bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of high-density genetic maps and detection of QTLs associated with Huanglongbing infection in citrus
Authors: Huang Ming , Roose Mikeal L. , Yu Qibin , Du Dongliang , Zhang Yi , Deng zhanao , Irey Michael , Stover Ed , Gmitter Fredrick G.
Published: May 2018

No true resistance to Huanglongbing (HLB), a citrus disease associated with infection ofCandidatusLiberibacter asiaticus (CLas), is found within commercial citrus cultivars, though trifoliate orange (Poncirus trifoliata) has been described as resistant or tolerant. Through genotyping an intergeneric F1population by Genotyping-by-Sequencing, high-density SNP-based genetic maps were constructed separately for trifoliate orange and sweet orange (Citrus sinensis). Both genetic maps exhibited high synteny and high coverage of citrus genome. After exposure to intense HLB pressure for two years, Ct value of qPCR forCLas detection in leaves throughout ten time points during the next three years was above 35 in trifoliate oranges, under 28 in sweet oranges, and ranged from 24 to 38 and exhibited obvious segregation among progenies. Phenotypic data of percentage of healthy trees showed high correlation with the Ct value. By mapping the two traits at all time points, a total of nine clusters of QTLs were detected, of which five, respectively located on LG-t7 and LG-t8 of trifoliate orange map and LG-s3, LG-s5 and LG-s9 of sweet orange map, collectively explained a major part of the phenotypic variation. This study provides a starting point for citrus breeding to support long-term control of this devastating disease.

Highlight

1). Constructed the first high-density genetic map for trifoliate orange (Poncirus trifoliata)

2). The first report on identification of QTLs related to Huanglongbing in citrus.

Abbreviations

ACP

Asian citrus psyllid

CLas

CandidatusLiberibacter asiaticus

cM

centiMorgans

Ct

Cycle threshold

HLB

Huanglongbing

IM

Interval mapping

KW

Kruskal-Wallis

LG

Linkage group

LOD

Logarithm of odds

QTL

Quantitative trait locus

RAD

Restriction site associated DNA

rMQM

restricted multiple QTL mapping

SNP

Single nucleotide polymorphism.
GenVectors: an integrative analytical tool for spatial genetics
Authors: Duarte Leandro , Lima Jacqueline Souza , Maestri Renan , Debastiani Vanderlei , Collevatti Rosane Garcia
Published: May 2018

Metapopulations are sets of local populations connected by dispersal. While genetic turnover informs about the number of alleles shared by (meta)populations, a set of populations that do not share alleles with a second set may still show low genetic divergence to it. Recent secondary contact driven by anthropogenic habitat fragmentation and/or current climate change, for instance, may erase the historical track of genetic turnover. On the other hand, genetic turnover among sets of populations is expected to be related to the degree of genetic divergence among them if metapopulations become isolated from others due to vicariance or ancient dispersal. Yet, current analytical tools do not permit direct inference about alternative processes underlying spatial, environmental and/or biogeographic correlates of genetic turnover among populations. We introduce GenVectors, a new R package that offers flexible analytical tools that allow evaluating biogeographic or environmental correlates of genetic turnover among sets of local populations based on fuzzy set theory. Analyses implemented in GenVectors allow exploring the distribution of haplotypes or SNPs across sets of local populations. Moreover, GenVectors provides tools to analyze environmental or biogeographic correlates of haplotype or SNP turnover among sets of local populations by applying appropriate null models, which enable to discriminate history-driven genetic turnover (vicariance, ancient dispersal) from non-historical ones (recent secondary contact). Finally, we demonstrate the application of GenVectors in two empirical datasets, one based on single-locus marker (haplotypes) and other based on multi-loci marker (SNPs).
High-resolution genetic and phenotypic analysis of KIR2DL1 alleles and their association with pre-eclampsia
Authors: Huhn Oisin , Chazara Olympe , Ivarsson Martin , Retiere Christelle , Venkatesan Tim , Ghadially Hormas , Moffett Ashley , Sharkey Andrew , Colucci Francesco
Published: May 2018

Killer-cell immunoglobulin-like receptor (KIR) genes are inherited as haplotypes, expressed by NK cells and linked to outcomes of infectious diseases and pregnancy. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family. Indeed, high-resolution KIR genotyping and phenotyping in single NK cells in the context of disease association is lacking. Here, we describe a new method to separate NK cells expressing allotypes of the KIR2DL1 gene carried by the KIR A haplotype (KIR2DL1A) from those expressing KIR2DL1 alleles carried by the KIR B haplotype (KIR2DL1B). We find that in KIR AB heterozygous individuals, different KIR2DL1 allotypes can be detected both in peripheral blood and in uterine single NK cells. Using this new method, we demonstrate that both blood and uterine NK cells co-dominantly express KIR2DL1A and KIR2DL1B allotypes, but with a predominance of KIR2DL1A variants, which associate with enhanced NK cell function. In a case-control study of pre-eclampsia, we show that KIR2DL1A, not KIR2DL1B, associates with increased disease risk. This method will facilitate our understanding of how individual KIR2DL1 allelic variants affect NK cell function and contribute to disease risk.
Removal of the C6 vaccinia virus interferon-β inhibitor in the hepatitis C vaccine candidate MVA-HCV elicited in mice high immunogenicity in spite of reduced host gene expression
Authors: Marín María Q. , Pérez Patricia , Gómez Carmen E. , Sorzano Carlos Óscar S. , Esteban Mariano , García-Arriaza Juan
Published: May 2018

Hepatitis C virus (HCV) represents a major global health problem for which a vaccine is not available. MVA-HCV is a unique HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector expressing the nearly full-length genome of HCV genotype 1a that elicits broad and polyfunctional CD8+T-cell responses in mice. With the aim to improve the immune response of MVA-HCV and due to the importance of interferon (IFN) in HCV infection, we deleted in MVA-HCV the vaccinia virus (VACV)C6Lgene, encoding an inhibitor of IFN-β that prevents activation of the transcription factors IRF3 and IRF7. The resulting vaccine candidate (MVA-HCV ΔC6L) expresses all HCV antigens and deletion ofC6Lhad no effect on viral growth in permissive chicken cells. In human monocyte-derived dendritic cells, infection with MVA-HCV ΔC6L triggered severe down-regulation of IFN-β, IFN-β-induced genes and cytokines similarly to MVA-HCV, as defined by real-time PCR and microarray analysis. In infected mice both vectors had a similar profile of recruited immune cells and induced comparable levels of adaptive and memory HCV-specific CD8+T-cells, mainly against p7+NS2 and NS3 HCV proteins, with a T cell effector memory (TEM) phenotype. Furthermore, antibodies against E2 were also induced. Overall, our findings showed that while these vectors had a profound inhibitory effect on gene expression of the host, they strongly elicited CD8+T cell and humoral responses against HCV antigens. These observations add support to the consideration of these vectors as potential vaccine candidates against HCV.

IMPORTANCE

Hepatitis C virus represents a global health problem with 71 million of people infected worldwide. While direct-acting antivirals agents can cure hepatitis C virus infection in most of patients, their high cost and the emergence of drug resistant variants make them not a feasible and affordable strategy to eradicate the virus. Therefore, a vaccine is an urgent goal that requires efforts in understanding the correlates of protection for hepatitis C virus clearance. Poxvirus vectors, in particular the attenuated modified vaccinia virus Ankara, are ideal as vaccine candidates due to their ability to induce both T and B cell immune responses against heterologous antigens and protection against a wide spectrum of pathogens. Here we describe the generation, genetics and immunogenicity elicited by MVA-HCV ΔC6L, a novel vaccine candidate for hepatitis C virus that expresses nearly all of hepatitis C proteins but lacks an IFN-β inhibitor, the C6 vaccinia virus protein.
Outbreak of Glomerulonephritis byStreptococcus zooepidemicusSzPHV5 type, in Monte Santo de Minas, Minas Gerais, Brazil
Authors: Torres Rosângela S.L.A. , Santos Talita Z. , Bernardes Andre F. L. , Soares Patricia A. , Soares Ana C. C. , Dias Ricardo S.
Published: May 2018

Streptococcus zooepidemicusis an emerging and opportunistic zoonotic pathogen, which playsan important role in the development of severe and life-threatening diseases and potentially capable of triggering large glomerulonephritis outbreaks. Between December 2012 and February 2013, 175 cases of glomerulonephritis were confirmed in the town of Monte Santo de Minas / MG / Brazil. During the outbreak, 19 isolates ofS. zooepidemicuswere recovered: one from ice cream, two from the oropharynx of food handlers and 16 from patients affected by acute post streptococcal glomerulonephritis (APSGN). AllS. zooepidemicusinvolved in the outbreak amplified the same sequence of the hypervariable region of the SzP protein (SzPHV5) and presented indistinguishable banding patterns with high similarity (> 99%) by rep-PCR technique. Inspection programs on the milk supply chain should be strengthened and continuously encouraged so that consumers’ health is preserved.
Proximodistal organization of the CA2 hippocampal area
Authors: Fernandez-Lamo I. , Gomez-Dominguez D. , Sanchez-Aguilera A. , Cid E. , Valero M. , la Prida L. Menendez de
Published: May 2018

The proximodistal axis is considered a major organizational principle of the hippocampus. Interfacing between the hippocampus and other brain systems, the CA2 region apparently breaks this rule. Apart from its specific role in social memory, CA2 has been involved in temporal and contextual memory but mechanisms remain elusive. Here, we used intracellular and extracellular recordings followed by neurochemical identification of single-cells to evaluate CA2 and surrounding areas in the rat. We found marked proximodistal trends of synaptic activity, as well as in subthreshold membrane potentials and phase-locked firing coupled to theta and gamma oscillations. Opposite proximodistal correlations between membrane potential fluctuations and theta sinks and sources at different layers revealed influences from up to three different generators. CA2 memory engrams established after a social memory task reflected these trends. We suggest that the structure and function of CA2 is segregated along the proximodistal hippocampal axis.
Reactive Initiation Training is more effective than Shuttle Run to improve the on-court agility of novice badminton players
Authors: Dong Minkai , Lyu Jidong , Hart Thomas , Zhu Qin
Published: May 2018

Purpose

Despite its well-known importance in sports, agility is ambiguously defined and lack of research. Shuttle Run (SR) is commonly used to improve the on-court agility of badminton players. Reactive Initiation Training (RIT) contrasts SR in that it only demands rapid generation of initiation step toward the direction of shuttlecock. The current study compared SR with RIT to determine which one is more effective for improving on-court agility of novice badminton players.

Method

20 novice badminton players were split in half to receive either RIT or SR on court for five days. Before and after training, participants were assessed on their ability to intercept the shuttlecocks randomly thrown by a coach to six corners of the court with and without visual occlusion of the coach. All trials of interception were recorded for video analysis of initiation time, running time and total time.

Results

The mean total times were greater with visual occlusion and varied systematically with the position of interception. Both training methods shortened the mean running time, however, only RIT additionally reduced the initiation time and its proportion on those time-consuming positions in the occluded condition.

Conclusion

RIT is more effective than SR to improve the on-court agility of novice badminton players.
Cofilin-actin rod formation in neuronal processes after brain ischemia
Authors: Won Seok Joon , Minnella Angela M. , Wu Long , Eun Claire H. , Rome Eric , Shaw Alisa E. , Herson Paco S. , Bamburg James R. , Swanson Raymond A.
Published: May 2018

Functional impairment after brain ischemia results in part from loss of neuronal spines and dendrites, independent of neuronal death. Cofilin-actin rods are covalently linked aggregates of colfilin-1 and actin that form in neuronal processes (neurites) under conditions of ATP depletion and oxidative stress, and which cause neurite degeneration if not disassembled. ATP depletion and oxidative stress occur with differing severity, duration, and time course in different ischemic conditions. Here we evaluated four mouse models of brain ischemia to define the conditions that drive formation of cofilin-actin rods. Three of the models provide early reperfusion: transient middle cerebral artery occlusion (MCAo), transient bilateral common carotid occlusion (CCAo), and cardiac arrest / cardiopulmonary resuscitation (CA/CPR). Early reperfusion restores ATP generating capacity, but also induces oxidative stress. The fourth model, photothrombotic cortical infarction, does not provide reperfusion. Cofilin-actin rods were formed in each of these models, but with differing patterns. Where acute reperfusion occurred, rod formation was maximal within 4 hours after reperfusion. Where infarction occurred, rods continued to form for at least 24 hours after ischemic onset, and extended into the adjacent non-ischemic tissue. Interventions that limit cofilin-actin rod formation may help to preserve integrity of neuronal processes in permanent ischemia.
Animal models with group-specific additive genetic variances: extending genetic group models
Authors: Muff Stefanie , Niskanen Alina K. , Saatoglu Dilan , Keller Lukas F. , Jensen Henrik
Published: May 2018

1.Theanimal modelis a key tool in quantitative genetics and has been used extensively to estimate fundamental parameters, such as additive genetic variance, heritability, or inbreeding effects. An implicit assumption of animal models is that all founder individuals derive from a single population. This assumption is commonly violated, for instance in cross-bred livestock breeds, when an observed population receive immigrants, or when a meta-population is split into genetically differentiated subpopulations. Ignoring genetic differences among different source populations of founders may lead to biased parameter estimates, in particular for the additive genetic variance.

2.To avoid such biases, genetic group models, extensions to the animal model that account for the presence of more than one genetic group, have been proposed. As a key limitation, the method to date only allows that the breeding values differ in their means, but not in their variances among the groups. Methodology previously proposed to account for group-specific variances included terms for segregation variance, which rendered the models infeasibly complex for application to most real study systems.

3.Here we explain why segregation variances are often negligible when analyzing the complex polygenic traits that are frequently the focus of evolutionary ecologists and animal breeders. Based on this we suggest an extension of the animal model that permits estimation of group-specific additive genetic variances. This is achieved by employing group-specific relatedness matrices for the breeding value components attributable to different genetic groups. We derive these matrices by decomposing the full relatedness matrix via the generalized Cholesky decomposition, and by scaling the respective matrix components for each group. To this end, we propose a computationally convenient approximation for the matrix component that encodes for the Mendelian sampling variance. Although convenient, this approximation is not critical.

4.Simulations and an example from an insular meta-population of house sparrows in Norway with three genetic groups illustrate that the method is successful in estimating group-specific additive genetic variances and that segregation variances are indeed negligible in the empirical example.

5.Quantifying differences in additive genetic variance within and among populations is of major biological interest in ecology, evolution, and animal and plant breeding. The proposed method allows to estimate such differences for subpopulations that form a connected meta-population, which may also be useful to study temporal or spatial variation of additive genetic variance.
Targeting light-gated chloride channels to neuronal somatodendritic domain reduces their excitatory effect in the axon
Authors: Messier Jessica E. , Chen Hongmei , Cai Zhao-Lin , Xue Mingshan
Published: May 2018

Light-gated chloride channels are emerging as promising optogenetic tools for inhibition of neural activity. However, their effects depend on the transmembrane chloride electrochemical gradient and may be complex due to the heterogeneity of this gradient in different developmental stages, neuronal types, and subcellular compartments. Here we characterized a light-gated chloride channel, GtACR2, in mouse cortical neurons. We found that GtACR2 activation inhibited the soma, but unexpectedly depolarized the presynaptic terminals resulting in neurotransmitter release. Other light-gated chloride channels had similar effects. Reducing the chloride concentrations in the axon and presynaptic terminals diminished the GtACR2-induced neurotransmitter release, indicating an excitatory effect of chloride channels in these compartments. A novel hybrid somatodendritic targeting motif reduced the GtACR2-induced neurotransmitter release while enhancing the somatic photocurrents. Our results highlight the necessity of precisely determining the effects of light-gated chloride channels under specific experimental conditions and provide a much-improved light-gated chloride channel for optogenetic inhibition.
GoFish: A Streamlined Environmental DNA Presence/Absence Assay for Marine Vertebrates
Authors: Stoeckle Mark Y. , Mishu Mithun Das , Charlop-Powers Zachary
Published: May 2018

Here we describe GoFish, a streamlined environmental DNA (eDNA) presence/absence assay. The assay amplifies a 12S segment with broad-range vertebrate primers, followed by nested PCR with M13-tailed, species-specific primers. Sanger sequencing confirms positives detected by gel electrophoresis. We first obtained 12S sequences from 77 fish specimens representing 36 northwestern Atlantic taxa not well documented in GenBank. Using the newly obtained and published 12S records, we designed GoFish assays for 11 bony fish species common in the lower Hudson River estuary and tested seasonal abundance and habitat preference at two sites. Additional assays detected nine cartilaginous fish species and a marine mammal, bottlenose dolphin, in southern New York Bight. GoFish sensitivity was equivalent to Illumina MiSeq metabarcoding. Unlike quantitative PCR (qPCR), GoFish does not require tissues of target and related species for assay development and a basic thermal cycler is sufficient. Unlike Illumina metabarcoding, indexing and batching samples are unnecessary and advanced bioinformatics expertise is not needed. The assay can be carried out from water collection to result in three days. The main limitations so far are species with shared target sequences and inconsistent amplification of rarer eDNAs. We think this approach will be a useful addition to current eDNA methods when analyzing presence/absence of known species, when turnaround time is important, and in educational settings.
Grape polyphenols reduce gut-localized reactive oxygen species associated with the development of metabolic syndrome in mice
Authors: Kuhn Peter , Kalariya Hetalben M. , Poulev Alexander , Ribnicky David M. , Jaja-Chimedza Asha , Roopchand Diana E. , Raskin Ilya
Published: May 2018

High-fat diet (HFD)-induced leaky gut syndrome combined with low-grade inflammation increase reactive oxygen species (ROS) in the intestine and may contribute to dysbiosis and metabolic syndrome (MetS). Poorly bioavailable and only partially metabolizable dietary polyphenols, such as proanthocyanidins (PACs), may exert their beneficial effects on metabolic health by scavenging intestinal ROS. To test this hypothesis, we developed and validated a novel, noninvasive, in situ method for visualizing intestinal ROS using orally administered ROS-sensitive indocyanine green (ICG) dye. C57BL/6J mice fed HFD for 10 weeks accumulated high levels of intestinal ROS compared to mice fed low-fat diet (LFD). Oral administration of poorly bioavailable grape polyphenol extract (GPE) and β-carotene decreased HFD-induced ROS in the gut to levels comparable to LFD-fed mice, while administration of more bioavailable dietary antioxidants (α- lipoic acid, vitamin C, vitamin E) did not. Forty percent of administered GPE antioxidant activity was measured in feces collected over 24 h, confirming poor bioavailability and persistence in the gut. The bloom of beneficial anaerobic gut bacteria, such asAkkermansia muciniphila, associated with improved metabolic status in rodents and humans may be directly linked to protective antioxidant activity of some dietary components. These findings suggest a possible mechanistic explanation for the beneficial effects of poorly bioavailable polyphenols on metabolic health.
Shorter telomere length is associated with a more recent diagnosis of coeliac disease
Authors: Goorkiz Pierre , Hearn Nerissa L , van der Kooi Saskia , Chiu Christine L , Lind Joanne M
Published: May 2018

Background

Coeliac disease (CD) is an autoimmune disease that causes an inappropriate inflammatory immune response to dietary gluten. Telomere length is a marker of biological ageing and is reduced in several autoimmune conditions. This observational study measured salivary telomere length (TL) in gluten-free diet (GFD) treated CD individuals to determine if CD, and length of time on a GFD, is associated with salivary TL.

Methods

Clinical and demographic information was collected from CD individuals currently treated with a GFD and healthy non-affected controls. Only participants aged under 35 years at recruitment were included. Relative telomere length was measured using quantitative PCR in oral mucosa collected from saliva. Linear regression was used to determine whether salivary TL was associated with CD, or length of time on a GFD, adjusting for age and sex.

Results

This study included 79 participants, 52 GFD-treated CD and 27 non-affected controls. No significant difference in salivary TL between individuals with treated CD and controls was found. Within CD individuals, salivary TL was associated with length of time on a GFD, with individuals who started a GFD ≤3 years ago having shorter salivary TL compared to those who started a GFD > 3 years ago (0.37±0.05 vs 0.50±0.04; p=0.002).

Conclusion

Our findings indicate that salivary TL shorten while CD is untreated, however following treatment on a GFD, they appear to recover to those seen in unaffected controls. This highlights the importance of early diagnosis and initiation of GFD to minimise mucosal damage and telomere shortening, to enable TL to recover.
MMOD-induced structural changes of hydroxylase in soluble methane monooxygenase
Authors: Kim Hanseong , An Sojin , Park Yeo Reum , Jang Hara , Park Sang Ho , Lee Seung Jae , Cho Uhn-Soo
Published: May 2018

Soluble methane monooxygenase in methanotrophs converts methane to methanol under ambient conditions1-3. The maximum catalytic activity of hydroxylase (MMOH) is achieved via interplay of its regulatory protein (MMOB) and reductase4-6. An additional auxiliary protein, MMOD, is believed to function as an inhibitor of the catalytic activity of MMOH; however, the mechanism of its action remains unknown7,8. Herein, we report the crystal structure of MMOH–MMOD complex fromMethylosinus sporiumstrain 5 (2.6 Å), which illustrates that two molecules of MMOD associate symmetrically with the canyon region of MMOH in a manner similar to MMOB, indicating that MMOD competes with MMOB for MMOH recognition. Further, MMOD binding disrupts the geometry of the di-iron centre and opens the substrate access channel. Notably, the electron density of 1,6-hexanediol at the substrate access channel mimics products of sMMO in hydrocarbon oxidation. The crystal structure of MMOH–MMOD unravels the inhibitory mechanism by which MMOD suppresses the MMOH catalytic activity, and reveals how hydrocarbon substrates/products access to the di-iron centre.
High Precision Detection of Rare Splice Isoforms Using Multiplexed Primer Extension Sequencing
Authors: Xu Hansen , Fair Benjamin J. , Dwyer Zach , Gildea Michael , Pleiss Jeffrey A.
Published: May 2018

Targeted RNA-sequencing aims to focus coverage on areas of interest that are inadequately sampled in standard RNA-sequencing experiments. Here we present a novel approach for targeted RNA-sequencing that uses complex pools of reverse transcription primers to enable sequencing enrichment at user-selected locations across the genome. We demonstrate this approach by targeting hundreds to thousands of pre-mRNA splice junctions, revealing high-precision detection of splice isoforms, including rare pre-mRNA splicing intermediates.
Ancestral resurrection reveals mechanisms of kinase regulatory evolution
Authors: Sang Dajun , Pinglay Sudarshan , Vatansever Sezen , Lou Hua Jane , Turk Benjamin , Gümüş Zeynep H. , Holt Liam J.
Published: May 2018

Protein kinases are crucial to coordinate cellular decisions and therefore their activities are strictly regulated. We used ancestral resurrection to uncover a mechanism underlying the evolution of kinase control within the ERK family of Mitogen Activated Protein Kinases (MAPKs). Kinase activities switched from high to low intrinsic autophosphorylation at the transition from the ancestors of ERKs1-5 and ERKs1-2. A shortening of the loop between β3-αC and a mutation in the gatekeeper residue drove this transition. Molecular dynamics simulations suggested that the change in the β3-αC loop length affected kinase cis-autophosphorylation by altering the positioning of catalytic residues and by allowing greater flexibility in the L16 kinase loop. This latter effect likely synergizes with the known role of gatekeeper mutations in facilitating domain closure and thus kinase activation, providing a rationale for the synergy between the two evolutionary mutations. Our results shed light on the evolutionary mechanisms that led to tight regulation of a central kinase in development and disease.
Identifying Parkinson’s disease and parkinsonism cases using routinely-collected healthcare data: a systematic review
Authors: Harding Zoe , Wilkinson Tim , Stevenson Anna , Horrocks Sophie , Ly Amanda , Schnier Christian , Breen David P , Rannikmäe Kristiina , Sudlow Cathie LM ,   on behalf of Dementias Platform UK
Published: May 2018

Background

Population-based, prospective studies can provide important insights into Parkinson’s disease (PD) and other parkinsonian disorders. Participant follow-up in such studies is often achieved through linkage to routinely-collected healthcare datasets. We systematically reviewed the published literature on the accuracy of these datasets for this purpose.

Methods

We searched four electronic databases for published studies that compared PD and parkinsonism cases identified using routinely-collected data to a reference standard. We extracted study characteristics and two accuracy measures: positive predictive value (PPV) and/or sensitivity.

Results

We identified 18 articles, resulting in 27 measures of PPV and 14 of sensitivity. For PD, PPVs ranged from 56-90% in hospital datasets, 53-87% in prescription datasets, 81-90% in primary care datasets and was 67% in mortality datasets. Combining diagnostic and medication codes increased PPV. For parkinsonism, PPVs ranged from 36-88% in hospital datasets, 40-74% in prescription datasets, and was 94% in mortality datasets. Sensitivities ranged from 15-73% in single datasets for PD and 43-63% in single datasets for parkinsonism.

Conclusions

In many settings, routinely-collected datasets generate good PPVs and reasonable sensitivities for identifying PD and parkinsonism cases. Further research is warranted to investigate primary care and medication datasets, and to develop algorithms that balance a high PPV with acceptable sensitivity.
The impact of mitotic errors on cell proliferation and tumorigenesis
Authors: Levine Michelle S. , Holland Andrew J.
Published: May 2018

Mitosis is a delicate event that must be executed with high fidelity to ensure genomic stability. Recent work has provided insight into how mitotic errors shape cancer genomes by driving both numerical and structural alterations in chromosomes that contribute to tumor initiation and progression. Here, we review the sources of mitotic errors in human tumors and their effect on cell fitness and transformation. We discuss new findings that suggest that chromosome missegregation can produce a proinflammatory environment and impact tumor responsiveness to immunotherapy. Finally, we survey the vulnerabilities exposed by cell division errors and how they can be exploited therapeutically.
Regulation of lipid peroxidation and ferroptosis in diverse species
Authors: Conrad Marcus , Kagan Valerian E. , Bayir Hülya , Pagnussat Gabriela C. , Head Brian , Traber Maret G. , Stockwell Brent R.
Published: May 2018

Lipid peroxidation is the process by which oxygen combines with lipids to generate lipid hydroperoxides via intermediate formation of peroxyl radicals. Vitamin E and coenzyme Q10 react with peroxyl radicals to yield peroxides, and then these oxidized lipid species can be detoxified by glutathione and glutathione peroxidase 4 (GPX4) and other components of the cellular antioxidant defense network. Ferroptosis is a form of regulated nonapoptotic cell death involving overwhelming iron-dependent lipid peroxidation. Here, we review the functions and regulation of lipid peroxidation, ferroptosis, and the antioxidant network in diverse species, including humans, other mammals and vertebrates, plants, invertebrates, yeast, bacteria, and archaea. We also discuss the potential evolutionary roles of lipid peroxidation and ferroptosis.
Telomerase can't handle the stress
Authors: Smith Susan
Published: May 2018

Telomerase counteracts the telomere shortening that occurs with each round of cell division. In normal human cells, telomerase is repressed, leading to telomere shortening that triggers replicative senescence. However, in most tumors, telomerase is up-regulated and is essential for telomere maintenance and tumor cell growth. Although long considered a viable target for tumor therapy, successful inhibition of telomerase in cancer therapy remains to be described. In this issue of Genes & Development, Ahmed and Lingner (pp. 658–669) uncover a vulnerability in telomerase upon exposure of cancer cells to oxidative stress. It has long been known that telomeres are sensitive to damage by reactive oxygen species (ROS), but the impact of oxidation on telomerase function in living cells was not known. Using gene knockouts in colon cancer cells, the investigators demonstrate that the antioxidant enzyme peroxiredoxin 1 (PRDX1) and the nudix phosphohydrolase superfamily enzyme (MTH1) cooperate to retain, upon oxidative stress, telomeres in a telomerase-extendible state. Considering that cancer cells are more vulnerable to ROS than noncancer cells, this work may open new avenues targeting telomeres and telomerase in tumor cells.
Size matters: conserved proteins function in length-dependent nuclear export of circular RNAs
Authors: Wan Yao , Hopper Anita K.
Published: May 2018

Circular RNAs (circRNAs) comprise a recently appreciated category of RNAs that are in high abundance and serve important biological functions. Although several discoveries have been made regarding the biogenesis and functions of circRNAs, their subcellular trafficking has remained largely unknown. In this issue of Genes & Development, Huang and colleagues (pp. 639–644) reported the first study of the nuclear export of circRNAs. Drosophila Hel25E and its human homologs, UAP56 and URH49, are required for nuclear export of circRNAs. Nuclear export of circRNAs is surprisingly length-dependent, and the length measurement mechanism was shown to be controlled by motifs in Hel25E and its homologs consisting of four amino acids.
Development of an in situ synchrotron X-ray total scattering setup under pressurized hydrogen gas
Authors: Sakaki Kouji , Kim Hyunjeong , Machida Akihiko , Watanuki Tetsu , Katayama Yoshinori , Nakamura Yumiko
Published: May 2018

This article describes the development of an in situ gas-loading sample holder for synchrotron X-ray total scattering experiments, particularly for hydrogen storage materials, designed to collect diffraction and pair distribution function (PDF) data under pressurized hydrogen gas. A polyimide capillary with a diameter and thickness of 1.4 and 0.06 mm, respectively, connected with commercially available Swagelok fittings was used as an in situ sample holder. Leakage tests confirmed that this sample holder allows 3 MPa of hydrogen gas pressure and 393 K to be achieved without leakage. Using the developed in situ sample holder, significant background and Bragg peaks from the sample holder were not observed in the X-ray diffraction patterns and their signal-to-noise ratios were sufficiently good. The PDF patterns showed sharp peaks in the r range up to 100 Å. The results of Rietveld and PDF refinements of Ni are consistent with those obtained using a polyimide capillary (1.0 mm diameter and 0.04 mm thickness) that has been used for ex situ experiments. In addition, in situ synchrotron X-ray total scattering experiments under pressurized hydrogen gas up to 1 MPa were successfully demonstrated for LaNi4.6Cu.
Evidence of new twinning modes in magnesium questioning the shear paradigm
Authors: Cayron Cyril , Logé Roland
Published: May 2018

Twinning is an important deformation mode of hexagonal close-packed metals. The crystallographic theory is based on the 150-year-old concept of simple shear. The habit plane of the twin is the shear plane; it is invariant. This article presents electron backscatter diffraction observations and crystallographic analysis of a millimetre-size twin in a magnesium single crystal whose habit plane, unambiguously determined both in the parent crystal and in its twin, is not an invariant plane. This experimental evidence demonstrates that macroscopic deformation twinning can be achieved by a mechanism that is not a simple shear. This unconventional twin is often co-formed with a new conventional twin that exhibits the lowest shear magnitude ever reported in metals. The existence of unconventional twinning introduces a shift of paradigm and calls for the development of new crystallographic theories of displacive transformations.
Stroboscopic time-of-flight neutron diffraction during cyclic testing using the event data recording system at J-PARC
Authors: Kawasaki Takuro , Inamura Yasuhiro , Ito Takayoshi , Nakatani Takeshi , Harjo Stefanus , Gong Wu , Aizawa Kazuya
Published: May 2018

A time-resolved time-of-flight neutron diffraction technique to characterize the structural properties of materials during cyclic tests has been developed for the neutron diffractometers at J-PARC. Using this technique, diffracted neutrons and the applied cyclic conditions are recorded as event data together with time information. The amplitude and phase of the conditions of all recorded neutron signals can be specified by using the characteristics of the event data. By adopting the developed technique, the behaviors of the crystal lattice and domains of the piezoelectric material in a multilayer-type piezoelectric actuator driven by a cyclic electric field were evaluated. The developed technique enabled the collection and processing of diffraction data for all levels of the applied electric field, as opposed to only the highest and lowest levels. The variation in diffraction intensity during the application of a cyclic electric field was obtained successfully, and the hysteresis-like behaviors of both the lattice strain and the 90° domain switching were revealed.
Experimental and theoretical study ofMatricaria recutitachamomile extract as corrosion inhibitor for steel in neutral chloride media
Authors: Nasr Khaoula , Fedel Michele , Essalah Khaled , Deflorian Flavio , Souissi Nebil
Published: May 2018

Purpose

This study aims to investigate the inhibition performance of an aqueous extract ofMatricaria recutitachamomile on the corrosion of S235JR steel in 0.5 M NaCl by using electrochemical impedance spectroscopy (EIS) and polarization measurements.

Design/methodology/approach

The inhibition performance was investigated using EIS and polarization measurements. Surface analysis demonstrates the presence of a protective layer on the steel surface in the presence of the extract. Quantum chemical parameters calculated for the molecules contained in the aqueous extract are interpreted to predict the corrosion inhibition efficiency of the considered extract.

Findings

The inhibition efficiency of chamomile aqueous extract for S235JR steel increases with increasing amounts of plant concentration and with an increase in the immersion time. The optimal inhibition efficiency of chamomile extract, 98.90 per cent, was achieved for S235JR steel when immersed in 15 per cent v/v of extract concentration for 2 h. The surface analysis in the absence and presence of the chamomile extract confirmed the formation of a protective layer on steel surface. The quantum chemical calculations allowed to explain the great inhibition efficiency values by interpreting the calculated quantum parameters.

Originality/value

This is the first study carrying out an experimental and theoretical investigation onM. recutitachamomile as a green corrosion inhibitor, with interesting potential industrial applications.
Getting rid of a heavy shield: downsizing the in-house legal department?
Authors: Alvarado-Vargas Marcelo J. , Zou Qi
Published: May 2018

Purpose

The purpose of this paper is to examine the effects of the number of lawsuits on firm performance and in-house legal department size. More importantly, this paper also aims to explore the interaction effect of in-house legal department size on the aforementioned lawsuit-performance relationship.

Design/methodology/approach

The empirical analyses are performed by using secondary data. Structural equation modeling is employed in order to examine multiple structural relationships between the number of lawsuits, size of in-house legal department, and firm performance.

Findings

Three key findings were generated: number of lawsuits has a significant detrimental effect on firm performance; number of lawsuits is positively associated with size of in-house legal departments; and size of in-house legal departments negatively moderates the relationship between number of lawsuits and firm performance.

Practical implications

The results corroborate the harmfulness of lawsuits. On the one hand, a large number of lawsuits damage the firm’s financial performance directly; on the other hand, more lawsuits lead to enlarged in-house legal departments which further aggravate the negative effects of lawsuits on firm performance. These results suggest that firms should spend more effort in properly managing legal departments.

Originality/value

This paper contributes to the literature by empirically examining the economic impacts of lawsuits on firm performance. Moreover, it also explored the notion that having a large size of in-house legal department does not mitigate, but aggravates the harmfulness of lawsuits on firm performance.
Causal relationship between material price fluctuation and project’s outturn costs
Authors: Olatunji Oluwole Alfred , Orundami Adenike Omolabake , Ogundare Oluwatomi
Published: May 2018

Purpose

A section of project management literature attributes overruns to estimators’ deceit and delusion. An example of this is Flyvbjerg’s theorisation of strategic misrepresentation and optimism bias. To show that such a notion is not true entirely, the study elicits evidence relating to how costs of projects often fluctuate erratically as prices of construction materials change throughout contract cycle times. The purpose of this paper is to examine the causal relationships between persistent changes in prices of construction materials and project’s outturn costs.

Design/methodology/approach

The authors obtained and analysed price data of construction materials published in a Nigerian national daily in the 16 years between 2000 and 2015. Additional data were obtained from a quantity surveying firm to validate the archival data on material prices, and to compare the firm’s robust database of project estimates and the corresponding outturn costs of specific building elements (detailed in the study). The goal of the analysis is to explore spontaneity and causal impact in the relationship between changes in prices of construction materials and project costs. Kolmogorov-Smirnov and Anderson-Darling tests were used to obtain the probability distributions of the causal relationships.

Findings

Findings show disproportionate positive correlations between changes in material prices and outturn costs in Nigeria. An important dimension to this, however, is that although fluctuations in material costs often trigger variations to project costs, outturn price only accounts for about one-third of actual cost variability. Recovery of costs, not least profit making, under these conditions is a complex process.

Originality/value

This paper concludes that dynamism in cost attributes is neither a deceit nor a delusion; understanding and tolerating them is not a systemic weakness, rather an essential key to project success and stakeholder satisfaction. Findings from the study also bring measured certainties to the transformation of variable costs into fixed price outcomes, an important consideration that will help contract estimators and project managers to understand the likelihood of fluctuation in material costs and how these might trigger variability in project costs.
Examining the effectiveness of using CSR communication in apology statements after bad publicity
Authors: Chung Angie
Published: May 2018

Purpose

The purpose of this paper is to contribute to understanding the effects of framing apology statements with corporate social responsibility (CSR) communications after a company has suffered negative publicity. Specifically, this study examined the role of CSR fit on consumers’ skepticism toward the apology statement and attitude toward the company compared to a no-CSR message condition. In addition, the study also analyzed the interaction effects between CSR fit and history on skepticism toward the apology statement and attitude toward the company.

Design/methodology/approach

A 2 (CSR fit: high or low) × 2 (CSR history: long or short) between-subject design was employed to examine the hypotheses. In addition, a no-CSR message group without any mention of CSR activities was included. To test the hypothesized constructs of main interest (i.e. CSR fit and CSR history) and incremental validity in the same set of model equations, this study used a hierarchical regression approach.

Findings

The high CSR fit condition led to less skepticism toward the apology statement and a more positive attitude toward the company than the no-CSR message condition did. The low CSR fit condition, in contrast, led to more skepticism toward the apology statement and a less positive attitude toward the company than the no-CSR message condition did. In addition, the results showed that the interaction effects between CSR fit and history will predict skepticism toward the apology statement and attitude toward the company.

Originality/value

There is little research on the effectiveness of high (congruent) and low (incongruent) CSR fit compared to a no-CSR message condition. To address this gap, this paper compared the effectiveness of the two conditions to a no-CSR condition.
Homeless shelters in urban India: life sans dignity
Authors: Ghosh Piyali , Goel Geetika , Ojha Mohit
Published: May 2018

Purpose

Government of India has been addressing the issue of homelessness through shelters in urban areas, mandated with provision of basic amenities including drinking water and washrooms. This research paper aims to investigate into the condition of such homeless shelters in terms of importance of and satisfaction from mandatory amenities therein as perceived by users, i.e. urban homeless poor.

Design/methodology/approach

Data from a survey spanning a sample of 401 shelter inmates have been used to construct a service quality performance matrix (SQPM) to analyse the importance of amenities and satisfaction of shelter inmates out of these amenities. A priority order of these amenities for improvement has been drawn thereafter with a customer satisfaction index (CSI).

Findings

The results of SQPM show ten items registering high importance-low satisfaction. Amenities such as utensils for cooking and psycho-social counselling are important but not available. Priority-wise amenities that need to be improved are: psycho-social counselling, facility of referral and transport, utensils for cooking, childcare facilities, waste management, adequate fire safety measures, recreation space, pest and mosquito control, first aid and kitchen/cooking space and equipment needed for cooking.

Practical implications

A total of 10 amenities have been ranked in order of priority, for which, the government needs to define its improvement action plans for delivering maximum satisfaction to inmates of shelters out of their stay.

Originality/value

The findings reveal that urban homeless staying in shelters are being deprived of many of the amenities earmarked as mandatory. Existing studies on shelters in India are usually descriptive, providing a summary of available amenities therein. This study is the first to contribute to literature on housing by applying SQPM and CSI on amenities available at homeless shelters.