bluuebunny/crossref_metadata_2025 huggingface dataset:
Fly and wasp diversity responds to elements of both the visible and invisible fire mosaic
Authors: Brown Julian , York Alan
Published: April 2017

It is increasingly recognised that fire management for biodiversity conservation must account for two kinds of landscape mosaics: 1) the ‘visible’ mosaic of post-fire age classes as it relates to organism responses to the most recent fire events; and 2) the ‘invisible’ mosaic of inter-fire intervals, frequencies and other components of the fire regime as they relate to the cumulative effects of multiple fires. Patch mosaic burning (PMB) aims to create landscape mosaics of fire ages to cater for the needs of a diversity of species differing in their age class preferences, but empirical studies often fail to detect a link between species richness and the visible mosaic. Empirical studies of cumulative effects have so far related species richness to the fire regimes of sample locations rather than the invisible mosaic, within which sample locations are embedded. Invertebrate responses to landscape fire mosaics are particularly poorly understood, so we investigated relationships between fire history heterogeneity and fly and wasp species richness. We find support for the PMB paradigm and the notion the invisible mosaic influences species richness. To the best of our knowledge, this is the first empirical test of the invisible mosaic’s influence on animal communities.
Estimating tadpole-detection rates using visual field surveys: effects of survey time, tadpole species and tadpole density
Authors: Iwai N.
Published: April 2017

Context
When understanding species occupancy, estimation of detection probability for the target species is often required, provided by repeated surveys. However, if the actual detection probability of the species is determined experimentally, such estimates are not required, and the reliability of the occupancy data obtained by a particular survey effort can be determined.

Aims
The aim of this study was to determine the detection rate of tadpoles using visual field surveys, as well as to explore the effects of survey time, species and tadpole density on the tadpole-detection rate. The suitability of visual surveys for detecting tadpole occupancy was also assessed.

Methods
Batch-identified tadpoles were released into several pools and repeatedly counted over successive days to calculate detection rates using visual observation. In Experiment 1, the effects of tag colour, survey time (morning vs night) and species on the detection rates of two species of tadpoles (Babina subaspera and Odorrana splendida) were examined. In Experiment 2, the effects of tadpole density on O. splendida were examined.

Key results
Detection rates varied by survey time, species and tadpole density; mean rates ranged from 0.2 to 0.6 for B. subaspera and 0.4 to 0.8 for O. splendida, with higher rates at night. There was a negative relationship between detection rate and tadpole density. Based on these detection rates, it was calculated that single visual surveys of O. splendida tadpoles can achieve detection probabilities near 1.0 when more than four individuals occur in a patch.

Conclusions
Variations in detection probability should be considered in field surveys. If the factors that cause variations in detection rates are controlled, visual surveys of tadpoles should, at least in some species, provide detection probabilities near 1.0.

Implications
When repeated surveys to estimate species occupancy are not practicable, determination of the actual detection probability of the target species using real detection rates provides a robust alternative approach.
Population genetics of the koala (Phascolarctos cinereus) in north-eastern New South Wales and south-eastern Queensland
Authors: Dennison S. , Frankham G. J. , Neaves L. E. , Flanagan C. , FitzGibbon S. , Eldridge M. D. B. , Johnson R. N.
Published: April 2017

Habitat loss and fragmentation are key threats to local koala (Phascolarctos cinereus) populations. Broad-scale management is suboptimal for koalas because distribution models are not easily generalised across regions. Therefore, it is imperative that data relevant to local management bodies are available. Genetic data provides important information on gene flow and potential habitat barriers, including anthropogenic disturbances. Little genetic data are available for nationally significant koala populations in north-eastern New South Wales, despite reported declines due to urbanisation and habitat loss. In this study, we develop 14 novel microsatellite loci to investigate koala populations in north-eastern New South Wales (Port Macquarie, Coffs Harbour, Tyagarah, Ballina) and south-eastern Queensland (Coomera). All locations were significantly differentiated (FST = 0.096–0.213; FʹST = 0.282–0.582), and this pattern was not consistent with isolation by distance (R2 = 0.228, P = 0.058). Population assignment clustered the more northern populations (Ballina, Tyagarah and Coomera), suggesting contemporary gene flow among these sites. For all locations, low molecular variation among (16%) rather than within (84%) sites suggests historical connectivity. These results suggest that koala populations in north-eastern New South Wales and south-eastern Queensland are experiencing contemporary impediments to gene flow, and highlight the importance of maintaining habitat connectivity across this region.
Genetic signatures of high-altitude adaptation in Tibetans
Authors: Yang Jian , Jin Zi-Bing , Chen Jie , Huang Xiu-Feng , Li Xiao-Man , Liang Yuan-Bo , Mao Jian-Yang , Chen Xin , Zheng Zhili , Bakshi Andrew , Zheng Dong-Dong , Zheng Mei-Qin , Wray Naomi R. , Visscher Peter M. , Lu Fan , Qu Jia
Published: April 2017

Significance

The origin of Tibetans and the mechanism of how they adapted to the high-altitude environment remain mostly unknown. We conduct the largest genome-wide study in Tibetans to date. We detect signatures of natural selection at nine gene loci, two of which are strongly associated with blood phenotypes in present day Tibetans. We further show the genetic relatedness of Tibetans with other ethnic groups in China and estimate the divergence time between Tibetans and Han. These findings provide important knowledge to understand the genetic ancestry of Tibetans and the genetic basis of high-altitude adaptation.
Structure–metabolism relationships in
human-
AOX: Chemical insights from a large database of aza-aromatic and amide compounds
Authors: Lepri Susan , Ceccarelli Martina , Milani Nicolò , Tortorella Sara , Cucco Andrea , Valeri Aurora , Goracci Laura , Brink Andreas , Cruciani Gabriele
Published: April 2017

Significance

The metabolism of xenobiotics is a critical aspect of drug discovery; nowadays, aldehyde oxidase (AOX) has emerged as a key metabolic enzyme having a pivotal role in the failures of several clinical candidates. The lack of homogenous data on possible substrates and not substrates of this enzyme represents a serious limit for the development of an in silico model for metabolism prediction. Here, we present a database of 270 chemically diverse compounds containing aza-aromatic and/or amide moieties (susceptible to human AOX), experimentally tested in vitro. The results herein reported should be useful in the development of a reliable prediction model, which should be of wide interest in chemistry, biology, biotechnology, and medicine.
Memory of recent oxygen experience switches pheromone valence in
Caenorhabditis elegans
Authors: Fenk Lorenz A. , de Bono Mario
Published: April 2017

Significance

Animals use memories of their recent environment to regulate their behavioral priorities. The basis for this cross-modal, experience-dependent plasticity is poorly understood.
Caenorhabditis elegans
feeds on bacteria in rotting fruit. It monitors O
2
levels, and switches behavioral state when O
2
approaches 21%. We show that
C. elegans
' memory of its recent O
2
environment reconfigures how it processes sensory information. Pheromones that attract animals acclimated to 21% O
2
repel animals acclimated to 7% O
2
. O
2
memory is encoded in the activity history of a circuit that continuously signals O
2
levels. This circuit is connected to neurons driving pheromone attraction and repulsion. O
2
experience changes the pheromone responsiveness of these sensors and their postsynaptic targets, correlating with the switch in pheromone valence.
Resistance to action potential depression of a rat axon terminal in vivo
Authors: Sierksma Martijn C. , Borst J. Gerard G.
Published: April 2017

Significance

During high-frequency firing, the shape of a presynaptic action potential (AP) can alter, thereby changing neurotransmitter release. In this paper, we describe how a giant terminal in the brainstem of newborn rats called the calyx of Held can fire in vivo at high frequencies without substantial AP depression. The underlying mechanism was found to be the presence of sodium channels that can recover rapidly from depression in combination with a close match between the potential that is attained following an AP with the potential that maximizes AP stability. Surprisingly, this match was already there shortly after formation of the calyx of Held. We speculate that these mechanisms help synapses to maximize timing precision during high-frequency firing.
Conformational equilibria of light-activated rhodopsin in nanodiscs
Authors: Van Eps Ned , Caro Lydia N. , Morizumi Takefumi , Kusnetzow Ana Karin , Szczepek Michal , Hofmann Klaus Peter , Bayburt Timothy H. , Sligar Stephen G. , Ernst Oliver P. , Hubbell Wayne L.
Published: April 2017

Significance

The existence of multiple conformational substates of G-protein–coupled receptors in equilibrium may provide for the interaction with multiple partners at the same interface. Here we provide evidence that photoactivated rhodopsin exists in a manifold of conformational substates in a lipid environment, but not in the extensively studied dodecyl maltoside detergent micelles. Moreover, the photoactivated state decays spontaneously to the inactive state on a timescale of minutes. Remarkably, binding of the activated receptor to the cognate G protein strongly biases the receptor to an interacting state that retains more than one conformation, suggesting flexibility in the complex.
NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice
Authors: Vartanian Vladimir , Minko Irina G. , Chawanthayatham Supawadee , Egner Patricia A. , Lin Ying-Chih , Earley Lauriel F. , Makar Rosemary , Eng Jennifer R. , Camp Matthew T. , Li Liang , Stone Michael P. , Lasarev Michael R. , Groopman John D. , Croy Robert G. , Essigmann John M. , McCullough Amanda K. , Lloyd R. Stephen
Published: April 2017

Significance

Human dietary exposures to aflatoxin in some of the most populated and underdeveloped portions of the world are a major contributing factor to the formation of human hepatocellular carcinomas (HCCs) that account for over 700,000 deaths annually. Although the genomic signatures for aflatoxin-driven carcinogenesis are G:C to T:A point mutations arising from bypass of aflatoxin-induced DNA adducts, maintenance of genome stability has been generally attributed to nucleotide excision repair. However, we present three lines of evidence that the DNA base excision repair pathway initiated by the DNA glycosylase NEIL1 is the major contributor in maintaining genomic stability following aflatoxin exposures. These findings suggest that inactivating NEIL1 polymorphic variants in the human population could affect susceptibility to aflatoxin-induced HCC.
CMG–Pol epsilon dynamics suggests a mechanism for the establishment of leading-strand synthesis in the eukaryotic replisome
Authors: Zhou Jin Chuan , Janska Agnieszka , Goswami Panchali , Renault Ludovic , Abid Ali Ferdos , Kotecha Abhay , Diffley John F. X. , Costa Alessandro
Published: April 2017

Significance

Faithful and efficient genome duplication is essential for the propagation of life. Aberrant DNA replication can lead to genomic instability and cancer. In eukaryotes, the replication machinery is composed of the DNA-unwinding enzyme Cdc45–MCM–GINS (CMG) and dedicated DNA synthesis factors. Three different polymerases act sequentially on the leading-strand template to establish DNA replication. We describe the architecture and dynamics of the main leading-strand polymerase bound to the CMG helicase, and we propose a mechanism for the establishment of efficient leading-strand synthesis. Our findings provide important insights into how the eukaryotic replication machinery functions to ensure that genome integrity is maintained during replication.
Decoupling of surface diffusion and relaxation dynamics of molecular glasses
Authors: Zhang Yue , Fakhraai Zahra
Published: April 2017

Significance

Diffusion on the surfaces of molecular glasses is observed to be greatly enhanced compared with the bulk diffusion with lower activation energies. However, the physical nature of the fast surface diffusion and its relation to the glassy dynamics remain unclear. Relaxation dynamics of these glasses can be enhanced by up to 14 orders of magnitude by reducing their film thickness below 50 nm. By investigating the relationship between surface diffusion and relaxation times of ultrathin films, we find that the fast surface diffusion remains invariant of the films’ relaxation dynamics even when the activation energy of the film becomes lower than the activation energy for the surface diffusion, indicating a complete decoupling of the relaxation dynamics and surface diffusion.
Phosphatidylinositol 3-phosphate–binding protein AtPH1 controls the localization of the metal transporter NRAMP1 inArabidopsis
Authors: Agorio Astrid , Giraudat Jérôme , Bianchi Michele Wolfe , Marion Jessica , Espagne Christelle , Castaings Loren , Lelièvre Françoise , Curie Catherine , Thomine Sébastien , Merlot Sylvain
Published: April 2017

Significance

Metal homeostasis is essential for living organisms. Metal transporters play key roles in metal uptake and compartmentalization. The tight regulation of metal homeostasis thus depends on accurate targeting of these metal transporters. Although the main metal transporters in plants have been identified, the mechanisms involved in their trafficking are still poorly understood. This study reveals that AtPH1, a pleckstrin homology (PH) domain containing protein binding to phosphatidylinositol 3-phosphate (PI3P), controls the subcellular localization of the iron and manganese transporter AtNRAMP1. Our results further indicate that, in addition to proteins containing the FYVE and PHOX domains, proteins containing the PH domain can decode the PI3P signal in endosomal function.
SCODE: an efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation
Authors: Matsumoto Hirotaka , Kiryu Hisanori , Furusawa Chikara , Ko Minoru S H , Ko Shigeru B H , Gouda Norio , Hayashi Tetsutaro , Nikaido Itoshi
Published: April 2017

Motivation

The analysis of RNA-Seq data from individual differentiating cells enables us to reconstruct the differentiation process and the degree of differentiation (in pseudo-time) of each cell. Such analyses can reveal detailed expression dynamics and functional relationships for differentiation. To further elucidate differentiation processes, more insight into gene regulatory networks is required. The pseudo-time can be regarded as time information and, therefore, single-cell RNA-Seq data are time-course data with high time resolution. Although time-course data are useful for inferring networks, conventional inference algorithms for such data suffer from high time complexity when the number of samples and genes is large. Therefore, a novel algorithm is necessary to infer networks from single-cell RNA-Seq during differentiation.

Results

In this study, we developed the novel and efficient algorithm SCODE to infer regulatory networks, based on ordinary differential equations. We applied SCODE to three single-cell RNA-Seq datasets and confirmed that SCODE can reconstruct observed expression dynamics. We evaluated SCODE by comparing its inferred networks with use of a DNaseI-footprint based network. The performance of SCODE was best for two of the datasets and nearly best for the remaining dataset. We also compared the runtimes and showed that the runtimes for SCODE are significantly shorter than for alternatives. Thus, our algorithm provides a promising approach for further single-cell differentiation analyses.

Availability and Implementation

The R source code of SCODE is available at https://github.com/hmatsu1226/SCODE

Supplementary information

Supplementary data are available at Bioinformatics online.
Non-surgical management of early-stage lung cancer
Authors: Brown Jim , Navani Neal
Published: April 2017

As low-dose computed tomography screening of ‘high-risk’ smokers is occurring with increasing frequency, the incidental discovery of solitary pulmonary nodules is becoming more frequent, and lung cancer multidisciplinary teams are now often faced with balancing risk and benefit when making decisions regarding the radical treatment of patients with a clinical diagnosis of early lung cancer but borderline fitness. Surgery offers the best prospect of cure but is associated with significant mortality and morbidity; the elderly and frail experience more toxicity and a greater impact on the quality of life. This chapter reviews the criteria for assessing surgical fitness and examines the evidence for minimally invasive and ablative techniques for the treatment of early peripheral lung cancer in the medically inoperable patient.
Occupational lung disease
Authors: Feary Johanna , Szram Joanna , Cullinan Paul
Published: April 2017

Occupational lung diseases are under-recognized by most general (and respiratory) physicians. When affected individuals are of working age, the diagnosis can result in significant socio-economic consequences. A comprehensive knowledge of all occupational lung diseases is beyond the remit of most respiratory physicians, but an understanding of the relationships between work and disease is crucial to ensure that cases are not missed. This chapter presents two contrasting cases. The first is a ‘traditional’ case of occupational asthma, the most commonly reported occupational lung disease in the United Kingdom (as well as in most ‘developed world’ countries). The second case describes a rare disease (obliterative bronchiolitis) recently linked to a few select work exposures, highlighting the complexity of establishing causation in suspected occupational disease, particularly one uncommon in the general population. An occupational history should be taken in all cases of respiratory disease; access to specialist advice is freely available and frequently invaluable.
Tuberculosis
Authors: Russell Georgina , Kon Onn Min
Published: April 2017

Tuberculosis is an important infection globally, with 1.45 million deaths attributed to tuberculosis in 2010 by the World Health Organization. Respiratory physicians need to be familiar with the varied presentations and management of this disease. In addition, the proportion of cases now presenting with extrapulmonary disease are approximately half of all cases, and of particular relevance is mediastinal node tuberculosis which represents about 10% of all cases of tuberculosis in the United Kingdom. This chapter presents the case of a patient with miliary tuberculosis who developed significant drug toxicities with antituberculous therapy. The chapter reviews the role of different investigations in making a diagnosis, including the role of the Mantoux test and interferon-gamma release assays, and discusses the often challenging job of contact tracing. Finally, the chapter reviews the management of both sensitive and drug-resistant disease, along with how to manage adverse drug reactions.
Personal Cancer Genome Reporter: variant interpretation report for precision oncology
Authors: Nakken Sigve , Fournous Ghislain , Vodák Daniel , Aasheim Lars Birger , Myklebost Ola , Hovig Eivind
Published: April 2017

Individual tumor genomes pose a major challenge for clinical interpretation due to their unique sets of acquired mutations. There is a general scarcity of tools that cani)systematically interrogate cancer genomes in the context of diagnostic, prognostic, and therapeutic biomarkers,ii)prioritize and highlight the most important findings, andiii)present the results in a format accessible to clinical experts. We have developed a stand-alone, open-source software package for somatic variant annotation that integrates a comprehensive set of knowledge resources related to tumor biology and therapeutic biomarkers, both at the gene and variant level. Our application generates a tiered report that will aid the interpretation of individual cancer genomes in a clinical setting.

Availability and Implementation

The software is implemented in Python/R, and is freely available through Docker technology. Documentation, example reports, and installation instructions are accessible via the project GitHub page:https://github.com/sigven/pcgr)

Contact

sigven@ifi.uio.no
Proteomic Analysis Defines Kinase Taxonomies Specific for Subtypes of Breast Cancer
Authors: Collins Kyla. A. L. , Stuhlmiller Timothy. J. , Zawistowski Jon. S. , East Michael. P. , Pham Trang T. , Hall Claire R. , Goulet Daniel R. , Bevill Samantha M. , Angus Steven P. , Velarde Sara H. , Sciaky Noah , Oprea Tudor I. , Graves Lee M. , Johnson Gary L. , Gomez Shawn M.
Published: April 2017

Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative, basal-like and claudin-low breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Kinases lacking defined functions in breast cancer were highly represented in the MIB-binding taxonomies. We show that these understudied kinases, whose disease associations and pharmacology are generally unexplored, are integrated in kinase signaling subnetworks with kinases that have been previously well characterized in breast cancer. Computationally it was possible to define subtypes using profiles of less than 50 of the more than 300 kinases bound to MIBs that included understudied as well as metabolic and lipid kinases. Furthermore, analysis of MIB-binding profiles established potential functional annotations for these understudied kinases. Thus, comprehensive MIBs-based capture of kinases provides a unique proteomics-based method for integration of poorly characterized kinases of the understudied kinome into functional subnetworks in breast cancer cells and tumors that is not possible using genomic strategies. The MIB-binding profiles readily defined subtype-selective differential adaptive kinome reprogramming in response to targeted kinase inhibition, demonstrating how MIB profiles can be used in determining dynamic kinome changes that result in subtype selective phenotypic state changes.
The C-terminal domain of ParB is critical for dynamic DNA binding and bridging interactions which condense the bacterial centromere
Authors: Fisher Gemma L. M. , Pastrana César L. , Higman Victoria A. , Koh Alan , Taylor James A. , Butterer Annika , Craggs Timothy D. , Sobott Frank , Murray Heath , Crump Matthew P. , Moreno-Herrero Fernando , Dillingham Mark S.
Published: April 2017

The ParB protein forms DNA bridging interactions aroundparSto form networks which condense DNA and earmark the bacterial chromosome for segregation. The mechanism underlying the formation of ParB nucleoprotein complexes is unclear. We show here that the central DNA binding domain is essential for anchoring atparS, and that this interaction is not required for DNA condensation. Structural analysis of the C-terminal domain reveals a dimer with a lysine-rich surface that binds DNA non-specifically and is essential for DNA condensationin vitro. Mutation of either the dimerisation or the DNA binding interface eliminates ParB foci formationin vivo. Moreover, the free C-terminal domain can rapidly decondense ParB networks independently of its ability to bind DNA. Our work reveals a dual role for the C-terminal domain of ParB as both a DNA binding and bridging interface, and highlights the dynamic nature of ParB networks.
“Characterisation of the biflavonoid hinokiflavone as a pre-mRNA splicing modulator that inhibits SENP”
Authors: Pawellek Andrea , Ryder Ursula , Tammsalu Triin , King Lewis J. , Kreinin Helmi , Ly Tony , Hay Ronald T. , Hartley Richard , Lamond Angus I.
Published: April 2017

Here, we identify the plant biflavanoid hinokiflavone as an inhibitor of splicingin vitroand modulater of alternative splicing in multiple human cell lines. Hinokiflavone inhibits splicingin vitroby blocking one or more early steps of spliceosome assembly, leading to accumulation of the A complex. Multiple human cell lines treated with hinokiflavone show changes in the alternative splicing of different pre-mRNA substrates, but little or no change in transcription. They also show altered subnuclear organization, specifically of splicing factors required for A complex formation, which relocalized together with SUMO1 and SUMO2 into enlarged nuclear speckles. While most cell lines treated with hinokiflavone showed cell cycle arrest and eventual cell death, dependent on time and concentration, the promyelocytic NB4 cell line, which expresses the SUMO target PML-RARalpha fusion protein, was exquisitely sensitive to apoptosis following hinokiflavone treatment. Hinokiflavone treatment increased protein SUMOylation levels, both inin vitrosplicing reactions and in cells, with little or no effect on levels of ubiquitinylated proteins. Hinokiflavone also inhibited the catalytic activity of purifiedE. coliexpressed SUMO protease, SENP1in vitro, indicating the increase in SUMOylated proteins results primarily from inhibition of de-SUMOylation. Using a quantitative proteomics assay we identified many SUMO2 sites whose levels increased following hinokiflavone treatment, with the major targets including 6 proteins that are associated with U2 snRNP and required for A complex formation. These data identify hinokiflavone as a SUMO protease inhibitor and indicate SUMOylation of splicing factors may be important for modulating splice site selection.
A Robust Targeted Sequencing Approach for Low Input and Variable Quality DNA from Clinical Samples
Authors: So Austin P. , Vilborg Anna , Bouhlal Yosr , Koehler Ryan T. , Grimes Susan M. , Pouliot Yannick , Mendoza Daniel , Ziegle Janet , Stein Jason , Goodsaid Federico , Lucero Michael Y. , De La Vega Francisco M. , Ji Hanlee P.
Published: April 2017

Next-generation deep sequencing of gene panels is being adopted as a diagnostic test to identify actionable mutations in cancer patient samples. However, clinical samples, such as formalin-fixed, paraffin-embedded specimens, frequently provide low quantities of degraded, poor quality DNA. To overcome these issues, many sequencing assays rely on extensive PCR amplification leading to an accumulation of bias and artifacts. Thus, there is a need for a targeted sequencing assay that performs well with DNA of low quality and quantity without relying on extensive PCR amplification. We evaluate the performance of a targeted sequencing assay based on Oligonucleotide Selective Sequencing, which permits the enrichment of genes and regions of interest and the identification of sequence variants from low amounts of damaged DNA. This assay utilizes a repair process adapted to clinical FFPE samples, followed by adaptor ligation to single stranded DNA and a primer-based capture technique. Our approach generates sequence libraries of high fidelity with reduced reliance on extensive PCR amplification - this facilitates the accurate assessment of copy number alterations in addition to delivering accurate SNV and indel detection. We apply this method to capture and sequence the exons of a panel of 130 cancer-related genes, from which we obtain high read coverage uniformity across the targeted regions at starting input DNA amounts as low as 10 ng per sample. We further demonstrate the performance of this assay using a series of reference DNA samples, and by identifying sequence variants in DNA from matched clinical samples originating from different tissue types.
Secretogranin-II plays a critical role in zebrafish neurovascular modeling
Authors: Tao Binbin , Hu Hongling , Mitchell Kimberly , Chen Ji , Jia Haibo , Zhu Zuoyan , Trudeau Vance L. , Hu Wei
Published: April 2017

Summary statement

Neurons expressingsgIIbalign with central arteries in hindbrain. We show thatsgIIbis critical for neurovascular modeling the larval zebrafish mediated by MAPK and PI3K/AKT signalingin vivo.

Secretoneurin (SN) is a neuropeptide derived from specific proteolytic processing of the precursor secretogranin II (SgII). In zebrafish and other teleosts there are 2 paralogs we previously namedsgIIaandsgIIb. Our results showed that neurons expressingsgIIbwere aligned with central arteries in hindbrain, demonstrating a close neurovascular association. BothsgIIb-/-andsgIIa-/-/sgIIb-/-mutant embryos were defective in hindbrain central artery development, while artery development insgIIa-/-mutant embryos was not affected. Hindbrain arterial and venous network identities were not affected insgIIb-/-mutant embryos, and the mRNA levels of Notch and VEGF pathway-related genes were not altered. However, the activation of MAPK and PI3K/AKT pathways were inhibited insgIIb-/-mutant embryos. Injection of a synthetic SNb mRNA or delivery of the protein kinase activator N-arachidonoyl-L-serine could partially rescue the central artery developmental defects in thesgIIbmutants. This study provides the firstin vivoevidence thatsgIIbplays a critical role in neurovascular modeling the hindbrain.
Sec17 (α-SNAP) and an SM-tethering complex control the outcome of SNARE zipperingin vitroandin vivo
Authors: Schwartz Matthew L. , Nickerson Daniel P. , Lobingier Braden T. , Angers Cortney G. , Zick Michael , Merz Alexey J.
Published: April 2017

Zippering of SNARE complexes spanning docked membranes is essential for most intracellular fusion events. Here we explore how SNARE regulators operate on discrete zippering states. The formation of a metastabletrans-complex, catalyzed by HOPS and its SM subunit Vps33, is followed by subsequent zippering transitions that increase the probability of fusion. Operating independently of Sec18 catalysis, Sec17 either inhibits or stimulates SNARE-mediated fusion. If HOPS or Vps33 are absent, Sec17 inhibits fusion at an early stage. Thus, HOPS and Vps33 accelerate SNARE zippering, particularly in the presence of otherwise inhibitory Sec17. Once SNAREs are partially-zipped, Sec17 promotes fusion in either the presence or absence of HOPS — but with faster kinetics when HOPS is absent. Our data further indicate that Sec17 promotes fusion both through its direct penetration of the membrane and by enhancing C-terminal SNARE zippering. In a working model, the interplay among Sec17, Sec18, SMs, and SNARE zippering can explain why SM proteins are indispensable for SNARE-mediated fusionin vivo.

Impact statement

Sec17 is shown to have divergent effects on pre-fusion SNARE complex activity, depending on the state of SNARE zippering. HOPS, an SM-tether complex, controls the outcome of Sec17-SNARE engagement. The results suggest a coherent working model for SM activityin vivo.
LncRNA-TUG1/EZH2 axis promotes cell proliferation, migration and the EMT phenotype formation through sponging miR-382
Authors: Zhao Liang , Sun Hongwei , Kong Hongru , Chen Zongjing , Chen Bicheng , Zhou Mengtao
Published: April 2017

Pancreatic carcinoma (PC) is the one of the most common and malignant cancer in the world. Despite many effort have been made in recent years, the survival rate of PC still remains unsatisfied. Therefore, investigating the mechanisms underlying the progression of PC might facilitate the development of novel treatments that improve patient prognosis. LncRNA Taurine Up–regulated Gene 1 (TUG1) was initially identified as a transcript up - regulated by taurine, siRNA - based depletion of TUG1 suppresses mouse retinal development, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in pancreatic carcinoma (PC) still needs to be further investigated. In the current study, the expression of TUG1 in the PC cell lines and tissues was measured by quantitative real-time PCR (qRT-PCR), and loss-of-function and gain-of-function approaches were applied to investigate the function of TUG1 in PC cell. Online database analysis tools showed that miR-382 could interact with TUG1 and we found an inverse correlation between TUG1 and miR-382 in PC specimens. Moreover, dual luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) and applied biotin-avidin pulldown system further provide evidence that TUG1 directly targeted miR-382 by binding with microRNA binding site harboring in the TUG1 sequence. Furthermore, gene expression array analysis using clinical samples and RT-qPCR proposed that EZH2 was a target of miR-382 in PC. Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression at least partially through function as an endogenous ‘sponge’ by competing for miR-382 binding to regulate the miRNA target EZH2.
PTSD blood transcriptome mega-analysis: Shared inflammatory pathways across biological sex and modes of traumas
Authors: Breen Michael S. , Tylee Daniel S. , Maihofer Adam X. , Neylan Thomas C. , Mehta Divya , Binder Elisabeth , Chandler Sharon D. , Hess Jonathan L. , Kremen William S. , Risbrough Victoria B. , Woelk Christopher H. , Baker Dewleen G. , Nievergelt Caroline M. , Tsuang Ming T. , Buxbaum Joseph D. , Glatt Stephen J.
Published: April 2017

Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module down-regulated in men exposed to combat traumas, one IL12-mediated signaling module up-regulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and MAPK-activity up-regulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.
A note on dynamical compensation and its relation to parameter identifiability
Authors: Karin Omer , Alon Uri , Sontag Eduardo
Published: April 2017

We recently identified a motif for dynamical compensation (DC) – a property where a system maintains the dynamics and steady-state of a regulated variable robust in the face of fluctuations in key parameters. Such parameters are therefore unidentifiable from measurements of the regulated variable at steady-state. On the other hand, since the models showing dynamical compensation are typically non-redundant, their parameters are identifiable from experimental data. We clarify this apparent discrepancy by requiring that the parameters of DC circuits be identifiable both away from steady-state and when measuring other system variables. We use this observation to provide a definition for DC in terms of parameter identifiability and discuss its relevance for the examples provided in Karin et al.
A role for the F-box protein HAWAIIAN SKIRT in plant miRNA function
Authors: Lang Patricia L.M. , Christie Michael D. , Dogan Ezgi , Schwab Rebecca , Hagmann Jörg , Van de Weyer Anna-Lena , Weigel Detlef
Published: April 2017

As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. While a plethora of factors involved in their biogenesis and action inArabidopsis thalianahave been described, these processes and their fine-tuning are not fully understood in plants. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156 activity. We identified a new mutant allele of the F-box protein HAWAIIAN SKIRT (HWS; At3G61590),hws-5, as a suppressor of theMIM156-induced developmental and molecular phenotypes. Inhwsplants, levels of endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS - but not a truncated version lacking the F-box domain - display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants,hwsloses its delayed floral organ abscission (‘skirt’) phenotype, suggesting epistasis. Also, the overallhwstranscriptome profile partially resembles well-known miRNA mutantshyl1-2 andse-3, indicating action in a common pathway. We thus propose HWS as a novel, F-box dependent regulator of miRNA biogenesis.

Summary statement

HAWAIIAN SKIRT is a regulator ofArabidopsis thalianamicroRNA biogenesis and acts in an F-box-dependent manner.
Behavioural competencies and organizational performance in Italian performing arts
Authors: Scapolan Annachiara , Montanari Fabrizio , Bonesso Sara , Gerli Fabrizio , Mizzau Lorenzo
Published: April 2017

Purpose

The purpose of this paper is to investigate the behavioural competencies of directors and managers working for cultural organizations and their relationship with organizational performance.

Design/methodology/approach

The study adopts an ESC competency modelling process and the technique of the Behavioural Event Interview as the primary source of data collection. In particular, the authors interviewed 14 directors and managers of six performing arts organizations operating in Emilia-Romagna, a region located in Northern Italy.

Findings

Findings show that directors and managers of cultural organizations are characterized by a specific set of social and emotional (e.g. persuasion and empathy), whereas cognitive competencies, such as quantitative analysis, are less frequent. Findings highlight also that a balanced portfolio of behavioural competencies emerges as importantly correlated with high organizational performance.

Practical implications

Findings offer relevant managerial implications for the design and implementation of a coherent set of human resource management practices, which allow cultural organizations to reach above-average performance.

Originality/value

This study contributes to a better understanding of the relationship between managerial competencies and the performance of cultural organizations, taking into account specific kinds of competencies – namely, behavioural competencies – which have been neglected by the previous literature.
Who will keep an eye on government policy? Evidence from Chinese pharmaceutical firms
Authors: Zheng Ying , Chen Chuanming , Ren Hualiang
Published: April 2017

Purpose

Studies on China suggest that institutional environment plays a significant role in business activities; however, the issue of how firms attend to institutional environment is largely under-explored. This paper responds to the oversight by examining the potential ways in which firms can demonstrate heterogeneity in terms of vigilance to government policy. Drawing from the attention-based view of firms and the institutional logic perspective, the authors aim to propose that firms with market logic or non-market logic will show difference in vulnerability to policy change. Further, firm ownership type and policy-leveraging capability would moderate the relationship between institutional logic and attention to policy environment.

Design/methodology/approach

The empirical background of this study is based on Chinese pharmaceutical firms. The new reform on health-care system launched by Chinese government in 2009 provides a fertile context to observe firms’ attention to government policy. The hypotheses are tested by using data of 145 Chinese pharmaceutical public firms from 2009 to 2013.

Findings

The results generally support the hypotheses: market logic has a positive effect on attention to policy, whereas non-market logic has a negative effect. The impact of market logic is weakened when firms have a higher policy-leveraging capability (in terms of getting government subsidies); the non-market logic effect is strengthened both when firms are state-owned enterprises and have a higher policy-leveraging capability.

Originality/value

Instead of focusing on how institutional environment have an influence on firm behavior as previous studies do, this paper examines the interaction between institution and firms by exploring how firms pay attention to government policy. Under the context of China, this study sheds light on how institutional logic plays a role in determining cognitive resource allocation of firms.
An alternative approach to thermal analysis using inverse problems in aluminum alloy welding
Authors: Magalhaes Elisan dos Santos , Silva Cristiano Pedro da , Lima e Silva Ana Lúcia Fernandes , Lima e Silva Sandro Metrevelle Marcondes
Published: April 2017

Purpose

The purpose of this article is the determination of the temperature fields in a weld region has always been an obstacle to the improvement of welding processes. As an alternative, the use of inverse problems to determine the heat flux during the welding process allows an analysis of these processes.

Design/methodology/approach

This paper studies an alternative for the thermal analysis of the tungsten inert gas welding process on a 6,060 T5 aluminum alloy. For this purpose, a C++ code was developed, based on a transient three-dimensional heat transfer model. To estimate the amount of heat delivered to the plate, the specification function technique was used. Lab experiments were carried out to validate the methodology. A different experimental methodology is proposed to estimate the emissivity (radiation coefficient).

Findings

The maximum difference between experimental and numerical temperatures is lower than 5 per cent. The determined emissivity value for the aluminum 6,060 T5 presented a good agreement with literature values. The thermal fields were analyzed as function of the positive polarity. The specification function method proved to be an adequate tool for heat input estimation in welding analysis.

Originality/value

The proposed methodology proves to be a cheaper way to estimate the heat flux on the sample. The estimated power curves for the welding process are presented. The methodology to calculate the emissivity (radiation coefficient) was validated.
The drivers of economic growth in China and India: globalization or financial development?
Authors: Kandil Magda , Shahbaz Muhammad , Mahalik Mantu Kumar , Nguyen Duc Khuong
Published: April 2017

Purpose

Using annual data from 1970 to 2013 for China and India, this paper aims to examine the impact of globalization and financial development on economic growth by endogenizing capital and inflation and drawing comparisons between the two fastest growing emerging market economies.

Design/methodology/approach

In the long run, co-integration test results indicate that financial development increases economic growth in China and India.

Findings

The results also reveal that globalization accelerates economic growth in India but, surprisingly, impairs economic growth in China, as it increases competition for exports. The results furthermore disclose that acceleration in capitalization and inflation, as a proxy for aggregate demand, are positively linked to economic growth in China and India.

Originality/value

Causality test results indicate that both financial development and economic growth are interdependent. In contrast, causality runs from higher economic growth to increased globalization in India, while the results do not support long-term causality between globalization and economic growth in China.
Usability evaluation (IEQ survey) in hospital buildings
Authors: Aalto Leena , Lappalainen Sanna , Salonen Heidi , Reijula Kari
Published: April 2017

Purpose

As hospital operations are undergoing major changes, comprehensive methods are needed for evaluating the indoor environment quality (IEQ) and usability of workspaces in hospital buildings. The purpose of this paper is to present a framework of the characteristics that have an impact on the usability of work environments for hospital renovations, and to use this framework to illustrate the usability evaluation process in the real environment.

Design/methodology/approach

The usability of workspaces in hospital environments was evaluated in two hospitals, as an extension of the IEQ survey. The evaluation method was usability walk-through. The main aim was to determine the usability characteristics of hospital facility workspaces that support health, safety, good indoor air quality, and work flow.

Findings

The facilities and workspaces were evaluated by means of four main themes: orientation, layout solution, working conditions, and spaces for patients. The most significant usability flaws were cramped spaces, noise/acoustic problems, faulty ergonomics, and insufficient ventilation. Due to rooms being cramped, all furnishing directly caused functionality and safety problems in these spaces.

Originality/value

The paper proposes a framework that links different design characteristics to the usability of hospital workspaces that need renovation.
From workaholism to burnout: psychological capital as a mediator
Authors: Moyer Fiona , Aziz Shahnaz , Wuensch Karl
Published: April 2017

Purpose

The purpose of this paper is to examine the relationships among workaholism, psychological capital (PsyCap), and burnout, as well as investigate the potential mediating effect of PsyCap on the relationship between workaholism and burnout.

Design/methodology/approach

Data on workaholism, PsyCap, and burnout were collected, through administration of an online survey, from 400 faculty and staff at a large Southeastern university.

Findings

Workaholism is negatively related to PsyCap and is positively related to burnout, while PsyCap is negatively correlated with burnout. Moreover, while tested in a mediation model, PsyCap appeared as a significant mediating variable for all three dimensions of burnout (i.e. emotional exhaustion, depersonalization, and personal accomplishment).

Research limitations/implications

Future researchers may benefit from examining a sample outside an educational institution. Also, both workaholism and burnout may be better suited for studies utilizing longitudinal designs. That said, the data reveal information about the process whereby tendencies indicative of heavy work investment lead to burnout within employees. That is, workaholism leads to lower PsyCap, which then results in burnout.

Practical implications

The results suggest that employers may benefit from considering the negative effects of heavy work investment and maintaining a culture that discourages such behavior. It might also be beneficial for employers to ensure that employees have a heightened PsyCap and, therefore, are safeguarded against burnout.

Originality/value

This is the first study to examine the influence that employee PsyCap has on the development of workaholism and burnout by examining its role as a mediator.