bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro selection of miltefosine resistance in promastigotes of Leishmania donovani from Nepal: genomic and metabolomic characterization
Authors: Shaw C. D. , Lonchamp J. , Downing T. , Imamura H. , Freeman T. M. , Cotton J. A. , Sanders M. , Blackburn G. , Dujardin J. C. , Rijal S. , Khanal B. , Illingworth C. J. R. , Coombs G. H. , Carter K. C. 
Published: December 2015

SummaryIn this study, we followed the genomic, lipidomic and metabolomic changes associated with the selection of miltefosine (MIL) resistance in two clinically derived Leishmania donovani strains with different inherent resistance to antimonial drugs (antimony sensitive strain Sb‐S; and antimony resistant Sb‐R). MIL‐R was easily induced in both strains using the promastigote‐stage, but a significant increase in MIL‐R in the intracellular amastigote compared to the corresponding wild‐type did not occur until promastigotes had adapted to 12.2 μM MIL. A variety of common and strain‐specific genetic changes were discovered in MIL‐adapted parasites, including deletions at the LdMT transporter gene, single‐base mutations and changes in somy. The most obvious lipid changes in MIL‐R promastigotes occurred to phosphatidylcholines and lysophosphatidylcholines and results indicate that the Kennedy pathway is involved in MIL resistance. The inherent Sb resistance of the parasite had an impact on the changes that occurred in MIL‐R parasites, with more genetic changes occurring in Sb‐R compared with Sb‐S parasites. Initial interpretation of the changes identified in this study does not support synergies with Sb‐R in the mechanisms of MIL resistance, though this requires an enhanced understanding of the parasite's biochemical pathways and how they are genetically regulated to be verified fully.
A phospholipase A1 antibacterial Type VI secretion effector interacts directly with the C‐terminal domain of the VgrG spike protein for delivery
Authors: Flaugnatti Nicolas , Le Thi Thu Hang , Canaan Stéphane , Aschtgen Marie‐Stéphanie , Nguyen Van Son , Blangy Stéphanie , Kellenberger Christine , Roussel Alain , Cambillau Christian , Cascales Eric , Journet Laure 
Published: December 2015

SummaryThe Type VI secretion system (T6SS) is a multiprotein machine that delivers protein effectors in both prokaryotic and eukaryotic cells, allowing interbacterial competition and virulence. The mechanism of action of the T6SS requires the contraction of a sheath‐like structure that propels a needle towards target cells, allowing the delivery of protein effectors. Here, we provide evidence that the entero‐aggregative Escherichia coli Sci‐1 T6SS is required to eliminate competitor bacteria. We further identify Tle1, a toxin effector encoded by this cluster and showed that Tle1 possesses phospholipase A1 and A2 activities required for the interbacterial competition. Self‐protection of the attacker cell is secured by an outer membrane lipoprotein, Tli1, which binds Tle1 in a 1:1 stoichiometric ratio with nanomolar affinity, and inhibits its phospholipase activity. Tle1 is delivered into the periplasm of the prey cells using the VgrG1 needle spike protein as carrier. Further analyses demonstrate that the C‐terminal extension domain of VgrG1, including a transthyretin‐like domain, is responsible for the interaction with Tle1 and its subsequent delivery into target cells. Based on these results, we propose an additional mechanism of transport of T6SS effectors in which cognate effectors are selected by specific motifs located at the C‐terminus of VgrG proteins.
Structural and functional analysis of RopB: a major virulence regulator in Streptococcus pyogenes
Authors: Makthal Nishanth , Gavagan Maire , Do Hackwon , Olsen Randall J. , Musser James M. , Kumaraswami Muthiah 
Published: December 2015

SummaryGroup A Streptococcus (GAS) is an exclusive human pathogen that causes significant disease burden. Global regulator RopB of GAS controls the expression of several major virulence factors including secreted protease SpeB during high cell density. However, the molecular mechanism for RopB‐dependent speB expression remains unclear. To understand the mechanism of transcription activation by RopB, we determined the crystal structure of the C‐terminal domain of RopB. RopB‐CTD has the TPR motif, a signature motif involved in protein–peptide interactions and shares significant structural homology with the quorum sensing RRNPP family regulators. Characterization of the high cell density‐specific cell‐free growth medium demonstrated the presence of a low molecular weight proteinaceous secreted factor that upregulates RopB‐dependent speB expression. Together, these results suggest that RopB and its cognate peptide signals constitute an intercellular signalling machinery that controls the virulence gene expression in concert with population density. Structure‐guided mutational analyses of RopB dimer interface demonstrated that single alanine substitutions at this critical interface significantly altered RopB‐dependent speB expression and attenuated GAS virulence. Results presented here suggested that a properly aligned RopB dimer interface is important for GAS pathogenesis and highlighted the dimerization interactions as a plausible therapeutic target for the development of novel antimicrobials.
Oxidative‐stress detoxification and signalling in cyanobacteria: the crucial glutathione synthesis pathway supports the production of ergothioneine and ophthalmate
Authors: Narainsamy Kinsley , Farci Sandrine , Braun Emilie , Junot Christophe , Cassier‐Chauvat Corinne , Chauvat Franck 
Published: December 2015

SummaryUsing genetics and metabolomics we investigated the synthesis (gshA and gshB genes) and catabolism (ggt) of the conserved antioxidant glutathione in the model cyanobacterium Synechocystis PCC6803. These three genes are crucial to Synechocystis, in agreement with the proposed invention of glutathione by ancient cyanobacteria to protect themselves against the toxicity of oxygen they produced through photosynthesis. Consistent with their indispensability, gshA and gshB also operate in the production of another antioxidant, ergothioneine, as well as of the glutathione analogues ophthalmate and norophthalmate. Furthermore, we show that glutathione, ophthalmate and norophthalmate are accumulated in cells stressed by glucose, and that the two glutathione‐dependent glyoxalase enzymes operate in the protection against glucose and its catabolite methylglyoxal. These findings are interesting because ophthalmate and norophthalmate were observed only in mammals so far, where ophthalmate is regarded as a biomarker of glutathione depletion. Instead, our data suggest that ophthalmate and norophthalmate are stress‐induced markers of cysteine depletion triggered by its accelerated incorporation into glutathione, to face its increased demand for detoxification purposes. Hence, Synechocystis is an attractive model for the analysis of the role of glutathione, ergothioneine, ophthalmate and norophthalmate, in signalling and detoxification of oxidants and metabolic by‐products.
Mechanistic insight into mycobacterial MmpL protein function
Authors: Székely R. , Cole S. T. 
Published: December 2015

SummaryMycobacterial cell walls are complex structures containing a broad range of unusual lipids, glycolipids and other polymers, some of which act as immunomodulators or virulence determinants. Better understanding of the enzymes involved in export processes would enlighten cell wall biogenesis. Bernut et al. () present the findings of a structural and functional investigation of one of the most important transporter families, the MmpL proteins, members of the resistance‐nodulation‐cell division (RND) superfamily. A Tyr842His missense mutation in the mmpL4a gene was shown to be responsible for the smooth‐to‐rough morphotype change of the near untreatable opportunistic pathogen Mycobacterium bolletii due to its failure to export a glycopeptidolipid (GPL). This mutation was pleiotropic and markedly increased virulence in infection models. Tyr842 is well conserved in all actinobacterial MmpL proteins suggesting that it is functionally important and this was confirmed by several approaches including replacing the corresponding residue in MmpL3 of Mycobacterium tuberculosis. Structural modelling combined with experimental results showed Tyr842 to be a critical residue for mediating the proton motive force required for GPL export. This mechanistic insight applies to all MmpL proteins and probably to all RND transporters.
Reflexivity and exploring the meaning of delirium through media depictions: Methodological insights from a phenomenological study
Authors: Day Jenny , Higgins Isabel 
Published: December 2015

AbstractIn the course of a phenomenological study that explored the experiences of family members during their older loved one's delirium, a range of delirium experiences depicted in artistic, creative, and linguistic media were reviewed. The search for, and compilation of, media sources for reflection during data analysis is described in this paper. In doing so, the researcher reveals how attentiveness and openness to varied depictions of lived experiences, as well as a valuing attitude toward challenging subjective perspectives, can enhance researcher reflexivity and appreciation of interpretive meanings. Turning to media depictions of delirium offered alternative perspectives on the experience. It challenged the researcher's assumptions, enhanced phenomenological reflection, promoted critique of evolving interpretations, and suggested meanings that might not have otherwise been realized. The approach used is a potent, although often overlooked, way to differentiate the nature of phenomena shared through lived experience data. Media‐based methods and their use in phenomenology continue to be explored. Illustrations of how to integrate media sources, as well as discussion about the benefits and alternatives to more common uses, are needed.
Gut microbiota‐derived lipopolysaccharide uptake and trafficking to adipose tissue: implications for inflammation and obesity
Authors: Hersoug L. ‐G. , Møller P. , Loft S. 
Published: December 2015

SummaryThe composition of the gut microbiota and excessive ingestion of high‐fat diets (HFD) are considered to be important factors for development of obesity. In this review we describe a coherent mechanism of action for the development of obesity, which involves the composition of gut microbiota, HFD, low‐grade inflammation, expression of fat translocase and scavenger receptor CD36, and the scavenger receptor class B type 1 (SR‐BI). SR‐BI binds to both lipids and lipopolysaccharide (LPS) from Gram‐negative bacteria, which may promote incorporation of LPS in chylomicrons (CMs). These CMs are transported via lymph to the circulation, where LPS is transferred to other lipoproteins by translocases, preferentially to HDL. LPS increases the SR‐BI binding, transcytosis of lipoproteins over the endothelial barrier,and endocytosis in adipocytes. Especially large size adipocytes with high metabolic activity absorb LPS‐rich lipoproteins. In addition, macrophages in adipose tissue internalize LPS‐lipoproteins. This may contribute to the polarization from M2 to M1 phenotype, which is a consequence of increased LPS delivery into the tissue during hypertrophy. In conclusion, evidence suggests that LPS is involved in the development of obesity as a direct targeting molecule for lipid delivery and storage in adipose tissue.
Effect of PMX‐DHP for sepsis due to ESBL‐producing E. coli in an extremely low‐birthweight infant
Authors: Nishizaki Naoto , Nakagawa Mayu , Hara Satoshi , Oda Hisayuki , Kantake Masato , Obinata Kaoru , Uehara Yuki , Hiramatsu Keiichi , Shimizu Toshiaki 
Published: December 2015

AbstractWe report a case of early onset sepsis caused by (CTX for cefotaximase and M for Munich)‐type extended‐spectrum β‐lactamase‐producing Escherichia coli (ESBL E. coli) in a preterm infant weighing 601 g. He was given meropenem and treated for endotoxin absorption with polymyxin B‐immobilized fibers with only 8 mL of priming volume. The patient survived without any short‐term neurological or respiratory sequelae. The choice of antibiotics is particularly important in seriously ill neonates with sepsis due to ESBL‐producing organisms. Polymyxin B hemoperfusion might be an innovative therapy for severe neonatal sepsis and could improve outcome even in an extremely low‐birthweight infant.
Focal Coxsackie virus B5 encephalitis with synchronous seizure cluster and eruption: Infantile case
Authors: Shiohama Tadashi , Omata Taku , Muta Kaori , Kodama Kazuo , Fujii Katsunori , Shimojo Naoki 
Published: December 2015

AbstractEnterovirus focal encephalitis is a rare clinical entity that is characterized by focal neurological signs including seizure, hemiparesis, hemichorea, and headache, which are mainly followed by rapid spontaneous improvement. We herein describe the case of a 9‐month‐old boy who developed Coxsackie virus B5 (CVB5) focal encephalitis with seizure clusters in the eruption stage of roseola infantum‐like illness, which were followed by rapid improvement and benign outcome. Lumbar puncture indicated pleocytosis, and CVB5 infection in the cerebrospinal fluid was subsequently identified on genome sequencing and virus isolation. Magnetic resonance imaging and electroencephalography showed no abnormal findings at the acute stage or on 2 month follow up. Although the pathogenesis of enterovirus focal encephalitis currently remains unclear, the pure synchronism of seizure cluster and eruption in this case suggests the involvement of local vascular impairment as the underlying pathogenesis.
Coronary ostium occlusion by coronary cusp displacement in Williams syndrome
Authors: Shiohama Tadashi , Fujii Katsunori , Ebata Ryota , Funabashi Nobusada , Matsumiya Goro , Saito Yuko Kazato , Takechi Fumie , Yonemori Yoko , Nakatani Yukio , Shimojo Naoki 
Published: December 2015

AbstractWilliams syndrome is a contiguous gene deletion syndrome resulting from a heterozygous deletion on chromosome 7q11.23, and is characterized by distinctive facial features and supravalvular aortic stenosis (SVAS). This syndrome rarely presents unpredictable cardiac death, and yet, as illustrated in the present case, it is still not possible to predict it, even on close monitoring. We herein describe the case of a 6‐year‐old Japanese girl with Williams syndrome, who had sudden cardiac collapse due to cardiac infarction after pharyngitis. Cardiac failure followed a critical course that did not respond to catecholamine support or heart rest with extracardiac mechanical support. Although marked coronary stenosis was not present, the left coronary cusp abnormally adhered to the aortic wall, which may synergistically cause coronary ostium occlusion with SVAS. Altered hemodynamic state, even that caused by the common cold, may lead to critical myocardial events in Williams syndrome with SVAS.
Haploidentical hematopoietic stem cell transplantation with post‐transplant high‐dose cyclophosphamide in high‐risk children: A single‐center study
Authors: Yesilipek M. Akif , Uygun Vedat , Karasu Gulsun , Daloglu Hayriye , Dincer Zeynep 
Published: December 2015

AbstractRecently, haploidentical transplantations have been performed with unmanipulated BM or PBSC. This approach is becoming more widely adopted with the use of PTCY. However, there is limited evidence about this approach in children. We present 15 children who received 16 haploidentical HSCT with unmanipulated BM or PBSC using PTCY for GVHD prophylaxis. Post‐transplant CY(50 mg/kg IV) was given on the third and fifth day, and CsA or tacrolimus with MMF or MP was also used for GVHD prophylaxis. All patients engrafted at a median of 16 and 18 days for neutrophil and thrombocyte recovery, respectively. Grades II–III acute GVHD developed in seven patients, and mild chronic GVHD was found in two patients. Two patients died within the first 100 days due to sepsis (TRM 12.5%). Eleven patients are currently alive, with a median follow‐up of 12 months (range 6–22 months). The 12‐month OS and DFS were 75 ± 10.8% and 68.8 ± 11.6%, respectively. Our results with these high‐risk patients are encouraging for haploidentical HSCT in pediatric patients. Future studies should continue to assess haploidentical HSCT, including comparison of other modalities, in a primary pediatric population.
Effect on plaque control in children patients with Down syndrome using Digital Brush with or without chlorhexidine: a randomized clinical trial
Authors: Stefanini Martina , Sangiorgi Matteo , Roncati Marisa , D'Alessandro Giovanni , Piana Gabriela 
Published: December 2015

ABSTRACTObjectivesThe aim of this study was to evaluate efficacy in children affected by Down syndrome of “Digital Brush” in terms of Plaque Index reduction added to the daily oral hygiene procedures.MethodsA total of 56 patients with Down syndrome were recruited and randomly assigned in two groups: both control and test groups underwent standard hygiene procedures of tooth brushing twice a day followed by the intervention of Digital Brush, TNT gauze impregnated with chlorhexidine 0.12%, for the test group and by sterile gauze soaked in water for the control group. Initial plaque index was measured for all patients (T0), subsequently were instructed to use either Digital Brush or gauze soaked with water for 2 weeks. At last, patients were reevaluated (T1) and the plaque index measured.ResultsPlaque index improvement from T0 to T1 in control group was 11.7%, while in test group was 24.1%. The mean differences between test and control group was statistically significant (p < 0.001).ConclusionsThis study demonstrates how the Digital Brush, added to the daily oral hygiene procedures, obtains significant improvements in supragingival plaque control in children with Down syndrome.
Imagining the Canadian Internet: A Case of Discursive Nationalization of Technology
Authors: Dumitrica Delia 
Published: December 2015

AbstractThis article explores the discursive nationalization of the Internet in the context of Canadian new media policy. A textual analysis of the federal policy documents on new media (1994–2001) brings forth four discursive strategies through which technology is temporarily articulated as a material, economic, and spatial resource for the Canadian nation. It is argued that nationalism remains an important mechanism to legitimize policy recommendations. More importantly, nationalism is a means through which the format and social roles of an unknown and emerging technology become imagined in official discourse.
Preschool Children's Negative Emotionality and Peer Acceptance: The Moderating Role of Sleep
Authors: Lu Ting , Tu Kelly M. , El‐Sheikh Mona , Vaughn Brian E. 
Published: December 2015

AbstractPreschool children's sleep was examined as a moderator of the association between negative emotionality and both peer acceptance and peer rejection. Participants were 115 children (47 percent girls, M age = 4.29 years, SD = .63). Preschool teachers reported on children's negative emotionality (anger/frustration, sadness, and fear). Sleep was measured objectively using actigraphy in the child's home for seven consecutive nights. Peer acceptance and rejection were assessed using children's choices in sociometric interviews. Controlling for potential confounds, moderation analyses revealed that negative emotionality predicted peer acceptance and rejection only among children with poorer sleep quality (lower sleep efficiency, more frequent wake episodes, longer sleep latency), but not better sleep quality. Findings suggest that sleep is important not only for predicting child functioning but also for moderating the adverse effects of negative emotionality on a salient indicator of interpersonal functioning for preschool age children.
Placing Science for Natural Resource Management and Climate Variability: Lessons from Narratives of Risk, Place and Identity
Authors: Leith Peat , Vanclay Frank 
Published: December 2015

AbstractMaking salient, credible and legitimate knowledge for natural resource management (NRM) and adaptation to climate change is achievable when scientific knowledge is grounded in place. Making scientific knowledge locally relevant can be assisted by an understanding of the way ‘placed knowledge’ comes into being. Taking two prominent conceptions of place (Massey and Ingold), we ground these empirically using narratives from graziers in the eastern Australian rangelands. We examine placed conceptions of risk and uncertainty and the ways they are linked to narratives of identity, local environmental change, and understandings of place. Paying heed to narratives enables a reframing of risk and uncertainty into locally‐meaningful forms. This fosters dialogue between various epistemic communities in ways that acknowledge and respect different ways of knowing and differences in the content of knowledge. It provides an analytical basis for scientists and institutions to reflect on the applicability of their information and technology in particular contexts. With this approach, scientists, policymakers and other rural community stakeholders can develop their awareness of how placed narratives link social practices and locally‐legitimate understandings of good farm management and biophysical systems. This will help to ‘place’ science for NRM, agricultural extension and rural development.
Modern‐day management of upper gastrointestinal haemorrhage
Authors: Jairath V. , Desborough M. J. R. 
Published: December 2015

SUMMARYAcute upper gastrointestinal haemorrhage (AUGIH) is a common medical emergency and can present with life threatening haemorrhage. In the UK, there are 70 000 hospital admissions per year. In the majority of cases, the aetiology is non‐variceal in origin, but in other cases it is due to variceal bleeding in patients with cirrhosis. It is also a leading indication for transfusion of blood components. This review explores recent randomised data on the efficacy and safety of red blood cell transfusion for AUGIH. In addition, the evidence base for use of other blood components and pro‐haemostatic pharmacological agents is discussed, including acid suppression, antifibrinolytics and fibrinogen.
Two NYN domain containing putative nucleases are involved in transcript maturation in Arabidopsis mitochondria
Authors: Stoll Birgit , Binder Stefan 
Published: December 2015

SummaryPlant mitochondrial transcripts frequently undergo maturation processes at their 5′ ends. This almost completely enigmatic process requires the function of several proteins such as RNA processing factors, which are selectively involved in distinct 5′ processing events. As RNA processing factors represent pentatricopeptide repeat proteins without apparent enzymatic function, it is hypothesized that a ribonuclease, most likely with endonucleolytic activity is involved in the 5′ end maturation. We have now applied a reverse genetic approach to analyze the role of two potential mitochondrial nucleases, MNU1 and MNU2, in Arabidopsis thaliana. Both proteins contain several RNA‐binding domains and NYN domains found in other endonucleases. A thorough analysis of various mitochondrial transcripts in MNU1 and MNU2 mutants revealed aberrant transcript pattern characterized by a decrease in mature RNA species often accompanied by an accumulation of larger, 5′ extended precursor molecules. In addition, severely reduced amounts of nad9 mRNAs in the rpf2‐1/mnu2‐1 double mutant indicate a corporate function of RNA processing factor 2 and MNU2 in the maturation of these transcripts. However, the dramatic reduction of the nad9 mRNA is not reflected by the level of the corresponding Nad9 protein, which is found to be only moderately lowered. Collectively, our analysis strongly suggests a function of MNU1 and MNU2 in 5′ processing of plant mitochondrial transcripts.