bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractExtensive 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

AbstractThe 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

AbstractHuman 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

AbstractModels 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

ABSTRACTCyclins 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

AbstractContractility 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 SummaryThroughin 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

Abstractlonotropic 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

ABSTRACTIn 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

AbstractThe 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

AbstractBackgroundHuman 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 FindingsHere 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 casesConclusionsThis 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

AbstractIntroductionMalaria 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.MethodsBlood (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..ResultsPrevalence 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).ConclusionPlasmodium 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

AbstractThe 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

AbstractCronobacter 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 summaryCronobacter 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.