bluuebunny/crossref_metadata_2025 huggingface dataset:
Auxin-sensitive Aux/IAA proteins mediate drought tolerance in Arabidopsis by regulating glucosinolate levels
Authors: Salehin M. , Li B. , Tang M. , Katz E. , Song L. , Ecker J. R. , Kliebenstein D. , Estelle M.
Published: March 2019

A detailed understanding of abiotic stress tolerance in plants is essential to provide food security in the face of increasingly harsh climatic conditions. Glucosinolates (GLSs) are secondary metabolites found in the Brassicaceae that protect plants from herbivory and pathogen attack. Here we report that in Arabidopsis, aliphatic GLS levels are regulated by the auxin-sensitive Aux/IAA repressors IAA5, IAA6, and IAA19. These proteins act in a transcriptional cascade that maintains expression of GLS levels when plants are exposed to drought conditions. Loss of IAA5/6/19 results in reduced GLS levels and decreased drought tolerance. Further, we show that this phenotype is associated with a defect in stomatal regulation. Application of GLS to the iaa5,6,19 mutants restores stomatal regulation and normal drought tolerance. GLS action is dependent on the receptor kinase GHR1, suggesting that GLS may signal via reactive oxygen species. These results provide a novel connection between auxin signaling, GLS levels and drought response.

One Sentence Summary

Aux/IAA proteins promote drought tolerance by regulating glucosinolate levels.
Clades of huge phage from across Earth’s ecosystems
Authors: Al-Shayeb Basem , Sachdeva Rohan , Chen Lin-Xing , Ward Fred , Munk Patrick , Devoto Audra , Castelle Cindy J. , Olm Matthew R. , Bouma-Gregson Keith , Amano Yuki , He Christine , Méheust Raphaël , Brooks Brandon , Thomas Alex , Lavy Adi , Matheus-Carnevali Paula , Sun Christine , Goltsman Daniela S. A. , Borton Mikayla A. , Nelson Tara C. , Kantor Rose , Jaffe Alexander L. , Keren Ray , Farag Ibrahim F. , Lei Shufei , Finstad Kari , Amundson Ronald , Anantharaman Karthik , Zhou Jinglie , Probst Alexander J. , Power Mary E. , Tringe Susannah G. , Li Wen-Jun , Wrighton Kelly , Harrison Sue , Morowitz Michael , Relman David A. , Doudna Jennifer A , Lehours Anne-Catherine , Warren Lesley , Cate Jamie H. D. , Santini Joanne M. , Banfield Jillian F.
Published: March 2019

Phage typically have small genomes and depend on their bacterial hosts for replication. DNA sequenced from many diverse ecosystems revealed hundreds of huge phage genomes, between 200 kbp and 716 kbp in length. Thirty-four genomes were manually curated to completion, including the largest phage genomes yet reported. Expanded genetic repertoires include diverse and new CRISPR-Cas systems, tRNAs, tRNA synthetases, tRNA modification enzymes, translation initiation and elongation factors, and ribosomal proteins. Phage CRISPR-Cas systems have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phage may repurpose bacterial CRISPR-Cas systems to eliminate competing phage. We phylogenetically define major clades of huge phage from human and other animal microbiomes, oceans, lakes, sediments, soils and the built environment. We conclude that their large gene inventories reflect a conserved biological strategy, observed over a broad bacterial host range and across Earth’s ecosystems.
Symbiont community diversity is more constrained in holobionts that tolerate diverse stressors
Authors: Howe-Kerr Lauren I. , Bachelot Benedicte , Wright Rachel M. , Kenkel Carly D. , Bay Line K. , Correa Adrienne M.S.
Published: March 2019

Coral reefs are experiencing global declines as climate change and other stressors cause environmental conditions to exceed the physiological tolerances of host organisms and their microbial symbionts (collectively termed the holobiont). To assess the role of symbiont community composition in holobiont stress tolerance, diversity metrics and abundances of obligate dinoflagellate endosymbionts (Family: Symbiodiniaceae) were quantified from eight Acropora millepora coral colonies (hereafter called genets) that thrived under or responded poorly to various stressors. Four ‘best performer’ coral genets were selected for analysis because they survived 10 days of high temperature, high pCO2, bacterial addition, or combined stressors, whereas four ‘worst performer’ coral genets were analyzed because they experienced significant mortality under these stressors. At the end of the experimental period, seven of eight coral genets mainly hosted Cladocopium symbionts, but also contained Brevolium, Durusdinium, and/or Gerakladinium symbionts at lower abundances (<0.1% of the total community). After 10 days of stress, symbiont communities varied significantly among host genets, but not stress treatments, based on alpha and beta diversity metrics. A generalized joint attribute model (GJAM) also predicted that symbiont communities were primarily sensitive to host genet at regional scales. Indicator species analysis and the regional GJAM model identified significant associations among particular symbionts and host genet performance. Specifically, Cladocopium 3k contributed to the success of best performer host genets under various stressful conditions, whereas Durusdinium glynnii and Durusdinium trenchii were significantly associated with one worst performer genet. Cladocopium 3k dominance should be more broadly investigated as a potential predictor of stress resistance in Acropora millepora populations across their geographic range. Symbiodiniaceae communities exhibited higher richness and variance (beta diversity) in the worst performing genets. These findings highlight that symbiont community diversity metrics may be important indicators of resilience in hosts central to diverse disciplines, from agriculture to medicine.
Modularity in the Microcircuitry of the Mouse Inferior Colliculus Yields Dual Processing Streams for Auditory and Multisensory Information
Authors: Lesicko Alexandria M. H. , Llano Daniel A.
Published: March 2019

The lateral cortex of the inferior colliculus (LCIC) is parcellated into two neurochemical compartments: one that comprises periodic neurochemical modules rich in GABAergic and cholinergic terminals and an extramodular matrix rich in calretinin neurons. We recently found that projections from auditory structures (auditory cortex and central nucleus of the IC) target the extramodular matrix, while somatosensory structures (somatosensory cortex and dorsal column nuclei) target the modules. What is peculiar about this finding of segregated inputs is that previous work has found that many LCIC neurons respond to both auditory and somatosensory stimuli. To investigate how these pathways interact, here we use laser photostimulation of caged glutamate to interrogate local LCIC circuits in brain slices from mouse. We found that most cell types in the LCIC receive inputs only from their home domain, but that GABAergic neurons in the modules serve as a bridge between modules and extramodular space. Further, we found that residence in- or out-of a module strongly predicted the output connectivity of that cell. These data suggest that distinct processing streams are seen in the LCIC and that GABAergic cells in modules serve to link these streams.
Motor context coordinates visually guided walking inDrosophila
Authors: Cruz Tomás , Fujiwara Terufumi , Varela Nélia , Mohammad Farhan , Claridge-Chang Adam , Chiappe M Eugenia
Published: March 2019

Course control is critical for the acquisition of spatial information during exploration and navigation, and it is thought to rely on neural circuits that process locomotive-related multimodal signals. However, which circuits underlie this control, and how multimodal information contributes to the control system are questions poorly understood. We used Virtual Reality to examine the role of self-generated visual signals (visual feedback) on the control of exploratory walking in flies. Exploratory flies display two distinct motor contexts, characterized by low speed and fast rotations, or by high speed and slow rotations, respectively. Flies use visual feedback to control body rotations, but in a motor-context specific manner, primarily when walking at high speed. Different populations of visual motion-sensitive cells estimate body rotations via congruent, multimodal inputs, and drive compensatory rotations. However, their effective contribution to course control is dynamically tuned by a speed-related signal. Our data identifies visual networks with a multimodal circuit mechanism for adaptive course control and suggests models for how visual feedback is combined with internal signals to guide exploratory course control.
Comprehensive Classification of the RNase H-like domain-containing Proteins in Plants
Authors: Li Shuai , Liu Kunpeng , Sun Qianwen
Published: March 2019

Background

R-loop is a nucleic acid structure containing an RNA-DNA hybrid and a displaced single-stranded DNA. Recently, accumulated evidence showed that R-loops widely present in various organisms’ genomes and are involved in many physiological processes, including DNA replication, RNA transcription, and DNA repair. RNase H-like superfamily (RNHLS) domain-containing proteins, such as RNase H enzymes, are essential in restricting R-loop levels. However, little is known about the function and relationship of other RNHLS proteins on R-loop regulation, especially in plants.

Results

In this study, we characterized 6193 RNHLS proteins from 13 representative plant species and clustered these proteins into 27 clusters, among which reverse transcriptases and exonucleases are the two largest groups. Moreover, we found 691 RNHLS proteins in Arabidopsis with a conserved catalytic alpha-helix and beta-sheet motif. Interestingly, each of the Arabidopsis RNHLS proteins is composed of not only an RNHLS domain but also another different protein domain. Additionally, the RNHLS genes are highly expressed in different meristems and metabolic tissues, which indicate that the RNHLS proteins might play important roles in the development and maintenance of these tissues.

Conclusions

In summary, we systematically analyzed RNHL proteins in plants and found that there are mainly 27 subclusters of them. Most of these proteins might be implicated in DNA replication, RNA transcription, and nucleic acid degradation. We classified and characterized the RNHLS proteins in plants, which may afford new insights into the investigation of novel regulatory mechanisms and functions of R-loops.
An equilibrium binding model for CpG DNA-dependent dimerization of Toll-like receptor 9
Authors: Reikine Stephanie , McLaughlin Stephen H. , Johnson Christopher M. , Modis Yorgo
Published: March 2019

Microbial nucleic acids in the extracellular milieu are recognized in vertebrates by Toll-like receptors (TLRs), one of the most important families of innate immune receptors. TLR9 recognizes single-stranded unmethylated CpG DNA in endosomes. DNA binding induces dimerization of TLR9 and activation of a potent inflammatory response. To provide insights on how DNA ligands induce TLR9 dimerization, we developed a detailed theoretical equilibrium ligand binding model. Light scattering and fluorescence polarization assays performed with a recombinant TLR9 ectodomain fragment and a panel of agonistic and antagonistic DNA ligands provide data that restrain the binding parameters in our binding model. This work brings us one step closer to establishing a rigorous biochemical understanding of how TLRs are activated by their ligands.
Transcriptomic and Cellular Decoding of Regional Brain Vulnerability to Neurodevelopmental Disorders
Authors: Seidlitz Jakob , Nadig Ajay , Liu Siyuan , Bethlehem Richard A.I. , Vértes Petra E. , Morgan Sarah E. , Váša František , Romero-Garcia Rafael , Lalonde François M. , Clasen Liv S. , Blumenthal Jonathan D. , Paquola Casey , Bernhardt Boris , Wagstyl Konrad , Polioudakis Damon , de la Torre-Ubieta Luis , Geschwind Daniel H. , Han Joan C. , Lee Nancy R. , Murphy Declan G. , Bullmore Edward T. , Raznahan Armin
Published: March 2019

Neurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i)in vivoneuroimaging data from patient subgroups with known causal genomic copy number variations (CNVs), and (ii) bulk and single-cell gene expression data from healthy cortex. First, for each of six different CNV disorders, we show that spatial patterns of cortical anatomy change in youth are correlated with spatial patterns of expression for CNV region genes in bulk cortical tissue from typically-developing adults. Next, by transforming normative bulk-tissue cortical expression data into cell-type expression maps, we further link each disorder’s anatomical change map to specific cell classes and specific CNV-region genes that these cells express. Finally, we establish convergent validity of this “transcriptional vulnerability model” by inter-relating patient neuroimaging data with measures of altered gene expression in both brain and blood-derived patient tissue. Our work clarifies general biological principles that govern the mapping of genetic risks onto regional brain disruption in neurodevelopmental disorders. We present new methods that can harness these principles to screen for potential cellular and molecular determinants of disease from readily available patient neuroimaging data.
Landscape of multi-nucleotide variants in 125,748 human exomes and 15,708 genomes
Authors: Wang Qingbo , Pierce-Hoffman Emma , Cummings Beryl B. , Karczewski Konrad J. , Alföldi Jessica , Francioli Laurent C. , Gauthier Laura D. , Hill Andrew J. , O’Donnell-Luria Anne H. ,   Genome Aggregation Database (gnomAD) Production Team, Genome Aggregation Database (gnomAD) Consortium, MacArthur Daniel G.
Published: March 2019

Multi-nucleotide variants (MNVs), defined as two or more nearby variants existing on the same haplotype in an individual, are a clinically and biologically important class of genetic variation. However, existing tools for variant interpretation typically do not accurately classify MNVs, and understanding of their mutational origins remains limited. Here, we systematically survey MNVs in 125,748 whole exomes and 15,708 whole genomes from the Genome Aggregation Database (gnomAD). We identify 1,996,125 MNVs across the genome with constituent variants falling within 2 bp distance of one another, of which 31,510 exist within the same codon, including 405 predicted to result in gain of a nonsense mutation, 1,818 predicted to rescue a nonsense mutation event that would otherwise be caused by one of the constituent variants, and 16,481 additional variants predicted to alter protein sequences. We show that the distribution of MNVs is highly non-uniform across the genome, and that this non-uniformity can be largely explained by a variety of known mutational mechanisms, such as CpG deamination, replication error by polymerase zeta, or polymerase slippage at repeat junctions. We also provide an estimate of the dinucleotide mutation rate caused by polymerase zeta. Finally, we show that differential CpG methylation drives MNV differences across functional categories. Our results demonstrate the importance of incorporating haplotype-aware annotation for accurate functional interpretation of genetic variation, and refine our understanding of genome-wide mutational mechanisms of MNVs.
Biomarkers for capturing disease pathology as molecular process hyperstructure
Authors: Lukas Arno , Heinzel Andreas , Mayer Bernd
Published: March 2019

Background

Precision of drugs in clinical development but also of approved treatment sees limits, documented as attrition in clinical stage drug testing and suboptimal number needed to treat in clinical practice. Precision medicine aims at approaching a causal relation of disease pathology, treatment mechanism of action and clinical outcome. The instance linking pathology, clinical phenotype and drug response is disease characteristics amenable for quantitation, including established clinical phenotyping parameters and upcoming molecular profiling and biomarkers. Molecular biomarkers situated at the interface of pathology-specific molecular process architecture and drug mechanism of action promise capturing aspects allowing assessment of treatment response.

Results

Approximating a set of 1,008 disease terms as pathology molecular networks provides 3,860 molecular processes involving 4,602 protein coding genes. Assembling this process set in a hierarchical cluster using mean shortest paths among processes as distance measure allows representation of molecular processes in cumulative aggregation. This procedure transforms human disease pathology into a static instance of a molecular process hyperstructure involving 1,340 aggregate levels in a molecular architecture. The hyperstructure allows evaluating molecular biomarker candidates at different levels of molecular process aggregation in terms of biomarker-specific entropies. Interpretation as information content reflects the capacity of a biomarker for sensing molecular process configuration.

Deriving entropies across aggregation levels for a reference set of 1,502 biomarker candidates identifies significant spread in information content of individual biomarkers. Exemplified on biomarker panels holding evidence for prognostic capacity and factors serving as drug targets from selected chronic diseases, biomarker entropies allow interpretation in terms of sensitivity for capturing process context and specificity for informing on the status of individual processes afflicted with a given pathology.

Conclusions

High entropy biomarkers provide candidate molecular proxies for clinical phenotyping parameters, and low entropy biomarkers add information on specifics of disease pathology. Combining high and low entropy biomarkers in panels may offer relevant resolution of molecular process configurations for improving patient stratification with respect to minimizing variance in drug response.
The Mut+strain ofKomagataella phaffii(Pichia pastoris) expresses PAOX15 and 10 times faster than Mutsand Mut−strains: Evidence that formaldehyde or/and formate are true inducers of AOX
Authors: Singh Anamika , Narang Atul
Published: March 2019

The methylotrophic yeastKomagataella phaffiiis among the most popular hosts for recombinant protein synthesis. Most recombinant proteins were expressed in the wild-type Mut+host strain from the methanol-inducible promoter PAOX1. Since methanol metabolism has undesirable consequences, two additional host strains, Muts(AOX1-) and Mut−(AOX1-AOX2-), were introduced which consume less methanol and reportedly also express recombinant protein better than Mut+. Both results follow from a simple model based on two widespread assumptions, namely methanol is transported by diffusion and the sole inducer of PAOX1. To test this model, we studied14C-methanol uptake in the Mut−strain and β-galactosidase expression in all three strains. We confirmed that methanol is transported by diffusion, but in contrast to the literature, Mut+expressed β-galactosidase 5- and 10-fold faster than Mutsand Mut−. These results imply that methanol is not the sole inducer of PAOX1— metabolites downstream of methanol also induce PAOX1. We find that formate or/and formaldehyde are probably true inducers since both induce PAOX1expression in Mut−which cannot synthesize intracellular methanol from formate or formaldehyde. Formate offers a promising substitute for methanol since it does not appear to suffer from the deficiencies that afflict methanol.
Evaluation of extraction solvents for untargeted metabolomics analysis of enrichment reactor cultures performing enhanced biological phosphorus removal (EBPR)
Authors: Thaw Saw Nay Min Min , Suwanchaikasem Pipob , Zuniga-Montanez Rogelio , Qiu Guanglei , Wuertz Stefan , Williams Rohan B. H.
Published: March 2019

Introduction

The extraction solvent mixtures were optimized for untargeted metabolomics analysis of microbial communities from two laboratory scale activated sludge reactors performing enhanced biological phosphorus removal (EBPR).

Objective

To develop a robust and simple analytical protocol to analyse microbial metabolomics from EBPR bioreactors.

Methods

Extra- and intra-cellular metabolites were extracted using five methods and analysed by ultraperformance liquid chromatography mass spectrometry (UPLC-MS).

Results

The optimal extraction method was biomass specific and methanol:water (1:1 v/v) and methanol:chloroform:water (2:2:1 v/v) were chosen, respectively, for each of the two different bioreactors.

Conclusion

Our approach provides direct surveys of the metabolic state of PAO-enriched EBPR communities, showing that extraction methods should be carefully tailored to the microbial community under study
Low temperature triggers genome-wide hypermethylation of transposable elements and centromeres in maize
Authors: Achour Zeineb , Joets Johann , Leguilloux Martine , Sellier Hélène , Pichon Jean-Philippe , Leveugle Magalie , Duborjal Hervé , Caius José , Brunaud Véronique , Roux Christine Paysant-Le , Mary-Huard Tristan , Giauffret Catherine , Vitte Clémentine
Published: March 2019

Characterizing the molecular processes developed by plants to respond to environmental cues is a major task to better understand local adaptation. DNA methylation is a chromatin mark involved in the transcriptional silencing of transposable elements (TEs) and gene expression regulation. While the molecular bases of DNA methylation regulation are now well described, involvement of DNA methylation in plant response to environmental cues remains poorly characterized. Here, using the TE-rich maize genome and analyzing methylome response to prolonged cold at the chromosome and feature scales, we investigate how genomic architecture affects methylome response to stress in a cold-sensitive genotype. Interestingly, we show that cold stress induces a genome-wide methylation increase through the hypermethylation of TE sequences and centromeres. Our work highlights a cytosine context-specific response of TE methylation that depends on TE types, chromosomal location and proximity to genes. The patterns observed can be explained by the parallel transcriptional activation of multiple DNA methylation pathways that methylate TEs in the various chromatin locations where they reside. Our results open new insights into the possible role of genome-wide DNA methylation in phenotypic response to stress.
Regional brain development analysis through registration using anisotropic similarity, a constrained affine transformation
Authors: Legouhy Antoine , Commowick Olivier , Proisy Maïa , Rousseau François , Barillot Christian
Published: March 2019

We propose a novel method to quantify brain growth in 3 arbitrary orthogonal directions of the brain or its sub-regions through linear registration. This is achieved by introducing a 9 degrees of freedom (dof) transformation called anisotropic similarity which is an affine transformation with constrained scaling directions along arbitrarily chosen orthogonal vectors. This gives the opportunity to extract scaling factors describing brain growth along those directions by registering a database of subjects onto a common reference. This information about directional growth brings insights that are not usually available in longitudinal volumetry analysis. The interest of this method is illustrated by studying the anisotropic regional and global brain development of 308 healthy subjects betwen 0 and 19 years old. A gender comparison of those scaling factors is also performed for 4 classes of age. We demonstrate through these applications the stability of the method to the chosen reference and its ability to highlight growth differences accros regions and gender.
Procaine and S-adenosyl-L-homocysteine (SAH) affect the expression of genes related to the epigenetic machinery and change the DNA methylation status ofin vitrocultured bovine skin fibroblasts
Authors: N.A.B. Schumann , Mendonça A.S. , Silveira M.M. , Vargas L.N. , Leme L.O. , de Sousa R.V. , Franco M.M.
Published: March 2019

Cloning using somatic cell nuclear transfer (SCNT) has many potential applications such as in transgenic and genomic-edited animal production. Abnormal epigenetic reprogramming of somatic cell nuclei is probably the major cause of the low efficiency associated with SCNT. Strategies to alter DNA reprogramming in donor cell nuclei may help improve the cloning efficiency. In the present study, we aimed to characterise the effects of procaine and S-adenosyl-L-homocysteine (SAH) as demethylating agents during the cell culture of bovine skin fibroblasts. We characterised the effects of procaine and SAH on the expression of genes related to the epigenetic machinery, including the DNMT1, DNMT3A, DNMT3B, TET1, TET2, TET3, and OCT4 genes, and on DNA methylation levels of bovine skin fibroblasts. We found that DNA methylation levels of satellite I were reduced by SAH (P=0.0495) and by the combination of SAH and procaine (P=0.0479) compared with that in the control group. Global DNA methylation levels were lower in cells that were cultivated with both compounds than in control cells [procaine (P=0.0116), SAH (P=0.0408), and both (P=0.0163)]. Regarding the transcriptional profile, there was a decrease in total DNMT transcript levels in cells cultivated with SAH and procaine. There was a higher level of TET3 transcripts in treated cells than in the controls. Our results showed that the use of procaine and SAH during bovine cell culture was able to alter the epigenetic profile of the cells. This approach may be a useful alternative strategy to improve the efficiency of reprogramming the somatic nuclei after fusion, which in turn will improve the SCNT efficiency.
In vitro evaluation of probiotic properties of lactic acid bacteria isolated from some traditionally fermented Ethiopian food products
Authors: Mulaw Guesh , Sisay Tesfaye , Muleta Diriba , Tesfaye Anteneh
Published: March 2019

Probiotics are live microorganisms which when consumed in large number together with a food promote the health of the consumer. The aim of this study was to evaluatein vitroprobiotic properties of lactic acid bacteria (LAB) isolated from traditional Ethiopian fermentedTeff injeradough,ErgoandKochoproducts. A total of 90 LAB were isolated, of which 4 (4.44%) isolates showed 45.35-97.11% and 38.40-90.49% survival rate at pH values (2, 2.5 and 3) for 3 and 6 h in that order. The four acid tolerant isolates were found tolerant to 0.3% bile salt for 24 h with 91.37 to 97.22% rate of survival. The acid-and-bile salt tolerant LAB isolates were found inhibiting some foodborne test pathogenic bacteria to varying degrees. All acid-and-bile tolerant isolates displayed varying sensitivity to different antibiotics. Thein vitroadherence to stainless steel plates of the 4 screened probiotic LAB isolates were ranged from 32.75 to 36.30% adhesion rate. The four efficient probiotic LAB isolates that belonged toLactobacillusspecies were identified to strain level using 16S rDNA gene sequence comparisons and namely wereLactobacillus plantarumstrain CIP 103151,Lactobacillus paracaseisubsp. tolerans strain NBRC 15906,Lactobacillus paracaseistrain NBRC 15889 andLactobacillus plantarumstrain JCM 1149. The fourLactobacillusstrains were found to have potentially useful to produce probiotic products.
Quadriceps and hamstrings coactivation in exercises used in prevention and rehabilitation of hamstring strain injury in young soccer players
Authors: Torres Gonzalo , Chorro David , Navandar Archit , Rueda Javier , Fernández Luís , Navarro Enrique
Published: March 2019

This study aimed to study the co-activation of hamstring-quadriceps muscles during submaximal strength exercises without the use of maximum voluntary isometric contraction testing and compare (i) the inter-limb differences in muscle activation, (ii) the intra-muscular group activation pattern, and (iii) the activation during different phases of the exercise. Muscle activation was recorded by surface electromyography of 19 elite male youth players. Participants performed five repetitions of the Bulgarian squat, lunge and the squat with an external load of 10 kg. Electrical activity was recorded for the rectus femoris, vastus medialis, vastus lateralis, biceps femoris and semitendinosus. No significant inter-limb differences were found (F1, 13=619;p=0.82; partial η2=0.045). Significant differences were found in the muscle activation between different muscles within the muscle group (quadriceps and hamstrings) for each of the exercises: Bulgarian squat (F1,18=331:p<0.001; partial η2=0.80), lunge (F4,72=114.5; p<0.001; partial η2=0.86) and squat (F1,16=247.31;p<0.001; partial η2=0.93).Differences were found between the concentric, isometric and eccentric phases of each of the exercises (F2, 26=52.27;p=0.02; partial η2=0.80). The existence of an activation pattern of each of the muscles in the three proposed exercises could be used for muscle assessment and as a tool for injury recovery.
Diet composition of introduced Barn Owls (Tyto alba javanica) in urban area in comparison with agriculture settings
Authors: Saufi Safwan , Ravindran Shakinah , Hamid Noor Hisham , Zainal Abidin Cik Mohd Rizuan , Ahmad Hamdan , Ahmad Abu Hassan , Salim Hasber
Published: March 2019

This study investigated the diet of introduced barn owls (Tyto alba javanica, Gmelin) in the urban area of the Main Campus of Universiti Sains Malaysia, Penang, Malaysia, based on collected regurgitated pellets. We also compared the diet of introduced urban barn owls with the diet of barn owls from two agricultural areas, i.e. oil palm plantations and rice fields. Pellet analysis of barn owls introduced in the urban area showed that commensal Norway rats,Rattus norvegicus, made up the highest proportion of the diet (65.37% prey biomass) while common shrews,Suncus murinuswere the second highest consumed prey (30.12% prey biomass). Common plantain squirrel,Callosciurus notatus, made up 4.45% of the diet while insects were taken in a relatively small amount (0.046% prey biomass). Introduced barn owls showed a preference for medium-sized prey, i.e. 40 to 120g (52.96% biomass and 38.71% total). In agricultural areas,Rattus argentiventerpredominated the diet of barn owls (98.24% prey biomass) in rice fields while Malayan wood rats,Rattus tiomanicus, were the most consumed prey in oil palm plantations (99.5% prey biomass). Food niche breadth value was highest for barn owls introduced in an urban area with a value of 2.90, and 1.06 in rice fields and 1.22 in oil palm plantations. Our analysis reiterates the prey preference of barn owls in various landscapes for small mammals. Our results also indicate the suitability of utilizing barn owls as a biological control not only in agricultural areas, but also as a biological control agent for commensal rodent pests in urban areas.
Multimorbidity and healthcare utilization: A register-based study in Denmark
Authors: Frølich Anne , Ghith Nermin , Schiøtz Michaela , Jacobsen Ramune , Stockmarr Anders
Published: March 2019

Background

People with multimorbidity have reduced functional capacity, lower quality of life, and higher mortality rates and use healthcare resources more intensively than healthy people or those with a single chronic condition. The aim of this study was to explore associations between multimorbidity and use of healthcare services and the impact of socioeconomic status on utilization of hospitalizations and bed days.

Methods

The study population included all individuals aged 16 years and older who lived in the Capital Region of Denmark on January 1st, 2012. Data on chronic conditions, use of healthcare services and demographics were obtained from Danish national administrative and health registries. Zero-inflated models were used to calculate anticipated annual use of hospitalizations and bed days.

Findings

The study population comprised 1,397,173 individuals; the prevalence of multimorbidity was 22%. Prevalence was inversely related to educational attainment. For people with multimorbidity, utilization of hospitalizations and bed days increased approximately linearly with the number of chronic conditions. However, a steep increase in utilization of bed days was observed between five and six or more chronic conditions. An educational gradient in hospitalization rates and use of bed days was observed regardless of the number of chronic conditions. Educational attainment was strongly associated with healthcare utilization.

Conclusion

Multimorbidity was associated with a significant increase in utilization of all healthcare services in Denmark. In addition, a socioeconomic gradient was observed in utilization of hospitalizations and bed days.
A mathematical model of Campylobacter dynamics within a broiler flock
Authors: Rawson Thomas , Dawkins Marian Stamp , Bonsall Michael B.
Published: March 2019

Globally, the bacterial genusCampylobacteris one of the leading causes of human gastroenteritis, with its primary route of infection being through poultry meat. Despite decades of study we appear to be no closer to preventing outbreaks within commercial chicken flocks, and the application of biosecurity measures is limited by a lack of understanding of the transmission dynamics within a flock. Our work is the first to undertake a mathematical modelling approach toCampylobacterpopulation dynamics within a flock of broilers (chickens bred specifically for meat). A system of stochastic differential equations is used to investigate the diverse and fluctuating conditions within the gut of a broiler, and models the routes of infection between co-housed birds. The presented model provides mechanistic explanations for key infection dynamics that have been long-observed but very poorly understood. We highlight several driving mechanisms behind observed infection phenomena, simulate experimentally observed inter-strain competition, and present a promising approach to hypothesising new methods of preventing flock outbreaks.

Author summary

The bacteriaCampylobacteris one of the most common causes of food poisoning globally. The most common route of infection is through raw chicken meat, as a result of many chicken farms across the world housing fully infected flocks. Despite the magnitude of this public health risk, little is understood of the specifics of how chickens become infected, and the ways that they then infect one another. Our work presents a mathematical model ofCampylobactertransmission dynamics within a flock of chickens. We compare the results of the model to real world data sets, explore key dynamical behaviours, and present a sensitivity analysis to highlight the most important factors underpinning outbreaks.
Managerial behavior and performance in China, the UK, and the USA
Authors: Paetzel Dennis W. , Quast Louis N. , Aroonsri Pimsiri , Surya Meida , Hart-Mrema Tasha S.
Published: March 2019

Purpose

The purpose of this study was determine which, if any, managerial behaviors were associated with high managerial job performance in three selected countries, China, the UK and the USA. After identifying which behaviors were associated with high managerial job performance, the study then compared the results from each country to identify behaviors that were unique to a country and those that recurred across multiple countries.

Design/methodology/approach

This study draws from an archival database of multisource (360°) feedback rating managerial job performance. Supervisors’ ratings on 23,877 national managers from China, the UK and the USA were examined using simultaneous stepwise regression analysis.

Findings

This study found that there were unique behaviors associated with high managerial job performance in each country examined. Additionally, the study found that were also behaviors associated with high managerial performance shared between all three countries.

Originality/value

This study offers another insight to the unique-versus-universal managerial behaviors debate in leadership development literature. Existing literature offers mixed messages regarding universal or unique behaviors across countries. Understanding which key managerial behaviors are associated with perceived high managerial job performance in each country may help to focus the development of these managers and enhance the specificity of selection, coaching, and training initiatives.
A roadmap for developing, implementing and evaluating performance management systems in Jordan public universities
Authors: Almohtaseb Ahmad Ali , Almahameed Mohmmad Adnan Yousef , Shaheen Hisham A. Kareem , Jarrar Al Khattab Mohammad Haroon
Published: March 2019

Purpose

The purpose of this paper is to formulate a model for developing, implementing and evaluating performance management systems in Jordan public universities that will ensure the successful achievement of their set goals in the competitive dynamic environment.

Design/methodology/approach

This is a conceptual paper that focuses on the model for developing, implementing and evaluating performance management systems by public universities in developing countries.

Findings

As the focus is on a conceptual model for performance management systems in public universities in developing country, it is yet to be empirically tested.

Research limitations/implications

The conceptual model is limited to developing, implementing and evaluating performance management systems by public universities in developing countries.

Practical implications

The implementation and evaluation of performance management systems by public universities in Jordan and developing countries will ensure successful achievement of their set goals in the competitive dynamic environment.

Originality/value

The originality of the paper lies in its methodology. In this paper, an innovative conceptual model is proposed for developing, implementing and evaluating performance management systems by public universities in developing countries.
Network centrality and innovation performance: the role of formal and informal institutions in emerging economies
Authors: Wang Haifeng , Zhao Yapu , Dang Beilei , Han Pengfei , Shi Xin
Published: March 2019

Purpose

The impact of network centrality on innovation performance is inconclusive. The purpose of this paper is to examine how formal and informal institutions affect the influence of network centrality on firms’ innovation performance in emerging economies by integrating social network theory and institutional theory.

Design/methodology/approach

Multisource and lagged data from 234 technology-based entrepreneurial firms listed on the Chinese Growth Enterprise Market were leveraged to test a proposed research model.

Findings

Results suggest that formal institutions (marketization) positively moderate the relationship between network centrality and innovation performance, whereas informal institutions (social cohesion) negatively moderate this relationship. Moreover, formal and informal institutions have a strong joint impact on such relationship, that is, the effect of network centrality on innovation performance is most positive when marketization is high and social cohesion is low.

Originality/value

This empirical research provides new insights into whether and how firms can grasp the innovation benefits of network centrality by exploring institutional contingencies. It further sheds on light the scope of the network centrality–innovation issue by extending its research context to Chinese entrepreneurial firms.
Better profit formulas for new business models: capital goods industries in a fragmented market
Authors: Windisch Georg
Published: March 2019

Purpose

Over the past years, traditional manufacturers of capital goods, such as Siemens, ABB and GE, have seen their business environments transform. As a response to these changes, firms began to change their business models from providing singularly developed, integrated one-off solutions to offering modular, mass-customizable systems, including increasingly sophisticated services. This paper aims to support such manufacturers in overcoming uncertainties in designing innovative profit formulas in this new approach.

Design/methodology/approach

This study is based on an 18-month research project at a multinational, multi-scope manufacturer in the capital goods industry.

Findings

To innovate profit formulas, this study recommends a three-step approach: first, categorize your customer requirements along new dimensions for each project; second, apply smart and novel combinations of competition- and value-based pricing and cost strategies within projects; and third, calculate your profits at the feature level instead of the aggregated project level. Based on this approach, managers can categorize projects through an introduced matrix tool and identify ways to improve profitability.

Research limitations/implications

Findings are applicable to the capital goods industry and to comparable sectors where vendors can tailor product features for each customer individually.

Originality/value

This study will help managers to overcome the challenge of rethinking ways of operating that are long established and, until now, very successful. It sets out a methodology – the profitability matrix – that managers can use to analyze the profitability of a specific customer offering and suggests ways to improve it based on a novel three-step approach for designing new profit formulas.
Effect of target-and-incentive-consistency of unexpected positive earnings news on investors’ responses to corporate social responsibility performance
Authors: Wang Lei
Published: March 2019

Purpose

This study examines the effect of target-and-incentive-consistency of unexpected positive earnings news on investors’ use of corporate social responsibility (CSR) performance information in their pricing decisions.

Design/methodology/approach

A 2 × 2 full factorial between-participants experiment is conducted.

Findings

Target-and-incentive-consistency of unexpected positive earnings news moderates the effect of CSR performance on investors’ pricing decisions.

Research limitations/implications

Its findings shed insights on investors’ use of a mix of CSR, financial and governance information, support the financial information elasticity effect and add to the effect of financial information on investors’ use of nonfinancial information.

Practical implications

The effect of inelastic financial information in mitigating the CSR information effect can benefit investors who do not plan to use a CSR investment strategy. Knowledge of investors’ conditional use of CSR information can benefit firm managers and policy makers.

Originality/value

Its findings support a heretofore unexamined theoretical underpinning for the effect of financial information on investors’ use of nonfinancial information.
Lanatoside C protects mice against bleomycin‐induced pulmonary fibrosis through suppression of fibroblast proliferation and differentiation
Authors: Nie Yunjuan , Zhang Dan , Jin Zhewu , Li Boyu , Wang Xue , Che Huilian , You Yaqian , Qian Xiaohang , Zhang Yang , Zhao Peng , Chai Gaoshang
Published: March 2019

It has been established that lanatoside C, a FDA‐approved cardiac glycoside, reduces proliferation of cancer cell lines. The proliferation of fibroblasts is critical to the pathogenesis of pulmonary fibrosis (PF), a progressive and fatal fibrotic lung disease lacking effective treatment. In this study we have investigated the impact of lanatoside C on a bleomycin (BLM)‐induced mouse model of PF and through the evaluation of fibroblast proliferation and activation in vitro. We evaluated explanted lung tissue by histological staining, western blot analysis, qRT‐PCR and survival analysis, demonstrating that lanatoside C was able to protect mice against BLM‐induced pulmonary fibrosis. The proliferation of cultured pulmonary fibroblasts isolated from BLM‐induced PF mice was suppressed by lanatoside C, as hypothesized, through the induction of cell apoptosis and cell cycle arrest at the G2/M phase. The Akt signalling pathway was involved in this process. Interestingly, the production of α‐SMA, fibronectin, and collagen I and III in response to TGF‐β1 in healthy mouse fibroblasts was suppressed following lanatoside C administration by inhibition of TGF‐β1/Smad signalling. In addition, TGF‐β1‐induced migration in lung fibroblasts was also impeded after lanatoside C treatment. Together, our data revealed that lanatoside C alleviated BLM‐induced pulmonary fibrosis in mice via attenuation of growth and differentiation of fibroblasts, suggesting that it has potential as a candidate therapy for PF patients.
Acid sphingomyelinase mediates the noise‐induced liver disorder in mice
Authors: Meng Xingxing , Gu Zhenghui , Xie Xiaoping , Su Yuting , Zhang Xi , Ma Hongzhe , Guo Yibin , Liu Xincheng , Cheng Yaoping , Chang Yaoming , Bao Junxiang
Published: March 2019

Noise‐induced structural and functional disorder of the liver has been realized, but the underlying mechanism remains to be characterized, which has limited the introduction of precautious measures. Over‐activation of acid sphingomyelinase (ASM)/ceramide (Cer) pathway takes centre stage in hepatocyte injury entailed by various stimulus. We aimed to investigate whether it mediated the noise elicited liver disorder on infrastructure, lipid metabolism, apoptosis, and oxidative stress. Mice were exposed to broad band noise (20–20k Hz, 90–110 dB) for 1, 3, 5 or 7 days by 3 hr/d. Doxepin hydrochloride (DOX), an ASM inhibitor was given by 5 mg/kg/d gavage. We showed that 5 or 7 days intense, broad band noise exposure caused significant infrastructure derangement and lipid droplets storage in hepatocytes. The content of cholesterol, free fatty acids or triglyceride was increased significantly in liver tissue upon noise stimulation. Moreover, the noise promoted apoptosis and superoxide generation in hepatocytes significantly, enhancing activity of aspartate aminotransferase (AST) or alanine amino transferase (ALT) in serum. Acid sphingomyelinase activity and Cer generation in liver tissue were elevated by noise exposure, which was normalized with DOX administrated. Accordingly, DOX alleviated steatosis, apoptosis, oxidative stress and enzymatic change in hepatocytes or serum of noise exposed mice substantially. In summary, our results suggest the ASM/Cer pathway contributes to the broad band noise elicited liver damage in mice.
Aged‐senescent cells contribute to impaired heart regeneration
Authors: Lewis‐McDougall Fiona C. , Ruchaya Prashant J. , Domenjo‐Vila Eva , Shin Teoh Tze , Prata Larissa , Cottle Beverley J. , Clark James E. , Punjabi Prakash P. , Awad Wael , Torella Daniele , Tchkonia Tamara , Kirkland James L. , Ellison‐Hughes Georgina M.
Published: March 2019

Aging leads to increased cellular senescence and is associated with decreased potency of tissue‐specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32–86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16INK4A, SA‐β‐gal, DNA damage γH2AX, telomere length, senescence‐associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. SASP factors secreted by senescent CPCs renders otherwise healthy CPCs to senescence. Elimination of senescent CPCs using senolytics abrogates the SASP and its debilitative effect in vitro. Global elimination of senescent cells in aged mice (INK‐ATTAC or wild‐type mice treated with D + Q senolytics) in vivo activates resident CPCs and increased the number of small Ki67‐, EdU‐positive cardiomyocytes. Therapeutic approaches that eliminate senescent cells may alleviate cardiac deterioration with aging and restore the regenerative capacity of the heart.