bluuebunny/crossref_metadata_2025 huggingface dataset:
Developmental and cell-specific expression ofCacna1dsplice variants
Authors: Brianna LaCarubba , Alexandra Bunda , Kitty Savage , Hannah Sargent , Marie Akiki , Thomas Foxall , Arturo Andrade
Published: April 2019

CaV1.3 is an L-type voltage-gated calcium channel implicated in several functions including gene expression, pacemaking activity, and neurotransmitter release. The gene that encodes the CaVα1-pore forming subunit of CaV1.3 (Cacna1d) is a multi-exon gene that undergoes extensive alternative splicing, which provides functional versatility to this gene across tissues and cell-types. The function and expression of severalCacna1dsplice variants within the C-terminus have been previously characterized. These splice variants differ in their voltage-dependence of activation, Ca2+-dependent inactivation, and their sensitivity to dihydropyridines. However, less is known about alternatively spliced exons inCacna1dlocated downstream of domain I and upstream of the C-terminus (e11, e22a/e22, e31a/e31b/e32). Here, we performed a systematic study to determine the developmental and cell-specific expression of severalCacna1dsplice variants. We found that the cassette e11 is upregulated during brain development, and in adult cortical tissue is more abundant in excitatory neurons relative to inhibitory interneurons. This exon is also upregulated upon nerve growth factor (NGF) induced differentiation of pheochromocytoma cells, PC12. At the functional level, the splice variants resulting from e11 alternative splicing (+e11-Cacna1dand Δe11-Cacna1d) form functional CaV1.3 channels with similar biophysical properties in expression mammalian systems. Of the pair of mutually exclusive exons, e22a and e22, the later dominates at all stages. However, we observed a slight upregulation of e22 from embryonic to adult human brain. A second pair of mutually exclusive exons, e31a and e31b, was also studied. We found that e31a increases during brain development. Finally, the cassette exon 32 is repressed in adult brain tissue.
The RNA binding protein DAZL functions as repressor and activator of maternal mRNA translation during oocyte maturation
Authors: Yang Cai-Rong , Rajkovic Gabriel , Daldello Enrico Maria , Luong Xuan G. , Chen Jing , Conti Marco
Published: April 2019

Deleted in azoospermia like (DAZL) is an RNA-binding protein playing critical function during gamete development. In fully-grown oocytes, DAZL protein is detected in prophase and levels increase four to five fold during reentry into the meiotic cell cycle. Here, we have investigated the functional significance of this DAZL accumulation in maturing oocytes. Oocyte depletion of DAZL prevents progression to MII. This maturation block is associated with widespread disruption in the pattern of maternal transcripts loading on ribosomes and their translation measured using a RiboTag IP/RNASeq or qPCR strategy. In addition to decreased ribosome loading of a subset of transcripts, we found that DAZL depletion causes also translational activation of distinct subset of mRNAs. DAZL binds to mRNAs whose translation is both repressed and activated during oocyte maturation. Unexpectedly, DAZL depletion also causes increased ribosome loading of a subset of mRNAs in quiescent GV-arrested oocytes. This dual role of repression and activation is recapitulated by using YFP reporters including the 3’UTR of DAZL targets. Injection of recombinant DAZL protein in DAZL-depleted oocytes rescues the translation of these targets as well as maturation to MII. Mutagenesis of putative DAZL-binding sites in these candidate mRNAs mimics the effect of DAZL depletion. These findings demonstrate that DAZL regulates translation of maternal mRNAs in mature oocytes, functioning both as translational repressor and activator.
Raptor genomes reveal evolutionary signatures of predatory and nocturnal lifestyles
Authors: Cho Yun Sung , Jun JeHoon , Kim Jung A , Kim Hak-Min , Chung Oksung , Kang Seung-Gu , Park Jin-Young , Kim Hwa-Jung , Kim Sunghyun , Kim Hee-Jong , Jang Jin-ho , Na Ki-Jeong , Kim Jeongho , Park Seung Gu , Lee Hwang-Yeol , Manica Andrea , Mindell David P. , Fuchs Jérôme , Edwards Jeremy S. , Weber Jessica A. , Witt Christopher C. , Yeo Joo-Hong , Kim Soonok , Bhak Jong
Published: April 2019

Background

Birds of prey (raptors) are dominant apex predators in terrestrial communities, with hawks (Accipitriformes) and falcons (Falconiformes) hunting by day, and owls (Strigiformes) hunting by night.

Results

Here, we report new genomes and transcriptomes for 20 species of birds, including 16 species of birds of prey, and high-quality reference genomes for the Eurasian eagle-owl (Bubo bubo), oriental scops-owl (Otus sunia), eastern buzzard (Buteo japonicus), and common kestrel (Falco tinnunculus). Our extensive genomic analysis and comparisons with non-raptor genomes identified common molecular signatures that underpin anatomical structure and sensory, muscle, circulatory, and respiratory systems related to a predatory lifestyle. Compared with diurnal birds, owls exhibit striking adaptations to the nocturnal environment, including functional trade-offs in the sensory systems (e.g., loss of color vision genes and selection for enhancement of nocturnal vision and other sensory systems) that are probably convergent with other nocturnal avian orders. Additionally, we found that a suite of genes associated with vision and circadian rhythm were differentially expressed between nocturnal and diurnal raptors, indicating adaptive expression change during the transition to nocturnality.

Conclusions

Overall, raptor genomes showed genomic signatures associated with the origin and maintenance of several specialized physiological and morphological features essential to be apex predators.
A generalization of partial least squares regression and correspondence analysis for categorical and mixed data: An application with the ADNI data
Authors: Beaton Derek ,   ADNI, Saporta Gilbert , Abdi Hervé
Published: April 2019

Current large scale studies of brain and behavior typically involve multiple populations, diverse types of data (e.g., genetics, brain structure, behavior, demographics, or “mutli-omics,” and “deep-phenotyping”) measured on various scales of measurement. To analyze these heterogeneous data sets we need simple but flexible methods able to integrate the inherent properties of these complex data sets. Here we introduce partial least squares-correspondence analysis-regression (PLS-CA-R) a method designed to address these constraints. PLS-CA-R generalizes PLS regression to most data types (e.g., continuous, ordinal, categorical, non-negative values). We also show that PLS-CA-R generalizes many “two-table” multivariate techniques and their respective algorithms, such as various PLS approaches, canonical correlation analysis, and redundancy analysis (a.k.a. reduced rank regression).
Tomato spotted wilt virusmanipulates the reproduction of its insect vector, western flower thrips (Frankliniella occidentalis), to facilitate transmission
Authors: Wan Yanran , Hussain Sabir , Xu Baoyun , Xie Wen , Wang Shaoli , Zhang Youjun , Zhou Xuguo , Wu Qingjun
Published: April 2019

BACKGROUND

Tomato spotted wilt virus(TSWV), one of the most devastating viruses of ornamental plants and vegetable crops worldwide, is transmitted by the western flower thrips,Frankliniella occidentalis(Pergande), in a persistent-propagative manner. How TSWV manipulates the reproduction of its vector to enhance transmission and whether infection with TSWV changes the mating behaviour of this thrips vector are not fully understood.

RESULTS

In this study, we found that TSWV-exposed thrips, in general, had a significantly longer developmental time than did non-exposed individuals. Such an increase was predominantly seen in adults, a stage associated with dispersal and virus transmission. TSWV-exposedF. occidentalis produced substantially more progeny than did non-exposed thrips. Interestingly, most of the increase in progeny came from an increase in males, a sex with a greater dispersal and virus transmission capability. Specifically, the sex ratio of progeny shifted from female biased (2-7:1) to evenly split or male biased. Regarding mating behaviour, compared to virus-free controls, TSWV-exposedF. occidentalis had significantly longer copulation duration, were more active in males, and remated less often in females.

CONCLUSION

These combined results suggest that TSWV alters the reproductive behaviour of its insect vector,F. occidentalis, to promote virus transmission. Consequently, a monitoring program capable of earlier detection of the virus and a reduced economic threshold for vector (thrips) control should be in consideration for the long-term, sustainable management of TSWV.
Streptococcus pneumoniae evades host cell phagocytosis and limits host mortality through its cell wall anchoring protein PfbA
Authors: Yamaguchi Masaya , Hirose Yujiro , Takemura Moe , Ono Masayuki , Sumitomo Tomoko , Nakata Masanobu , Terao Yutaka , Kawabata Shigetada
Published: April 2019

Streptococcus pneumoniae is a Gram-positive bacterium belonging to the oral streptococcus species, mitis group. This pathogen is a leading cause of community-acquired pneumonia, which often evades host immunity and causes systemic diseases, such as sepsis and meningitis. Previously, we reported that PfbA is a β-helical cell surface protein contributing to pneumococcal adhesion to and invasion of human epithelial cells in addition to its survival in blood. In the present study, we investigated the role of PfbA in pneumococcal pathogenesis. Phylogenetic analysis indicated that the pfbA gene is specific to S. pneumoniae within the mitis group. Our in vitro assays showed that PfbA inhibits neutrophil phagocytosis, leading to pneumococcal survival. We found that PfbA activates NF-κB through TLR2, but not TLR4. In addition, TLR2/4 inhibitor peptide treatment of neutrophils enhanced the survival of the S. pneumoniae ΔpfbA strain as compared to a control peptide treatment, whereas the treatment did not affect survival of a wild-type strain. In a mouse pneumonia model, the host mortality and level of TNF-α in bronchoalveolar lavage fluid were comparable between wild-type and ΔpfbA-infected mice, while deletion of pfbA increased the bacterial burden in bronchoalveolar lavage fluid. In a mouse sepsis model, the ΔpfbA strain demonstrated significantly increased host mortality and TNF-α levels in plasma, but showed reduced bacterial burden in lung and liver. These results indicate that PfbA may contribute to the success of S. pneumoniae species by inhibiting host cell phagocytosis, excess inflammation, and mortality.

Importance

Streptococcus pneumoniae is often isolated from the nasopharynx of healthy children, but the bacterium is also a leading cause of pneumonia, meningitis, and sepsis. In this study, we focused on the role of a cell wall anchoring protein, PfbA, in the pathogenesis of S. pneumoniae-related disease. We found that PfbA is a pneumococcus-specific anti-phagocytic factor that functions as a TLR2 ligand, indicating that PfbA may represent a pneumococcal-specific therapeutic target. However, a mouse pneumonia model revealed that PfbA deficiency reduced the bacterial burden, but did not decrease host mortality. Furthermore, in a mouse sepsis model, PfbA deficiency increased host mortality. These results suggest that S. pneumoniae optimizes reproduction by regulating host mortality through PfbA; therefore, PfbA inhibition would not be an effective strategy for combatting pneumococcal infection. Our findings underscore the challenges involved in drug development for a bacterium harboring both commensal and pathogenic states.
Hybridization preceded radiation in diploid wheats
Authors: Huynh Stella , Marcussen Thomas , Felber François , Parisod Christian
Published: April 2019

Evolutionary relationships among theAegilops-Triticumrelatives of cultivated wheats have been difficult to resolve owing to incomplete lineage sorting and reticulate evolution. Recent studies have suggested that the wheat D-genome lineage (progenitor ofAe. tauschii) originated through homoploid hybridization between the A-genome lineage (progenitor ofTriticums.str.) and the B-genome lineage (progenitor ofAe. speltoides). Scenarios of reticulation have been debated, calling for adequate phylogenetic analyses based on comprehensive sampling. To reconstruct the evolution ofAegilops-Triticumdiploids, we here combined high-throughput sequencing of 38 nuclear low-copy loci of multiple accessions of all 13 species with inferences of the species phylogeny using the full-parameterized MCMC_SEQ method. Phylogenies recovered a monophyleticAegilops-Triticumlineage that began diversifying ~6.5 Ma ago and gave rise to four sublineages, i.e. the A- (2 species), B- (1 species), D- (9 species) and T- (Ae. mutica) genome lineage. Full-parameterized phylogenies as well as patterns of tree dilation and tree compression supported a hybrid origin of the D-genome lineage from A and B ~4.1 Ma ago, and did not indicate additional hybridization events. This comprehensive and dated phylogeny of wheat relatives indicates that the origin of the hybrid D-genome was followed by intense diversification into almost all diploid as well as allopolyploid wild wheats.
Investigating Population-scale Allele Specific Expression in Wild Populations of Oithona similis (Cyclopoida, Claus 1866)
Authors: Laso-Jadart Romuald , Sugier Kevin , Petit Emmanuelle , Labadie Karine , Peterlongo Pierre , Ambroise Christophe , Wincker Patrick , Jamet Jean-Louis , Madoui Mohammed-Amin
Published: April 2019

Allele-specific expression (ASE) is a widely studied molecular mechanism at cell, tissue and organism levels. Here, we extrapolated the concept of ASE to the population-scale (psASE), aggregating ASEs detected at smaller scales. We developed a novel approach to detect psASE based on metagenomic and metatranscriptomic data of environmental samples containing communities of organisms. This approach which measures the deviation between the frequency and the relative expression of biallelic loci, was applied on samples collected during the Tara Oceans expedition (2009-2013), in combination to new Oithona similis transcriptomes, a widespread marine copepod. Among a total of 25,768 single nucleotide variants (SNVs) of O. similis, 587 (2.3%) were targeted by psASE in at least one population. The distribution of SNVs targeted by psASE in different populations is significantly shaped by population genomic differentiation (p-value = 9.3×10−9), supporting a partial genetic control of psASE. To investigate the link between evolution and psASE, loci under selection were compared to loci under psASE. A significant amount of SNVs (0.6%) were targeted by both selection and psASE (p-values < 9.89×10−3), supporting the hypothesis that natural selection and ASE may lead to the same phenotype. Population-scale ASE offers new insights into the gene regulation control in populations and its link with natural selection.
Computing wide range of protein/peptide features from their sequence and structure
Authors: Pande Akshara , Patiyal Sumeet , Lathwal Anjali , Arora Chakit , Kaur Dilraj , Dhall Anjali , Mishra Gaurav , Kaur Harpreet , Sharma Neelam , Jain Shipra , Usmani Salman Sadullah , Agrawal Piyush , Kumar Rajesh , Kumar Vinod , Raghava Gajendra P.S.
Published: April 2019

Motivation

In last three decades, a wide range of protein descriptors/features have been discovered to annotate a protein with high precision. A wide range of features have been integrated in numerous software packages (e.g., PROFEAT, PyBioMed, iFeature, protr, Rcpi, propy) to predict function of a protein. These features are not suitable to predict function of a protein at residue level such as prediction of ligand binding residues, DNA interacting residues, post translational modification etc.

Results

In order to facilitate scientific community, we have developed a software package that computes more than 50,000 features, important for predicting function of a protein and its residues. It has five major modules for computing; composition-based features, binary profiles, evolutionary information, structure-based features and patterns. The composition-based module allows user to compute; i) simple compositions like amino acid, dipeptide, tripeptide; ii) Properties based compositions; iii) Repeats and distribution of amino acids; iv) Shannon entropy to measure the low complexity regions; iv) Miscellaneous compositions like pseudo amino acid, autocorrelation, conjoint triad, quasi-sequence order. Binary profile of amino acid sequences provides complete information including order of residues or type of residues; specifically, suitable to predict function of a protein at residue level. Pfeature allows one to compute evolutionary information-based features in form of PSSM profile generated using PSIBLAST. Structure based module allows computing structure-based features, specifically suitable to annotate chemically modified peptides/proteins. Pfeature also allows generating overlapping patterns and feature from whole protein or its parts (e.g., N-terminal, C-terminal). In summary, Pfeature comprises of almost all features used till now, for predicting function of a protein/peptide including its residues.

Availability

It is available in form of a web server, named as Pfeature (https://webs.iiitd.edu.in/raghava/pfeature/), as well as python library and standalone package (https://github.com/raghavagps/Pfeature) suitable for Windows, Ubuntu, Fedora, MacOS and Centos based operating system.
Unique Neurophysiological Vulnerability of Visual Attention Networks to Acute Inflammation
Authors: Balter Leonie JT , Bosch Jos A , Aldred Sarah , Drayson Mark T , van Zanten Jet JCS Veldhuijzen , Higgs Suzanne , Raymond Jane E , Mazaheri Ali
Published: April 2019

Illness is often accompanied by perceived cognitive sluggishness, a symptom that may stem from immune system activation. The current study used electroencephalography (EEG) to assess how inflammation affected three different distinct attentional processes: alerting, orienting and executive control. In a double-blinded placebo-controlled within-subjects design (20 healthy males, mean age = 24.5, SD = 3.4), Salmonella typhoid vaccination (0.025 mg; Typhim Vi, SanofiPasteur) was used to induce transient mild inflammation, while a saline injection served as a placebo-control. Participants completed the Attention Network Test with concurrent EEG recorded six hours post-injection. Analyses focused on behavioral task performance and on modulation of oscillatory EEG activity in the alpha band (9-12 Hz) for alerting as well as orienting attention and frontal theta band (4-8 Hz) for executive control. Vaccination induced mild systemic inflammation, as assessed by interleukin-6 (IL-6) levels. While no behavioral task performance differences between the inflammation and placebo condition were evident, inflammation caused significant alterations to task-related brain activity. Specifically, inflammation produced greater cue-induced suppression of alpha power in the alerting aspect of attention while individual variation in the inflammatory response was significantly correlated with the degree of alpha power suppression. Notably, inflammation did not affect orienting (i.e., alpha lateralization) or executive control (i.e., frontal theta activity). These results reveal a unique neurophysiological vulnerability to acute mild inflammation of the neural network that underpins attentional alerting functions. Observed in the absence of performance decrements, these novel findings suggest that acute inflammation requires individuals to exert greater cognitive effort when preparing for a task in order to maintain adequate behavioral performance.

Highlights

Typhoid vaccination induced a transient mild inflammatory state

Mild inflammation alters neurophysiological process associated with attention

Mild inflammation selectively increased alerting-related alpha suppression while behavior was unaffected

A greater inflammatory response was correlated with more alpha suppression
Deficiency in the autophagy modulator Dram1 exacerbates pyroptotic cell death of Mycobacteria-infected macrophages
Authors: Zhang Rui , Varela Monica , Forn-Cuni Gabriel , Torraca Vincenzo , van der Vaart Michiel , Meijer Annemarie H.
Published: April 2019

DNA Damage Regulated Autophagy Modulator 1 (DRAM1) is a stress-inducible regulator of autophagy and cell death. DRAM1 has been implicated in cancer, myocardial infarction, and infectious diseases, but the molecular and cellular functions of this transmembrane protein remain poorly understood. Previously, we have proposed DRAM1 as a host resistance factor for tuberculosis (TB) and a potential target for host-directed anti-infective therapies. In this study, we generated a zebrafish dram1 mutant and investigated its loss-of-function effects during Mycobacterium marinum (Mm) infection, a widely used model in TB research. In agreement with previous knockdown analysis, dram1 mutation increased the susceptibility of zebrafish larvae to Mm infection. RNA sequencing revealed major effects of Dram1 deficiency on metabolic, immune response, and cell death pathways during Mm infection, whereas only minor effects on proteinase and metabolic pathways were found under uninfected conditions. Furthermore, unchallenged dram1 mutants did not display overt autophagic defects, but autophagic targeting of Mm was reduced in absence of Dram1. The phagocytic ability of macrophages in dram1 mutants was unaffected, but acidification of Mm-containing vesicles was strongly reduced, indicating that Dram1 is required for phagosome maturation. By in vivo imaging we observed that Dram1-deficient macrophages fail to restrict Mm during early stages of infection. The resulting increase in bacterial burden could be reverted by knockdown of inflammatory caspase a (caspa) and gasdermin Eb (gsdmeb), demonstrating pyroptosis as the mechanism underlying premature cell death of Mm-infected macrophages in dram1 mutants. Collectively, these data demonstrate that dissemination of mycobacterial infection in zebrafish larvae is promoted in absence of Dram1 due to reduced maturation of mycobacteria-containing vesicles, failed intracellular containment, and consequent pyroptotic cell death of infected macrophages. These results provide new evidence that Dram1 plays a central role in host resistance to intracellular infection, acting at the crossroad of autophagy and cell death.
Sequence Analysis and Homology Modelling of SmHQT Protein, a Key Player in Chlorogenic Acid Pathway of Eggplant
Authors: Kaushik Prashant , Saini Dinesh Kumar
Published: April 2019

Eggplant is an important vegetable that belongs to family Solanaceae. Fruits of eggplant are rich in phenolic acids. Chlorogenic acid makes up to 90 per cent of total phenolic acids present in the eggplants fruit flesh. Eggplant hydroxycinnamoyl CoA-quinate (SmHQT) is the central enzyme that modulates the last step of the chlorogenic acid pathway of eggplant. Here, we have analysed the sequence of eggplant SmHQT protein in eggplant. The sequence obtained from the NCBI was aligned using MUSCLE. After that, homology modelling was performed using MODELLER 9v15. Model with Dope Z-Score of −1.596 was selected and verified for viability under real conditions using several online tools. Also, the docking was performed with this model. Overall, this could be useful in developing eggplant varieties rich in phenolic acids especially chlorogenic acid.
Hippocampal subfields revealed through unfolding and unsupervised clustering of laminar and morphological features in 3D BigBrain
Authors: DeKraker J. , Lau J.C. , Ferko K.M. , Khan A.R. , Köhler S.
Published: April 2019

The internal structure of the human hippocampus is challenging to map using histology or neuroimaging due to its complex archicortical folding. Here, we aimed to overcome this challenge using a unique combination of three methods. First, we leveraged a histological dataset with unprecedented 3D coverage, 3D BigBrain. Second, we imposed a computational unfolding framework that respects the topological continuity of hippocampal subfields, which are traditionally defined by laminar composition. Third, we adapted neocortical parcellation techniques to map the hippocampus with respect to not only laminar but also morphological features. Unsupervised clustering of these features revealed subdivisions that closely resemble ground-truth manual subfield segmentations. Critically, we also show that morphological features alone are sufficient to derive most hippocampal subfield boundaries. Moreover, some features showed differences within subfields along the hippocampal longitudinal axis. Our findings highlight new characteristics of internal hippocampal structure, and offer new avenues for its characterization with in-vivo neuroimaging.
Precocious Chondrocyte Differentiation Disrupts Skeletal Growth in Kabuki Syndrome Mice
Authors: Fahrner Jill A. , Lin Wan-Ying , Riddle Ryan C. , Boukas Leandros , DeLeon Valerie B. , Chopra Sheetal , Lad Susan E. , Luperchio Teresa Romeo , Hansen Kasper D. , Bjornsson Hans T.
Published: April 2019

Kabuki syndrome 1 (KS1) is a Mendelian disorder of the epigenetic machinery caused by mutations in the gene encoding KMT2D, which methylates lysine 4 on histone H3 (H3K4). KS1 is characterized by intellectual disability, postnatal growth retardation, and distinct craniofacial dysmorphisms. A mouse model (Kmt2d+/ β Geo) exhibits features of the human disorder and has provided insight into other phenotypes; however, the mechanistic basis of skeletal abnormalities and growth retardation remains elusive. Using high-resolution micro-computed tomography we show thatKmt2d+/βGeomice have shortened long bones and ventral bowing of skulls.In vivoexpansion of growth plates within both the skull and long bones suggests disrupted endochondral ossification as a common disease mechanism. Stable chondrocyte cell lines harboring inactivating mutations inKmt2dexhibit increased proliferation and differentiation, which further supports this mechanism. A known inducer of chondrogenesis, SOX9, and its targets show markedly increased expression inKmt2d-/-chondrocytes. By transcriptome profiling, we identifyShox2as a putative KMT2D target. We propose that decreased KMT2D-mediated H3K4me3 atShox2releasesSox9inhibition and thereby leads to enhanced chondrogenesis, providing a novel and plausible explanation for precocious chondrocyte differentiation. Our findings not only provide insight into the pathogenesis of growth retardation in KS1, but also suggest novel therapeutic targets to rescue growth retardation in KS1 and related disorders.
Muscle oxygenation maintained during repeated sprints despite inspiratory muscle loading
Authors: Rodriguez Ramón F. , Townsend Nathan E. , Aughey Robert J. , Billaut François
Published: April 2019

A high work of breathing can compromise limb oxygen delivery during sustained high-intensity exercise. However, it is unclear if the same is true for intermittent sprint exercise. This project examined the addition of an inspiratory load on locomotor muscle tissue reoxygenation during repeated-sprint exercise. Ten healthy males completed three experimental sessions of ten 10 s sprints, separated by 30 s of passive rest on a cycle ergometer. The first two sessions were “all-out’ efforts performed without (CTRL) or with inspiratory loading (INSP) in a randomised and counterbalanced order. The third experimental session (MATCH) consisted of ten 10 s work-matched intervals. Tissue saturation index (TSI) and deoxy-haemoglobin (HHb) of the vastus lateralis and sixth intercostal space was monitored with near-infrared spectroscopy. Vastus lateralis reoxygenation (ΔReoxy) was calculated as the difference from peak HHb (sprint) to nadir HHb (recovery). Total mechanical work completed was similar between INSP and CTRL (effect size: −0.18, 90% confidence limit ±0.43), and differences in vastus lateralis TSI during the sprint (−0.01, ±0.33) and recovery (−0.08, ±0.50) phases were unclear. There was also no meaningful difference in ΔReoxy (0.21, ±0.37). Intercostal HHb was higher in the INSP session compared to CTRL (0.42, ±0.34), whilst the difference was unclear for TSI (−0.01, ±0.33). During MATCH exercise, differences in vastus lateralis TSI were unclear compared to INSP for both sprint (0.10, ±0.30) and recovery (−0.09, ±0.48) phases, and there was no meaningful difference in ΔReoxy (−0.25, ±0.55). Intercostal TSI was higher during MATCH compared to INSP (0.95, ±0.53), whereas HHb was lower (−1.09, ±0.33). The lack of difference in ΔReoxy between INSP and CTRL suggests that for intermittent sprint exercise, the metabolic O2demands of both the respiratory and locomotor muscles can be met. Additionally, the similarity of the MATCH suggests that ΔReoxy was maximal in all exercise conditions.
A parallel cell-cycle entry pathway with inverted G1 signaling and alternate point of no return
Authors: Liu Chad , Konagaya Yumi , Chung Mingyu , Daigh Leighton H. , Fan Yilin , Won Yang Hee , Terai Kenta , Matsuda Michiyuki , Meyer Tobias
Published: April 2019

Cell-cycle entry relies on an orderly progression of signaling events. To start, cells first activate the kinase cyclin D-CDK4/6, which leads to eventual inactivation of the retinoblastoma protein Rb. Hours later, cells inactivate APC/CCDH1and cross the final commitment point. However, many cells with genetically deleted cyclin Ds, which activate and confer specificity to CDK4/6, can compensate and proliferate. Despite its importance in cancer, how this alternate pathway operates and whether wild-type cells use this pathway remain unknown. Here, using single-cell microscopy, we demonstrate that cells with acutely inhibited CDK4/6 enter the cell cycle with slowed and fluctuating cyclin E-CDK2 activity. Surprisingly, in this alternate pathway, the order of APC/CCDH1and Rb inactivation is inverted in both cell lines and wild-type mice. Finally, we show that as a consequence of the signaling inversion, Rb inactivation replaces APC/CCDH1inactivation as the point of no return. Together, we provide molecular characterization of a parallel cell-cycle entry pathway, and reveal temporal plasticity that underlies the G1 regulatory circuit.
COUSIN (COdon Usage Similarity INdex): A normalized measure of Codon Usage Preferences
Authors: Bourret Jérôme , Alizon Samuel , Bravo Ignacio G.
Published: April 2019

Codon Usage Preferences (CUPrefs) describe the unequal usage of synonymous codons at the gene, genomic region or genome scale. Numerous indices have been developed to measure the CUPrefs of a sequence. We introduce a normalized index to calculate CUPrefs called COUSIN for COdon Usage Similarity INdex. This index compares the CUPrefs of a query against those of a reference dataset and normalizes the output over a Null Hypothesis of random codon usage. COUSIN results can be easily interpreted, quantitatively and qualitatively. We exemplify the use of COUSIN and highlight its advantages with an analysis on the complete coding sequences of eight divergent genomes, two of them with extreme nucleotide composition. Strikingly, COUSIN captures a hitherto unreported bimodal distribution in CUPrefs in genes in the human and in the chicken genomes. We show that this bimodality can be explained by the global nucleotide composition bias of the chromosome in which the gene resides, and by the precise location within the chromosome. Our results highlight the power of the COUSIN index and uncover unexpected characteristics of the CUPrefs in human and chicken. An eponymous tool written in python3 to calculate COUSIN is available for online or local use.
Membrane Protrusion Formation Mediated by Rho/ROCK Signalling and Modulation of Chloride Flux
Authors: Hori Akiko , Nishide Kenji , Yasukuni Yuki , Haga Kei , Kakuta Wataru , Ishikawa Yasuyuki , Hayes Matthew J , Ohnuma Shin-ichi , Kiyonari Hiroshi , Kimura Kazuhiro , Kondo Toru , Sasai Noriaki
Published: April 2019

Membrane protrusion is an important structural property associated with various cellular functions. The pentaspan membrane protein Prominin-1 (Prom1/CD133) is known to be localised to the protrusions and plays a pivotal role in migration and the determination of cellular morphology; however, the underlying mechanisms have been elusive. Here, we demonstrate that Prom1 is sufficient to trigger membrane protrusion formation. Overexpression of Prom1 in the RPE-1 cells triggers multiple long cholesterol-enriched protrusions, independently from actin and tubulin polymerisation. For this protrusion formation, the five amino acid stretch located at the carboxyl cytosolic region is essential. Moreover, the small GTPase Rho and its effector kinase ROCK are essential for this protrusion formation, and the intersection point of active Rho and Prom1 is where the protrusion formation initiates. Importantly, Prom1 causes the chloride ion efflux induced by calcium ion uptake, and protrusion formation is closely associated with the chloride efflux activity. Altogether, this study has elucidated that Prom1 plays critical roles for the membrane morphology and chloride ion flux.
Pangenome analysis reveals genetic isolation inCampylobacter hyointestinalissubspecies adapted to different mammalian hosts
Authors: Costa Daniela , Lévesque Simon , Kumar Nitin , Fresia Pablo , Ferrés Ignacio , Lawley Trevor D. , Iraola Gregorio
Published: April 2019

Campylobacter hyointestinalisis an emerging pathogen currently divided in two subspecies:C. hyointestinalissubsp.lawsoniiwhich is restricted to pigs, andC. hyointestinalissubsp.hyointestinaliswhich can be found in a much wider range of mammalian hosts. DespiteC. hyointestinalishas been reported as an emerging pathogen, its evolutionary and host-associated diversification patterns are still vastly unexplored. For this reason, we whole-genome sequenced 13C. hyointestinalissubsp.hyointestinalisstrains and performed a comprehensive comparative analysis including publicly available genomes ofC. hyointestinalissubsp.hyointestinalisandC. hyointestinalissubsp.lawsoniito gain insight into the genomic variation of these differentially-adapted subspecies. Both subspecies are distinct phylogenetic lineages which present a barrier to homologous recombination, suggesting genetic isolation. This is further supported by accessory gene patterns that recapitulate the core genome phylogeny. Additionally,C. hyointestinalissubsp.hyointestinalispresents a bigger and more diverse accessory genome, which probably reflects its capacity to colonize different mammalian hosts unlikeC. hyointestinalissubsp.lawsoniithat is host-restricted. This greater plasticity in the accessory genome ofC. hyointestinalissubsp.hyointestinaliscorrelates to a higher incidence of genome-wide recombination events, that may be the underlying mechanism driving its diversification. Concordantly, both subspecies present distinct patterns of gene families involved in genome plasticity and DNA repair like CRISPR-associated proteins and restriction-modification systems. Together, our results provide an overview of the genetic mechanisms shaping the genomes ofC. hyointestinalissubspecies, contributing to understand the biology ofCampylobacterspecies that are increasingly found as emerging pathogens.
Resolution of the proteome, transcript and ionome dynamics upon Zn re-supply in Zn-deficient Arabidopsis
Authors: Arsova Borjana , Amini Sahand , Scheepers Maxime , Baiwir Dominique , Mazzucchelli Gabriel , Carnol Monique , Bosman Bernard , Motte Patrick , de Pauw Edwin , Watt Michelle , Hanikenne Marc
Published: April 2019

Regulation of plant Zn acquisition is poorly understood, while Zn deficiency affects over 2 billion people worldwide. We therefore dissected the dynamic response to changes in Zn supply in Arabidopsis.

Hydroponically-grown Zn starved plants were re-supplied with Zn. Subsequent time-resolved sampling strategy allowed concomitant quantification of the dynamics of Zn uptake, microsomal and soluble proteins, and specific transcripts, in space (roots and shoots) and time.

Zn accumulates in roots within 10min, but 8h are needed before shoot Zn increases. By 8h, root Zn concentration was ~60% of non-starved plants. Overexpressed root Zn transporters further peaked in 10-30min post re-supply, before reaching a minimum in 120min and 200 ppm Zn. Zn-responding signaling/regulatory molecules include receptor and MAP kinases, calcium signaling proteins, phosphoinositides, G-proteins, COP9 signalosome members, as well as multiple transcription factors.

Zn acquisition is a highly controlled dynamic process. Our study identifies novel players in Zn homeostasis and points to cross-talk with other nutrients. It paves the way for directed investigation of so far omitted candidates which dynamically respond to sudden changes in Zn supply but are expressed at similar levels at steady-state Zn deficiency and sufficiency.
Impact of demonetization on diffusion of mobile payment service in India
Authors: Sobti Neharika
Published: April 2019

Purpose

The purpose of this paper is to explore the antecedents of the behavioral intention and adoption of mobile payment services like m-wallets and m-banking by users in India. This is done by examining the diffusion of mobile payment technology within an extended framework of the Unified Theory of Acceptance and Use of Technology (UTAUT) model. The study attempts to extend the UTAUT model further by introducing three more constructs, namely- perceived cost, perceived risk and demonetization effect and analyzes the impact of demonetization that happened in India from November 8, 2016 to December 30, 2016 on the mobile payment service adoption process. Demonetization event is a case in point to assess whether forced adoption breaks the normal diffusion process or lends support to the same in the long term.

Design/methodology/approach

A survey was conducted in order to gauge the intention behind the adoption of mobile payment modes by users in India. The questionnaire was administered online solely and 880 responses were received within a period of 20 days from February 3, 2017, to February 23, 2017, using Google Forms as a medium. Usable responses were 640. The study adopted partial least square based structural equation modeling (PLS-SEM) technique to analyze the relation between latent variables: performance expectation, effort expectation, social influence, facilitating conditions, perceived cost, perceived risk, demonetization effect, behavioral intention and usage. For this purpose, SmartPLS3.0 software was used to create path diagrams and calculate estimate the significance of factor loadings using the bootstrap technique.

Findings

The key results indicates that behavioral intention, demonetization and facilitating conditions have a positive and significant impact on the adoption of mobile payment services in India. Overall, Model 3, which was extended UTAUT model, was observed to be a better model in explaining the antecedents of behavioral intention and usage. In addition to UTAUT antecedents, perceived cost and perceived risk proved to have additional explanatory power as antecedents of behavioral intention. Age acts as a moderating variable consistently across three models, implying that younger users give more importance to effortless interface of mobile payment services and get more influenced by peers and society that shapes their intention to use mobile payment services.

Originality/value

It is first of its kind attempt to assess the role of Demonetization in examining the antecedents of behavioral intention and adoption of mobile payment services by users in India under an extended UTAUT model. This study comprehensively examined the impact of forced adoption of mobile payment services by users in India in a natural setting provided by demonetization event that took place in India by conducting a primary survey right itself in the month of February, 2017 to get first hand response from the Indian users.
Reconciling the historical divide between strategy process and strategy content
Authors: Randall Craig , Dent Eric B.
Published: April 2019

Purpose

Early works in strategic management described strategy process and were quickly followed by aplethoraof strategy content articles focusing on tools, theories, frameworks and models for use in strategizing. Subsequently, strategy research and pedagogy diverged along these lines and the two streams have not been satisfactorily reconciled. As the process incorporates content and content requires process, this paper seeks to answer the question; can some relational consistency and historical reconciliation be developed? The purpose of this paper is to propose a process/content interrelation and a generic model of strategizing.

Design/methodology/approach

The authors first identify the opportunity for this integration through the historical development of the two streams. The authors then review contemporary scholarly literature, strategic management textbooks and university syllabi to determine which elements of the strategy process and content are most frequently promulgated.

Findings

The authors discover a generally ubiquitous core of concepts, but great inconsistency in how they are emphasized, linked and/or applied. Beyond these core concepts, faculty syllabi included a wide range of more idiosyncratic content (appearing very infrequently – possibly related to instructor research or interest areas), such as blue ocean or game theory. The authors then propose a 2 × 2 matrix with axes of the level of analysis and stage of activity. The authors provide a populated matrix and discuss the implications of this matrix for future scholarship and teaching.

Originality/value

This paper begins a process of integrating the historical divide between strategy process and strategy content. It provides insights for classroom faculty, historians and practitioners.
Formation of management thought in Russia and early USSR from the 1800s to the 1920s
Authors: Marshev Vadim
Published: April 2019

Purpose

During the first quarter of the twentieth century in Russia rapidly developed management thought, generated by many reasons, including socio-economic and political transformations, the results of scientific and practical activities of domestic and foreign experts in management. The purpose of this paper is, first, to acquaint readers with some of factors of the development of the history of Russian Management Thought in nineteenth century and at the beginning of twentieth century and, second, to present the most striking results of the formation of the History of Soviet Management Thought (SMT) in post-revolutionary Russia in the form of the movement of the so-called “The scientific organization of labor” (SOL), including “The scientific organization of managerial labor” (or SOML).

Design/methodology/approach

The review and causal analysis of the process of formation of the SMT and historiography of the SMT, a brief description of the institutions of SOL and SOMT and a comparative analysis of little-known works of some Russian authors on management topics of nineteenth century are chosen as research methods.

Findings

The paper emphasizes the action of objectivehistorical inertia(or “non-Markoviness”) of the process of development of managerial thought, manifested, on the one hand, in the stable action of some management paradigms but, on the other hand, in identifying paradigmatic anomalies, in identifying the need for constant development of managerial thought, in the development of sought-after ideas and concepts of management, and even in the institutionalization of applied scientific research in the field of management throughout the country (in the form of SOL and SOML).

Originality/value

The paper attempts to attract the attention of researchers to the little-known Russian and Soviet authors and their little-known works in the field of management thought.
Losing control: the gap in multi-level government reporting
Authors: Caruana Josette , Zammit Kimberly
Published: April 2019

Purpose

The purpose of this paper is to analyse the relationship between control by the Maltese Central Government on Local Government and the format and basis of budgetary and financial reporting used. The study analyses the role of reporting in agency and fiscal federalism theories.

Design/methodology/approach

Semi-structured interviews were carried out with the controller (Central Government officials and the National Audit Office), while a survey was carried out with the controlled (Maltese Local Councils).

Findings

The type of reporting used by Maltese Local Councils may be undermining the control that Central Government seeks to exercise on overspending and debt levels. The Local Councils’ financial statements report accrual deficits and increasing liabilities. This overspending appears to slip through Parliamentary scrutiny because the latter approves cash allocations to Local Councils; the financial reports submitted to Parliament do not highlight overspending in cash terms; and the cash budget execution report that should be prepared by Local Councils is not given due importance.

Originality/value

Central Government should be consistent in its policy towards Local Government, which may require more elaborate reporting. This study highlights the importance of aligning the reporting required (top-down) and the reporting presented (bottom-up) – otherwise, control is at stake.
Nitrogen deposition slows down the litter decomposition induced by soil macrofauna in the soil of subtropical forests in China
Authors: Jia Yanyan , Gu Dalu , Wu Chuanwan , Yang Wenfei , Du Xiaofeng , Wen Tinggang , Lv Yanna , Kong Xiangshi , Tian Xingjun
Published: April 2019

As atmospheric nitrogen (N) deposition elevates, extensive researches into the consequences of N deposition on litter decomposition process have been triggered; yet, responses of aboveground macro‐detritivores to atmospheric N deposition and their interactive effects on saprotrophic microorganisms and litter decomposition process are not thoroughly understood. By soil incubation, we assessed the influence of N deposition on the decomposition process of broad leaf (Quercus acutissima) and needle (Pinus massoniana) litter mediated by macro‐detritivore isopods (Armadillidium vulgare) and soil microorganisms. Changes in litter chemical composition (total carbohydrate and N), litter mass loss, soil pH values, soil microbial biomass and the activities of degradative enzymes were determined during a 6‐month laboratory incubation. Results showed that N addition enhanced Q. acutissima litter decomposition in the absence of A. vulgare, but decreased that when A. vulgare presence. N addition had no significant effect on P. massoniana litter decomposition regardless of A. vulgare presence or absence. However, N addition decreased isopod feeding contributions, with litter mass loss of 1.83–2.92 times lower than those of only isopod addition treatments in the two litter types. N addition inhibited soil microbial biomass and enzymatic activities related to N and phenolic metabolism of needle litter when isopods presence. Our findings suggest that N addition likely weakens the feeding activity of soil fauna and slows down the litter decomposition in broad‐leaved forests. This implies that a long‐term consequence of N deposition may induce the soil C accumulation and affect the balance of ecosystem nutrient flux in subtropical broad‐leaved forests.
Four new species of the genusLissonota(Ichneumonidae: Banchinae) from South Korea
Authors: Kang Gyu‐Won , Kolarov Janko , Lee Jong‐Wook
Published: April 2019

South Korean species ofLissonotaare studied. Just two species of this genus were previously known from South Korea. In the present study 22 species are newly recorded from South Korea. Among them, four species,Lissonota coriaceasp. nov.,L. koreanasp. nov.,L.punctasp. nov. andL.sobaekensis, are described. In this paper, we provided key to South Korean species and descriptions for new species, diagnoses for newly recorded species and digital images.