bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation
Authors: Hodgetts Carl J. , Shine Jonathan P. , Williams Huw , Postans Mark , Sims Rebecca , Williams Julie , Lawrence Andrew D. , Graham Kim S.
Published: March 2018

Young adult APOE-ε4 carriers show increased activity in posterior regions of the default mode network (pDMN), but how this is related to structural connectivity is unknown. Thirty young adults (half APOE-ε4 carriers, the other half APOE-ε3ε3/ε2ε3; mean age 20 years) were scanned using both diffusion and functional magnetic resonance imaging. Diffusion tractography was used to quantify the microstructure (mean diffusivity, MD; fractional anisotropy, FA) of the parahippocampal cingulum bundle (PHCB), which links pDMN and the medial temporal lobe. APOE-ε4 carriers had lower MD and higher FA relative to non-carriers in PHCB. Further, PHCB microstructure was selectively associated with pDMN activity during a scene discrimination task known to be sensitive to Alzheimer’s disease (AD). These findings are consistent with a lifespan view of AD risk, where early-life structural and functional brain changes in specific, vulnerable networks leads to increased neural activity that may ultimately trigger amyloid-ß deposition.
Hierarchical modeling of the effect of pre-exposure prophylaxis on HIV in the US
Authors: Dale Renee , Chen Ying , He Hongyu
Published: March 2018

1.

Abstract

In this paper we present a differential equation model stratified by behavioral risk and sexual activity. Some susceptible individuals have higher rates of risky behavior that increase their chance of contracting the disease. Infected individuals can be considered to be generally sexually active or inactive. The sexually active infected population is at higher risk of transmitting the disease to a susceptible individual. We further divide the sexually active population into diagnosed or undiagnosed infected individuals. We define model parameters for both the national and the urban case. These parameter sets are used to study the predicted population dynamics over the next 5 years. Our results indicate that the undiagnosed high risk infected group is the largest contributor to the epidemic. Finally, we apply a preventative medication protocol to the susceptible population and observe the effective reduction in the infected population. The simulations suggest that preventative medication effectiveness extends outside of the group that is taking the drug (herd immunity). Our models suggest that a strategy targeting the high risk undiagnosed infected group would have the largest impact in the next 5 years. We also find that such a protocol has similar effects for the national as the urban case, despite the smaller sexual network found in rural areas.
Gene2Vec: Distributed Representation of Genes Based on Co-Expression
Authors: Du Jingcheng , Jia Peilin , Dai Yulin , Tao Cui , Zhao Zhongming , Zhi Degui
Published: March 2018

Existing functional description of genes are categorical, discrete, and mostly through manual process. In this work, we explore the idea of gene embedding, distributed representation of genes, in the spirit of word embedding. From a pure data-driven fashion, we trained a 300 dimension vector representation of all human genes, using gene co-expression patterns in 984 data sets from the GEO databases. These vectors capture functional relatedness of genes in terms of recovering known pathways - the average inner product (similarity) of genes within a pathway is 1.68X greater than that of random genes. Using t-SNE, we produced a gene co-expression map that shows local concentrations of tissue specific genes. We also illustrated the usefulness of the embedded gene vectors, laden with rich information on gene co-expression patterns, in tasks such as gene-gene interaction prediction. Overall, we believe that this distributed representation of genes may be useful for more bioinformatics applications.
Evidence for a potential role of miR-1908-5p and miR-3614-5p in autoimmune disease risk using genome-wide analyses
Authors: Wohlers Inken , Bertram Lars , Lill Christina M.
Published: March 2018

Genome-wide association studies (GWAS) have identified a large number of genetic risk loci for autoimmune diseases. However, the functional variants underlying these disease associations remain largely unknown. There is evidence that microRNA-mediated regulation may play an important role in this context. Therefore, we assessed whether autoimmune disease loci unfold their effects via altering microRNA expression in relevant immune cells.

To this end, we performed microRNA expression quantitative trait loci (eQTL) analyses across 115 GWAS regions associated with 12 autoimmune diseases using next-generation sequencing data of 345 lymphoblastoid cell lines. Statistical analyses included the application and extension of a recently proposed framework (joint likelihood mapping), to microRNA expression data and microRNA target gene enrichment analyses of relevant GWAS data.

Overall, only a minority of autoimmune disease risk loci may exert their pathophysiologic effects by altering miRNA expression based on JLIM. However, detailed functional fine-mapping revealed two independent GWAS regions harboring autoimmune disease risk SNPs with significant effects on microRNA expression. These relate to SNPs associated with Crohn’s disease (CD; rs102275) and rheumatoid arthritis (RA; rs968567), which affect the expression of miR-1908-5p (prs102275=1.44e-20, prs968567=2.54e-14). In addition, an independent CD risk SNP, rs3853824, was found to alter the expression of miR-3614-5p (p=5.70e-7). To support these findings, we demonstrate that GWAS signals for RA and CD were enriched in genes predicted to be targeted by both miRNAs (all with p<0.05).

In summary, our study points towards a pathophysiological role of miR-1908-5p and miR- 3614-5p in autoimmunity.
Weak and equally balanced synaptic inputs to interneurons in the CA1 hippocampus characterize in vivo rhythmic states
Authors: Guet-McCreight Alexandre , Skinner Frances K.
Published: March 2018

Brain coding strategies are enabled by the balance of synaptic inputs that individual neurons receive as determined by the networks in which they reside. Inhibitory cell types contribute to brain function in distinct ways but recording from specific, inhibitory cell types during behaviour to determine their contributions is difficult. In particular, the in vivo activities of vasoactive intestinal peptide-expressing interneuron specific 3 (IS3) cells in the hippocampus that only target other inhibitory cells are unknown at present. We perform a massive, computational exploration of possible synaptic inputs to IS3 cells using multi-compartment models and optimized synaptic parameters. We find that asynchronous in vivo-like states that are sensitive to additional theta-timed inputs exist when excitatory and inhibitory synaptic conductances are equally balanced and there are low amounts of correlated inputs. Thus, using a generally applicable computational approach we predict the existence of balanced states in hippocampal circuits during rhythmic activities.
Agricultural fungicides inadvertently influence the fitness of Colorado potato beetles,Leptinotarsa decemlineata, and their susceptibility to insecticides
Authors: Clements Justin , Schoville Sean , Clements Anna , Amezian Dries , Davis Tabatha , Sanchez-Sedillo Benjamin , Bradfield Christopher , Huseth Anders S. , Groves Russell L.
Published: March 2018

The Colorado potato beetle (CPB),Leptinotarsa decemlineata(Say), is an agricultural pest of solanaceous crops which has developed insecticide resistance at an alarming rate. Up to this point, little consideration has been given to unintended, or inadvertent effects that non-insecticide xenobiotics may have on insecticide susceptibility inL. decemlineata. Fungicides, such as chlorothalonil and boscalid, are often used to control fungal pathogens in potato fields and are applied at regular intervals whenL. decemlineatapopulations are present in the crop. In order to determine whether fungicide use may be associated with elevated levels of insecticide resistance inL. decemlineata, we examined phenotypic responses inL. decemlineatato the fungicides chlorothalonil and boscalid. Using enzymatic and transcript abundance investigations we also examined modes of molecular detoxification in response to both insecticide (imidacloprid) and fungicide (boscalid and chlorothalonil) application to more specifically determine if fungicides and insecticides induce similar metabolic detoxification mechanisms. Both chlorothalonil and boscalid exposure induced a phenotypic, enzymatic and transcript response inL. decemlineatawhich correlates with known mechanisms of insecticide resistance.

Key Messages

Prior-exposure to a fungicidal application changes the phenotypic response ofLeptinotarsa decemlineatato the insecticide imidacloprid

Both a fungicide and insecticide application activates similar molecular mechanisms of detoxification inLeptinotarsa decemlineata

Fungicidal xenobiotics may contribute to insecticide resistance inLeptinotarsa decemlineata

Author Contribution Statement

JC, SS, CB, AH, and RG conceived and designed research. JC, AC, DA, TD, and BS conducted experiments. JC and AC analyzed data. JC and RG wrote the manuscript. All authors read and approved the manuscript.
Scute structure reveals sex of juvenile and young sturgeon in caviar aquaculture technology
Authors: Barulin Nikolai V.
Published: March 2018

Sturgeons are valued as specialty black caviar, which is very expensive. Only females are used in the technology of caviar aquaculture. Universal method of sex determination has not yet been developed. Most of known methods are not sufficiently accurate, or used at a relatively late age, or difficult to use. Perfect early determination of sex is considered to be impossible. Because of the dark color of most sturgeon, important morphological differences, which fish of almost all ages have, were overlooked. We first found that the scute structure of Sterlet and Siberian sturgeon depends on the sex, such a pattern is typical for sturgeon of all ages. We found that sex determination is possible at very early stages. Dependencies found with the help of machine learning method open a possibility for creation of sex determination equipment using the artificial intelligence. Our results open a perspective for creation of the sex determination methods for other 23 sturgeon species, which can increase the efficiency of caviar aquaculture and sturgeon restoration in natural waters.
Overexpression of RsMYB1 enhances heavy metal stress tolerance in transgenic petunia by elevating the transcript levels of stress tolerant and antioxidant genes
Authors: Ai Trinh Ngoc , Naing Aung Htay , Yun Byung-Wook , Kim Chang Kil
Published: March 2018

The RsMYB1 transcription factor (TF) controls the regulation of anthocyanin in radish (Raphanus sativus), and its overexpression in tobacco and petunia strongly enhances anthocyanin production. However, no data exists on whether RsMYB1 is involved in the mechanism that leads to abiotic stress tolerance. Under normal conditions, transgenic petunia plants expressing RsMYB1 and WT were able to thrive by producing well-developed broad leaves and regular roots. In contrast, a reduction in plant growth was observed when they were exposed to heavy metals (CuSO4, ZnSO4, MnSO4, and K2Cr2O7). However, RsMYB1-overexpressing plants were found to be more tolerant to the stresses than the WT plants because the expressions of stress tolerant genes (GSH and PCs) and antioxidant genes (SOD, CAT, and POX) were enhanced. In addition, according to the phylogenetic analysis, RsMYB1 has a strong sequence similarity with other MYB TFs that confer different abiotic stresses. These results suggest that overexpression of RsMYB1 enhances the expression levels of metal-induced stress tolerance genes and antioxidant genes, and the resultant increase in gene expression improves heavy metal stress tolerance in petunia.
Characterisation of molecular motions in cryo-EM single-particle data by multi-body refinement in RELION
Authors: Nakane Takanori , Kimanius Dari , Lindahl Erik , Scheres Sjors H.W.
Published: March 2018

Macromolecular complexes that exhibit continuous forms of structural flexibility pose a challenge for many existing tools in cryo-EM single-particle analysis. We describe a new tool, called multi-body refinement, which models flexible complexes as a user-defined number of rigid bodies that move independently from each other. Using separate focused refinements with iteratively improved partial signal subtraction, the new tool generates improved reconstructions for each of the defined bodies in a fully automated manner. Moreover, using principal component analysis on the relative orientations of the bodies over all particles in the data set, we generate movies that describe the most important motions in the data. Our results on two test cases, a cytoplasmic ribosome from Plasmodium falciparum, and the spliceosomal B-complex from yeast, illustrate how multi-body refinement can be useful to gain unique insights into the structure and dynamics of large and flexible macromolecular complexes.

Please note that this bioRxiv submission is ahead of the availability of the multi-body software in relion-3.0. We take great care in distributing stable software, but this does take time. We will announce the (beta-)release of relion-3.0 through the ccp-em mailing list (https://www.jiscmail.ac.uk/CCPEM) and on twitter (@SjorsScheres).
Substrate channeling in oxylipin biosynthesis through a protein complex in the plastid envelope ofArabidopsis thaliana
Authors: Pollmann Stephan , Springer Armin , Rustgi Sachin , von Wettstein Diter , Kang ChulHee , Reinbothe Christiane , Reinbothe Steffen
Published: March 2018

Oxygenated membrane fatty acid derivatives dubbed oxylipins play important roles in the plant’s defense against biotic and abiotic cues. Plants challenged by insect pests, for example, synthesize a blend of different defense compounds that, amongst others, comprise volatile aldehydes and jasmonic acid (JA). Because all oxylipins are derived from the same pathway, we asked how their synthesis might be regulated and focused on two closely related, atypical cytochrome P450 enzymes designated CYP74A and CYP74B, i.e., allene oxide synthase (AOS) and hydroperoxide lyase (HPL). Both enzymes compete for the same substrate but give rise to different products. While the final product of the AOS branch is JA, those of the HPL branch comprise volatile aldehydes and alcohols. AOS and HPL are plastid envelope enzymes inArabidopsis thalianabut accumulate at different locations. Biochemical experiments identified AOS as constituent of complexes also containing lipoxygenase 2 (LOX2) and allene oxide cyclase (AOC), which catalyze consecutive steps in JA precursor biosynthesis, while excluding the concurrent HPL reaction. Based on published X-ray data, the structure of this complex could be modelled and amino acids involved in catalysis and subunit interactions identified. Genetic studies identified the microRNA 319 (miR319)-regulated clade of TCP (TEOSINTE BRANCHED/CYCLOIDEA/PCF) transcription factor genes and CORONATINE INSENSITIVE 1 (COI1) to control JA production through the AOS-LOX2-AOC2 complex. Together, our results define a molecular branch point in oxylipin biosynthesis that allows fine-tuning the plant’s defense machinery in response to biotic and abiotic stimuli.
Symbiosis-related genes sustain the development of a downy mildew pathogen onArabidopsis thaliana
Authors: Ried Martina K. , Banhara Aline , Binder Andreas , Hwu Fang-Yu , Gust Andrea A. , Höfle Caroline , Hückelhoven Ralph , Nürnberger Thorsten , Parniske Martin
Published: March 2018

Abstract

The interfaces through which nutrients are transferred from plant cells to arbuscular mycorrhiza fungi and biotrophic hyphal pathogens are structurally similar. We report that inArabidopsis thaliana, mutations in homologs of common symbiosis genes (CSGs) encoding homologs of the symbiosis receptor kinase SYMRK, the nucleoporins NUP133 and SEC13 or the cation channel POLLUX reduce the reproductive success ofHyaloperonospora arabidopsidis (Hpa).Analysis of the multiplication of extracellular bacterial pathogens,Hpa-induced cell death or callose accumulation, as well asHpa-or flg22-induced defence marker gene expression, did not reveal any traces of constitutive or exacerbated defence responses. We discovered an age-dependent, possibly senescence-related transition of haustorial shape that occurred significantly earlier and at higher frequency in the CSG mutants. These findings point to a function of the homologs of common symbiosis genes in haustorial maintenance thus revealing an overlapping gene set for the intracellular accommodation of hyphal symbionts and pathogens.
Intronic miRNA Mediated Gene Expression Regulation Controls Protein Crowding Inside the Cell
Authors: Sinha Prashant , Jaiswal Pragya , Jainarayanan Ashwin K. , Brahmachari Samir K.
Published: March 2018

Gene regulatory effects of microRNAs at a posttranscriptional level has been established over the last decade. In this study, we analyze the interaction networks of mRNA translation regulation through intronic miRNA, under various tissue-specific cellular contexts, taking into account the thermodynamic affinity, kinetics, and the presence of competitive interactors. This database, and analysis has been made available through an open-access web-server, miRiam, to promote further exploration.

Here we report that expression of genes involved in Apoptosis Processes, Immune System Processes, Translation Regulator Activities, and Molecular Transport Activities within the cell are predominately regulated by miRNA mediation. Our findings further indicate that this regulatory effect has a profound effect in controlling protein crowding inside the cell. A miRNA mediated gene expression regulation serves as a temporal regulator, allowing the cellular machinery to temporarily ‘pause’ the translation of mRNA, indicating that the miRNA–mRNA interactions may be important for governing the optimal usage of cell volume.
Common antigenic motif recognized by human VH5-51/VL4-1 tau antibodies with distinct functionalities
Authors: Apetri Adrian , Crespo Rosa , Juraszek Jarek , Pascual Gabriel , Janson Roosmarijn , Zhu Xueyong , Zhang Heng , Keogh Elissa , Holland Trevin , Wadia Jay , Verveen Hanneke , Siregar Berdien , Mrosek Michael , Taggenbrock Renske , van Ameijde Jeroen , Inganäs Hanna , van Winsen Margot , Koldijk Martin H. , Zuijdgeest David , Borgers Marianne , Dockx Koen , Stoop Esther J.M. , Yu Wenli , Brinkman-van der Linden Els C. , Ummenthum Kimberley , van Kolen Kristof , Mercken Marc , Steinbacher Stefan , de Marco Donata , Hoozemans Jeroen J. , Wilson Ian A. , Koudstaal Wouter , Goudsmit Jaap
Published: March 2018

Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer’s Disease (AD). By interrogating IgG+ memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated VH5-51/VL4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of VH5-51 and VL4-1 recognizes a common Pro-Xn-Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD.
Smart Region-Growing: a novel algorithm for the segmentation of 3D clarified confocal image stacks
Authors: Callara Alejandro Luis , Magliaro Chiara , Ahluwalia Arti , Vanello Nicola
Published: March 2018

Motivation

Accurately mapping the brain at the micro-scale is still a challenge in cellular neuroscience. While notable success has been reached in the field of tissue clarification and confocal imaging to obtain high-fidelity maps of three-dimensional neuron organization, neuron segmentation is still far away of ground-truth and manual segmentation performed by experts may be needed. The need of an expert is in part related to the limited success of the algorithms and tools performing single-neuron segmentation from 3D microscopic image data available in the State of Art, in part to the non-complete information given by these methods, which typically perform neuron tracing and thus limit the interpret-ability of results.

Results

In this paper, a novel algorithm for segmenting single neurons in their own arrangement within the brain is presented. The algorithm performs a region growing procedure with local thresholds based on the pixel intensity statistics typical of confocal acquisitions of biological samples and described by a mixture model. The algorithm is developed and tested on 3D confocal datasets obtained from clarified tissues. We compare the result of our algorithm with those obtained by manual segmentation performed by 6 different experts in terms of neuron surface area, volume and Sholl profiles. Statistical analysis performed on morphologic features extracted from the segmented structures confirms the feasibility of our approach.

Availability

The Smart Region Growing (SmRG) algorithm used in the analysis along with test confocal image stacks is available on request to the authors.

Contact

alejandrocallara@gmail.com

Supplementary information

Supplementary data are available on request to the authors.
The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors
Authors: Selkrig Joel , Mohammad Farhan , Ng Soon Hwee , Yi Chua Jia , Tumkaya Tayfun , Ho Joses , Chiang Yin Ning , Rieger Dirk , Pettersson Sven , Helfrich-Förster Charlotte , Yew Joanne Y. , Claridge-Chang Adam
Published: March 2018

In animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved.
Crystallographic observation of nonenzymatic RNA primer extension
Authors: Zhang Wen , Walton Travis , Li Li , Szostak Jack W.
Published: March 2018

The importance of genome replication has inspired detailed crystallographic studies of enzymatic DNA/RNA polymerization. In contrast, the mechanism of nonenzymatic polymerization is less well understood, despite its critical role in the origin of life. Here we report the direct observation of nonenzymatic RNA primer extension through time-resolved crystallography. We soaked crystals of an RNA primer-template-dGMP complex with guanosine-5′-phosphoro-2-aminoimidazolide for increasing times. At early times we see the activated ribonucleotides bound to the template, followed by formation of the imidazolium-bridged dinucleotide intermediate. At later times, we see a new phosphodiester bond forming between the primer and the incoming nucleotide. The intermediate is pre-organized because of the constraints of base-pairing with the template and hydrogen bonding between the imidazole amino group and both flanking phosphates. Our results provide atomic-resolution insight into the mechanism of nonenzymatic primer extension, and set the stage for further structural dissection and optimization of the RNA copying process.
How do blind people represent rainbows? Disentangling components of conceptual representations
Authors: Striem-Amit Ella , Wang Xiaoying , Bi Yanchao , Caramazza Alfonso
Published: March 2018

How do we represent information that has no sensory features? How are abstract concepts like “freedom”, devoid of external perceptible referents, represented in the brain? To address the role of sensory information in the neural representation of concepts, we investigated how people born blind process concepts whose referents are imperceptible to them because of their visual nature (e.g. “rainbow”, or “red”). We find that the left dorsal anterior temporal lobe (ATL) shows preference both to typical abstract concepts (“freedom”) and to concepts whose referents are not sensorially-available to the blind (“rainbow”), as compared to partially sensorially-perceptible referents (e.g. “rain”). Activation pattern similarity in dorsal ATL is related to the sensorial-accessibility ratings of the concepts in the blind. Parts of inferior-lateral aspects of ATL and the temporal pole responded preferentially to abstract concepts devoid of any external referents (“freedom”) relative to imperceptible objects, in effect distinguishing between object and non-object concepts. The medial ATL showed a preference for concrete concepts (“cup”), along with a preference for partly perceptible items to the blind (“rain”, as compared with “rainbow”), indicating this region’s role in representing concepts with sensory referents beyond vision. The findings point to a new division of labor among medial, dorsal and lateral aspects of ATL in representing different properties of object and non-object concepts.
An aged human heart tissue model showing age-related molecular and functional deterioration resembling the native heart
Authors: Acun Aylin , Nguyen Trung Dung , Zorlutuna Pinar
Published: March 2018

Deaths attributed to ischemic heart disease increased by 41.7% from 1990 to 2013. This is primarily due to an increase in the aged population, however, research on cardiovascular disease (CVD) has been overlooking aging, a well-documented contributor to CVD. The field heavily depends on the use of young animals due to lower costs and ready availability, despite the prominent differences between young and aged heart structure and function. Here we present the first human induced pluripotent stem cell (hiPSC)-derived cardiomyocyte (iCM)-based, in vitro aged myocardial tissue model as an alternative research platform. Within 4 months, iCMs go through accelerated senescence and show cellular characteristics of aging. Furthermore, the model tissues fabricated using these aged iCMs, with stiffness resembling that of aged human heart, show functional and pharmacological deterioration specific to aged myocardium. Our novel tissue model with age-appropriate physiology and pathology presents a promising new platform for investigating CVD or other age-related diseases.
FAM35A associates with REV7 and modulates DNA damage responses of normal and BRCA1-defective cells
Authors: Tomida Junya , Takata Kei-ichi , Bhetawal Sarita , Person Maria D. , Chao Hsueh-Ping , Tang Dean G. , Wood Richard D.
Published: March 2018

In order to exploit the specific vulnerabilities of tumors, it is urgent to identify the basis of associated defects in genome maintenance. One unsolved problem is the mechanism of inhibition of processing of DNA double-strand break repair by REV7 and its influence on DNA repair pathways. We searched for REV7-associated proteins in human cells and found FAM35A, a protein of previously unknown function. By analyzing the FAM35A sequence we discovered that FAM35A has an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single-stranded binding protein RPA. Knockdown of FAM35A caused sensitivity to DNA damaging agents, and FAM35A re-localized in damaged cell nuclei. In a BRCA1 mutant cell line, however, depletion of FAM35A increased resistance to camptothecin, suggesting that FAM35A participates in processing of DNA ends to allow more efficient DNA repair. Moreover, we found FAM35A absent in one widely used BRCA1-mutant cancer cell line (HCC1937) with anomalous resistance to PARP inhibitors. A survey of FAM35A alterations in cancer revealed that the gene is altered at the highest frequency in prostate cancers (up to 13%) and significantly less expressed in metastatic cases. The results reveal a new DNA repair factor with promise as a therapeutically relevant cancer marker.
Optical activation of TrkA signaling
Authors: Duan Liting , Hope Jen M. , Guo Shunling , Ong Qunxiang , François Amaury , Kaplan Luke , Scherrer Grégory , Cui Bianxiao
Published: March 2018

Nerve growth factor/tropomyosin receptor kinase A (NGF/TrkA) signaling plays a key role in neuronal development, function, survival, and growth. The pathway is implicated in neurodegenerative disorders including Alzheimer’s disease, chronic pain, inflammation, and cancer. NGF binds the extracellular domain of TrkA, leading to the activation of the receptor’s intracellular kinase domain. TrkA signaling is highly dynamic, thus mechanistic studies would benefit from a tool with high spatial and temporal resolution. Here we present the design and evaluation of four strategies for light-inducible activation of TrkA in the absence of NGF. Our strategies involve the light-sensitive proteinArabidopsiscryptochrome 2 (CRY2) and its binding partner CIB1. We demonstrate successful recapitulation of native NGF/TrkA functions by optical induction of plasma membrane recruitment and homo-interaction of the intracellular domain of TrkA. This approach activates PI3K/AKT and Raf/ERK signaling pathways, promotes neurite growth in PC12 cells, and supports the survival of dorsal root ganglion neurons in the absence of NGF. This ability to activate TrkA using light bestows high spatial and temporal resolution for investigating NGF/TrkA signaling.
Crystal structure of chorismate mutase fromBurkholderia phymatum
Authors: Asojo Oluwatoyin A. , Subramanian Sandhya , Abendroth Jan , Exley Ilyssa , Lorimer Donald D. , Edwards Thomas E. , Myler Peter J.
Published: March 2018

The bacteriumBurkholderia phymatumis a promiscuous symbiotic nitrogen-fixating bacterium that belongs to one of the largest groups of Betaproteobacteria. OtherBurkholderiaspecies are known to cause disease in plants and animals, and some are potential agents for biological warfare. Structural genomics efforts include characterizing the structures of enzymes from pathways that can be targeted for drug development. As part of these efforts, chorismate mutase fromB. phymatumwas produced and crystallized, and a 1.95 Å resolution structure is reported. This enzyme shares less than 33% sequence identity with other homologs of known structure. There are two classes of chorismate mutase: AroQ and AroH. The bacterial subclass AroQγ has reported roles in virulence. Chorismate mutase fromB. phymatumhas the prototypical AroQγ topology and retains the characteristic chorismate mutase active site. This suggests that substrate-based chorismate mutase inhibitors will not be specific and are likely to affect beneficial bacteria such asB. phymatum.
Structure of proliferating cell nuclear antigen (PCNA) bound to an APIM peptide reveals the universality of PCNA interaction
Authors: Hara Kodai , Uchida Masayuki , Tagata Risa , Yokoyama Hideshi , Ishikawa Yoshinobu , Hishiki Asami , Hashimoto Hiroshi
Published: March 2018

Proliferating cell nuclear antigen (PCNA) provides a molecular platform for numerous protein–protein interactions in DNA metabolism. A large number of proteins associated with PCNA have a well characterized sequence termed the PCNA-interacting protein box motif (PIPM). Another PCNA-interacting sequence termed the AlkB homologue 2 PCNA-interacting motif (APIM), comprising the five consensus residues (K/R)-(F/Y/W)-(L/I/V/A)-(L/I/V/A)-(K/R), has also been identified in various proteins. In contrast to that with PIPM, the PCNA–APIM interaction is less well understood. Here, the crystal structure of PCNA bound to a peptide carrying an APIM consensus sequence, RFLVK, was determined and structure-based interaction analysis was performed. The APIM peptide binds to the PIPM-binding pocket on PCNA in a similar way to PIPM. The phenylalanine and leucine residues within the APIM consensus sequence and a hydrophobic residue that precedes the APIM consensus sequence are crucially involved in interactions with the hydrophobic pocket of PCNA. This interaction is essential for overall binding. These results provide a structural basis for regulation of the PCNA interaction and might aid in the development of specific inhibitors of this interaction.
Will farmland transfer reduce grain acreage? Evidence from Gansu province, China
Authors: Liu Ying , Wang Chenggang , Tang Zeng , Nan Zhibiao
Published: March 2018

Purpose

The purpose of this paper is to examine the impacts of farmland renting-in on planted grain acreage.

Design/methodology/approach

A survey data of five counties were analyzed with the two-stage ordinary least squares model.

Findings

Households renting-in land trended to plant more maize, and the more land was rented by a household the more maize was planted, while wheat acreage showed non-response to farmland renting-in.

Practical implications

Overall, the analysis suggests that policy makers should be prepared for different changing trends of grain crop acreage across the nation as farmland transfer continues. Future research should pay attention to the effect of farmland transfer on agricultural productivity and rural household income growth.

Originality/value

As the Chinese Government is promoting larger-scale and more mechanized farms as a way of protecting grain security, it is important to understand whether farmland renting-in will reduce planted grain acreage. This study provides empirical evidence showing the answer to that question may differ across different regions and depend on the particular grain crop in question.
Workplace bullying
Authors: McCormack Darcy , Djurkovic Nikola , Nsubuga-Kyobe Apollo , Casimir Gian
Published: March 2018

Purpose

The purpose of this paper is to examine if the gender of the perpetrator and the gender of the target have interactive effects on the frequency of downward workplace bullying to which targets are subjected.

Design/methodology/approach

A cross-sectional design was used on a sample of 125 schoolteachers in Uganda. Self-report data on downward workplace bullying were obtained using the Negative Acts Questionnaire.

Findings

The perpetrator’s gender and the target’s gender have interactive effects on the level of downward bullying to which targets are subjected. Although targets in within-gender dyads reported higher levels of overall downward workplace bullying than did targets in between-gender dyads, a significant gender-gender interaction was found for personal harassment and work-related harassment but not for intimidation nor organisational harassment.

Research limitations/implications

The generalisability of the findings is limited due to the sample consisting entirely of schoolteachers in Uganda. Self-report data are a limitation as they are subjective and thus susceptible to various perceptual biases (e.g. social desirability, personality of the respondent). Examining the interactive effects of gender on workplace bullying helps to provide a better understanding of the potential influence of gender in bullying scenarios. The findings from research that considers only the main effects of gender whilst ignoring interactive effects can misinform any theory or policy development.

Practical implications

Organisations need to resocialise their members so that they learn new attitudes and norms regarding aggressive behaviour in the workplace.

Originality/value

This paper contributes to the literature on workplace bullying by examining the interactive effects of gender on the frequency of downward workplace bullying.
Communicating effectively about CSR on Twitter
Authors: Araujo Theo , Kollat Jana
Published: March 2018

Purpose

Corporate social responsibility (CSR) communication is becoming increasingly important for brands and companies. Social media such as Twitter may be platforms particularly suited to this topic, given their ability to foster dialogue and content diffusion. The purpose of this paper is to investigate factors driving the effectiveness of CSR communication on Twitter, with a focus on the communication strategies and elements of storytelling.

Design/methodology/approach

Using a sample of 281,291 tweets from top global companies in the food sector, automated content analysis (including supervised machine learning) was used to investigate the influence of CSR communication, emotion, and aspirational talk on the likelihood that Twitter users will retweet and like tweets from the companies.

Findings

The findings highlight the importance of aspirational talk and engaging users in CSR messages. Furthermore, the study revealed that the companies and brands on Twitter that tweeted more frequently about CSR were associated with higher overall levels of content diffusion and endorsement.

Originality/value

This study provides important insights into key aspects of communicating about CSR issues on social networking sites such as Twitter and makes several practical recommendations for companies.
Government intervention and firm long-term bank debt: evidence from China
Authors: Liu Fei , Bian Chao , Gan Christopher
Published: March 2018

Purpose

This paper aims to examine whether government intervention acts as a substitution mechanism for laws and institutions in affecting firms’ long-term debt financing decision and the moderating effect of firm ownership on the relationship between law and finance in Chinese capital market.

Design/methodology/approach

This study uses ordinary least squares with standard errors clustered at the firm level in the regressions. To address the potential endogeneity problem, the authors also use the system generalized method of moments in their estimation.

Findings

The results show that both long-term bank debt and long-term bank debt maturity structure ratios are positively related to government intervention. The results also reveal that with improvement in the legal environment, public non-state-owned firms have more access to long-term bank debt in the regions where the level of government intervention is low.

Research limitations/implications

Government intervention appears to replace laws and institutions in influencing the allocation of financial resources in China.

Originality/value

The finding suggests the necessity of increasing the protection of both creditors and investors, and shows the importance of a free and independent judiciary system in allocating funds to private firms. The results also imply that the non-state-owned Chinese firms also benefit from the improved laws and institutions.
External factors critical to success in the business of estate surveying firms in Lagos State, Nigeria
Authors: Oladokun Timothy Tunde , Ogunbiyi James Olayinka
Published: March 2018

Purpose

This paper aims to identify external factors that are critical to the success of estate surveying business in Lagos State, Nigeria.

Design/methodology/approach

Primary data were collected with the aid of questionnaires from estate surveying firms in the study area. Using a sampling interval computed as 1.93-2, 186 firms were selected from the 359 estate surveying firms based in the study area. The sampling interval required that, after the first selection, every subsequent second estate firm in the group (List) was selected for the survey. Data collected were analysed with the aid of criticality assessment index method such as the Relative Criticality Index and Criterion Criticality Score.

Findings

The result showed that it was critical for an estate surveying to interdepend with surrounding businesses and maintain good corporate social responsibility for it to succeed. Also, good social relations of the practitioners with the society was found to be an external factor critical to success. In addition, the study found the need to use the advantage of ICT for real estate marketing as an external technological factor for success. It was also found that the economic situation of the immediate locality of the firm and the economic buoyancy of the nation at large influenced both the planning for and the execution of real estate activities of the firm.

Research limitations/implications

Limiting the findings of the study to external factors alone could subject the findings of the study to bias. Further research targeted at identifying internal factors will provide a balanced view.

Practical implications

The study will serve as useful tools for existing and upcoming real estate practitioners to chart a performance course for their businesses. It will help estate surveyors to understand what to place more emphasis on if they will succeed in business.

Originality/value

The findings from this study will provide the estate surveyors and valuers and the professional body with data on things that are critical to their success in business and enhance the practice of real estate management.
Developing facilities management (FM) competencies for Malaysia
Authors: Kamaruzzaman Syahrul Nizam , Myeda Nik Elyna , Zawawi Emma Marinie Ahmad , Ramli Rozita Mohamed
Published: March 2018

Purpose

The purpose of this paper is to investigate the significance of facilities management (FM) competency levels from three different stages, namely, strategic, tactical and operational levels, to propose a set of FM competencies for an enhanced FM industry in Malaysia.

Design/methodology/approach

The overall focus for this paper is to discuss on the area for each level of competencies for asset and facilities management (AFM). This is done through a questionnaire survey focusing on the competency areas posed by FM companies in Malaysia and a comparison review of all FM levels as outlined by the international professional bodies, namely, International Facility Management Association, British Institute of Facilities Management and Royal Institute of Chartered Surveyors. This paper also looks at formulating a holistic framework for an effective AFM for the benefit of FM industry in general and Malaysian FM industry specifically.

Findings

The findings indicate that among the significant factors for the respective strategic, tactical and operational practice of FM are strategic: managing change, benchmarking and strategic facilities planning; tactical: risk management, emergency preparedness, FM technology, service-level agreement and supply management; and operational: space planning and management. This study also proposes a set of holistic FM competency areas which can be implemented by the FM industry in Malaysia.

Originality/value

This research sets a baseline for a set of FM competencies, an area of FM which has not been regulated in the FM practice in Malaysia.
Islamic banking: an exploratory study of public perception in Uganda
Authors: Lujja Sulaiman , Mohammed Mustafa Omar , Hassan Rusni
Published: March 2018

Purpose

Islamic banking (IB) has been globally embraced by over 76 countries, with over $2tn in assets. Despite this remarkable progress, there are countries that are yet to fully embrace IB (Uganda inclusive). All the ongoing initiatives in Uganda (at policy level) to establish IB require supporting study of public awareness and attitudes toward IB. This will stimulate a down-top approach to the feasibility of IB and policymaking, thus providing a fertile ground for wider consideration of the majority stakeholders’ views in formulating standards and policy guidelines regulating IB. This study aims to explore the perception of Ugandans towards IB.

Design/methodology/approach

The study is exploratory in nature and uses a quantitative method. Out of the 400 questionnaires distributed, only 354 were usable for further analysis. SPSS 21 was used to analyze data using descriptive statistics and factor analysis.

Findings

Major findings indicate that unlike non-Muslims, Muslims are more knowledgeable about the IB culture, although both groups have low awareness about IB terminologies. There were inconsistences in Muslim and non-Muslim attitudes toward IB, for instance; while non-Muslims are motivated by “profitability”, Muslims’ inclination to IB is mainly due to “religious and profitability combined”. Both groups demonstrated some uniformity in their selection criteria of banks such as “third party influence”, although they are inconsistent in other factors.

Originality/value

The novelty of this study rests in its down-top approach to feasibility of IB by gauging the perception of majority stakeholders before IB is established. The study is conducted in a heterogeneous society unlike many of similar studies that have focused on Muslim majority countries. As most studies (with similar background) are at least 18 years old, this study remains outstanding in gauging the dynamics of stakeholders in Muslim minority countries which have yet established IB.
Bridging and bonding: having a Muslim diversity on corporate boards and firm performance
Authors: Hassan Rohail , Marimuthu Maran
Published: March 2018

Purpose

This paper aims to examine the demographic diversity at top-level management and its impact on the performance of Malaysian-listed companies. In addition, Muslim diversity on corporate boards is examined.

Design/methodology/approach

Although many organisations aspire to be socially diverse, diversity’s consequences for organisational performance remain unclear. This study specifies the whole distinct mechanism and measures it independently, bridging as the demographic diversity among the board of directors (BODs) and bonding as the firm’s financial performance. To maintain the homogeneity factor, the empirical analysis has been confined to 12 fully fledged sectors and 529 Malaysian listed firms out of 798 firms selected on the basis of judgmental sampling during the period of 2013. The paper applies the correlation matrix and linear regression model to justify this phenomenon.

Findings

The empirical findings suggest that gender diversity (Muslim and Non-Muslim women) is positively significant with firm performance with regards to management, shareholders and market perspectives. It means that both Muslim and non-Muslim women are contributing to firm performance. Ethnic diversity (minority) and Muslim diversity (majority) have no impact on firm performance. On the other hand, interaction variables are positively significant with firm performance. It means that majority and minorities are essential for corporate boards to produce a greater performance.

Research limitations/implications

Future research could include more variables such as director’s age profile and foreign participation as well as other types of diversities, such as cognitive diversity and corporate diversity. In addition, another possible extension could be the investigation of diversity issues between small scale and large or high and low-profit firms. The findings provide insightful information to firms, as this study suggests that the diverse corporate boards can enhance firm performance.

Originality/value

In recent years, diversity issues have been examined with regard to firm performance of the listed companies. Whilst extensive literature exists on diversity issues, this issue is still under debate and has had inconsistent results. The paper attempts to fill the gap in the existing literature, discuss the empirically diverse corporate boards with the interaction approach and impact on the firm performance.