bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractAnaerobic 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

AbstractRecently, 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

AbstractDe 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

AbstractCentromeres 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.SynopsisCENP-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 specificallyDNA ends of the CENP-A nucleosome are further unwrapped in the CENP-A/CENP-C complex, due to flexible H2A C-terminal tailsThe 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

SummaryMost 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

AbstractBackgroundBlood-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 MaterialsThis 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.ResultsThe 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).ConclusionThe 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

AbstractOsteoporosis 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

AbstractMucopolysaccharidosis 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

AbstractUnderstanding 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

AbstractADrosophilaegg 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.
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

PurposeThis 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/approachThe 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.FindingsResults 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/valueThis 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

PurposeThe 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/approachA combination of phenomenological inquiry on preferred workspaces in different project types is combined with a conceptual study on related leadership styles in these settings.FindingsFour 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/implicationsThe 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 implicationsPractitioners benefit from a more conscious selection of appropriate leadership styles, which positively impacts project results.Originality/valueBy linking workspace, project type and leadership styles, the study is the first of its kind and a novel contribution to theory in project leadership.