (re = 0.08) factors. GxE models incorporating moderator effects were built by using CPD as trait and BDI as moderator and vice versa. The importance of the genetic variance component increased with increasing moderator value in both models. Thus, the influence of genetic effects on variance of smoking quantity was enhanced in individuals with elevated depression score and vice versa; the genetic effects on depression variance were potentiated among heavy smokers. In conclusion, shared genetic and environmental factors as well as GxE underlie the association of smoking with depression.
Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models
Authors: Arevalo Hermenegild J. , Vadakkumpadan Fijoy , Guallar Eliseo , Jebb Alexander , Malamas Peter , Wu Katherine C. , Trayanova Natalia A.
Published: May 2016

Sudden cardiac death (SCD) from arrhythmias is a leading cause of mortality. For patients at high SCD risk, prophylactic insertion of implantable cardioverter defibrillators (ICDs) reduces mortality. Current approaches to identify patients at risk for arrhythmia are, however, of low sensitivity and specificity, which results in a low rate of appropriate ICD therapy. Here, we develop a personalized approach to assess SCD risk in post-infarction patients based on cardiac imaging and computational modelling. We construct personalized three-dimensional computer models of post-infarction hearts from patients’ clinical magnetic resonance imaging data and assess the propensity of each model to develop arrhythmia. In a proof-of-concept retrospective study, the virtual heart test significantly outperformed several existing clinical metrics in predicting future arrhythmic events. The robust and non-invasive personalized virtual heart risk assessment may have the potential to prevent SCD and avoid unnecessary ICD implantations.
Generation of stem cell-derived β-cells from patients with type 1 diabetes
Authors: Millman Jeffrey R. , Xie Chunhui , Van Dervort Alana , Gürtler Mads , Pagliuca Felicia W. , Melton Douglas A.
Published: May 2016

We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology.
Tumour resistance in induced pluripotent stem cells derived from naked mole-rats
Authors: Miyawaki Shingo , Kawamura Yoshimi , Oiwa Yuki , Shimizu Atsushi , Hachiya Tsuyoshi , Bono Hidemasa , Koya Ikuko , Okada Yohei , Kimura Tokuhiro , Tsuchiya Yoshihiro , Suzuki Sadafumi , Onishi Nobuyuki , Kuzumaki Naoko , Matsuzaki Yumi , Narita Minoru , Ikeda Eiji , Okanoya Kazuo , Seino Ken-ichiro , Saya Hideyuki , Okano Hideyuki , Miura Kyoko
Published: May 2016

The naked mole-rat (NMR, Heterocephalus glaber), which is the longest-lived rodent species, exhibits extraordinary resistance to cancer. Here we report that NMR somatic cells exhibit a unique tumour-suppressor response to reprogramming induction. In this study, we generate NMR-induced pluripotent stem cells (NMR-iPSCs) and find that NMR-iPSCs do not exhibit teratoma-forming tumorigenicity due to the species-specific activation of tumour-suppressor alternative reading frame (ARF) and a disruption mutation of the oncogene ES cell-expressed Ras (ERAS). The forced expression of Arf in mouse iPSCs markedly reduces tumorigenicity. Furthermore, we identify an NMR-specific tumour-suppression phenotype—ARF suppression-induced senescence (ASIS)—that may protect iPSCs and somatic cells from ARF suppression and, as a consequence, tumorigenicity. Thus, NMR-specific ARF regulation and the disruption of ERAS regulate tumour resistance in NMR-iPSCs. Our findings obtained from studies of NMR-iPSCs provide new insight into the mechanisms of tumorigenicity in iPSCs and cancer resistance in the NMR.
The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic landscapes
Authors: Pereira Bernard , Chin Suet-Feung , Rueda Oscar M. , Vollan Hans-Kristian Moen , Provenzano Elena , Bardwell Helen A. , Pugh Michelle , Jones Linda , Russell Roslin , Sammut Stephen-John , Tsui Dana W. Y. , Liu Bin , Dawson Sarah-Jane , Abraham Jean , Northen Helen , Peden John F. , Mukherjee Abhik , Turashvili Gulisa , Green Andrew R. , McKinney Steve , Oloumi Arusha , Shah Sohrab , Rosenfeld Nitzan , Murphy Leigh , Bentley David R. , Ellis Ian O. , Purushotham Arnie , Pinder Sarah E. , Børresen-Dale Anne-Lise , Earl Helena M. , Pharoah Paul D. , Ross Mark T. , Aparicio Samuel , Caldas Carlos
Published: May 2016

The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies.
The RanBP2/RanGAP1*SUMO1/Ubc9 SUMO E3 ligase is a disassembly machine for Crm1-dependent nuclear export complexes
Authors: Ritterhoff Tobias , Das Hrishikesh , Hofhaus Götz , Schröder Rasmus R. , Flotho Annette , Melchior Frauke
Published: May 2016

Continuous cycles of nucleocytoplasmic transport require disassembly of transport receptor/Ran-GTP complexes in the cytoplasm. A basic disassembly mechanism in all eukaryotes depends on soluble RanGAP and RanBP1. In vertebrates, a significant fraction of RanGAP1 stably interacts with the nucleoporin RanBP2 at a binding site that is flanked by FG-repeats and Ran-binding domains, and overlaps with RanBP2’s SUMO E3 ligase region. Here, we show that the RanBP2/RanGAP1*SUMO1/Ubc9 complex functions as an autonomous disassembly machine with a preference for the export receptor Crm1. We describe three in vitro reconstituted disassembly intermediates, which show binding of a Crm1 export complex via two FG-repeat patches, cargo-release by RanBP2’s Ran-binding domains and retention of free Crm1 at RanBP2 after Ran-GTP hydrolysis. Intriguingly, all intermediates are compatible with SUMO E3 ligase activity, suggesting that the RanBP2/RanGAP1*SUMO1/Ubc9 complex may link Crm1- and SUMO-dependent functions.
Atomistic understanding of cation exchange in PbS nanocrystals using simulations with pseudoligands
Authors: Fan Zhaochuan , Lin Li-Chiang , Buijs Wim , Vlugt Thijs J. H. , van Huis Marijn A.
Published: May 2016

Cation exchange is a powerful tool for the synthesis of nanostructures such as core–shell nanocrystals, however, the underlying mechanism is poorly understood. Interactions of cations with ligands and solvent molecules are systematically ignored in simulations. Here, we introduce the concept of pseudoligands to incorporate cation-ligand-solvent interactions in molecular dynamics. This leads to excellent agreement with experimental data on cation exchange of PbS nanocrystals, whereby Pb ions are partially replaced by Cd ions from solution. The temperature and the ligand-type control the exchange rate and equilibrium composition of cations in the nanocrystal. Our simulations reveal that Pb ions are kicked out by exchanged Cd interstitials and migrate through interstitial sites, aided by local relaxations at core–shell interfaces and point defects. We also predict that high-pressure conditions facilitate strongly enhanced cation exchange reactions at elevated temperatures. Our approach is easily extendable to other semiconductor compounds and to other families of nanocrystals.
Predicting quantitative traits from genome and phenome with near perfect accuracy
Authors: Märtens Kaspar , Hallin Johan , Warringer Jonas , Liti Gianni , Parts Leopold
Published: May 2016

In spite of decades of linkage and association studies and its potential impact on human health, reliable prediction of an individual’s risk for heritable disease remains difficult. Large numbers of mapped loci do not explain substantial fractions of heritable variation, leaving an open question of whether accurate complex trait predictions can be achieved in practice. Here, we use a genome sequenced population of ∼7,000 yeast strains of high but varying relatedness, and predict growth traits from family information, effects of segregating genetic variants and growth in other environments with an average coefficient of determination R2 of 0.91. This accuracy exceeds narrow-sense heritability, approaches limits imposed by measurement repeatability and is higher than achieved with a single assay in the laboratory. Our results prove that very accurate prediction of complex traits is possible, and suggest that additional data from families rather than reference cohorts may be more useful for this purpose.
Direct electronic measurement of Peltier cooling and heating in graphene
Authors: Vera-Marun I. J. , van den Berg J. J. , Dejene F. K. , van Wees B. J.
Published: May 2016

Thermoelectric effects allow the generation of electrical power from waste heat and the electrical control of cooling and heating. Remarkably, these effects are also highly sensitive to the asymmetry in the density of states around the Fermi energy and can therefore be exploited as probes of distortions in the electronic structure at the nanoscale. Here we consider two-dimensional graphene as an excellent nanoscale carbon material for exploring the interaction between electronic and thermal transport phenomena, by presenting a direct and quantitative measurement of the Peltier component to electronic cooling and heating in graphene. Thanks to an architecture including nanoscale thermometers, we detected Peltier component modulation of up to 15 mK for currents of 20 μA at room temperature and observed a full reversal between Peltier cooling and heating for electron and hole regimes. This fundamental thermodynamic property is a complementary tool for the study of nanoscale thermoelectric transport in two-dimensional materials.
Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits
Authors: Robinson James E. , Hastie Kathryn M. , Cross Robert W. , Yenni Rachael E. , Elliott Deborah H. , Rouelle Julie A. , Kannadka Chandrika B. , Smira Ashley A. , Garry Courtney E. , Bradley Benjamin T. , Yu Haini , Shaffer Jeffrey G. , Boisen Matt L. , Hartnett Jessica N. , Zandonatti Michelle A. , Rowland Megan M. , Heinrich Megan L. , Martínez-Sobrido Luis , Cheng Benson , de la Torre Juan C. , Andersen Kristian G. , Goba Augustine , Momoh Mambu , Fullah Mohamed , Gbakie Michael , Kanneh Lansana , Koroma Veronica J. , Fonnie Richard , Jalloh Simbirie C. , Kargbo Brima , Vandi Mohamed A. , Gbetuwa Momoh , Ikponmwosa Odia , Asogun Danny A. , Okokhere Peter O. , Follarin Onikepe A. , Schieffelin John S. , Pitts Kelly R. , Geisbert Joan B. , Kulakoski Peter C. , Wilson Russell B. , Happi Christian T. , Sabeti Pardis C. , Gevao Sahr M. , Khan S. Humarr , Grant Donald S. , Geisbert Thomas W. , Saphire Erica Ollmann , Branco Luis M. , Garry Robert F.
Published: May 2016

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design.
Erratum: A pyrosequencing insight into sprawling bacterial diversity and community dynamics in decaying deadwood logs of Fagus sylvatica and Picea abies
Authors: Hoppe Björn , Krüger Dirk , Kahl Tiemo , Arnstadt Tobias , Buscot François , Bauhus Jürgen , Wubet Tesfaye
Published: May 2016

Deadwood is an important biodiversity hotspot in forest ecosystems. While saproxylic insects and wood-inhabiting fungi have been studied extensively, little is known about deadwood-inhabiting bacteria. The study we present is among the first to compare bacterial diversity and community structure of deadwood under field conditions. We therefore compared deadwood logs of two temperate forest tree species Fagussylvatica and Piceaabies using 16S rDNA pyrosequencing to identify changes in bacterial diversity and community structure at different stages of decay in forest plots under different management regimes. Alphaproteobacteria, Acidobacteria and Actinobacteria were the dominant taxonomic groups in both tree species. There were no differences in bacterial OTU richness between deadwood of Fagussylvatica and Piceaabies. Bacteria from the order Rhizobiales became more abundant during the intermediate and advanced stages of decay, accounting for up to 25% of the entire bacterial community in such logs. The most dominant OTU was taxonomically assigned to the genus Methylovirgula, which was recently described in an experiment of Fagussylvatica woodblocks. Besides tree species we were able to demonstrate that deadwood physico-chemical properties, in particular remaining mass, relative wood moisture, pH, and C/N ratio serve as drivers of community composition of deadwood-inhabiting bacteria.
Characterization of a Citrus R2R3-MYB Transcription Factor that Regulates the Flavonol and Hydroxycinnamic Acid Biosynthesis
Authors: Liu Chaoyang , Long Jianmei , Zhu Kaijie , Liu Linlin , Yang Wei , Zhang Hongyan , Li Li , Xu Qiang , Deng Xiuxin
Published: May 2016

Flavonols and hydroxycinnamic acids are important phenylpropanoid metabolites in plants. In this study, we isolated and characterized a citrus R2R3-MYB transcription factor CsMYBF1, encoding a protein belonging to the flavonol-specific MYB subgroup. Ectopic expression of CsMYBF1 in tomato led to an up-regulation of a series of genes involved in primary metabolism and the phenylpropanoid pathway, and induced a strong accumulation of hydroxycinnamic acid compounds but not the flavonols. The RNAi suppression of CsMYBF1 in citrus callus caused a down-regulation of many phenylpropanoid pathway genes and reduced the contents of hydroxycinnamic acids and flavonols. Transactivation assays indicated that CsMYBF1 activated several promoters of phenylpropanoid pathway genes in tomato and citrus. Interestingly, CsMYBF1 could activate the CHS gene promoter in citrus, but not in tomato. Further examinations revealed that the MYBPLANT cis-elements were essential for CsMYBF1 in activating phenylpropanoid pathway genes. In summary, our data indicated that CsMYBF1 possessed the function in controlling the flavonol and hydroxycinnamic acid biosynthesis, and the regulatory differences in the target metabolite accumulation between two species may be due to the differential activation of CHS promoters by CsMYBF1. Therefore, CsMYBF1 constitutes an important gene source for the engineering of specific phenylpropanoid components.
Cinema audiences reproducibly vary the chemical composition of air during films, by broadcasting scene specific emissions on breath
Authors: Williams Jonathan , Stönner Christof , Wicker Jörg , Krauter Nicolas , Derstroff Bettina , Bourtsoukidis Efstratios , Klüpfel Thomas , Kramer Stefan
Published: May 2016

Human beings continuously emit chemicals into the air by breath and through the skin. In order to determine whether these emissions vary predictably in response to audiovisual stimuli, we have continuously monitored carbon dioxide and over one hundred volatile organic compounds in a cinema. It was found that many airborne chemicals in cinema air varied distinctively and reproducibly with time for a particular film, even in different screenings to different audiences. Application of scene labels and advanced data mining methods revealed that specific film events, namely “suspense” or “comedy” caused audiences to change their emission of specific chemicals. These event-type synchronous, broadcasted human chemosignals open the possibility for objective and non-invasive assessment of a human group response to stimuli by continuous measurement of chemicals in air. Such methods can be applied to research fields such as psychology and biology and be valuable to industries such as film making and advertising.
Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth
Authors: Holst Frederik , Hoivik Erling A. , Gibson William J. , Taylor-Weiner Amaro , Schumacher Steven E. , Asmann Yan W. , Grossmann Patrick , Trovik Jone , Necela Brian M. , Thompson E. Aubrey , Meyerson Matthew , Beroukhim Rameen , Salvesen Helga B. , Cherniack Andrew D.
Published: May 2016

The estrogen receptor alpha (ERα) is highly expressed in both endometrial and breast cancers, and represents the most prevalent therapeutic target in breast cancer. However, anti-estrogen therapy has not been shown to be effective in endometrial cancer. Recently it has been shown that hormone-binding domain alterations of ERα in breast cancer contribute to acquired resistance to anti-estrogen therapy. In analyses of genomic data from The Cancer Genome Atlas (TCGA), we observe that endometrial carcinomas manifest recurrent ESR1 gene amplifications that truncate the hormone-binding domain encoding region of ESR1 and are associated with reduced mRNA expression of exons encoding the hormone-binding domain. These findings support a role for hormone-binding alterations of ERα in primary endometrial cancer, with potentially important therapeutic implications.
Treponema pallidum Lipoprotein TP0435 Expressed in Borrelia burgdorferi Produces Multiple Surface/Periplasmic Isoforms and mediates Adherence
Authors: Chan Kamfai , Nasereddin Thayer , Alter Laura , Centurion-Lara Arturo , Giacani Lorenzo , Parveen Nikhat
Published: May 2016

The ability of Treponema pallidum, the syphilis spirochete to colonize various tissues requires the presence of surface-exposed adhesins that have been difficult to identify due to the inability to culture and genetically manipulate T. pallidum. Using a Borrelia burgdorferi-based heterologous system and gain-in-function approach, we show for the first time that a highly immunogenic lipoprotein TP0435 can be differentially processed into multiple isoforms with one variant stochastically displayed on the spirochete surface. TP0435 was previously believed to be exclusively located in T. pallidum periplasm. Furthermore, non-adherent B. burgdorferi strain expressing TP0435 acquires the ability to bind to a variety of host cells including placental cells and exhibits slow opsonophagocytosis in vitro similar to poor ex vivo phagocytosis of T. pallidum by host macrophages reported previously. This phenomenon of production of both surface and periplasmic immunogenic lipoprotein isoforms has possible implications in immune evasion of the obligate pathogen T. pallidum during infection.
Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2
Authors: Patmanathan Sathya Narayanan , Johnson Steven P. , Lai Sook Ling , Panja Bernam Suthashini , Lopes Victor , Wei Wenbin , Ibrahim Maha Hafez , Torta Federico , Narayanaswamy Pradeep , Wenk Markus R. , Herr Deron R. , Murray Paul G. , Yap Lee Fah , Paterson Ian C.
Published: May 2016

Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. Inin vitrostudies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
Genetic Relationship between Schizophrenia and Nicotine Dependence
Authors: Chen Jingchun , Bacanu Silviu-Alin , Yu Hui , Zhao Zhongming , Jia Peilin , Kendler Kenneth S. , Kranzler Henry R. , Gelernter Joel , Farrer Lindsay , Minica Camelia , Pool Rene , Milaneschi Yuri , Boomsma Dorret I. , Penninx Brenda W. J. H. , Tyndale Rachel F. , Ware Jennifer J. , Vink Jacqueline M. , Kaprio Jaakko , Munafò Marcus , Chen Xiangning ,   Cotinine meta-analysis group, Ware Jennifer J. , Chen Xiangning , Vink Jacqueline M. , Loukola Anu , Minica Camelia , Pool Rene , Milaneschi Yuri , Mangino Massimo , Menni Cristina , Chen Jingchun , Peterson Roseann , Auro Kirsi , Lyytikäinen Leo-Pekka , Wedenoja Juho , Stiby Alex I. , Hemani Gibran , Willemsen Gonneke , Hottenga Jouke Jan , Korhonen Tellervo , Heliövaara Markku , Perola Markus , Rose Richard , Paternoster Lavinia , Timpson Nic , Wassenaar Catherine A. , Zhu Andy Z. X. , Smith George Davey , Raitakari Olli , Lehtimäki Terho , Kähönen Mika , Koskinen Seppo , Spector Timothy , Penninx Brenda W. J. H. , Salomaa Veikko , Boomsma Dorret I. , Tyndale Rachel F. , Kaprio Jaakko , Munafò Marcus ,   FTND meta-analysis group, Ware Jennifer J. , Chen Xiangning , Vink Jacqueline M. , Loukola Anu , Minica Camelia , Chen Jingchun , Peterson Roseann , Timpson Nic , Taylor Michelle , Boomsma Dorret I. , Kaprio Jaakko , Munafò Marcus , Maes Hermine , Riley Brien , Kendler Kenneth S. , Gelernter Joel , Sherva Richard , Farrer Lindsay , Kranzler Henry R. , Maher Brion , Vanyukov Michael
Published: May 2016

It is well known that most schizophrenia patients smoke cigarettes. There are different hypotheses postulating the underlying mechanisms of this comorbidity. We used summary statistics from large meta-analyses of plasma cotinine concentration (COT), Fagerström test for nicotine dependence (FTND) and schizophrenia to examine the genetic relationship between these traits. We found that schizophrenia risk scores calculated at P-value thresholds of 5 × 10−3and larger predicted FTND and cigarettes smoked per day (CPD), suggesting that genes most significantly associated with schizophrenia were not associated with FTND/CPD, consistent with the self-medication hypothesis. The COT risk scores predicted schizophrenia diagnosis at P-values of 5 × 10−3and smaller, implying that genes most significantly associated with COT were associated with schizophrenia. These results implicated that schizophrenia and FTND/CPD/COT shared some genetic liability. Based on this shared liability, we identified multiple long non-coding RNAs and RNA binding protein genes (DA376252, BX089737, LOC101927273, LINC01029, LOC101928622, HY157071, DA902558,RBFOX1andTINCR), protein modification genes (MANBA,UBE2D3, andRANGAP1) and energy production genes (XYLB,MTRF1andENOX1) that were associated with both conditions. Further analyses revealed that these shared genes were enriched in calcium signaling, long-term potentiation and neuroactive ligand-receptor interaction pathways that played a critical role in cognitive functions and neuronal plasticity.
Solid-state supercapacitors with rationally designed heterogeneous electrodes fabricated by large area spray processing for wearable energy storage applications
Authors: Huang Chun , Zhang Jin , Young Neil P. , Snaith Henry J. , Grant Patrick S.
Published: May 2016

Supercapacitors are in demand for short-term electrical charge and discharge applications. Unlike conventional supercapacitors, solid-state versions have no liquid electrolyte and do not require robust, rigid packaging for containment. Consequently they can be thinner, lighter and more flexible. However, solid-state supercapacitors suffer from lower power density and where new materials have been developed to improve performance, there remains a gap between promising laboratory results that usually require nano-structured materials and fine-scale processing approaches and current manufacturing technology that operates at large scale. We demonstrate a new, scalable capability to produce discrete, multi-layered electrodes with a different material and/or morphology in each layer and where each layer plays a different, critical role in enhancing the dynamics of charge/discharge. This layered structure allows efficient utilisation of each material and enables conservative use of hard-to-obtain materials. The layered electrode shows amongst the highest combinations of energy and power densities for solid-state supercapacitors. Our functional design and spray manufacturing approach to heterogeneous electrodes provide a new way forward for improved energy storage devices.
Development of a loop-mediated isothermal amplification method for the rapid diagnosis of Ascochyta rabiei L. in chickpeas
Authors: Chen Xiaolu , Ma Lijuan , Qiang Song , Ma Deying
Published: May 2016

Ascochyta blight (AB) is a devastating fungal disease of chickpeas that has spread to nearly all of the chickpea cultivating regions of the world. The rapid diagnosis of Ascochyta rabiei L. (A. rabiei), the pathogen that causes AB, plays an important role in A. rabiei epidemic tracking and AB management. In this study, a group of loop-mediated isothermal amplification (LAMP) primers was designed to detect A. rabiei in chickpea plants and seeds via a LAMP method and a conventional PCR method based on an internal transcribed spacer (ITS) sequence analysis of A. rabiei. Compared with the conventional PCR method, the LAMP method not only exhibited greater sensitivity and specificity in the detection of A. rabiei but also used simpler equipment and required less operational time. The minimum detectable concentration of the A. rabiei genomic DNA solution with the LAMP method was 6.01 × 10−6 ng/μl, which was 100 times lower than that of the conventional PCR method with the same outer primers. The greatest advantage of the LAMP method is that results can be observed via the visualization of color changes in SYBR Green I dye with the naked eye and it does not require expensive instruments, also with less time consumption.
Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks
Authors: Nishtala Sneha , Neelamraju Yaseswini , Janga Sarath Chandra
Published: May 2016

RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.
Taste substance binding elicits conformational change of taste receptor T1r heterodimer extracellular domains
Authors: Nango Eriko , Akiyama Shuji , Maki-Yonekura Saori , Ashikawa Yuji , Kusakabe Yuko , Krayukhina Elena , Maruno Takahiro , Uchiyama Susumu , Nuemket Nipawan , Yonekura Koji , Shimizu Madoka , Atsumi Nanako , Yasui Norihisa , Hikima Takaaki , Yamamoto Masaki , Kobayashi Yuji , Yamashita Atsuko
Published: May 2016

Sweet and umami tastes are perceived by T1r taste receptors in oral cavity. T1rs are class C G-protein coupled receptors (GPCRs), and the extracellular ligand binding domains (LBDs) of T1r1/T1r3 and T1r2/T1r3 heterodimers are responsible for binding of chemical substances eliciting umami or sweet taste. However, molecular analyses of T1r have been hampered due to the difficulties in recombinant expression and protein purification, and thus little is known about mechanisms for taste perception. Here we show the first molecular view of reception of a taste substance by a taste receptor, where the binding of the taste substance elicits a different conformational state of T1r2/T1r3 LBD heterodimer. Electron microscopy has showed a characteristic dimeric structure. Förster resonance energy transfer and X-ray solution scattering have revealed the transition of the dimerization manner of the ligand binding domains, from a widely spread to compactly organized state upon taste substance binding, which may correspond to distinct receptor functional states.
Heat-Treatment-Induced Switching of Magnetic States in the Doped Polar Semiconductor Ge1−xMnxTe
Authors: Kriener M. , Nakajima T. , Kaneko Y. , Kikkawa A. , Yu X. Z. , Endo N. , Kato K. , Takata M. , Arima T. , Tokura Y. , Taguchi Y.
Published: May 2016

Cross-control of a material property - manipulation of a physical quantity (e.g., magnetisation) by a nonconjugate field (e.g., electrical field) – is a challenge in fundamental science and also important for technological device applications. It has been demonstrated that magnetic properties can be controlled by electrical and optical stimuli in various magnets. Here we find that heat-treatment allows the control over two competing magnetic phases in the Mn-doped polar semiconductor GeTe. The onset temperatures Tc of ferromagnetism vary at low Mn concentrations by a factor of five to six with a maximum Tc ≈ 180 K, depending on the selected phase. Analyses in terms of synchrotron x-ray diffraction and energy dispersive x-ray spectroscopy indicate a possible segregation of the Mn ions, which is responsible for the high-Tc phase. More importantly, we demonstrate that the two states can be switched back and forth repeatedly from either phase by changing the heat-treatment of a sample, thereby confirming magnetic phase-change-memory functionality.
Redox potential driven aeration during very-high-gravity ethanol fermentation by using flocculating yeast
Authors: Liu Chen-Guang , Hao Xue-Mi , Lin Yen-Han , Bai Feng-Wu
Published: May 2016

Ethanol fermentation requires oxygen to maintain high biomass and cell viability, especially under very-high-gravity (VHG) condition. In this work, fermentation redox potential (ORP) was applied to drive the aeration process at low dissolved oxygen (DO) levels, which is infeasible to be regulated by a DO sensor. The performance and characteristics of flocculating yeast grown under 300 and 260 g glucose/L conditions were subjected to various aeration strategies including: no aeration; controlled aeration at −150, −100 and −50 mV levels; and constant aeration at 0.05 and 0.2 vvm. The results showed that anaerobic fermentation produced the least ethanol and had the highest residual glucose after 72 h of fermentation. Controlled aerations, depending on the real-time oxygen demand, led to higher cell viability than the no-aeration counterpart. Constant aeration triggered a quick biomass formation, and fast glucose utilization. However, over aeration at 0.2 vvm caused a reduction of final ethanol concentration. The controlled aeration driven by ORP under VHG conditions resulted in the best fermentation performance. Moreover, the controlled aeration could enhance yeast flocculating activity, promote an increase of flocs size, and accelerate yeast separation near the end of fermentation.
Fatal influenza A (H5N1) virus Infection in zoo-housed Tigers in Yunnan Province, China
Authors: Hu Tingsong , Zhao Huanyun , Zhang Yan , Zhang Wendong , Kong Qiang , Zhang Zhixiao , Cui Qinghua , Qiu Wei , Deng Bo , Fan Quanshui , Zhang Fuqiang
Published: May 2016

From 2014 to 2015, three cases of highly pathogenic avian influenza infection occurred in zoo-housed north-east China tigers (Panthera tigris ssp.altaica) and four tigers died of respiratory distress in succession in Yunnan Province, China. We isolated and characterized three highly pathogenic avian influenza A(H5N1) viruses from these tigers. Phylogenetic analysis indicated that A/tiger /Yunnan /tig1404 /2014(H5N1) belongs to the provisional subclade 2.3.4.4e which were novel reassortant influenza A (H5N1) viruses with six internal genes from avian influenza A (H5N2) viruses. The HA gene of the isolated A/tiger /Yunnan /tig1412 /2014(H5N1) virus belongs to the subclade 2.3.2.1b. The isolated A/tiger /Yunnan /tig1508/2015 (H5N1) virus was a novel reassortant influenza A (H5N1) virus with three internal genes (PB2, PB1 and M) from H9N2 virus and belongs to the subclade 2.3.2.1c.
Novel European free-living, non-diazotrophic Bradyrhizobium isolates from contrasting soils that lack nodulation and nitrogen fixation genes – a genome comparison
Authors: Jones Frances Patricia , Clark Ian M. , King Robert , Shaw Liz J. , Woodward Martin J. , Hirsch Penny R.
Published: May 2016

The slow-growing genus Bradyrhizobium is biologically important in soils, with different representatives found to perform a range of biochemical functions including photosynthesis, induction of root nodules and symbiotic nitrogen fixation and denitrification. Consequently, the role of the genus in soil ecology and biogeochemical transformations is of agricultural and environmental significance. Some isolates of Bradyrhizobium have been shown to be non-symbiotic and do not possess the ability to form nodules. Here we present the genome and gene annotations of two such free-living Bradyrhizobium isolates, named G22 and BF49, from soils with differing long-term management regimes (grassland and bare fallow respectively) in addition to carbon metabolism analysis. These Bradyrhizobium isolates are the first to be isolated and sequenced from European soil and are the first free-living Bradyrhizobium isolates, lacking both nodulation and nitrogen fixation genes, to have their genomes sequenced and assembled from cultured samples. The G22 and BF49 genomes are distinctly different with respect to size and number of genes; the grassland isolate also contains a plasmid. There are also a number of functional differences between these isolates and other published genomes, suggesting that this ubiquitous genus is extremely heterogeneous and has roles within the community not including symbiotic nitrogen fixation.
Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo
Authors: Tchurikov Nickolai A. , Yudkin Dmitry V. , Gorbacheva Maria A. , Kulemzina Anastasia I. , Grischenko Irina V. , Fedoseeva Daria M. , Sosin Dmitri V. , Kravatsky Yuri V. , Kretova Olga V.
Published: May 2016

Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics1,2. There are nine hot spots of DSBs located in human rDNA units3–6. Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics.
Matrix description of the complete topology of three-dimensional cells
Authors: Xue Weihua , Wang Hao , Liu Guoquan , Meng Li , Xiang Song , Ma Guang , Li Wenwen
Published: May 2016

A new, efficient method based on a series of matrices is introduced to completely describe the detailed topology of individual domains and their topology evolution in three-dimensional cellular structures. With this approach, we found a lot of new topological grain forms which are never reported before, i.e., there are total 8 and 32 topological forms for 7- and 8-faced grains respectively, other than the reported 7 and 27. This method is proved to be a practical tool to predict all possible grain forms efficiently. Moreover, a connectivity index of grain forms serves as a new convenient differentiator of different multicellular structures.
Genetic deletion of fibroblast growth factor 14 recapitulates phenotypic alterations underlying cognitive impairment associated with schizophrenia
Authors: Alshammari T K , Alshammari M A , Nenov M N , Hoxha E , Cambiaghi M , Marcinno A , James T F , Singh P , Labate D , Li J , Meltzer H Y , Sacchetti B , Tempia F , Laezza F
Published: May 2016

Cognitive processing is highly dependent on the functional integrity of gamma-amino-butyric acid (GABA) interneurons in the brain. These cells regulate excitability and synaptic plasticity of principal neurons balancing the excitatory/inhibitory tone of cortical networks. Reduced function of parvalbumin (PV) interneurons and disruption of GABAergic synapses in the cortical circuitry result in desynchronized network activity associated with cognitive impairment across many psychiatric disorders, including schizophrenia. However, the mechanisms underlying these complex phenotypes are still poorly understood. Here we show that in animal models, genetic deletion of fibroblast growth factor 14 (Fgf14), a regulator of neuronal excitability and synaptic transmission, leads to loss of PV interneurons in the CA1 hippocampal region, a critical area for cognitive function. Strikingly, this cellular phenotype associates with decreased expression of glutamic acid decarboxylase 67 (GAD67) and vesicular GABA transporter (VGAT) and also coincides with disrupted CA1 inhibitory circuitry, reduced in vivo gamma frequency oscillations and impaired working memory. Bioinformatics analysis of schizophrenia transcriptomics revealed functional co-clustering of FGF14 and genes enriched within the GABAergic pathway along with correlatively decreased expression of FGF14, PVALB, GAD67 and VGAT in the disease context. These results indicate that Fgf14−/− mice recapitulate salient molecular, cellular, functional and behavioral features associated with human cognitive impairment, and FGF14 loss of function might be associated with the biology of complex brain disorders such as schizophrenia.
Guidelines for Reporting Articles on Psychiatry and Heart rate variability (GRAPH): recommendations to advance research communication
Authors: Quintana D S , Alvares G A , Heathers J A J
Published: May 2016

The number of publications investigating heart rate variability (HRV) in psychiatry and the behavioral sciences has increased markedly in the last decade. In addition to the significant debates surrounding ideal methods to collect and interpret measures of HRV, standardized reporting of methodology in this field is lacking. Commonly cited recommendations were designed well before recent calls to improve research communication and reproducibility across disciplines. In an effort to standardize reporting, we propose the Guidelines for Reporting Articles on Psychiatry and Heart rate variability (GRAPH), a checklist with four domains: participant selection, interbeat interval collection, data preparation and HRV calculation. This paper provides an overview of these four domains and why their standardized reporting is necessary to suitably evaluate HRV research in psychiatry and related disciplines. Adherence to these communication guidelines will help expedite the translation of HRV research into a potential psychiatric biomarker by improving interpretation, reproducibility and future meta-analyses.
Electrocatalytic reduction of CO2 to CO by a mononuclear ruthenium(ii) complex
Authors: Hadadzadeh Hassan , Farrokhpour Hossein , Simpson Jim , Shakeri Jamaladin , Daryanavard Marzieh , Shokrollahi Marzieh
Published: May 2016

A new mononuclear ruthenium(ii) complex, [Ru(dmbpy)(tptz)(Cl)](PF6) (where dmbpy = 4,4′-dimethyl-2,2′-bipyridine and tptz = 2,4,6-tris(2-pyridyl)-1,3,5-triazine), has been prepared and characterized by spectroscopic methods, cyclic voltammetry (CV), and single-crystal X-ray crystallography.
Computational cell analysis for label-free detection of cell properties in a microfluidic laminar flow
Authors: Zhang Alex Ce , Gu Yi , Han Yuanyuan , Mei Zhe , Chiu Yu-Jui , Geng Lina , Cho Sung Hwan , Lo Yu-Hwa
Published: May 2016

This method utilizes machine learning algorithms and fluid mechanic properties of cells in a microfluidic channel to find the compositions of cell mixtures.
A peptide with a cysteine terminus: probe for label-free fluorescent detection of thrombin activity
Authors: Feng Jingjing , Zhuo Caixia , Ma Xuejuan , Li Shuangqin , Zhang Yaodong
Published: May 2016

A label-free fluorescent method for detection of thrombin activity has been developed by using a probe with a thrombin-cleavable peptide sequence and a cysteine terminus.
Correlating microscopy techniques and ToF-SIMS analysis of fully grown mammalian oocytes
Authors: Gulin Alexander , Nadtochenko Victor , Astafiev Artyom , Pogorelova Valentina , Rtimi Sami , Pogorelov Alexander
Published: May 2016

An innovative protocol for the 2D-molecular thin film analysis applying ToF-SIMS, SEM, AFM and optical microscopy imaging of fully grown mice oocytes is described.
Post-synthetic modifications of cadmium-based knots and links
Authors: Prakasam Thirumurugan , Bilbeisi Rana A. , Lusi Matteo , Olsen John-Carl , Platas-Iglesias Carlos , Trabolsi Ali
Published: May 2016

Three topologically non-trivial cadmium(ii)-based complexes—Cd-[2]C, Cd-TK and CD-SL—were self-assembled in a dynamic library, individually isolated and fully characterized and subjected to postsynthetic modification including demetallation and transmetallation.
Lewis acid–base interactions between platinum(ii) diaryl complexes and bis(perfluorophenyl)zinc: strongly accelerated reductive elimination induced by a Z-type ligand
Authors: Liberman-Martin Allegra L. , Levine Daniel S. , Ziegler Micah S. , Bergman Robert G. , Tilley T. Don
Published: May 2016

Z-type interactions between bis(perfluorophenyl)zinc and platinum(ii) diaryl complexes supported by 1,10-phenanthroline (phen), 2,2′-bipyridine (bpy), and bis(dimethylphosphino)ethane (dmpe) ligands are reported.
Gold coated magnetic nanoparticles: from preparation to surface modification for analytical and biomedical applications
Authors: Moraes Silva Saimon , Tavallaie Roya , Sandiford Lydia , Tilley Richard D. , Gooding J. Justin
Published: May 2016

Gold coated magnetic nanoparticles (Au@MNPs) have become increasingly interesting to nanomaterial scientists due to their multifunctional properties and their potential in both analytical chemistry and nanomedicine.
Temperature-dependent effect of percolation and Brownian motion on the thermal conductivity of TiO2–ethanol nanofluids
Authors: Li Chien-Cheng , Hau Nga Yu , Wang Yuechen , Soh Ai Kah , Feng Shien-Ping
Published: May 2016

Ethanol-based nanofluids have attracted much attention due to the enhancement in heat transfer and their potential applications in nanofluid-type fuels and thermal storage.
The optical characterization of metal-mediated aggregation behaviour of amphiphilic Zn(ii) phthalocyanines
Authors: Batat P. , Bayar M. , Pur B. , Çoker E. , Ahsen V. , Yuksel F. , Demirel A. L.
Published: May 2016

Addition of Ag+ cations induces J-aggregation in ultrathin films of both symmetrically and asymmetrically substituted Zn(ii) phthalocyanines.
How protonation and deprotonation of 9-methylguanine alter its singlet O2 addition path: about the initial stage of guanine nucleoside oxidation
Authors: Lu Wenchao , Teng Huayu , Liu Jianbo
Published: May 2016

Protonated and deprotonated 9-methylguanine follow completely different oxidation routes.
Halogenated earth abundant metalloporphyrins as photostable sensitizers for visible-light-driven water oxidation in a neutral phosphate buffer solution
Authors: Chen Hung-Cheng , Reek Joost N. H. , Williams René M. , Brouwer Albert M.
Published: May 2016

Chlorinated porphyrins containing earth abundant Cu(ii) and Ni(ii) are powerful and photostable photosensitizers for water oxidation catalysts.
Pressure dependent low temperature kinetics for CN + CH3CN: competition between chemical reaction and van der Waals complex formation
Authors: Sleiman Chantal , González Sergio , Klippenstein Stephen J. , Talbi Dahbia , El Dib Gisèle , Canosa André
Published: May 2016

The gas phase reaction between the CN radical and acetonitrile CH3CN was investigated experimentally with a CRESU apparatus and a slow flow reactor as well as theoretically to explore the temperature and pressure dependence of its rate coefficient from 354 K down to 23 K.