bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasminogen repairs abnormal pain perception through improving sensory function recovery and regeneration of peripheral small nerve fiber in db/db mice
Authors: Li Weiquan , Wang Ting , Chen Fen , Guo Chunying , Liao Yanghui , Quan Congcong , Zheng Fei , Li Jinan
Published: October 2019

Painful diabetic peripheral neuropathy (PDPN) is a devastating complication of diabetes and severely threatens the health of humankind. The plasminogen activator system and plasminogen (Plg) have multiple functional roles in tissue regeneration and extracellular matrix remodeling, which suggests that Plg may have a potentially pivotal role in anti-PDPN. In the present study, we explore whether an increased level of circulating Plg has positive effect on repairing abnormal pain perception in diabetic mice model. Our data demonstrated that additional Plg not only helps healing pain allodynia or hyperalgesia on the mice at the age of 8 weeks old in early PDPN, but more important, also has positive effects of regaining normal pain perception from hypoalgesia on the mice at ages of 14-15 or 24-25 weeks in advanced PDPN. Furthermore, our data also reveal a possible mechanism for Plg’s contribution to rebuilding normal pain perception among db/db mice by promoting axonal myelination and regeneration of small nerve fiber in peripheral nervous system. Therefore, our data suggest that Plg show promise to become a drug candidate for treating diabetic peripheral neuropathic pain.
Evaluation of bacterial proliferation with a microfluidic-based device: Antibiochip
Authors: Gallo Valentina , Ruiba Alessia , Zanin Massimo , Begnamino Paolo , Ledda Sabina , Pesce Tiziana , Melioli Giovanni , Pizzi Marco
Published: October 2019

The measurement of the proliferation (and the relevant inhibition of proliferation) of microbes is used in different settings, from industry to laboratory medicine. Thus, in this study, the capacity of the Antibiochip (ELTEK spa), a microfluidic-based device, to measure the amount ofE. coliin certain culture conditions, was evaluated. An Antibiochip is composed of V-shaped microchannels, and the amount of microparticles (such as microbes) is measured by the surface of the pellet after centrifugation. In the present study, different geometries, volumes and times were analyzed. When the best conditions were identified, serial dilutions of microbial cultures were tested to validate the linearity of the results. Then, with the use of wildE. colistrains isolated from medical samples, the relationship between bacterial susceptibility to antibiotics (gentamicin, amikacin and ceftriaxone) measured by standard methods and that measured by the Antibiochip was evaluated. In this report, the good quality performances of the methods, their linearity and the capacity to identify susceptible microbial strains after 60 minutes of incubation are shown. These results represent a novel approach for ultrarapid antibiograms in clinics.
Pupil diameter differentiates expertise in dental radiography visual search
Authors: Castner Nora , Appel Tobias , Eder Thérése , Richter Juliane , Scheiter Katharina , Keutel Constanze , Hüttig Fabian , Duchowski Andrew , Kasneci Enkelejda
Published: October 2019

Expert behavior is characterized by rapid information processing abilities, dependent on more structured schemata in long-term memory designated for their domain-specific tasks. From this understanding, expertise can effectively reduce cognitive load on a domain-specific task. However, certain tasks could still evoke different gradations of load even for an expert, e.g., when having to detect subtle anomalies in dental radiographs. Our aim was to measure pupil diameter response to anomalies of varying levels of difficulty in expert and student dentists’ visual examination of panoramic radiographs. We found that students’ pupil diameter dilated significantly from baseline compared to experts, but anomaly difficulty had no effect on pupillary response. In contrast, experts’ pupil diameter responded to varying levels of anomaly difficulty, where more difficult anomalies evoked greater pupil dilation from baseline. Experts thus showed proportional pupillary response indicative of increasing cognitive load with increasingly difficult anomalies, whereas students showed pupillary response indicative of higher cognitive load for all anomalies when compared to experts.
Grass Carp Reovirus (GCRV) Giving Its All to Suppress IFN Production by Countering MAVS-TBK1 Activation
Authors: Lu Long-Feng , Li Zhuo-Cong , Zhang Can , Zhou Xiao-Yu , Zhou Yu , Jiang Jing-Yu , Chen Dan-Dan , Li Shun , Zhang Yong-An
Published: October 2019

As a crucial signaling pathway for interferon (IFN) production, the RIG-I-like receptor (RLR) axis is usually the host target of viruses to enhance viral infection. To date, though immune evasion methods to contrapose IFN production have been characterized for a series of terrestrial viruses, the strategies employed by fish viruses remain unclear. Here, we report that all grass carp reovirus (GCRV) proteins encoded by segments S1 to S11 interact with fish RLR factors, specifically for mitochondrial antiviral signaling protein-TANK-binding kinase 1 (MAVS-TBK1) signaling transduction, leading to decreased IFN expression. First, the GCRV viral proteins blunted the MAVS-induced expression of IFN but had little effect on TBK1-induced IFN expression. Subsequently, interestingly, co-immunoprecipitation experiments demonstrated that all GCRV viral proteins interacted with several RLR cascades, especially with TBK1. To further illustrate the mechanisms of these interactions between GCRV viral proteins and host RLRs, two of the viral proteins, NS79 (S4) and VP3 (S3), were selected as representative proteins for the study. The obtained data demonstrated that NS79 did not affect the stability of the host RLR protein, but was phosphorylated by gcTBK1, leading to the reduction of host substrate gcIRF3/7 phosphorylation. On the other hand, VP3 degraded gcMAVS and the degradation was significantly reversed by 3-MA. The biological effects of both NS79 and VP3 were consistently found to be related to the suppression of IFN expression and the promotion of viral evasion. Our findings shed light on the special evasion mechanism utilized by fish virus through IFN regulation, which might differ between fish and mammals.

Author summary

The RLR signaling pathway is crucial for IFN induction when host cells are infected with virus and RLR factors are targeted by virus. To date, the evasion mechanisms of fish viruses remain mysterious. In this study, we reveal that all 11 GCRV proteins interact with fish RLR factors and suppress the activation of MAVS-TBK1 signaling transduction, leading to the reduction of IFN expression. Two viral proteins were employed as examples to investigate the different evasion mechanisms of GCRV. These findings reveal the novel countermeasures used by fish virus to avoid the host IFN response.
Predicting Alzheimer’s disease progression trajectory and clinical subtypes using machine learning
Authors: Satone Vipul K. , Kaur Rachneet , Dadu Anant , Leonard Hampton , Iwaki Hirotaka , Makarious Mary , Sargent Lana ,   for the Alzheimer’s Disease Neuroimaging Initiative, Daneshmand Ali , Scholz Sonja W. , Singleton Andrew B. , Nalls Mike A. , Campbell Roy H. , Faghri Faraz
Published: October 2019

Background

Alzheimer’s disease (AD) is a common, age-related, neurodegenerative disease that impairs a person’s ability to perform day-to-day activities. Diagnosing AD is challenging, especially in the early stages. Many patients still go undiagnosed, partly due to the complex heterogeneity in disease progression. This highlights a need for early prediction of the disease course to assist its treatment and tailor therapy options to the disease progression rate. Recent developments in machine learning techniques provide the potential to not only predict disease progression and trajectory of AD but also to classify the disease into different etiological subtypes.

Methods and findings

The work shown here clusters participants in distinct and multifaceted progression subgroups of AD and discusses an approach to predict the progression rate from baseline diagnosis. We observed that the myriad of clinically reported symptoms summarized in the proposed AD progression space corresponds directly with memory and cognitive measures, which are routinely used to monitor disease onset and progression. Our analysis demonstrated accurate prediction of disease progression after four years from the first 12 months of post-diagnosis clinical data (Area Under the Curve of 0.96 (95% confidence interval (CI), 0.92-1.0), 0.81 (95% CI, 0.74-0.88) and 0.98 (95% CI, 0.96-1.0) for slow, moderate and fast progression rate patients respectively). Further, we explored the long short-term memory (LSTM) neural networks to predict the trajectory of an individual patient’s progression.

Conclusion

The machine learning techniques presented in this study may assist providers in identifying different progression rates and trajectories in the early stages of the disease, hence allowing for more efficient and personalized healthcare deliveries. With additional information about the progression rate of AD at hand, providers may further individualize the treatment plans. The predictive tests discussed in this study not only allow for early AD diagnosis but also facilitate the characterization of distinct AD subtypes relating to trajectories of disease progression. These findings are a crucial step forward for early disease detection. These models can be used to design improved clinical trials for AD research.
Beneficial bacteria activate type-I interferon production via the cytosolic sensors STING and MAVS
Authors: Gutierrez-Merino Jorge , Isla Beatriz , Combes Theo , Martinez-Estrada Fernando , de Motes Carlos Maluquer
Published: October 2019

Type-I interferon (IFN-I) cytokines are produced by innate immune cells in response to microbial infections, cancer and autoimmune diseases. These cytokines trigger protective responses in neighbouring cells through the activation of IFN-I stimulated genes. One of the most predominant pathways associated with IFN-I production is mediated by the cytosolic sensors STING and MAVS, intracellular adaptors that become activated in the presence of microbial nucleic acids in the cytoplasm, leading to IFN-I production via TANK-binding kinase (TBK)-1 and IFN regulatory factors. However, the role of these sensors in responses induced by beneficial microbes has been relatively unexplored. Here we have screened 12 representative strains of lactic acid bacteria (LAB), a group of beneficial microbes found in fermented food and probiotic formulations worldwide, for their ability to trigger IFN-I responses. Two isolates (Lactobacillus plantarumandPediococcus pentosaceus) induced an IFN-I production that was significantly higher that the rest, both in macrophage cell lines and human primary macrophages. This response correlated with stronger interaction with macrophages and was susceptible to phagocytosis inhibitors, suggesting bacterial internalisation. Accordingly, macrophages deficient for STING and, to a lesser extent, MAVS failed to respond to the two LAB, showing reduced TBK-1 phosphorylation and IFN-I activation. Furthermore, LAB-induced IFN-I was biologically active and resulted in expression of interferon stimulated genes, which was also STING- and MAVS-dependent. Our findings demonstrate a major role for STING in the production of IFN-I by beneficial bacteria and the existence of bacteria-specific immune signatures, which can be exploited to modulate protective responses in the host.
Sphingomyelinase disables Piezo1 channel inactivation to enable sustained response to mechanical force
Authors: Shi Jian , Hyman Adam J , De Vecchis Dario , Chong Jiehan , Lichtenstein Laeticia , Futers T. Simon , Rouahi Myriam , Salvayre Anne Negre , Auge Nathalie , Kalli Antreas C , Beech David J
Published: October 2019

Piezo1 channels are determinants of vascular responses to fluid flow. They importantly provide sustained response to flow, but this property contrasts with the rapid inactivation that has become a hallmark of the channels in heterologous overexpression studies. Here we reveal a mechanism by which blood vessels disable inactivation to enable sustained physiological response. Creation of a molecular model of Piezo1 channel in defined lipid membranes suggested potential modulation by sphingomyelin and its product ceramide. Biological relevance was indicated by the observation that exogenous sphingomyelinase enhanced Piezo1-mediated Ca2+ entry in cultured endothelial cells. We therefore hypothesised that endogenous sphingomyelinase suppresses channel inactivation. Remarkably, in endothelium freshly-isolated from murine artery, neutral sphingomyelinase inhibitors or genetic disruption of sphingomyelin phosphodiesterase 3 (SMPD3) caused flow- and pressure-activated Piezo1 channels to become inactivating. SMPD3 retained its ability to disable inactivation in cell-free membrane patches, providing evidence for a membrane localised effect. The data suggest that inherent inactivation of Piezo1 channels is disabled by enzymatic control of lipid environment to enable physiological response to mechanical force.
Historical recombination variability contributes to deciphering the genetic basis of phenotypic traits
Authors: Ruiz-Arenas Carlos , Cáceres Alejandro , López Marcos , Pelegrí-Sisó Dolors , González Josefa , González Juan R.
Published: October 2019

Recombination is a main source of genetic variability. However, the potential role of the variation generated by recombination in phenotypic traits, including diseases, remains unexplored as there is currently no method to infer chromosomal subpopulations based on recombination patterns differences. We developedrecombClust, a method that uses SNP-phased data to detect differences in historic recombination in a chromosome population. We validated our method by performing simulations and by using real data to accurately predict the alleles of well known recombination modifiers, including common inversions inDrosophila melanogasterand human, and the chromosomes under selective pressure at the lactase locus in humans. We then appliedrecombClustto the complex human 1q21.1 region, where nonallelic homologous recombination produces deleterious phenotypes. We discovered and validated the presence of two different recombination histories in these regions that significantly associated with the differential expression ofANKRD35in whole blood and that were in high linkage with variants previously associated with hypertension. By detecting differences in historic recombination, our method opens a way to assess the influence of recombination variation in phenotypic traits.
RESTORE: Robust intEnSiTy nORmalization mEthod for Multiplexed Imaging
Authors: Chang Young Hwan , Chin Koei , Thibault Guillaume , Eng Jennifer , Burlingame Erik , Gray Joe W.
Published: October 2019

Recent advances in multiplexed imaging technologies promise to improve the understanding of the functional states of individual cells and the interactions between the cells in tissues. This often requires compilation of results from multiple samples. However, quantitative integration of information between samples is complicated by variations in staining intensity and background fluorescence that obscure biological variations. Failure to remove these unwanted artefacts will complicate downstream analysis and diminish the value of multiplexed imaging for clinical applications. Here, to compensate for unwanted variations, we automatically identify negative control cells for each marker within the same tissue and use their expression levels to infer background signal level. The intensity profile is normalized by the inferred level of the negative control cells to remove between-sample variation. Using a tissue microarray data and a pair of longitudinal biopsies sample, we demonstrated that the proposed approach can remove unwanted variations effectively and shows robust performance.
Transgene-mediated skeletal phenotypic variation in zebrafish
Authors: Kimmel Charles B. , Wind Alexander L. , Oliva Whitney , Ahlquist Samuel D. , Walker Charline , Dowd John , Blanco-Sánchez Bernardo , Titus Tom A. , Batzel Peter , Postlethwait John H. , Nichols James T.
Published: October 2019

When considering relationships between genotype and phenotype we frequently ignore the fact that the genome of a typical animal, notably including that of a fish and a human, harbors a huge amount of foreign DNA. Some of it, including the DNA of “autonomous” transposable elements, can spontaneously mobilize to occupy new chromosomal sites and take on new functions, presenting a challenge to the host organism and also possibly introducing new fuel for evolutionary change. Transposable elements are useful for introducing transgenes, integrating them into host genomes with high efficiency. Transgenesis has become very widespread in biological research, and in our society at large. This year the governments of both Canada and the United States have approved the first use of ‘genetically engineered’ animals in food production, Atlantic salmon,Salmo salar. With the recent advent of amazing gene-editing technology, there is no doubt that the transgene industry will grow explosively in the coming years. The biology of transgenes needs to be included in our understanding of the genome. It is in this spirit that we have investigated an unexpected and novel phenotypic effect of the chromosomally integrated transgenefli1a-F-hsp70l:Gal4VP16. We examine larvalfras1mutant zebrafish (Danio rerio). Gal4VP16 is a potent transcriptional activator, and already well known for toxicity and mediating unusual transcriptional effects. In the presence of the transgene, phenotypes in the neural crest-derived craniofacial skeleton, notably fusions and shape changes associated with loss of functionfras1mutations, are made more severe, as we quantify by scoring phenotypic penetrance, the fraction of mutants expressing the trait. A very interesting feature is that the enhancements are highly specific forfras1mutant phenotypes – occurring in the apparent absence of more wide-spread changes. Except for the features due to thefras1mutation, the transgene-bearing larvae appear generally healthy and to be developing normally. The transgene behaves as a genetic partial dominant: A single copy is sufficient for the enhancements, yet, for some traits, two copies may exert a stronger effect. We made new strains bearing independent insertions of thefli1a-F-hsp70l:Gal4VP16transgene in new locations in the genome, and observed increased severities of the same phenotypes as observed for the original insertion. This finding suggests that sequences within the transgene, e.g. Gal4VP16, are responsible for the enhancements, rather than effect on neighboring host sequences (such as an insertional mutation). The specificity, and biological action underlying the traits, are subjects of considerable interest for further investigation, as we discuss. Our findings show that work with transgenes needs to be undertaken with caution and attention to detail.
The metalloproteinase Papp-aa functions as a molecular switch linking IGF signaling to adaptive epithelial growth
Authors: Liu Chengdong , Li Shuang , Noer Pernille Rimmer , Kjaer-Sorensen Kasper , Ke Caihuan , Oxvig Claus , Duan Cunming
Published: October 2019

Human patients carrying inactivating mutations in the pregnancy-associated plasma protein-a2 (PAPP-A2) gene display short status and lower bone mineral density. The underlying mechanisms are not well understood. Using a zebrafish model, here we report a [Ca2+]-dependent mechanism by which Papp-aa regulates bone calcification via promoting Ca2+-transporting epithelial cell (ionocyte) reactivation. Ionocyte, normally quiescent, re-enter the cell cycle in response to low [Ca2+] stress. Deletion of Papp-aa abolished ionocyte reactivation and resulted in a complete lack of calcified bone. Re-expression of Papp-aa, but not its active site mutant, rescued ionocyte reactivation. Inhibition of Papp-aa activity pharmacologically or by overexpressing STC1 or STC2 impaired ionocyte reactivation. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-mediated Akt-Tor signaling activity in ionocytes and expression of a constitutively active Akt rescued ionocyte reactivation. Biochemically, Papp-aa cleaved Igfbp5a, a high-affinity IGF binding protein specifically expressed in ionocytes. Under normal [Ca2+] conditions, the Papp-aa-mediated Igfbp5a proteolysis was suppressed and IGFs sequestered in the IGF/Igfbp5a complex. Forced release of IGFs from the complex was sufficient to activate the IGF-Akt-Tor signaling and promote ionocyte reactivation. These findings suggest that Papp-aa functions as a [Ca2+]-regulated molecular switch linking IGF signaling to adaptive epithelial growth and bone calcification.
Singing training predicts increased insula connectivity with speech and respiratory sensorimotor areas at rest
Authors: Zamorano A.M. , Zatorre R.J. , Vuust P. , Friberg A. , Birbaumer N. , Kleber B.
Published: October 2019

The insula contributes to the detection of salient events during goal-directed behavior and participates in the coordination of motor, multisensory, and cognitive systems. Recent task-fMRI studies with trained singers suggest that singing experience can enhance the access to these resources. However, the long-term effects of vocal training on insula based networks are still unknown. In this study, we employed resting-state fMRI to assess experience-dependent differences in insula co-activation patterns between conservatory-trained singers and non-singers. Results indicate enhanced bilateral insula connectivity in singers relative to non-singers with constituents of the speech sensorimotor network in both hemispheres. Specifically, with the cerebellum (lobule VI, crus 2), primary somatosensory cortex, the parietal lobes, and the thalamus. Furthermore, singing training predicted enhanced bilateral co-activation of primary sensorimotor areas representing the larynx (with left dorsal anterior insula, dAI) and the diaphragm (with bilateral dAI)—crucial regions for cortico-motor control of complex vocalizations, as well as the thalamus (with bilateral posterior insula/left dAI) and the left putamen (with left dAI). Together, these data support a crucial role of the insula in respiratory and laryngeal control and suggest that singing experience enhances the integration of somatosensory information within the speech motor system, perhaps by strengthening salient associations of bodily signals associated with conscious and non-conscious aspects of expressive language production within a musical framework.
Long non-coding RNA gene regulation and trait associations across human tissues
Authors: de Goede O. M. , Ferraro N. M. , Nachun D. C. , Rao A. S. , Aguet F. , Barbeira A. N. , Castel S. E. , Kim-Hellmuth S. , Park Y. , Scott A. J. , Strober B. J. ,   GTEx Consortium, Brown C. D. , Wen X. , Hall I. M. , Battle A. , Lappalainen T. , Im H. K. , Ardlie K. G. , Quertermous T. , Kirkegaard K. , Montgomery S. B.
Published: October 2019

Long non-coding RNA (lncRNA) genes are known to have diverse impacts on gene regulation. However, it is still a major challenge to distinguish functional lncRNAs from those that are byproducts of surrounding transcriptional activity. To systematically identify hallmarks of biological function, we used the GTEx v8 data to profile the expression, regulation, network relationships and trait associations of lncRNA genes across 49 tissues encompassing 87 distinct traits. In addition to revealing widespread differences in regulatory patterns between lncRNA and protein-coding genes, we identified novel disease-associated lncRNAs, such asC6orf3for psoriasis andLINC01475/RP11-129J12.1for ulcerative colitis. This work provides a comprehensive resource to interrogate lncRNA genes of interest and annotate cell type and human trait relevance.

One Sentence Summary

lncRNA genes have distinctive regulatory patterns and unique trait associations compared to protein-coding genes.
Fibroblastic Reticular Cell Response to Dendritic Cells Requires Coordinated Activity of Podoplanin, CD44 and CD9
Authors: de Winde Charlotte M. , Makris Spyridon , Millward Lindsey , Rebordinos Jesús Cantoral , Benjamin Agnesska C. , Martínez Víctor G. , Acton Sophie E.
Published: October 2019

Lymph node expansion is pivotal for adaptive immunity. CLEC-2+ migratory dendritic cells (DCs) interact with fibroblastic reticular cells (FRCs) to inhibit podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. However, the molecular mechanisms controlling lymph node remodelling are not fully understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion in vivo, and further, which other FRC markers are required for FRCs to respond to CLEC-2+ DCs. We find that expression of podoplanin and its partner proteins CD44 and CD9 in FRCs is coregulated by CLEC-2, and is differentially expressed by specific lymph node stromal populations in vivo. We find that beyond contractility, podoplanin is required for polarity and alignment of FRCs. Both CD44 and CD9 act to dampen podoplanin-dependent contractility, and colocalize with podoplanin in different areas of the cell membrane. Independently of podoplanin, CD44 and CD9 affect the degree of cell-cell contact and overlap between neighbouring FRCs. Further, we show that both CD44 and CD9 are required for FRCs to spread and form protrusions in response to DCs. Our data show that remodelling of the FRC cytoskeleton is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2/podoplanin-binding drives relaxation of actomyosin contractility, and secondly FRCs form protrusions and spread which requires both CD44 and CD9. Together, we show a multi-faceted response of FRCs to DCs, which requires CD44 and CD9 in addition to podoplanin.
Minimalin vivorequirements for developmentally regulated cardiac long intergenic non-coding RNAs
Authors: George Matthew R. , Duan Qiming , Nagle Abigail , Kathiriya Irfan S. , Huang Yu , Rao Kavitha , Haldar Saptarsi M. , Bruneau Benoit G.
Published: October 2019

Long intergenic non-coding RNAs (lincRNAs) have been implicated in aspects of gene regulation, but their requirement for development needs empirical interrogation. To begin to understand the roles lincRNAs might play in heart development, we computationally identified nine murine lincRNAs that have developmentally regulated transcriptional and epigenomic profiles specific to early heart differentiation. Six of the nine lincRNAs had in vivo expression patterns supporting a potential function in heart development, including a transcript downstream of the cardiac transcription factorHand2that we namedHandlr (Hand2-associated lincRNA),Rubie,andAtcayos. We genetically ablated these six lincRNAs in mouse, which implicated genomic regulatory roles to four of the cohort, However, none of the lincRNA deletions led to severe cardiac phenotypes. Thus, we stressed the hearts of adultHandlrandAtcayosmutant mice by transverse aortic banding and found that absence of these lincRNAs did not affect cardiac hypertrophy or left ventricular function post-stress. Our results support roles for lincRNA transcripts and/or transcription to regulation of topologically associated genes. However, the individual importance of developmentally-specific lincRNAs is yet to be established. Their status as either gene-like entities or epigenetic components of the nucleus should be further considered.
Genome-Wide Classification of Type I, Type II and Type III Interferon-Stimulated Genes in Chicken Fibroblasts
Authors: Santhakumar Diwakar , Rohaim Mohammed A. , Munir Muhammad
Published: October 2019

Interferons (IFNs) play central roles in establishing innate immunity and mediating adaptive immunity against multiple pathogens. Three known types of IFNs identify their cognate receptors, initiate cascades of signalling events and eventually result in the induction of myriad of IFN-stimulated genes (ISGs). These ISGs perform multitude of functions and cumulatively corroborate a bespoke antiviral state to safeguard hosts against invading viruses. Owing to unique nature of chicken’s immune system and lack of foundational profiling information on the nature and dynamic expression of IFN-specific ISGs at the genome scale, we performed a systematic and extensive analysis of type I, II and III IFN-induced genes in chicken. Employing pan-IFN responsive chicken fibroblasts coupled with transcriptomics we observed an overwhelming over-representation of up-regulated ISGs by all types of IFNs. Intriguingly, prediction of IFN-stimulated response element (ISRE) and gamma-IFN activation sequence (GAS) revealed a substantial number of GAS motifs in selective significantly induced ISGs in chicken. Extensive comparative, genome-wide and differential expression analysis of ISGs under equivalent signalling input catalogue a set of genes that were either IFN-specific or independent of types of IFNs used to prime fibroblasts. These comprehensive datasets, first of their kinds in chicken, will establish foundations to elucidate the mechanisms of actions and breadth of antiviral action of ISGs which may propose alternative avenues for the targeted antiviral therapy against viruses of poultry and public health importance.
A framework for gene mapping in wheat demonstrated using the Yr7 yellow rust resistance gene
Authors: Gardiner Laura-Jayne , Bansept-Basler Pauline , El-Soda Mohamed , Hall Anthony , O’Sullivan Donal M.
Published: October 2019

We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene.

Highlight

We show progression from genetic mapping to mapping-by-sequencing and the overlap of defined intervals by each approach culminating with interval refinement and identification of a candidate gene for disease resistance.
Combining free energy simulations and NMR chemical-shift perturbation to identify transient cation-π contacts in proteins
Authors: Reis André A. O. , Sayegh Raphael S. R. , Marana Sandro R. , Arantes Guilherme M.
Published: October 2019

Flexible protein regions containing cationic and aromatic side-chains exposed to solvent may form transient cation-π interactions with structural and functional roles. To evaluate their stability and identify important intramolecular cation-π contacts, a combination of free energy profiles estimated from umbrella sampling with molecular dynamics simulations and chemical shift perturbations (CSP) obtained from NMR experiments is applied here to the complete catalytic domain of human phosphatase Cdc25B. This protein is a good model system for transient cation-π interactions as it contains only one Trp residue (W550) in the disordered C-terminal segment and a total of 17 Arg residues, many exposed to solvent. Eight putative Arg-Trp pairs were simulated here. Only R482 and R544 show bound profiles corresponding to important transient cation-π interactions, while the others have dissociative or almost flat profiles. These results are corroborated by CSP analysis of three Cdc25B point mutants (W550A, R482A and R544A) disrupting cation-π contacts. The proposed validation of statistically representative molecular simulations by NMR spectroscopy could be applied to identify transient contacts of proteins in general but carefully, as NMR chemical shifts are sensitive to changes in both molecular contacts and conformational distributions.
The Medicago truncatula DREPP protein triggers microtubule fragmentation in membrane nanodomains during symbiotic infections
Authors: Su Chao , Klein Marie-Luise , Hernández-Reyes Casandra , Batzenschlager Morgane , Ditengou Franck Anicet , Keller Jean , Delaux Pierre-Marc , Ott Thomas
Published: October 2019

The initiation of intracellular host cell colonization by symbiotic rhizobia in Medicago truncatula requires repolarization of root hairs, which includes the re-arrangement of cytoskeletal filaments. The molecular players governing microtubule (MT) re-organization during infection remain to be discovered. Here, we identified the M. truncatula DREPP protein and investigated its functions during rhizobial infections. We show that rhizobial colonization of drepp mutant roots as well as transgenic roots over-expressing DREPP is impaired. DREPP re-localizes into symbiosis-specific membrane nanodomains in a stimulus-dependent manner. This subcellular segregation coincides with DREPP-dependent MT fragmentation and a partial loss of the ability to re-organize the MT cytoskeleton in response to rhizobia, which might relay on an interaction between DREPP and MT organizing protein SPIRAL2 (SPR2). Taken together, our results reveal that establishment of symbiotic associations in M. truncatula require DREPP in order to regulate MT reorganization during initial root hair responses to rhizobia.
The low-temperature barium fluoridozirconate variety α-BaZr2F10
Authors: Laval Jean-Paul
Published: October 2019

The low-temperature triclinic variety α-BaZr2F10 constitutes a new structure type, less symmetrical than the higher-temperature β-variety. It is based on the stacking of double sheets of Zr polyhedra, connecting three different kinds of ZrF7 polyhedra and one ZrF8 polyhedron via vertices and edges, separated by corrugated Ba2+ layers. It is compared to the high-temperature β-variety, directly recrystallizing from barium fluoridozirconate glass, and also to BaTe2F10 and KTe2F9.
Inter-regional innovation correlation effects and influencing factors in China
Authors: Pan Xiongfeng , Ming Yang , Li Mengna , Guo Shucen , Han Cuicui
Published: October 2019

Purpose

The purpose of this paper is to find out the characteristics and evolutionary trends of China’s inter-regional innovation correlation network, the status and roles of each province in China’s inter-regional innovation correlation network and the influencing factors of China’s inter-regional innovation correlation effect.

Design/methodology/approach

Based on the patent data of 30 provinces (autonomous regions and municipalities) in China from 1991 to 2017, social network analysis was used to find out the characteristics and evolutionary trends of China’s inter-regional innovation correlation network and the status and roles of each province in China’s inter-regional innovation correlation network. Furthermore, the QAP method was used to find out the influencing factors of China’s inter-regional innovation correlation effect.

Findings

China’s inter-regional innovation correlation is becoming increasingly close and inter-regional innovation correlation network is becoming increasingly stable. Jiangsu, Zhejiang, Beijing, Shanghai, Guangdong and other eastern coastal provinces are at the core in the inter-regional innovation correlation network, while the western regions are marginal actors. China’s regional innovation development territory can be divided into four blocks, namely, “bidirectional spillover block,” “net spillover block,” “main beneficial block” and “net beneficial block,” and gradient transfer mechanism is obvious between the blocks. The geographical adjacency and similarity in regional industrial structure, urbanization level and government attention degree have significant positive effect on China’s inter-regional innovation correlation effects.

Research limitations/implications

This paper only uses patent application as a measure of regional innovation level to analyze inter-regional innovation correlation effect. Meanwhile, this paper carries out an empirical study only from the provincial level and not from the city level.

Practical implications

This paper provides the practical basis for further promoting the coordinated development of regional innovation and promoting the construction of regional innovation systems with different characteristics.

Originality/value

This paper contributes to understand the status and role of each province in inter-regional innovation correlation network. Meanwhile, this paper also helps to understand the influence of the proximity and external environmental factors on inter-regional innovation correlation effect.
The impact of high insider ownership on SOX 404 internal controls
Authors: Diala Lucy Uche , Houmes Robert
Published: October 2019

Purpose

This study aims to investigate the effect of high insider ownership on firms’ internal controls over financial reporting. In particular, it examines how high insider ownership affects the likelihood of an adverse Sarbanes–Oxley Act Section (SOX Section 404) opinion and its subsequent remediation.

Design/methodology/approach

Tests of hypotheses use ineffective controls and remediation models. The initial tests in this study use ineffective internal controls over financial reporting probit regression models to investigate how high insider ownership affects the ex-post likelihood of an adverse 404 opinion. Two remediation models – a multinominal probit regression and probit regression model – are used to investigate the effect of high insider ownership on the likelihood of successfully remediating an adverse 404 opinion.

Findings

Results show that while the ex-ante likelihood of an adverse SOX Section 404 auditor’s internal control opinion increases with high insider ownership, high insider ownership firms are more likely to remediate ineffective 404 controls. This study rationalizes these diverse findings by asserting that prior to an adverse 404 opinion, entrenched managers avoid internal control financial reporting oversight and monitoring. After an adverse opinion, however, and within the context of an imminent and explicit value reducing 404 opinion, powerful high insider owner managers are motivated to remedy ineffective controls.

Originality/value

This research synthesizes existing streams of literature on insider ownership and the effectiveness of internal control over financial reporting quality to provide new information on the effects of high insider ownership on firms’ internal controls.
Crossvergence of socially (ir)responsible employment practices in supplier firms
Authors: Holzberg Britta
Published: October 2019

Purpose

The purpose of this paper is to introduce the notion of crossvergence from international human resource management (IHRM) as a conceptual lens for understanding and analyzing the formation of socially (ir)responsible employment practices in supplier firms in global production networks (GPNs). The crossvergence perspective can particularly contribute to understanding how the agency of suppliers is influenced by the interaction of global–local dynamics.

Design/methodology/approach

The paper illustrates how the formation of socially (ir)responsible employment practices can be understood as a process of crossvergence. Subsequently, it reviews and structures insights from GPN and IHRM literature to detail the process.

Findings

The paper underscores the complicated role of suppliers in ensuring decent work in GPNs. Suppliers face a multitude of global and local interacting, and partially conflicting, demands. They process these demands as active agents and need to develop suitable employment practices in response.

Originality/value

The paper supports the nascent discourse on supplier agency in forming socially responsible employment practices. It connects different streams of literature to illuminate the perspective of suppliers, introduces IHRM insights to the debate and offers conceptual guidance for analyzing interacting global and local pressures on suppliers.
Absorptive capacity, marketing capabilities, and innovation commercialisation in Nigeria
Authors: Medase Kehinde , Barasa Laura
Published: October 2019

Purpose

The purpose of this paper is to investigate how specialised capabilities including absorptive capacity and marketing capabilities influence innovation commercialisation in manufacturing and service firms in Nigeria. The authors hypothesise that absorptive capacity measures including openness and formal training for innovation, and marketing capabilities encompassing new product marketing and marketing innovation are positively associated with innovation performance.

Design/methodology/approach

The authors examine commercialisation of innovation within the profiting from innovation (PFI) and dynamic capabilities (DC) framework and use data from the 2012 Nigeria Innovation Survey to test the hypothesis by means of a Heckman sample selection model.

Findings

The authors find that absorptive capacity measures comprising openness and formal training are positively associated with innovation performance. The authors also find that marketing capabilities as indicated by new product marketing and marketing innovation are positively associated with innovation performance.

Research limitations/implications

The authors acknowledge that firms undergo continuous changes and that there may be the presence of unobserved or unmeasured heterogeneity. Taking into cognisance that Nigeria is a federal state, cultural diversity and economic factors are likely to differ widely between geographical regions. Also, while the proposed conceptual framework offers a deeper understanding of innovation performance, examining how integrating activities of the R&D department, human resource department and marketing department affect innovation commercialisation is likely to provide more meaningful insights.

Practical implications

The role that inter-organisational learning and intra-organisational learning play in driving innovation performance provide managers with a basis for incorporating absorptive capacity building programs that boost employees’ ability to recognise and apply valuable external knowledge to commercial ends. Similarly, firms may benefit from offering marketing capabilities development programs. Furthermore, innovation policies in Nigeria are generally designed to focus on fostering innovation activities aimed at developing innovative output. Accordingly, government support explicitly targeting new product marketing and marketing innovation is likely to play a vital role in the successful commercialisation of innovation in Nigeria.

Originality/value

This study fuses the PFI and DC framework to examine why innovating firms may not necessarily succeed. This area of study has received scant attention in sub-Saharan Africa given that extant literature focusses on value creation as opposed to value capture.
The scientific nature of work-based learning and research
Authors: Fergusson Lee , Shallies Bradley , Meijer Gerry
Published: October 2019

Purpose

The purpose of this paper is to explore the scientific nature of work-based learning (WBL) and research as operationalized in Professional Studies by examining first principles of scientific inquiry.

Design/methodology/approach

This paper introduces a Professional Studies program as it has been implemented at University of Southern Queensland in Australia and examines it from the perspective of five first principles of scientific inquiry: systematic exploration and reporting, use of models, objectivity, testability and applicability. The authors do so not to privilege the meritorious qualities of science or to legitimise WBL or its example in Professional Studies by conferring on them the status of science, but to highlight their systematised approach to learning and research.

Findings

If the authors define Professional Studies to mean the systematic inquiry of work-based people, processes and phenomena, evidence affirmatively suggests that it is scientific “in nature”.

Originality/value

WBL has been well documented, but its orientation to research, particularly mixed methods (MM) research through Professional Studies, and its adherence to first principles of science have never been explored; this paper begins to uncover the value of work-based pedagogical approaches to learning and research.
Response biases in policy compliance research
Authors: Kurowski Sebastian
Published: October 2019

Purpose

The purpose of this study is to use a developed and pre-tested scenario-based measurement instrument for policy compliance and determine whether policy compliance measurements in the current policy compliance research are biased as has been postulated during a pre-study. The expected biases are because of social desirability and because of biases based on identity theory.

Design/methodology/approach

A survey was conducted (n = 54) that used policy compliance scales from literature and the developed self-reporting policy compliance (SRPC) scale, along with the Marlow–Crowne social desirability (MC-SDB) scale. Differences between the policy compliance scales were assessed. Moreover, a transformation of the SRPC measurements into the literature-based scales was examined using pair-wise t-testing. Finally, correlations between the MC-SDB and the policy compliance scales were examined.

Findings

There are no significant influences on the desire for social approval of the respondents as was exhibited by the MC-SDB values and policy compliance on either scale. However, the SRPC scale measurements show deviations from the literature-based policy compliance scales. Individuals that exhibit secure behaviour, which is not rooted in a policy but rather in anything but the policy, are also captured as being policy compliant in the current scales. This shows that a response bias exists in current scales. Respondents, who perceive to exhibit secure behaviours, may think that they are in compliance with the policy, even when they are not.

Practical implications

These findings mean that several contributions in the field of policy compliance must be questioned and that a revisit of several factors influencing policy compliance may be required.

Originality/value

To the best of the authors’ knowledge, response biases in policy compliance research have not been considered to date.