bluuebunny/crossref_metadata_2025 huggingface dataset:
Bushmeat biogeochemistry: hunting tropical mammals alters ecosystem phosphorus budgets
Authors: Brodie Jedediah F. , McIntyre Peter B.
Published: July 2019

Wild meat (or ‘bushmeat’) hunting is nearly ubiquitous across the tropics and is very often unsustainable—driving declines and extirpation of numerous mammal populations. Loss of these animals can alter the transport of nutrients within and between ecosystems. But whether the physical removal of vertebrate carcasses and the nutrients that they store can reduce overall nutrient availability in ecosystems has been little explored. At 32 sites on three continents, we show that annual phosphorus (P) loss via mammal exploitation was low relative to the rate of atmospheric P deposition. But at four sites in Africa and Southeast Asia, removal of P in the skeletons of hunted mammals exceeded the atmospheric input of this nutrient by 10-fold or more. Because P is the growth-limiting nutrient for many tropical terrestrial ecosystems and certain large mammals, the imbalance created by the removal of mammal biomass under very high hunting scenarios could reduce ecosystem carrying capacity if no compensatory P additions occur in the system. This biogeochemical perspective on bushmeat exploitation raises further concerns about harvest sustainability and human food security in areas where hunting rates are high and ecosystem P inputs low.
Neuroimaging biomarkers differentiate Parkinson disease with and without cognitive impairment and dementia
Authors: Owens-Walton Conor , Jakabek David , Power Brian D. , Walterfang Mark , Hall Sara , van Westen Danielle , Looi Jeffrey C.L. , Shaw Marnie , Hansson Oskar
Published: July 2019

Mild cognitive impairment in Parkinson disease places a high burden on patients and is likely a precursor to Parkinson disease-related dementia. Studying the functional connectivity and morphology of subcortical structures within basal ganglia-thalamocortical circuits may uncover neuroimaging biomarkers of cognitive dysfunction in PD. We used an atlas-based seed region-of-interest approach to investigate resting-state functional connectivity of important subdivisions of the caudate nucleus, putamen and thalamus, between controls (n = 33), cognitively unimpaired Parkinson disease subjects (n = 33), Parkinson disease subjects with mild cognitive impairment (n = 22) and Parkinson disease subjects with dementia (n = 17). We then investigated how the morphology of the caudate, putamen and thalamus structures and differed between groups. Results indicate that cognitively unimpaired Parkinson disease subjects, compared to controls, displayincreasedfunctional connectivity of the dorsal caudate, anterior putamen and mediodorsal thalamic subdivisions with areas across the frontal lobe, as well asreducedfunctional connectivity of the dorsal caudate with posterior cortical and cerebellar regions. Compared to cognitively unimpaired subjects, Parkinson disease subjects with mild cognitive impairment demonstratedreducedfunctional connectivity of the mediodorsal thalamus with midline nodes within the executive-control network. Compared to subjects with mild cognitive impairment, subjects with dementia demonstratedreducedfunctional connectivity of the mediodorsal thalamus with the posterior cingulate cortex, a key node within the default-mode network. Extensive volumetric and surface-based deflation was found in Parkinson disease subjects with dementia. Our research demonstrates how functional connectivity of the caudate, putamen and thalamus are implicated in the pathophysiology of cognitive impairment and dementia in Parkinson disease, with mild cognitive impairment and dementia in Parkinson disease associated with a breakdown in functional connectivity of the mediodorsal thalamus with para- and posterior cingulate regions of the brain.
Highly multiplexed immunofluorescence images and single-cell data of immune markers in tonsil and lung cancer
Authors: Rashid Rumana , Gaglia Giorgio , Chen Yu-An , Lin Jia-Ren , Du Ziming , Maliga Zoltan , Schapiro Denis , Yapp Clarence , Muhlich Jeremy , Sokolov Artem , Sorger Peter , Santagata Sandro
Published: July 2019

In this data descriptor, we document a dataset of multiplexed immunofluorescence images and derived single-cell measurements of immune lineage and other markers in formaldehyde-fixed and paraffin-embedded (FFPE) human tonsil and lung cancer tissue. We used tissue cyclic immunofluorescence (t-CyCIF) to generate fluorescence images which we artifact corrected using the BaSiC tool, stitched and registered using the ASHLAR algorithm, and segmented using ilastik software and MATLAB. We extracted single-cell features from these images using HistoCAT software. The resulting dataset can be visualized using image browsers and analyzed using high-dimensional, single-cell methods. This dataset is a valuable resource for biological discovery of the immune system in normal and diseased states as well as for the development of multiplexed image analysis and viewing tools.

METADATA SUMMARY
Identification of 2CS-CHXToperon signature of chlorhexidine tolerance amongEnterococcus faecium
Authors: Duarte Bárbara , Pereira Ana P. , Freitas Ana R. , Coque Teresa M. , Hammerum Anette M. , Hasman Henrik , Antunes Patrícia , Peixe Luísa , Novais Carla
Published: July 2019

Chlorhexidine (CHX) is a broad-spectrum antiseptic widely used in community and clinical contexts for many years, recently acquiring higher relevance in nosocomial infections control worldwide. Despite of this, CHX tolerance has been poorly understood amongEnterococcus faecium, one of the leading agents causing nosocomial infections. This study provides new phenotypic and molecular data for a better identification of CHX tolerantE. faeciumsubpopulations in community and clinical contexts. MICCHXdistribution of 106E. faeciumsuggested the occurrence of tolerant subpopulations in diverse sources (human, animal, food, environment) and phylogenomic backgrounds (clades A1/A2/B), with predominance in clade A1. They carried a specific variant of 2CS-CHXToperon, here identified. It encodes a glucose and an amino-acid-polyamine-organocation family transporters, besides the DNA-binding-response-regulator ChtR with a P102H mutation previously described in only CHX tolerant clade A1E. faecium, and the ChtS sensor. Combined data from normal MIC distribution and 2CS-CHXToperon characterization supports a tentative epidemiological cut-off (ECOFF) of 8 mg/L to CHX, useful to detect tolerantE. faeciumpopulations in future surveillance studies. The spread of tolerantE. faeciumin diverse epidemiological backgrounds alerts for a prudent use of CHX in multiple contexts.

Importance

Chlorhexidine is one of the substances included in the World Health Organization’s List of Essential Medicines which comprises the safest and most effective medicines needed in global health systems. Although it has been widely applied as a disinfectant and antiseptic since the 1950s in healthcare (skin, hands, mouthwashes, eye drops), its use in hospitals to prevent nosocomial infections has increased worldwide in recent years. Here we provide a comprehensive study on chlorhexidine tolerance amongEnterococcus faecium, one of the leading nosocomial agents worldwide, and identified a novel 2CS-CHXToperon as a signature of tolerant strains occurring in diverse phylogenomic groups. Finally, our data allowed to propose a tentative epidemiological cut-off of 8 mg/L, useful to detect tolerantE. faeciumpopulations in future surveillance studies in community and clinical contexts.
Compartment-dependent chromatin interaction dynamics revealed by liquid chromatin Hi-C
Authors: Belaghzal Houda , Borrman Tyler , Stephens Andrew D. , Lafontaine Denis L. , Venev Sergey V. , Weng Zhiping , Marko John F. , Dekker Job
Published: July 2019

Chromosomes are folded so that active and inactive chromatin domains are spatially segregated. Compartmentalization is thought to occur through polymer phase/microphase separation mediated by interactions between loci of similar type. The nature and dynamics of these interactions are not known. We developed liquid chromatin Hi-C to map the stability of associations between loci. Before fixation and Hi-C, chromosomes are fragmented removing the strong polymeric constraint to enable detection of intrinsic locus-locus interaction stabilities. Compartmentalization is stable when fragments are over 10-25 kb. Fragmenting chromatin into pieces smaller than 6 kb leads to gradual loss of genome organization. Dissolution kinetics of chromatin interactions vary for different chromatin domains. Lamin-associated domains are most stable, while interactions among speckle and polycomb-associated loci are more dynamic. Cohesin-mediated loops dissolve after fragmentation, possibly because cohesin rings slide off nearby DNA ends. Liquid chromatin Hi-C provides a genome-wide view of chromosome interaction dynamics.

Highlights

Liquid chromatin Hi-C detects chromatin interaction dissociation rates genome-wide

Chromatin conformations in distinct nuclear compartments differ in stability

Stable heterochromatic associations are major drivers of chromatin phase separation

CTCF-CTCF loops are stabilized by encirclement of loop bases by cohesin rings
Finding MEMo: Minimum sets of elementary flux modes
Authors: Röhl Annika , Bockmayr Alexander
Published: July 2019

Metabolic network reconstructions are widely used in computational systems biology for in silico studies of cellular metabolism. A common approach to analyse these models are elementary flux modes (EFMs), which correspond to minimal functional units in the network. Already for medium-sized networks, it is often impossible to compute the set of all EFMs, due to their huge number. From a practical point of view, this might also not be necessary because a subset of EFMs may already be sufficient to answer relevant biological questions. In this article, we study MEMos or minimum sets of EFMs that can generate all possible steady-state behaviours of a metabolic network. The number of EFMs in a MEMo may be by several orders of magnitude smaller than the total number of EFMs. Using MEMos, we can compute generating sets of EFMs in metabolic networks where the whole set of EFMs is too large to be enumerated.
Predicting mechanism of action of cellular perturbations with pathway activity signatures
Authors: Ren Yan , Sivaganesan Siva , Clark Nicholas A. , Zhang Lixia , Biesiada Jacek , Niu Wen , Plas David R. , Medvedovic Mario
Published: July 2019

Motivation

Misregulation of signaling pathway activity is etiologic for many human diseases, and modulating activity of signaling pathways is often the preferred therapeutic strategy. Understanding the mechanism of action (MOA) of bioactive chemicals in terms of targeted signaling pathways is the essential first step in evaluating their therapeutic potential. Changes in signaling pathway activity are often not reflected in changes in expression of pathway genes which makes MOA inferences from transcriptional signatures a difficult problem.

Results

We developed a new computational method for implicating pathway targets of bioactive chemicals and other cellular perturbations by integrated analysis of pathway network topology, the LINCS transcriptional signatures of genetic perturbations of pathway genes and the transcriptional signature of the perturbation. Our methodology accurately predicts signaling pathways targeted by the perturbation when current pathway analysis approaches utilizing only a transcriptional signature of the perturbation fail.

Availability and Implementation

Open source R package paslincs is available at https://github.com/uc-bd2k/paslincs.
Linkage Disequilibrium and Heterozygosity Modulate the Genetic Architecture of Human Complex Phenotypes
Authors: Holland Dominic , Frei Oleksandr , Desikan Rahul , Fan Chun-Chieh , Shadrin Alexey A. , Smeland Olav B. , Andreassen Ole A. , Dale Anders M.
Published: July 2019

We propose an extended Gaussian mixture model for the distribution of causal effects of common single nucleotide polymorphisms (SNPs) for human complex phenotypes that depends on linkage disequilibrium (LD) and heterozygosity (H), while also allowing for independent components for small and large effects. Using a precise methodology showing how genome-wide association studies (GWAS) summary statistics (z-scores) arise through LD with underlying causal SNPs, we applied the model to GWAS of multiple human phenotypes. Our findings indicated that causal effects are distributed with dependence on total LD and H, whereby SNPs with lower total LD and H are more likely to be causal with larger effects; this dependence is consistent with models of the influence of negative pressure from natural selection. Compared with the basic Gaussian mixture model it is built on, the extended model – primarily through quantification of selection pressure – reproduces with greater accuracy the empirical distributions of z-scores, thus providing better estimates of genetic quantities, such as polygenicity and heritability, that arise from the distribution of causal effects.
A canstatin-derived peptide provides insight into the role of Capillary Morphogenesis Gene 2 in angiogenic regulation and matrix uptake
Authors: Finnell Jordan G. , Tsang Tsz-Ming , Cryan Lorna , Garrard Samuel , Lee Sai-Lun , Ackroyd P. Christine , Rogers Michael S. , Christensen Kenneth A.
Published: July 2019

Capillary Morphogenesis Gene 2 protein (CMG2) is a transmembrane, integrin-like receptor and the primary receptor for the anthrax toxin. In addition to its role as an anthrax toxin receptor, CMG2 has been repeatedly shown to play a role in angiogenic processes. However, the molecular mechanism mediating observed CMG2-related angiogenic effects has not been fully elucidated. Previous studies have found that CMG2 binds type IV collagen (Col-IV), a key component of the vascular basement membrane, as well as other ECM proteins. Currently, no link has been made between these CMG2-ECM interactions and angiogenesis; however, ECM fragments are known to play a role in regulating angiogenesis. Here, we further characterize the CMG2-Col-IV interaction and explore the effect of this interaction on angiogenesis. Using a peptide array, we observed that CMG2 preferentially binds peptide fragments of the NC1 (non-collagenous domain 1) domains of Col-IV. These domains are also known as the fragments arresten (from the α1 chain) and canstatin (from the α2 chain) and have documented antiangiogenic properties. A second peptide array was probed to map a putative binding epitope. A top hit from the initial array, a canstatin-derived peptide, binds to the CMG2 ligand-binding von Willebrand factor A (vWA) domain with sub-micromolar affinity (peptide S16, Kd= 400 ± 200 nM). This peptide competes with anthrax protective antigen (PA) for CMG2 binding, and does not bind CMG2 in the presence of EDTA. Together these data suggest that, like PA, S16 interacts with CMG2 at the metal-ion dependent adhesion site (MIDAS) of its vWA domain. We demonstrate that CMG2 specifically mediates endocytic uptake of S16, since CMG2-/- endothelial cells show markedly reduced S16 uptake, without reducing total endocytosis. Furthermore, we show that S16 reduces endothelial migration but not cell proliferation. Taken together, our data demonstrate that a Col IV-derived anti-angiogenic peptide acts via CMG2, suggesting a possible link between CMG2-Col IV interactions and angiogenesis.
Isolation of a putative S-layer protein from anammox biofilm extracellular matrix using ionic liquid extraction
Authors: Wong Lan Li , Natarajan Gayathri , Boleij Marissa , Thi Sara Swi , Winnerdy Fernaldo Richtia , Mugunthan Sudarsan , Lu Yang , Lee Jong-Min , Lin Yuemei , van Loosdrecht Mark , Law Yingyu , Kjelleberg Staffan , Seviour Thomas
Published: July 2019

Anaerobic ammonium oxidation (anammox) performing bacteria self-assemble into compact biofilms by expressing extracellular polymeric substances (EPS). Anammox EPS are poorly characterized, largely due to their low solubility in typical aqueous solvents. Pronase digestion achieved 19.5 ± 0.9 and 41.4 ± 1.4% (w/w) more solubilization ofCandidatusBrocadia sinica-enriched anammox granules than DNase and amylase respectively. Nuclear magnetic resonance profiling of the granules confirmed that proteins were dominant. We applied ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate and N,N- dimethylacetamide (EMIM-Ac/DMAc) mixture to extract the major structural proteins. Further treatment by anion exchange chromatography isolated homologous S/T-rich proteins BROSI_A1236 and UZ01_01563, which were major components of the extracted proteins and sequentially highly similar to putative anammox surface-layer (S-layer) protein KUSTD1514. EMIM-Ac/DMAc extraction enriched for these putative S-layer proteins against all other major proteins, along with six monosaccharides (i.e. arabinose, xylose, rhamnose, fucose, galactose and mannose). The sugars, however, contributed <0.5% (w/w) of total granular biomass, and were likely co-enriched as glycoprotein appendages. This study demonstrates that S-layer proteins are major constituents of anammox biofilms and can be isolated from the matrix using an ionic liquid-based solvent.
Mechanistic insights into the deleterious role of nasu-hakola disease associated TREM2 variants
Authors: Dash Raju , Choi Ho Jin , Moon Il Soo
Published: July 2019

Recently, critical roles of genetic variants in Triggering Receptor Expressed on Myeloid cells 2 (TREM2) for myeloid cells to Alzhimer’s disease have been aggressively highlighted. However, little studies focused to the deleterious role of Nasu-Hakola disease (NHD) associated TREM2 variants. In order to get insights into the contributions of these variants in neurodegeneration, we investigated the influences of three well-known NHD associated TREM2 mutations (Y38C, T66M and V126G) on the loss-of-function by using conventional molecular dynamics simulation. Compared to the wild type, the mutants produced substantial differences in the collective motions in the loop regions, which not only promotes structural remodelling in complementarity-determining region 2 (CDR2) loop but also in CDR1 loop, through changing the inter and intra-loop hydrogen bonding network. In addition, the structural studies from free energy landscape showed that Y38, T66 and V126 are crucial for maintaining structural features of CDR1 and CDR2 loops, while their mutation at this position produced steric clash and thus contributes to the structural impact and loss of ligand binding. These results revealed that the presence of the mutations in TREM2 ectodomain induced flexibility and promotes structural alterations. Dynamical scenarios, which are provided by the present study, may be critical to our understanding of the role of the three TREM2 mutations in neurodegenerative diseases.
Human Genome Assembly in 100 Minutes
Authors: Chin Chen-Shan , Khalak Asif
Published: July 2019

De novo genome assembly provides comprehensive, unbiased genomic information and makes it possible to gain insight into new DNA sequences not present in reference genomes. Many de novo human genomes have been published in the last few years, leveraging a combination of inexpensive short-read and single-molecule long-read technologies. As long-read DNA sequencers become more prevalent, the computational burden of generating assemblies persists as a critical factor. The most common approach to long-read assembly, using an overlap-layout-consensus (OLC) paradigm, requires all-to-all read comparisons, which quadratically scales in computational complexity with the number of reads. We assert that recently achievements in sequencing technology (i.e. with accuracy ~99% and read length ~10-15k) enables a fundamentally better strategy for OLC that is effectively linear rather than quadratic. Our genome assembly implementation, Peregrine uses sparse hierarchical minimizers (SHIMMER) to index reads thereby avoiding the need for an all-to-all read comparison step. Peregrine can assemble 30x human PacBio CCS read datasets in less than 30 CPU hours and around 100 wall-clock minutes to a high contiguity assembly (N50 > 20Mb). The continued advance of sequencing technologies coupled with the Peregrine assembler enables routine generation of human de novo assemblies. This will allow for population scale measurements of more comprehensive genomic variations -- beyond SNPs and small indels -- as well as novel applications requiring rapid access to de novo assemblies.
CENP-C unwraps the CENP-A nucleosome through the H2A C-terminal tail
Authors: Ali-Ahmad Ahmad , Bilokapić Silvija , Schäfer Ingmar B. , Halić Mario , Sekulić Nikolina
Published: July 2019

Centromeres are defined epigenetically by nucleosomes containing the histone H3 variant CENP-A, upon which the constitutive centromere-associated network of proteins (CCAN) is built. CENP-C, is considered to be a central organizer of the CCAN. We provide new molecular insights into the structure of CENP-A nucleosomes, in isolation and in complex with the CENP-C central region (CENP-CCR), the main CENP-A binding module of CENP-C. We establish that the short αN-helix of CENP-A promotes DNA flexibility at the nucleosome ends, independently of the sequence it wraps.

Furthermore, we show that, in vitro, two regions of CENP-C (CENP-CCRand CENP-Cmotif) both bind exclusively to the CENP-A nucleosome. We find CENP-CCRto bind with high affinity due to an extended hydrophobic area made up of CENP-AV532and CENP-AV533. Importantly, we identify two key conformational changes within the CENP-A nucleosome upon CENP-C binding. First, the loose DNA wrapping of CENP-A nucleosomes is further exacerbated, through destabilization of the H2A N-terminal tail. Second, CENP-CCRrigidifies the N-terminal tail of H4 in the conformation favoring H4K20monomethylation, essential for a functional centromere.

Synopsis

CENP-A nucleosomes have a short αN helix incompatible with complete DNA wrapping, independently of DNA sequence. CENP-C binds exclusively to CENP-A nucleosomes and this binding induces conformational changes that further differentiate CENP-A-containing from canonical nucleosomes.

CENP-C binds CENP-A nucleosomes specifically

DNA ends of the CENP-A nucleosome are further unwrapped in the CENP-A/CENP-C complex, due to flexible H2A C-terminal tails

The N-terminal tail of H4 adopts a conformation favored for centromere specific H4K20monomethylation when CENP-C is bound
Detailed Regulatory Interaction Map of the Human Heart Facilitates Gene Discovery for Cardiovascular Disease
Authors: Bianchi Valerio , Geeven Geert , Tucker Nathan , Hilvering Catharina R.E. , Hall Amelia W. , Roselli Carolina , Hill Matthew C. , Martin James F. , Margulies Kenneth B. , Ellinor Patrick T. , de Laat Wouter
Published: July 2019

Most disease-associated variants identified by population based genetic studies are non-coding, which compromises finding causative genes and mechanisms. Presumably they interact through looping with nearby genes to modulate transcription. Hi-C provides the most complete and unbiased method for genome-wide identification of potential regulatory interactions, but finding chromatin loops in Hi-C data remains difficult and tissue specific data are limited. We have generated Hi-C data from primary cardiac tissue and developed a method, peakHiC, for sensitive and quantitative loop calling to uncover the human heart regulatory interactome. We identify complex CTCF-dependent and -independent contact networks, with loops between coding and non-coding gene promoters, shared enhancers and repressive sites. Across the genome, enhancer interaction strength correlates with gene transcriptional output and loop dynamics follows CTCF, cohesin and H3K27Ac occupancy levels. Finally, we demonstrate that intersection of the human heart regulatory interactome with cardiovascular disease variants facilitates prioritizing disease-causative genes.
Multi-drug resistance bacteria predict mortality in blood stream infection in a tertiary setting in Tanzania
Authors: Manyahi Joel , Kibwana Upendo , Mgimba Edna , Majigo Mtebe
Published: July 2019

Background

Blood-stream infections (BSI’s) are serious and life-threatening infections associated with high mortality and morbidity. In resource limited settings, there is paucity of data on predictors of outcome in patients with BSI. This study aimed at examining the predictors of mortality in patients with BSI as well as bacteria causing BSI.

Methods and Materials

This was cross-sectional study conducted in Muhimbili National Hospital between April and May 2018. Blood culture results from all inpatients at clinical microbiology laboratory were recorded and clinical information were retrieved retrospectively from the files. Bacteria from positive blood culture were identified and antimicrobial susceptibility was performed.

Results

The overall prevalence of BSI was 11.4% (46/402), with case fatality rate of 37%. There was significant high rate of BSI in patient who had died compared to those survived p= 0.008. Gram-negative bacteria (74%) were the common cause of BSI, with predominance of Enterobacteriaceae (22), followed by Pseudomonas aeruginosa (11). Majority (70.5%) of the bacteria isolated from patients with BSI were multi-drug resistant. Forty six percent of Pseudomonas aeruginosa were resistance to meropenem. Sixty eight percent 68.2% (15/22) of Enterobacteriaceae were ESBL producers. Carbapenemases production were detected in 27% (3/11) of Pseudomonas aeruginosa and in one Proteus mirabillis. Forty percent (40%) of Staphylococcus aureus were methicillin resistant Staphylococcus aureus (MRSA). Positive blood culture (cOR 7.4, 95%CI 1.24 – 43.83, p 0.03) and admission in ICU cOR 4 (95%CI 1.7 – 9.41, p 0.001) were independent factors for mortality in suspected BSI. Isolation of Multi-drug resistant bacteria was independent predictor for mortality in confirmed BSI (cOR 7.4, 95%CI 1.24 – 43.83, p 0.03).

Conclusion

The prevalence of BSI was 11.4%, with majority of bacteria in BSI were MDR. Positive blood culture and MDR were predictors for mortality.
Bile acids and bilirubin effects on osteoblastic gene profile. Implications in the pathogenesis of osteoporosis in liver diseases
Authors: Ruiz-Gaspà Silvia , Guañabens Nuria , González Susana Jurado , Dubreuil Marta , Combalia Andres , Peris Pilar , Monegal Ana , Parés Albert
Published: July 2019

Osteoporosis in advanced cholestatic and end-stage liver disease is related to low bone formation. Previous studies have demonstrated the deleterious consequences of lithocholic acid (LCA) and bilirubin on osteoblastic cells. These effects are partially or completely neutralized by ursodeoxycholic acid (UDCA). We have assessed the differential gene expression of osteoblastic cells under different culture conditions. The experiments were performed in human osteosarcoma cells (Saos-2) cultured with LCA 10 μM), bilirubin (50 μM) or UDCA (10 and 100 μM) at 2 and 24 hours. Expression of 87 genes related to bone metabolism and other signalling pathways were assessed by TaqMan micro fluidic cards. Several genes were up-regulated by LCA, most of them pro-apoptotic (BAX,BCL10,BCL2L13,BCL2L14), but alsoMGP(matrix Gla protein), BGLAP(osteocalcin),SPP1(osteopontin) andCYP24A1, and down-regulated bone morphogenic protein genes (BMP3andBMP4) andDKK1(Dickkopf-related protein 1). Parallel effects were observed with bilirubin, which up-regulated apoptotic genes andCSF2(colony-stimulating factor 2) and down-regulated antiapoptotic genes (BCL2andBCL2L1),BMP3,BMP4and RUNX2. UDCA 100 μM had specific consequences since differential expression was observed, up-regulatingBMP2,BMP4,BMP7,CALCR(calcitonin receptor),SPOCK3(osteonectin),BGLAP(osteocalcin) andSPP1(osteopontin), and down-regulating pro-apoptotic genes. Furthermore, most of the differential expression changes induced by both LCA and bilirubin were partially or completely neutralized by UDCA.Conclusion: Our observations reveal novel target genes, whose regulation by retained substances of cholestasis may provide additional insights into the pathogenesis of osteoporosis in cholestatic and end-stage liver diseases.
Sexual behaviour in a murine model of Mucopolysaccharidosis type I (MPS I)
Authors: Mendes Ana Beatriz Barbosa , do Nascimento Cinthia Castro , D’ Almeida Vânia
Published: July 2019

Mucopolysaccharidosis Type I (MPS I) is a rare genetic lysosomal storage disease caused by a mutation ofIDUAgene.IDUAcodes for α-L-iduronidase (IDUA), a lysosomal hydrolase that degrades glycosaminoglycans (GAGs): heparan sulphate and dermatan sulphate. GAGs are structural and signalling molecules that have a crucial role in controlling a variety of cell functions and their interaction with extracellular matrix. Because of GAG’s widespread action in cellular metabolism, MPS I is a progressive and disabling multisystemic disorder. Nowadays, the therapies availability allowed patients to reach the adult life and the consequences of the disease in their reproductive system is still little known. We aimed to investigate whether IDUA disruption influences sexual behaviour and sexual steroid production in male and female MPS I mice. We used 3 and 6-month-old male and 3-month-old femaleIdua+/_ andIdua−/− mice to evaluate typical rodent copulatory behaviours. In males we observed the frequency and latency of mounts, intromissions and ejaculations. In females we evaluated the lordosis quotient. We also analysed the locomotor capacity of mice in the open field test, since copulatory behaviour requires mobility. We also quantified steroidal hormonal levels in plasmatic samples. We detected an increase in the latencies of intromissions in male copulatory behaviour ofIdua−/− males when compared toIdua+/_. However, the number of intromissions was not statistically different between groups. No parameter of female sexual behaviour was statistically different between control and knockout females. In both sexes, we detected diminished mobility inIdua−/− mice. Plasma hormone levels did not differ betweenIdua+/_ andIdua−/− mice, both in males and females. We concluded that in the considered time point of MPS I progression, mice are able to perform sexual behaviour, but the male performance may be influenced due to the motor disability predicted to MPS I.
Nanopore direct RNA sequencing maps an Arabidopsis N6 methyladenosine epitranscriptome
Authors: Parker Matthew T. , Knop Katarzyna , Sherwood Anna V. , Schurch Nicholas J. , Mackinnon Katarzyna , Gould Peter D. , Hall Anthony , Barton Geoffrey J. , Simpson Gordon G.
Published: July 2019

Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of m6A from 3’ untranslated regions is associated with decreased relative transcript abundance and defective RNA 3′ end formation. A functional consequence of disrupted m6A is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode.
The role of integrins inDrosophilaegg chamber morphogenesis
Authors: Lovegrove Holly E. , Bergstralh Dan T. , St Johnston Daniel
Published: July 2019

ADrosophilaegg chamber is comprised of a germline cyst surrounded by a tightly-organised epithelial monolayer, the follicular epithelium (FE). Loss of integrin function from the FE disrupts epithelial organisation at egg chamber termini, but the cause of this phenotype remains unclear. Here we show that the β-integrin Myospheroid (Mys) is only required during early oogenesis when the pre-follicle cells form the FE.mysmutants disrupt both the formation of a monolayered epithelium at egg chamber termini and the morphogenesis of the stalk between adjacent egg chambers, which develops through the intercalation of two rows of cells into a single-cell wide stalk. Secondary epithelia, like the FE, have been proposed to require adhesion to the basement membrane to polarise. However, Mys is not required for pre-follicle cell polarisation, as both follicle and stalk cells localise polarity factors correctly, despite being mispositioned. Instead, loss of integrins causes pre-follicle cells to basally constrict, detach from the basement membrane and become internalised. Thus, integrin function is dispensable for pre-follicle cell polarity but is required to maintain cellular organisation and cell shape during morphogenesis.
Profiling the long noncoding RNA interaction network in the regulatory elements of target genes by chromatin in situ reverse transcription sequencing
Authors: Zhang Shilin , Wang Yichen , Jia Lin , Wen Xue , Du Zhonghua , Wang Cong , Hao Yajing , Yu Dehai , Zhou Lei , Chen Naifei , Chen Jingcheng , Chen Huiling , Zhang Hui , Celik Ilkay , Gülsoy Günhan , Luo Jianjun , Qin Baoming , Cui Xueling , Liu Zhonghui , Zhang Songling , Esteban Miguel A. , Ay Ferhat , Xu Wei , Chen Runsheng , Li Wei , Hoffman Andrew R. , Hu Ji-Fan , Cui Jiuwei
Published: July 2019

Long noncoding RNAs (lncRNAs) can regulate the activity of target genes by participating in the organization of chromatin architecture. We have devised a “chromatin-RNA in situ reverse transcription sequencing” (CRIST-seq) approach to profile the lncRNA interaction network in gene regulatory elements by combining the simplicity of RNA biotin labeling with the specificity of the CRISPR/Cas9 system. Using gene-specific gRNAs, we describe a pluripotency-specific lncRNA interacting network in the promoters of Sox2 and Pou5f1, two critical stem cell factors that are required for the maintenance of pluripotency. The promoter-interacting lncRNAs were specifically activated during reprogramming into pluripotency. Knockdown of these lncRNAs caused the stem cells to exit from pluripotency. In contrast, overexpression of the pluripotency-associated lncRNA activated the promoters of core stem cell factor genes and enhanced fibroblast reprogramming into pluripotency. These CRIST-seq data suggest that the Sox2 and Pou5f1 promoters are organized within a unique lncRNA interaction network that determines the fate of pluripotency during reprogramming. This CRIST approach may be broadly used to map lncRNA interaction networks at target loci across the genome.
Imperfect certification and eco-labelling of products
Authors: Grover Charu , Bansal Sangeeta
Published: July 2019

Purpose

This paper aims to investigate the role of certification in providing information and reducing market inefficiencies when the “certification process is imperfect”. In the setting, eco-labels imperfectly signal environmental product quality to consumers where the error in the process of certification could be either Type 1 or Type 2 error. The paper examines firms' incentive to get certified, equilibrium quantities and profits. The authors use perfect Bayesian equilibrium concept for the analysis. They then examine conditions for separating and pooling equilibrium to exist and welfare implications of certification process.

Design/methodology/approach

The paper uses a vertical product differentiated model where firms are competing in quantities. Consumers are unable to observe the environmental quality of the product. To signal the product quality to consumers, firms may adopt certification by a third party. Using a framework where certification process is imperfect, the paper derives conditions for Perfect Bayesian separating and pooling equilibrium to exist.

Findings

The paper shows that the existence of separating and pooling equilibrium depends on the certification fee. A separating equilibrium, where one firm seeks certification and other firm does not seek certification exists for an intermediate value of certification fee. A pooling equilibrium, where both firms seek certification, exists only when the certification fee is sufficiently small. The paper shows conditions for the certification fee for which welfare will be higher under separating equilibrium as compared to pooling equilibrium and analyses welfare implications for subsidy policy for the certification fee.

Originality/value

The paper contributes to the literature by examining the role of labelling under imperfect certification.
The influence of cognitive style diversity on intra-group relationship conflict, individual-level organizational citizenship behaviors and the moderating role of leader-member-exchange
Authors: Qi Meng , Armstrong Steven John
Published: July 2019

Purpose

This paper aims to investigate the influence of cognitive style diversity on intra-group relationship conflict and individual-level organizational citizenship behaviors (OCBs). The role of leader-member exchange as a moderating variable is also examined.

Design/methodology/approach

The authors used hierarchical linear modeling and hierarchical regression analysis to analyze results from a sample of 344 members from 83 teams nested within 126 departments in six manufacturing organizations in the People’s Republic of China.

Findings

Results yielded general support for our hypothesized relationships between cognitive style diversity and intra-group relationship conflict. Leader-member exchange was also found to moderate the relationship between these two variables. Contrary to expectations, there were no relationships between these variables and individual-level organizational citizenship behaviors.

Originality/value

This research addresses calls from the team diversity and conflict literature to address the understudied area of deep-level cognitive diversity. Second, this study addresses previous calls for more team-level and mixed-level theory and methodology to inform OCB research. Third, this is the first study of group-level cognitive style diversity and the moderating influence of leader-member-exchange and provides valuable insights into ways of mitigating some of the negative effects of cognitive diversity on teams.
Project managers adjust their leadership: to workspace and project type
Authors: Vaagaasar Anne Live , Müller Ralf , De Paoli Donatella
Published: July 2019

Purpose

The purpose of this paper is to investigate the triadic relationship between project workspace (i.e. spatial context), project type and project manager’s leadership style. It develops the concept of leadership construct (i.e. mental models of leadership to predispose the way leadership is performed) to explain related preferences for workspace and behaviors.

Design/methodology/approach

A combination of phenomenological inquiry on preferred workspaces in different project types is combined with a conceptual study on related leadership styles in these settings.

Findings

Four different leadership constructs are identified, which are conditioned by workspace and project type: one-on-one, virtual, interactive and mixed leadership. Also, four leadership patterns are identified, and these are related to open office and virtual office settings in product, service, software development and infrastructure construction projects.

Research limitations/implications

The results show the interaction of workspace, project type and leadership styles, which extends existing leadership theory and provides more granularity in determining appropriate leadership styles for project managers.

Practical implications

Practitioners benefit from a more conscious selection of appropriate leadership styles, which positively impacts project results.

Originality/value

By linking workspace, project type and leadership styles, the study is the first of its kind and a novel contribution to theory in project leadership.
Examining customer-oriented positive deviance intentions of retail employees
Authors: Fazel-e-Hasan Syed Muhammad , Mortimer Gary , Lings Ian , Drennan Judy
Published: July 2019

Purpose

Occasionally, retail employees “break the rules” in order to help customers. Currently, there is little research on the mechanisms by which a sales assistants’ positive deviance intentions help them attain specific personal and organisational goals. The purpose of this paper is to examine one mechanism, hope, which develops employees’ deviance intentions to provide benefits to the customer, themselves and the organisation.

Design/methodology/approach

A survey captured responses from 270 frontline employees from the retail and services sector. AMOS 23 was used to conduct measurement, path and mediation analyses.

Findings

This study highlights the role of employee hope in developing employees’ positive deviance intentions, and improving perceptions of organisational performance. Results demonstrate that the direct positive impact of hope on positive deviance intention was significant. Furthermore, positive deviance intention was found to positively impact employee goal attainment and perceived organisational performance. The authors’ employee hope model offers a better understanding of positive outcomes of employee deviance, suggesting that retail managers should invest resources to build strong employee–organisation relationships.

Originality/value

This is the first study to empirically demonstrate that employee hope can explain how customer-oriented positive deviance intentions help employee goal attainment and improve their perceptions of organisational performance.
Effects of 3D vs 2D interfaces and product-coordination methods
Authors: Sina Ahmad Saquib , Wu Juanjuan
Published: July 2019

Purpose

The purpose of this paper is to examine the effects of product display based on colour, discount and brand on retail pleasure, arousal, flow, perceived merchandise quality, time spent, satisfaction and patronage intentions in both 3D and 2D interfaces. This study uses the flow theory and stimulus-organism-response framework to understand the effects of product coordination methods and interface dimensions on consumers’ emotional, cognitive and behavioural outcomes.

Design/methodology/approach

This study conducted a 2 (interface: 3D and 2D) × 3 (product coordination method: colour, discount and brand) between-subjects experimental design. The coordination of display refers to the way products are arranged based on similar properties, such as similar colour, discount or brand. 3D stores were designed using Mockshop, a 3D virtual retailing software. A total of 144 US female college students from various universities participated in the study.

Findings

The findings showed that the 3D interface produced higher flow, satisfaction, time spent and patronage intention than the 2D interface. Also, among the six display scenarios, participants who were in the colour-coordinated 3D store showed the highest levels of emotional, cognitive and behavioural outcomes except for retail pleasure and arousal.

Originality/value

This study investigates product display based on colour, discount and brand in both 3D and 2D interfaces. Although product coordination methods have been tested in 3D stores in previous studies, they have not been compared with their effects in the 2D interface such as online shopping sites. Therefore, this study fills in this gap in the literature, which can guide retailers in making the right decisions for visuals.
Architectural marketing capabilities of exporting ventures
Authors: Theoharakis Vasilis , Angelis Yannis , Batsakis Georgios
Published: July 2019

Purpose

The importance of architectural marketing capabilities (i.e. marketing planning and implementation) in exporting ventures has been recognised. However, extant literature has not taken into account the explicit roles and required synergy between the exporter and their foreign distributor in delivering these capabilities. Drawing from the resource-based theory, the purpose of this paper is to examine the complementarity of distributor implementation capability and market orientation with exporter planning capability.

Design/methodology/approach

The study was carried out using a survey. Data were collected from 147 Greek exporters who replied to our questionnaire and the hypotheses were tested using the full information maximum likelihood estimation procedure.

Findings

The results support the hypotheses about the importance of exporter planning capability on financial performance and the complementary role of distributor market orientation. Further, the authors find that the distributor’s implementation capability partially mediates the impact of the exporter’s planning capability on financial performance.

Originality/value

This study contributes to a better understanding about the complementarity of exporter and distributor capabilities. It demonstrates the crucial role of the distributor in the deployment of architectural capabilities for the export venture: the distributor’s market orientation and implementation capability have the final say in achieving higher levels of export performance.
High precise and zero-cost solution for fully automatic industrial robot TCP calibration
Authors: Cakir Mustafa , Deniz Cengiz
Published: July 2019

Purpose

The purpose of this study is to present a novel method for industrial robot TCP (tool center point) calibration. The proposed method offers fully automated robot TCP calibration within a defined cycle time. The method is applicable for large-scale installations due to its zero cost for each robot.

Design/methodology/approach

Precise and expensive measuring equipment or specially designed reference devices are required for robot calibration. The calibration can be performed by using only one plane plate in this method, and the calibration procedure is defined step by step: the robot moves to the target plane position. Then, the TCP touches the plane and the actual robot configuration is recorded. Then robot moves back into position and the same step is repeated for a new sample. Alternatively, the robot can be stationary and the plane can be moved towards the robot TCP. TCP is calculated by processing the difference of the contact points recorded at different positions. The process is fully automated. No special equipment is used. The calculations are very simple, and the robot controller can easily be realized.

Findings

The conventional manual robot TCP calibration process takes about 15 min and takes more time in case of the high accuracy. The proposed method reduces this time to less than 3 min without operator support. Practical tests have shown that TCP calibration can be performed with 0.1-0.6 mm of accuracy. This solution is an automated process and does not require special installation and it also has approximately zero cost. For this reason, this study recommends using the proposed solution widely in areas where even one or hundreds of robots are located.

Research limitations/implications

In this study, the data were directly taken from the robot controller without using any special measuring equipment. The industrial robot used in the tests has no absolute calibration. The classical “four-point method” was used for reference TCP data. It is the initial acceptance that this process conducted with extreme care and by using a needle-tipped tool will not produce exact values. It was observed that deviation of the TCP from a fixed point in reorient motions was not more than 0.5 mm. This method has been validated for different bits. The pilot works for different robot applications in Ford Otosan Gölcük Plant have been completed and dissemination has started.

Originality/value

Although the approach uses is clear and simple, it is surprising that the calculation of TCP using plane equations has so far not been mentioned in the literature. The disadvantage of using either fixed point or sphere as a reference is that the TCP cannot automatically guide to the target. This problem was overcome with the use of a larger target plane plate and the process was fully automated. The proposed method can be widely used in practical applications.