bluuebunny/crossref_metadata_2025 huggingface dataset:
The ghr-miR164 and GhNAC100 module participates in cotton plant defence against Verticillium dahliae
Authors: Hu Guang , Lei Yu , Wang Le , Liu Jianfen , Tang Ye , Zhang Zhennan , Chen Aiming , Peng Qingzhong , Yang Zuoren , Wu Jiahe
Published: October 2018

Previous reports have shown that many miRNAs were identified at the early induction stage during which Verticillium dahliae localizes at the root surface. In this study, we constructed two sRNA libraries of cotton root responses to this fungus at the later induction stage when the pathogen enters the root vascular tissue. We identified 71 known miRNAs and 378 novel miRNAs from two pathogen-induced sRNAs and the control libraries. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the ghr-miR164-GhNAC100 module in the response of the plant to V dahliae infection. A GUS fusion reporter showed that ghr-miR164 directly cleaved the mRNA of GhNAC100 in the post-transcriptional process. ghr-miR164-silencing increased the resistance of the plant to this fungus, while the knockdown of GhNAC100 elevated the susceptibility of the plant, indicating that ghr-miR164-GhNAC100 modulates plant defence through the post-transcriptional regulation. Our data documented that there are numerous miRNAs at the later induction stage that participate in the plant response to V. dahliae, suggesting that miRNAs play important roles in plant resistance to vascular disease.

Highlight

According to degradome and sRNA sequencings of cotton root in responses to Verticillium dahliae at the later induction stage, many miRNAs and corresponding targets including ghr-miR164-GhNAC100 module participate plant defence.
PREPRINT: Using digital epidemiology methods to monitor influenza-like illness in the Netherlands in real-time: the 2017-2018 season
Authors: Schneider PP , van Gool CJAW , Spreeuwenberg P , Hooiveld M , Donker GA , Barnett DJ , Paget J
Published: October 2018

Introduction

Despite the early development of Google Flu Trends in 2009, digital epidemiology methods have not been adopted widely, with most research focusing on the USA. In this article we demonstrate the prediction of real-time trends in influenza-like illness (ILI) in the Netherlands using search engine query data.

Methods

We used flu-related search query data from Google Trends in combination with traditional surveillance data from 40 general sentinel practices to build our predictive models. We introduced an artificial 4-week delay in the use of GP data in the models, in order to test the predictive performance of the search engine data.

Simulating the weekly use of a prediction model across the 2017/2018 flu season we used lasso regression to fit 52 prediction models (one for each week) for weekly ILI incidence. We used rolling forecast cross-validation for lambda optimization in each model, minimizing the maximum absolute error.

Results

The models accurately predicted the number of ILI cases during the 2017/18 ILI epidemic in real time with a mean absolute error of 1.40 (per 10,000 population) and a maximum absolute error of 6.36. The model would also have identified the onset, peak, and end of the epidemic with reasonable accuracy

The number of predictors that were retained in the prediction models was small, ranging from 3 to 5, with a single keyword (‘Griep’ = ‘Flu’) having by far the most weight in all models.

Discussion

This study demonstrates the feasibility of accurate real-time ILI incidence predictions in the Netherlands using internet search query data. Digital ILI monitoring strategies may be useful in countries with poor surveillance systems, or for monitoring emergent diseases, including influenza pandemics. We hope that this transparent and accessible case study inspires and supports further developments in field of digital epidemiology in Europe and beyond.
Activation of the endoplasmic reticulum unfolded protein response reverses an inflammation-like response to cytoplasmic DNA
Authors: Williams Ashley B. , Heider Felix , Messling Jan-Erik , Bloch Wilhelm , Schumacher Björn
Published: October 2018

Innate immune responses protect organisms against various insults, but may lead to tissue damage when aberrantly activated. In higher organisms, cytoplasmic DNA can trigger inflammation that can lead to tissue degeneration. Simpler in vivo models could shed new mechanistic light on how inflammatory responses to cytoplasmic DNA lead to pathology. Here we show that in DNase II-deficient Caenorhabditis elegans, persistent foreign cytoplasmic DNA leads to systemic tissue degeneration, and we identify impaired protein homeostasis as an inflammatory pathomechanism. This pathological outcome can be alleviated by improving protein homeostasis, either via ectopic induction of the endoplasmic reticulum unfolded protein response (UPRER) or by treatment with N-acetylglucosamine. Our results establish C. elegans as an ancestral metazoan model for studying outcomes of inflammation-like conditions caused by persistent cytoplasmic DNA and provide insight into potential therapies for conditions involving chronic inflammation.
∆9-tetrahydrocannabinol negatively regulates neurite outgrowth and Akt signaling in hiPSC-derived cortical neurons
Authors: Shum Carole , Dutan Lucia , Annuario Emily , Warre-Cornish Katherine , Taylor Samuel E. , Taylor Ruth D. , Andreae Laura C. , Buckley Noel J. , Price Jack , Bhattacharyya Sagnik , Srivastava Deepak P.
Published: October 2018

Endocannabinoids regulate different aspects of neurodevelopment. In utero exposure to the exogenous psychoactive cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC), has been linked with abnormal cortical development in animal models. However, much less is known about the actions of endocannabinoids in human neurons. Here we investigated the effect of the endogenous endocannabinoid 2-arachidonoyl glycerol (2AG) and Δ9-THC on the development of neuronal morphology and activation of signaling kinases, in cortical glutamatergic neurons derived from human induced pluripotent stem cells (hiPSCs). Our data indicate that the cannabinoid type 1 receptor (CB1R), but not the cannabinoid 2 receptor (CB2R), GPR55 or TRPV1 receptors, is expressed in young, immature hiPSC-derived cortical neurons. Consistent with previous reports, 2AG and Δ9-THC negatively regulated neurite outgrowth. Interestingly, acute exposure to both 2AG and Δ9-THC inhibited phosphorylation of serine/threonine kinase extracellular signal-regulated protein kinases (ERK1/2), whereas Δ9-THC also reduced phosphorylation of Akt (aka PKB). Moreover, the CB1R inverse agonist SR 141716A attenuated the negative regulation of neurite outgrowth and ERK1/2 phosphorylation induced by 2AG and Δ9-THC. Taken together, our data suggest that hiPSC-derived cortical neurons express CB1Rs and are responsive to both endogenous and exogenous cannabinoids. Thus, hiPSC-neurons may represent a good cellular model for investigating the role of the endocannabinoid system in regulating cellular processes in human neurons.
The causal structure of age-dependent limbic decline: fornix white matter glia damage causes hippocampal grey matter damage, notvice versa
Authors: Metzler-Baddeley Claudia , Mole Jilu P. , Sims Rebecca , Fasano Fabrizio , Evans John , Jones Derek K. , Aggleton John P. , Baddeley Roland J.
Published: October 2018

Aging leads to gray and white matter decline but their causation remains unclear. We explored two broad classes of models of age and dementia risk related brain changes. The first class of models emphasises the importance of gray matter: age and risk-related processes cause neurodegeneration and this causes damage in associated white matter tracts. The second class of models reverses the direction of causation: aging and risk factors cause white matter damage and this leads to gray matter damage. We compared these models with linear mediation analysis and quantitative multi-modal MRI indices (from diffusion, quantitative magnetization transfer and relaxometry imaging) of tissue properties in two limbic structures implicated in age-related memory decline: the hippocampus and the fornix in 166 asymptomatic individuals (aged 38 - 71 years). Aging was associated with apparent glia but not axon density damage in the fornix. Mediation analysis unambiguously supported white matter damage causing gray matter decline; controlling for fornix glia damage, the correlation between age and hippocampal damage disappears, but notvice versa. Fornix and hippocampal tissue loss were both associated with reductions in episodic memory performance. The implications of these findings for neuroglia and neurodegenerative models of aging and late onset dementia are discussed.
Evolutionary characteristics of intergenic transcribed regions indicate widespread noisy transcription in the Poaceae
Authors: Lloyd John P. , Bowman Megan J. , Azodi Christina B. , Sowers Rosalie P. , Moghe Gaurav D. , Childs Kevin L. , Shiu Shin-Han
Published: October 2018

Extensive transcriptional activity occurring in unannotated, intergenic regions of genomes has raised the question whether intergenic transcription represents the activity of novel genes or noisy expression. To address this, we evaluated cross-species and post-duplication sequence and expression conservation of intergenic transcribed regions (ITRs) in four Poaceae species. Most ITR sequences are species-specific. Those found across species tend to be more divergent in expression and have more recent duplicates compared to annotated genes. To assess if ITRs are functional (under selection), machine learning models were established in Oryza sativa (rice) that could distinguish between benchmark functional (phenotype genes) and nonfunctional (pseudogenes) sequences with high accuracy based on 44 evolutionary and biochemical features. Based on the prediction models, 584 rice ITRs (8%) are classified as likely functional that tend to have conserved expression and ancient retained duplicates. However, most ITRs do not exhibit sequence or expression conservation across species or following duplication, consistent with computational predictions that suggest 61% ITRs are not under selection. We outline key evolutionary characteristics that are tightly associated with likely-functional ITRs and provide a framework to identify novel genes to improve genome annotation and move toward connecting genotype to phenotype in crop and model systems.
Can Metabolic Thresholds be used as Exercise Intensity Markers in Adult men with Obesity?
Authors: Ratko Peric , Zoran Nikolovski
Published: October 2018

The first aim of the study was to identify the exercise intensity eliciting the highest (FATmax) and the lowest (FATmin) fat oxidation rate in men with obesity. The second aim was to evaluate if FATmax and FATmin correlate with aerobic (AeT) and anaerobic (AnT) thresholds, which in turn could be used as exercise intensity markers. Nineteen adult sedentary men participated in the study. Breath-by-breath analysis was performed throughout the test to assess maximal oxygen consumption (VO2max) with stoichiometric equations used to calculate fat oxidation rate. Pearson correlation coefficient (r), coefficient of determination (R2) and paired t-test were used to evaluate differences between VO2 at AeT and at FATmax and VO2 at AnT and at FATmin, respectively. FATmax and AeT occurred at 42.80 ± 2.68 % of VO2max and 43.02 ± 2.73 % of VO2max, while FATmin and AnT occurred at 53.40 ± 3.65 % of VO2max and 53.38 ± 3.65 % of VO2max, respectively. A high correlations were found between VO2 at FATmax and at AeT (r = 0.86, p < 0.01) and VO2 at FATmin and at AnT (r = 0.99, p < 0.01). The existing correlations suggest that metabolic thresholds may be used as exercise intensity markers in men with obesity.
Spheroid culture of mesenchymal stromal cells results in morpho-rheological properties appropriate for improved microcirculation
Authors: Tietze Stefanie , Krater Martin , Jacobi Angela , Taubenberger Anna , Herbig Maik , Wehner Rebekka , Schmitz Marc , Otto Oliver , List Catrin , Kaya Berna , Wobus Manja , Bornhauser Martin , Guck Jochen
Published: October 2018

Human bone marrow mesenchymal stromal cells (MSCs) have been used in clinical trials for the treatment of systemic inflammatory diseases due to their regenerative and immunomodulatory properties. However, intravenous administration of MSCs is hampered by cell trapping within the pulmonary capillary networks. Here, we hypothesize that traditional twodimensional (2D) plastic-adherent cell expansion fails to result in appropriate morphorheological properties required for cell-circulation. To address this issue, we adapted a novel method to culture MSCs in non-adherent three-dimensional (3D) spheroids (mesenspheres). The biological properties of mesensphere-cultured MSCs remained identical to conventional 2D cultures. Morpho-rheological analyses revealed a smaller size and lower cell stiffness of mesensphere-derived MSCs compared to plastic-adherent MSCs, measured using real-time deformability cytometry (RT-DC) and atomic force microscopy, resulting in an increased ability to pass through micro-constrictions in an ex vivo microcirculation assay. This ability was confirmed in vivo by analysis of cell accumulation in various organ capillary networks after intravenous injection of mesensphere-derived MSCs in mouse. Our findings generally identify cellular morpho-rheological properties as attractive targets to improve microcirculation and specifically suggest mesensphere cultures as a promising approach for optimized MSC-based therapies.
Flux-Balance Based Modeling of Biofilm Communities
Authors: Zhang T. , Parker A. , Carlson R.P. , Stewart P.S. , Klapper I.
Published: October 2018

Models of microbial community dynamics generally rely on a sub-scale model for microbial metabolisms. In systems such as distributed multispecies communities like biofilms, where it is not reasonable to simplify to a small number of limiting substrates, tracking the large number of active metabolites likely requires measurement or estimation of large numbers of kinetic and regulatory parameters. Alternatively, a largely kinetics-free methodology is proposed combining cellular level constrained, steady state metabolic flux analysis with macro scale microbial community models. The methodology easily allows coupling of macroscale information, including measurement data, with cell-scale metabolism. Illustrative examples are included.
Cyclin B2 is required for progression through meiosis in mouse oocytes
Authors: Daldello Enrico Maria , Luong Xuan G. , Yang Cai-Rong , Kuhn Jonathan , Conti Marco
Published: October 2018

Cyclins associate with CDK1 to generate the M-phase-promoting factor (MPF) essential for progression through mitosis and meiosis. Previous studies concluded that CCNB2 is dispensable for cell cycle progression. Given our findings of high translation rates ofCcnB2mRNA in prophase-arrested oocytes, we have reevaluated its role during meiosis.CcnB2−/−oocytes undergo delayed germinal vesicle breakdown followed by a defective M-phase due to reduced pre-MPF activity. This disrupted maturation is associated with compromisedCcnB1andMosmRNA translation and delayed spindle assembly. Given these defects, a significant population of oocytes fail to complete meiosis I because SAC remains activated and APC function is inhibited.In vivo, CCNB2 depletion leads to decreased oocyte developmental competence, compromised fecundity, and premature ovarian failure. These findings demonstrate that CCNB2 is required to assemble sufficient pre-MPF for timely meiosis reentry and progression. Although endogenous cyclins cannot compensate, overexpression of CCNB1 rescues the meiotic phenotypes, demonstrating similar molecular properties but divergent modes of regulation of these cyclins.
The RhoGAP SPV-1 regulates calcium signaling to control the contractility of theC. elegansspermatheca during embryo transits
Authors: Bouffard Jeff , Cecchetelli Alyssa D. , Clifford Coleman , Sethi Kriti , Zaidel-Bar Ronen , Cram Erin J.
Published: October 2018

Contractility of the non-muscle and smooth muscle cells that comprise biological tubing is regulated by the Rho-ROCK and calcium signaling pathways. Although many molecular details about these signaling pathways are known, less is known about how they are coordinated spatiotemporally in biological tubes. The spermatheca of theC. elegansreproductive system enables study of the signaling pathways regulating actomyosin contractility in live adult animals. The RhoGAP SPV-1 was previously identified as a negative regulator of RHO-1/Rho and spermathecal contractility. Here, we uncover a role for SPV-1 as a key regulator of calcium signaling.spv-1mutants expressing the calcium indicator GCaMP in the spermatheca exhibit premature calcium release, elevated calcium levels, and disrupted spatial regulation of calcium signaling during spermathecal contraction. Although RHO-1 is required for spermathecal contractility, RHO-1 does not play a significant role in regulating calcium. In contrast, activation of CDC-42 recapitulates many aspects ofspv-1mutant calcium signaling. Depletion ofcdc-42by RNAi does not suppress the premature or elevated calcium signal seen inspv-1mutants, suggesting other targets remain to be identified. Our results suggest SPV-1 works through both the Rho-ROCK and calcium signaling pathways to coordinate cellular contractility.

Highlight Summary

Throughin vivoimaging of the calcium sensor GCaMP, we show that the RhoGAP SPV-1 is a key regulator of calcium signaling in theC. elegansspermatheca. Our data suggests SPV-1 acts at least partially through the small GTPase CDC-42 to modulate calcium signaling, while also acting on RHO-1 to modulate Rho-ROCK signaling. This places SPV-1 as a central regulator of cellular contractility.
In vivo assembly and trafficking of olfactory Ionotropic Receptors
Authors: Abuin Liliane , Prieto-Godino Lucia L. , Pan Haiyun , Gutierrez Craig , Huang Lan , Jin Rongsheng , Benton Richard
Published: October 2018

lonotropic Receptors (IRs) are a large, divergent subfamily of ionotropic glutamate receptors(iGluRs), with roles in chemosensation, thermosensation and hygrosensation. Analogous to the synaptic targeting mechanisms of their iGluR ancestors, IRs are thought to form complexes of broadly-expressed co-receptors and selectively-expressed ‘tuning’ receptors to localise to sensory cilia. While tuning receptors’ extracellular ligand-binding domain (LBD) defines sensory specificity, the role of this domain in co-receptors is unclear. We identify a coreceptor-specific sequence in the LBD, which contains a single N-glycosylation site. Combining molecular genetic and cell biological analyses, we show that this site is dispensable for assembly of IR complexes in olfactory sensory neurons, but essential for endoplasmic reticulum exit of some,but not all, IR complexes. Our data reveal an important role for the IR co-receptor LBD in control of intracellular transport, provide novel insights into the stoichiometry and assembly of IR complexes, and uncover an unexpected heterogeneity in the trafficking regulation of this sensory receptor family.
The ULK1-FBXW5-SEC23B nexus controls autophagy
Authors: Jeong Yeon-Tae , Simoneschi Daniele , Keegan Sarah , Melville David , Adler Natalia S. , Saraf Anita , Florens Laurence , Washburn Michael P. , Cavasotto Claudio N. , Fenyö David , Cuervo Ana-Maria , Rossi Mario , Pagano Michele
Published: October 2018

In response to nutrient deprivation, the cell needs to mobilize an extensive amount of membrane to form and grow the autophagosome, allowing the progression of autophagy. By providing membranes and a source for LC3 lipidation, COPII (Coat Protein Complex II) localizes to the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC) and promotes autophagosome biogenesis. However, the molecular mechanisms that, in response to starvation, divert COPII from the secretory pathway to the autophagic pathway are largely unknown. Here, we show that the F-box protein FBXW5 targets SEC23B, a component of COPII, for proteasomal degradation and that this event limits the autophagic flux in the presence of nutrients. In response to starvation, ULK1 phosphorylates SEC23B on Serine 186, preventing the interaction of SEC23B with FBXW5 and, therefore, inhibiting its degradation. Phosphorylated and stabilized SEC23B associates with SEC24A and SEC24B, but not SEC24C and SEC24D, and they re-localize to the ERGIC, promoting autophagic flux. Induction of autophagy and localization of both SEC23B and SEC24B to the ERGIC in response to nutrient deprivation are significantly reduced in SEC23B(S186A) knock-in cells. We propose that, in the presence of nutrients, FBXW5 limits COPII-mediated autophagosome biogenesis. Inhibition of this event by ULK1 ensures efficient execution of the autophagic cascade in response to nutrient starvation.
Dynamic regulation of the Trypanosoma brucei transferrin receptor in response to iron starvation is mediated via the 3’UTR
Authors: Benz Corinna , Lo Winston , Fathallah Nadin , Connor-Guscott Ashley , Benns Henry J. , Urbaniak Michael D
Published: October 2018

The bloodstream form of the parasite Trypanosoma brucei obtains iron from its mammalian host by receptor-mediated endocytosis of host transferrin through its own unique transferrin receptor (TbTfR). Expression of TbTfR rapidly increases upon iron starvation by post-transcriptional regulation through a currently undefined mechanism that is distinct from the mammalian iron response system. We have created reporter cell lines by fusing the TbTfR 3′UTR or a control Aldolase 3’UTR to reporter genes encoding GFP or firefly Luciferase, and inserted the fusions into a bloodstream form cell line at a tagged ribosomal RNA locus. Fusion of the TbTfR 3’UTR is sufficient to significantly repress the expression of the reporter proteins under normal growth conditions. Under iron starvation conditions we observed upregulation of the TbTfR 3’UTR fusions only, with a magnitude and timing consistent with that reported for upregulation of the TbTfR. We conclude that the dynamic regulation of the T. brucei transferrin receptor in response to iron starvation is mediated via its 3’UTR, and that the effect is independent of genomic location.
Insights into the genetic diversity ofMycobacterium tuberculosisin Tanzania
Authors: Rutaihwa Liliana K. , Sasamalo Mohamed , Jaleco Aladino , Hella Jerry , Kingazi Ally , Kamwela Lujeko , Kingalu Amri , Malewo Bryceson , Shirima Raymond , Doetsch Anna , Feldmann Julia , Reinhard Miriam , Borrell Sonia , Reither Klaus , Doulla Basra , Fenner Lukas , Gagneux Sebastien
Published: October 2018

Background

Human tuberculosis (TB) is caused by seven phylogenetic lineages of theMycobacterium tuberculosiscomplex (MTBC), Lineage 1–7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for rapid and phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, different strains of the MTBC influence the outcome of TB infection and disease. In Tanzania, such molecular epidemiological studies of TB however are scarce in spite of a high TB burden.

Methods and Findings

Here we used a SNP-typing method to genotype a nationwide collection of 2,039 MTBC clinical isolates obtained from new and retreatment TB cases diagnosed in 2012 and 2013. Four lineages, namely Lineage 1–4 were identified. The distribution and frequency of these lineages varied across the regions but overall, Lineage 4 was the most frequent (n=866, 42.5%), followed by Lineage 3 (n=681, 33.4%) and 1 (n=336, 16.5%), with Lineage 2 being the least frequent (n=92, 4.5%). A total of 64 (3.1%) isolates could not be assigned to any lineage. We found Lineage 2 to be associated with female sex (adjusted odds ratio [aOR] 2.25; 95% confidence interval [95% CI] 1.38 – 3.70, p<0.001) and retreatment (aOR 1.78; 95% CI 1.00 – 3.02, p=0.040). We found no associations between MTBC lineage and patient age or HIV status. Our sublineage typing based on spacer oligotyping revealed the presence of mainly EAI, CAS and LAM families. Finally, we detected low levels of multidrug resistant isolates among a subset of retreatment cases

Conclusions

This study provides novel insights into the influence of pathogen-related factors on the TB epidemic in Tanzania.
Haematological parameters and plasma levels of 8-iso-prostaglandin F2α in malaria-sickle cell co-morbidity: A cross sectional study
Authors: Aninagyei Enoch , Doku Tetteh Emmanuel , Banini Josephine , Nani Emmanuel , Adu Patrick , Ephraim Richard K. D. , Egyir-Yawson Alexander , Omane Acheampong Desmond
Published: October 2018

Introduction

Malaria and sickle cell disease (SCD) co-morbidity have previously been reported in Ghana. However, there is paucity of data on haematological profiles and oxidative stress in comorbidity states. This study identified novel inflammatory biomarkers associated with malaria in SCD and analyzed the levels of 8-iso-prostaglandin F2α oxidative stress biomarker in malaria-SCD co-morbidity in Ghanaian patients.

Methods

Blood (5ml) was collected from malaria patients into K3-EDTA tube. Malaria parasites speciation and quantification were then done according WHO guidelines. All eligible samples were assayed for haematological profile, sickle cell phenotyping, infectious markers (hepatitis B, hepatitis C, syphilis and HIV 1&2) and plasma levels of 8-epi-prostaglandin F2α..

Results

Prevalence of malaria in SCD (malaria-SCD) was 13.4% (45/335). Male: female ratio was 0.8:1 (X2=1.43, p=0.231). Mean ages for malaria in normal haemoglobin type (malaria-HbAA) and malaria-SCD were 12.79±4.91 and 11.56±3.65 years respectively (p=0.048). Geometric mean of parasite density was higher in malaria-HbAA (20394 parasites/μl vs. 9990 parasites/μl, p=0.001) whilst mean body temperature was higher in malaria-SCD (39.0±0.87°C vs. 37.9±1.15°C, p=0.001). Mean leukocytes, lymphocytes, eosinophils, monocytes, platelets and platelet indices values were significantly elevated in malaria-SCD. Significant reduction in RBC and RBC indices in malaria-SCD were also observed. Eosinophils-to-basophils ratio (EBR) and monocytes-to-basophils ratio (MBR) were novel cellular inflammatory biomarkers which could predict malaria in SCD. The sensitivities of cut-off values of EBR>14, MBR>22 and combined use of EBR>14 and MBR>22 were 79.55%, 84.09% and 91.11% respectively. Mean 8-iso-prostaglandin F2α was 338.1pg/ml in malaria-HbAA and 643.8pg/ml in malaria-SCD (p=0.001). 8-iso-prostaglandin F2α correlated with parasite density (r=0.787, p=0.001), temperature (r=0.566, p=0.001) and leucocytes (r=0.573, p=0.001) and negatively correlated with RBC (r=−0.476, p=0.003), haemoglobin (r=−0.851, p=0.001) and haematocrit (r=−0.735, p=0.001).

Conclusion

Plasmodium falciparumparasitaemia increases oxidative damage and causes derangement haematological parameters. Cut of values of EBR>14 and MBR>22 could predict malaria in SCD.
The influence of truncating the carboxy-terminal amino acid residues of Streptococcal enolase on its ability to interact with canine plasminogen
Authors: Deshmukh Sasmit S. , Kornblatt M. Judith , Kornblatt Jack A.
Published: October 2018

The native octameric structure of streptococcal enolase from Streptococcus pyogenes increasingly dissociates as amino acid residues are removed one by one from the carboxy-terminus. These truncations gradually convert native octameric enolase into monomers and oligomers. In this work, we investigated how these truncations influence the interaction between Streptococcal enolase and canine plasminogen. We used dual polarization interferometry (DPI), localized surface plasmon resonance (LSPR), and sedimentation velocity analytical ultracentrifugation (AUC) to study the interaction. The DPI was our first technique, was performed on all the truncations and used one exclusive kind of chip. The LSRP was used to show that the DPI results were not dependent on the type of chip used. The AUC was required to show that our surface results were not the result of selecting a minority population in any given sample; the majority of the protein was responsible for the binding phenomenon we observed. By comparing results from these techniques we identified one detail that is essential for streptococcal enolase to bind plasminogen: In our hands the individual monomers bind plasminogen; dimers, trimers, tetramers may or may not bind, the fully intact, native, octamer does not bind plasminogen. We also evaluated the contribution to the equilibrium constant made by surface binding as well as in solution. On a surface, the association coefficient is about twice that in solution. The difference is probably not significant. Finally, the fully octameric form of the protein that does not contain a hexahis N-terminal peptide does not bind to a silicon oxynitride surface, does not bind to a Au-nanoparticle surface, does not bind to a surface coated with Ni-NTA nor does it bind to a surface coated with DPgn. The likelihood is great that the enolase species on the surface of Streptococcus pyogenes is an x-mer of the native octamer.
Bacteroides fragilis defense against Cronobacter sakazakii-induced pathogenicity by regulating the intestinal epithelial barrier function and attenuating both apoptotic and pyroptotic cell death
Authors: Fan Hongying , Lin Ruqin , Chen Zhenhui , Leng Xingyu , Wu Xianbo , Zhang Yiduo , Zhu Bo , Zhang Qiwei , Bai Yang , Zhi Fachao
Published: October 2018

Cronobacter sakazakii (CS), an important pathogen, is associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of CS infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was a cross-talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, which revealed that ZY-312 inhibited CS invasion, CS-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. ZY-312 also decreased the expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities, and decreased the relative abundances of Proteobacteria, Gamma proteobacteria, but increased the relative abundance of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic, B. fragilis ZY-312, suppresses CS-induced NEC by modulating the pro-inflammatory response and dual cell death (apoptosis and pyroptosis).

Author summary

Cronobacter sakazakii, a major necrotizing enterocolitis pathogen, is used as a model microorganism for the study of opportunistic bacteria in the pathogenesis of necrotizing enterocolitis. Here, we have now unequivocally demonstrated that both apoptotic and pyroptotic stimuli contribute to the pathogenesis of Cronobacter sakazakii -induced necrotizing enterocolitis. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. We found that the ZY-312 defense against Cronobacter sakazakii-induced necrotizing enterocolitis by inhibiting Cronobacter sakazakii invasion, epithelial barrier dysfunction, the expression of inflammatory cytokines and dual cell death (pyroptosis and apoptosis). This study demonstrates the utility of ZY-312 as a promising probiotic agent for the prevention and treatment of various intestinal diseases, including NEC.
EZH2 is essential for fate determination in the mammalian Isthmic area
Authors: Wever Iris , Wagemans Cindy M.R.J. , Smidt Marten P.
Published: October 2018

The polycomb group proteins (PcGs) are a group of epigenetic factors associated with gene silencing. They are found in several families of multiprotein complexes, including Polycomb Repressive Complex (PRC) 2. EZH2, EED and SUZ12 form the core components of the PRC2 complex, which is responsible for the mono, di- and trimethylation of lysine 27 of histone 3 (H3K27Me3), the chromatin mark associated with gene silencing. Loss-of-function studies ofEzh2, the catalytic subunit of PRC2, have shown that PRC2 plays a role in regulating developmental transitions of neuronal progenitor cells; from self-renewal to differentiation and the neurogenic-to-gliogenic fate switch.

To further address the function of EZH2 and H3K27me3 during neuronal development we generated a conditional mutant in whichEzh2was removed in the mammalian isthmic (mid-hindbrain) region from E10.5 onward. Loss ofEzh2changed the molecular coding of the anterior ventral hindbrain leading to a fate switch and the appearance of ectopic dopaminergic neurons. The correct specification of the isthmic region is dependent on the signaling factors produced by the Isthmic organizer (IsO), located at the border of the mid- and hindbrain. We propose that the change of cellular fate is a result of the presence ofOtx2in the hindbrain ofEzh2conditional knock-outs and a dysfunctional IsO, as represented by the loss ofFgf8andWnt1.Our work implies that next to controlling developmental transitions, EZH2 mediated gene silencing is important for specification of the isthmic region by influencing IsO functioning and repressingOtx2in the hindbrain.
Intensity distribution profile of double Bragg scattering in the small-angle region from highly oriented pyrolytic graphite
Authors: Ohmasa Yoshinori , Chiba Ayano
Published: October 2018

It is observed that radial streak patterns of double Bragg scattering appear in the small-angle X-ray scattering from highly oriented pyrolytic graphite (HOPG). The intensity profile of double Bragg scattering from an HOPG sample is calculated theoretically. Assuming that the c axes of the graphite crystallites in the HOPG sample are distributed around an orientation vector and their distribution function has a Gaussian form, it is found that the intensity profile of double Bragg scattering is expressed by a double Gaussian function of the scattering angle and the azimuthal angle of the streak. The calculated intensity profile is compared with the experimental one. The method developed in this article can be used to estimate the orientational distribution of crystallites in uniaxial polycrystalline materials.
Crystal structure and metabolic activity of 4-(thien-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid ethoxycarbonylphenylmethylester
Authors: Mishnev Anatoly , Bisenieks Egils , Mandrika Ilona , Petrovska Ramona , Kalme Zenta , Bruvere Imanta , Duburs Gunars
Published: October 2018

In the title compound, C25H25NO5S, which exhibits metabolism-regulating activity, the 1,4-dihydropyridine ring adopts a flattened boat conformation while the cyclohexenone ring is in an envelope conformation. Molecules in the crystal are assembled into C(6) chains along the a-axis direction via N—H...O hydrogen bonds. The thienyl fragment is disordered over two sets of sites in a 0.7220 (19):0.2780 (19) ratio.
Corporate performance management: process of organizational-tailored flow chart
Authors: Yilmaz Ayşe Kucuk , Yazgan Ebru
Published: October 2018

Purpose

Main issue in management and strategy is corporate performance. Managers seek effective and strategic way to improve their performance. Authorization, which includes reputational and strategic indicators, is one of these ways. The applying authorization and using this authorization are decision-making process for managers. These processes have potential to make considerable effect on corporate performance. As a considerable result of this research that need of resource dependency type certified aircraft technicians in Anadolu University are decreased owing to this research and, also the purpose of this study is that technicians have got opportunity to creating own human resource in view of both sustainability, and competition in training field.

Design/methodology/approach

In this study, both specified and organizational-tailored flowchart as the problem solving techniques in decision-making process of maintenance training organization have been developed, compiled after taking the opinions of experts, for the effective implementation of type rating training, following approval, that cover the types of fleet at Anadolu University. This flowchart may guide to the relevant aircraft maintenance training organizations in their type trainings implementation process.

Findings

Human factor is both vital and necessary element to achieve high corporate performance. By following the flow chart, the implementation process is shortened by eliminating the difficulties in complying with the depth and complexity of the required regulation.

Originality/value

The development of the necessary skills and competencies of the workforce is one of the critical points for the creation, preservation and improvement of corporate value. This research has been carried out with the aim of effective utilization of institutional resources, development of personnel and hence corporate value creation. Anadolu University, which is aware of the importance of core competence, is trying to make it one of its strengths institutionally. The Anadolu University Faculty of Aeronautics and Astronautics, as an organization that has completed the necessary steps to become authorized to give type rating training, may guide other aviation organizations using the organization-specified tailored flow chart developed with the help of expert opinion.
Knowledge management, organizational commitment and knowledge-worker performance
Authors: Razzaq Shahid , Shujahat Muhammad , Hussain Saddam , Nawaz Faisal , Wang Minhong , Ali Murad , Tehseen Shehnaz
Published: October 2018

Purpose

Knowledge management in the public sector is relatively an ignored avenue of research and practice that has recently been given attention. Knowledge management initiatives in the public sector are now not limited to the developed countries anymore. The public sectors of various developing countries including Pakistan have developed knowledge management functions to address the problems of low organizational commitment (higher turnover rates) and knowledge-workers’ performance. Consequently, the purpose of this paper is to examine the mediation role of organizational commitment in the relationship between knowledge management practices and knowledge-worker performance.

Design/methodology/approach

The data were gathered from 341 knowledge workers of the public sector health department of Punjab Province, Pakistan, where knowledge management unit initiative has been taken. It was then analyzed using the structural equation modeling.

Findings

Organizational commitment partially mediates the relationship between knowledge management practices and knowledge-work performance.

Practical implications

The public sector policy makers are strongly advised to implement knowledge management units and practices in order to enhance knowledge-work performance as well as organizational commitment.

Originality/value

First, the model on the mediating role of organizational commitment has never been examined before. Second, the data collection from the public Health Department of Pakistan, a developing country, is relatively rare because the public sector knowledge management studies have mostly been conducted in developed countries. Finally, this study extends the literature on knowledge management in the public sector that is the developing theme in knowledge management discipline while adding knowledge management as a toolkit to enhance knowledge-workers’, organizational commitment and knowledge-work performance.
Wireless technologies and policies for connecting rural areas in emerging countries: a case study in rural Peru
Authors: Espinoza David , Reed David
Published: October 2018

Purpose

This paper aims to compare the costs of deploying different wireless terrestrial broadband technologies in the Andes and Amazon Regions of Peru. These areas are representatives of different and challenging geographic regions throughout the globe that currently are severely underserved or unserved for vital broadband services necessary to bridge the “Digital Divide”.

Design/methodology/approach

The broadband technologies studied include Wi-Fi, Worldwide Interoperability for Microwave Access (WiMAX), long term evolution (LTE), TVWS and new stratospheric platforms (super-pressure balloons). This study conducts a technical analysis (design and simulation) of wireless broadband networks, and a bottom-up engineering cost analysis to estimate and compare the deployment and operating costs of the networks over a 10-year period. The analysis also identifies potential regulatory barriers to deployment associated with spectrum allocation licenses and overbooking requirements intended to improve quality of service.

Findings

Comparison of the capital and operating expenses of these options over a 10-year period finds that LTE and Wi-Fi can be the lowest cost alternatives, though significantly, stratospheric balloons have the lowest initial costs for the first few years and can factor as a low-cost broadband catalyst early in deployment. Finally, the lowest cost technology broadband roadmap for the 10-year period is presented, which includes using stratospheric balloons (carrying micro-LTE base stations) for the first years and deploying complementary terrestrial LTE networks for the rest of the 10-year period.

Originality/value

This study presents detailed technical and engineering cost analysis results of wireless access network deployments, including advanced wireless technologies and new unmanned aerial systems, to expand broadband services to rural areas in mountainous (Andes Region) and rainforest (Amazon Region) geographies to reduce the digital divide in emerging countries. Results aim to aid governments, regulators, internet service providers (incumbents and competitive) and content providers to assess current alternatives to expand broadband service in these rural areas.
Differential quadrature method for nonlinear fractional partial differential equations
Authors: Saeed Umer , Rehman Mujeeb ur , Din Qamar
Published: October 2018

Purpose

The purpose of this paper is to propose a method for solving nonlinear fractional partial differential equations on the semi-infinite domain and to get better and more accurate results.

Design/methodology/approach

The authors proposed a method by using the Chebyshev wavelets in conjunction with differential quadrature technique. The operational matrices for the method are derived, constructed and used for the solution of nonlinear fractional partial differential equations.

Findings

The operational matrices contain many zero entries, which lead to the high efficiency of the method and reasonable accuracy is achieved even with less number of grid points. The results are in good agreement with exact solutions and more accurate as compared to Haar wavelet method.

Originality/value

Many engineers can use the presented method for solving their nonlinear fractional models.
Integrating value management into sustainable construction projects in Hong Kong
Authors: Yu Ann Tit Wan , Javed Arshad Ali , Lam Tsun Ip , Shen Geoffrey Qiping , Sun Ming
Published: October 2018

Purpose

Integrating sustainability into the value management (VM) process can provide a strategic platform for promoting and incorporating sustainable design and development during the lifespans of construction projects. The purpose of this paper is to investigate the strengths, weaknesses, opportunities and threats (SWOT) for integrating sustainability into the VM process in Hong Kong.

Design/methodology/approach

Following an extensive literature review, 45 attributes were identified and grouped into strength, weakness, opportunity and threat elements. A questionnaire survey based on these groupings was supported by semi-structured interviews with public sector clients, value managers and VM facilitators. They shared their experience and views on how to integrate sustainability into the VM exercises.

Findings

The triangulated results of the survey and interviews are presented in this paper. The ranking of the SWOT analysis results indicate that VM does provide opportunities for multidisciplinary professionals and stakeholders to focus on issues relating to society and the environment, which is considered a main strength. The major weakness of integration is the lack of well-trained staff and low levels of VM participant expertise in relation to the sustainable construction issue.

Research limitations/implications

Current practices generally neglect integration of sustainability into the VM process due to cost and time constraints. There are ample strengths and opportunities recommended by this study for integrating sustainability into the VM process which are beneficial for the clients and contractors for achieving value for money and meeting sustainability targets.

Practical implications

There are immense opportunities for integrating sustainability into the VM process, including encouragement of the reduction, reuse and recycling of construction and demolition waste. However, threats presented by integration include the additional time and costs required for achieving sustainability targets.

Originality/value

Findings and recommendations provided in this paper should be helpful to decision makers including clients and VM facilitators for the successful integration of the sustainability concept into the VM process.