bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving in the Spirit
Authors: Robra Martin
Published: December 2016

Together towards Life (TTL) holds together a theology of the God of life and the transforming power of the Holy Spirit with the renewal and transformation that begins with a commitment to justice and peace at the margins and anticipates the eschatological vision of the renewal of the whole creation. The theme of the forthcoming World Mission Conference in 2017 in Arusha (Tanzania), “Moving in the Spirit: Called to Transforming Discipleship,” marks the intersection between TTL and the Busan call for the pilgrimage of justice and peace. The theme invites participants to advance reflection on the life‐giving power of the Holy Spirit and the role of transformative communities moving together in hope of God's reign to come. The example of the World Council of Churches’ work on a Theology of Life shows that choosing this direction has implications for the practices of doing theology and even the organization of the forthcoming World Mission Conference. A fascinating task indeed!
Matangi Teka (Wind Shift)
Authors: Havea Jione
Published: December 2016

Matangi teka (when the wind shifts), in Pasifika, is an opportunity to rethink how to live and behave. When the wind shifts, island people (for the sake of survival) respond appropriately. Based upon such an awareness, this article invites matangi teka (wind shift) in the act of interpretation, in the consideration of traditional readings and theologies, and in the understanding and practices of discipleship. I do these by reading the commission of Abram, and the shifting of his mission, in Genesis 12. He was called on a mission of blessing for other families, and he shifted things so that he wins and controls the blessings for himself and his family. He did (in the text) a matangi teka on Yhwh and (beyond the text) on generations of readers; this article is an invitation to shift the wind from Abram in return.
Mission and Discipleship from the Perspective of Gender and Indigenous Culture
Authors: De La Torre Saransig María Margarita
Published: December 2016

The presence and history of Indigenous Peoples present special problems for mission and missiology and requires some rethinking of basic concepts and the cultural location of mission. Because the next World Mission Conference will take place in Tanzania, this article looks more carefully at the basis of mission, the experience of Indigenous Peoples with missions, and the New Testament warrent for mission. In the latter we find, particularly in the gospel narratives of the resurrection appearances of Jesus and his sending of the disciples the particular and exemplary role of women. These narratives offer some guidance for framing mission with Indigenous Peoples and in relation to colonial legacies and global capitalism.
Ecumenical Tensions among Nigerian Christians
Authors: Ude Asue Daniel
Published: December 2016

This article focuses on recent disturbing trends opposed to Christian unity in Nigeria that have both remote and immediate causes. Although the Christian Association of Nigeria (CAN) was formed to promote unity among the various Christian denominations in the country, it has not been able to achieve its goal. After describing this present situation and the historical factors that caused it, this paper looks to the resources of the Second Vatican Council which CAN should adopt to ease the tension in the country and promote greater dialogue. The article looks at the Roman Catholic‐Lutheran Declaration that was signed in 1999, and officially resolved the disagreements that led to the split led by Martin Luther in 1517. Finally this paper looks at the style of Pope Francis as a living example of effective ecumenism and interfaith dialogue.
Transforming Discipleship
Authors: Hong‐jung Lee
Published: December 2016

The nature of oikoumene has constantly challenged a Christendom‐oriented lineal understanding of mission. The environment of doing theology of mission has changed from the denominational to the ecumenical era, from the Eurocentric to the global context, and from the mechanistic domination of the world to the age of ecological worldwide community; and the paradigm of mission has changed from evangelization to shalom, from missio ecclesiae to missio Dei, and from monologue to dialogue. Critically thinking of the dominant milieu of the people which challenges the church to transform her way of participation in the world, the church must discern the socio‐political and religio‐cultural biographies of the people as the most important language of people‐ and life‐centric missio Dei. The primary missiological question should be, then, not what God is doing with the church, but rather what God is doing with the people and creation. In the course of answering this question, the church may discern where the Spirit is at work and how to respond to it. The following article is an attempt to seek a Korean way of imitatio missionis Christi in terms of finding a contextualized spirituality and a strategy of a transforming discipleship.
Coping With Dependence: A Logistics Strategy Based on Interorganizational Learning for Managing Buyer–Supplier Relations
Authors: Kull Thomas J. , Ellis Scott C.
Published: December 2016

The rise of outsourcing has heightened interest in the role of logistics managers in coping with dependence in buyer–supplier relations. Buying firm dependence on a supplier potentially reduces supplier performance to expectations because the buying firm cannot leverage power to capture value in the relationship. Drawing from interorganizational learning theory, we advance a logistics strategy that consists of supplier cost analysis and supplier integration as a means to create value and thereby mitigate the negative effects of dependence. By facilitating the acquisition and use of knowledge, supplier cost analysis and supplier integration enable buying firms to identify improvement opportunities while engaging in collaborative supplier relations. Using survey responses from 222 buying firms, we find that while buyer dependence decreases the buyer's perceived supplier performance, supplier integration suppresses these negative effects. Furthermore, we show that supplier cost analysis is a valuable knowledge acquisition tool that logistics managers can use to enable supplier integration as a relational form of governance. As such, we provide new insights into interorganizational learning theory and suggest to logistics managers the important role supplier cost analysis plays in managing buyer–supplier relationships.
Previous dropout from diabetic care as a predictor of patients' willingness to use mobile applications for self‐management: A cross‐sectional study
Authors: Yamaguchi Satoko , Waki Kayo , Tomizawa Nobuko , Waki Hironori , Nannya Yasuhito , Nangaku Masaomi , Kadowaki Takashi , Ohe Kazuhiko
Published: December 2016

Aims/Introduction

Preventing dropout is crucial in managing diabetes. Accordingly, we investigated whether patients who had dropped out of diabetic care are suitable candidates for the use of mobile technologies – such as smartphone applications – to support self‐management (mHealth), which might help prevent dropout.

Materials and Methods

We carried out a cross‐sectional study in Tokyo, Japan. Patients aged 20 years or older who were clinically diagnosed as diabetic and who regularly visited the outpatient unit at the University of Tokyo Hospital were recruited between August 2014 and March 2015. Data were collected through face‐to‐face structured interviews, physical measurements and medical records. Participants were asked whether they were willing to use mHealth after being shown DialBetics – an mHealth application for diabetics – as an example, and about their history of dropout and previous mHealth experience. Data were analyzed by multivariate logistic regression models.

Results

Of 307 patients with type 1 and type 2 diabetes, 34 (11.1%) had previously dropped out from diabetic care. Multivariate analysis identified previous mHealth experience as a negative predictor of dropout (odds ratio 0.211, P = 0.023). Of those 34 patients, 27 (79.4%) expressed willingness to use mHealth, a significantly higher percentage than for those who had never dropped out (51.5%, P = 0.002). After adjusting for confounders, history of dropout remained a strong predictor of willingness (odds ratio 3.870, P = 0.004).

Conclusions

Patients who previously dropped out of diabetic care are suitable candidates for mHealth. Future studies must evaluate whether mHealth is effective for preventing repeated dropout and improving glycemic control among this population.
How phylogeny and foraging ecology drive the level of chemosensory exploration in lizards and snakes
Authors: Baeckens S. , Van Damme R. , Cooper W. E.
Published: December 2016

The chemical senses are crucial for squamates (lizards and snakes). The extent to which squamates utilize their chemosensory system, however, varies greatly among taxa and species’ foraging strategies, and played an influential role in squamate evolution. In lizards, ‘Scleroglossa’ evolved a state where species use chemical cues to search for food (active foragers), whereas ‘Iguania’ retained the use of vision to hunt prey (ambush foragers). However, such strict dichotomy is flawed as shifts in foraging modes have occurred in all clades. Here, we attempted to disentangle effects of foraging ecology from phylogenetic trait conservatism as leading cause of the disparity in chemosensory investment among squamates. To do so, we used species’ tongue‐flick rate (TFR) in the absence of ecological relevant chemical stimuli as a proxy for its fundamental level of chemosensory investigation, that is baseline TFR. Based on literature data of nearly 100 species and using phylogenetic comparative methods, we tested whether and how foraging mode and diet affect baseline TFR. Our results show that baseline TFR is higher in active than ambush foragers. Although baseline TFRs appear phylogenetically stable in some lizard taxa, that is a consequence of concordant stability of foraging mode: when foraging mode shifts within taxa, so does baseline TFR. Also, baseline TFR is a good predictor of prey chemical discriminatory ability, as we established a strong positive relationship between baseline TFR and TFR in response to prey. Baseline TFR is unrelated to diet. Essentially, foraging mode, not phylogenetic relatedness, drives convergent evolution of similar levels of squamate chemosensory investigation.
Heterogeneity and concordance in locus‐specific differentiation and introgression between species of towhees
Authors: Kingston S. E. , Parchman T. L. , Gompert Z. , Buerkle C. A. , Braun M. J.
Published: December 2016

The maintenance or breakdown of reproductive isolation is an observable outcome of secondary contact between species. In cases where hybrids beyond the F1 are formed, the representation of each species' ancestry can vary dramatically among genomic regions. This genomic heterogeneity in ancestry and introgression can offer insight into evolutionary processes, particularly if introgression is compared in multiple hybrid zones. Similarly, considerable heterogeneity exists across the genome in the extent to which populations and species have diverged, reflecting the combined effects of different evolutionary processes on genetic variation. We studied hybridization across two hybrid zones of two phenotypically well‐differentiated bird species in Mexico (Pipilo maculatusandP. ocai), to investigate genomic heterogeneity in differentiation and introgression. Using genotyping‐by‐sequencing (GBS) and hierarchical Bayesian models, we genotyped 460 birds at over 41 000 single nucleotide polymorphism (SNP) loci. We identified loci exhibiting extreme introgression relative to the genome‐wide expectation using a Bayesian genomic cline model. We also estimated locus‐specificFSTand identified loci with exceptionally high genetic divergence between the parental species. We found some concordance of locus‐specific introgression in the two independent hybrid zones (6–20% of extreme loci shared across zones), reflecting areas of the genome that experience similar gene flow when the species interact. Additionally, heterogeneity in introgression and divergence across the genome revealed another subset of loci under the influence of locally specific factors. These results are consistent with a history in which reproductive isolation has been influenced by a common set of loci in both hybrid zones, but where local environmental and stochastic factors also lead to genomic differentiation.
Critical infrastructure impact assessment due to flood exposure
Authors: Pant R. , Thacker S. , Hall J.W. , Alderson D. , Barr S.
Published: December 2016

Critical national infrastructures, including energy, transport, digital communications, and water, are prone to flood damage. Their geographical extent is a determinant of, and is determined by, patterns of human development, which is often concentrated in floodplains. It is important to understand how infrastructure systems react to large‐scale flooding. In this paper, we present an integrated framework for critical infrastructure flood impact assessment. Within this integrated framework, we represent interdependent infrastructure assets through spatial network models. We quantify infrastructure flood impacts in terms of disrupted customers linked directly to flood assets and customers disrupted indirectly due to network effects. The analysis shows how spatial network models inform flood risk management practitioners to identify and compare critical infrastructures risks on flooded and non‐flooded land, for prioritising flood protection investments and improve resilience of cities. A case study of the Thames catchment in England is presented, which contains key infrastructure assets and highest population concentrations in United Kingdom.
Development and validation of a food frequency questionnaire to assess omega‐3 long chain polyunsaturated fatty acid intake in Australian children aged 9–13 years
Authors: Rahmawaty S. , Charlton K. , Lyons‐Wall P. , Meyer B. J.
Published: December 2016

Background

The present study aimed to develop a food frequency questionnaire (FFQ) assessing dietary omega‐3 long chain polyunsaturated fatty acid (n‐3 LCPUFA) intake in Australian children and to validate the FFQ against a 7‐day food diary.

Methods

The investigation comprised a cross‐sectional and validation study. The study setting was two private primary schools in the in the Illawarra region of New South Wales. Twenty‐two Australian children, aged 9–13 years, who were not on a special diet or receiving medical care that limited their food choice in the 3 months prior to recruitment, were recruited into the study.

Results

A total of 131 items, classified according to seven food group categories, was included in the n‐3 LCPUFA FFQ, as identified from published dietary surveys and a supermarket survey. Good correlations between the FFQ and the 7‐day food diary were observed for eicosapentaenoic acid (EPA) [r = 0.691, 95% confidence interval (CI) = 0.51–0.83, P < 0.001], docosahexaenoic acid (DHA) (r = 0.684, 95% CI = 0.45–0.84, P < 0.001) and total n‐3 LCPUFA (r = 0.687, 95% CI = 0.48–0.85, P < 0.001). Bland–Altman plots showed an acceptable limit of agreement between the FFQ and the average 7‐day food diary. However, the mean EPA, DHA and total n‐3 LCPUFA intakes estimated from the FFQ were significantly higher than those from the average 7‐day food diary estimates (P < 0.001).

Conclusions

A novel n‐3 LCPUFA FFQ that has been developed to estimate dietary n‐3 LCPUFA intakes in Australian children has been shown to have relative validity. The FFQ provides a useful contribution to dietary assessment methodology in this age group; however, reproducibility remains to be demonstrated.
The precise regulation of different COR genes by individual CBF transcription factors in Arabidopsis thaliana
Authors: Shi Yihao , Huang Jiaying , Sun Tianshu , Wang Xuefei , Zhu Chenqi , Ai Yuxi , Gu Hongya
Published: December 2016

The transcription factors CBF1/2/3 are reported to play a dominant role in the cold responsive network of Arabidopsis by directly regulating the expression levels of cold responsive (COR) genes. In this study, we obtained CRISPR/Cas9‐mediated loss‐of‐function mutants of cbf1∼3. Over 3,000 COR genes identified by RNA‐seq analysis showed a slight but significant change in their expression levels in the mutants compared to the wild‐type plants after being treated at 4 °C for 12 h. The C‐repeat (CRT) motif (5′‐CCGAC‐3′) was enriched in promoters of genes that were up‐regulated by CBF2 and CBF3 but not in promoters of genes up‐regulated by CBF1. These data suggest that CBF2 and CBF3 play a more important role in directing the cold response by regulating different sets of downstream COR genes. More than 2/3 of COR genes were co‐regulated by two or three CBFs and were involved mainly in cellular signal transduction and metabolic processes; less than 1/3 of the genes were regulated by one CBF, and those genes up‐regulated were enriched in cold‐related abiotic stress responses. Our results indicate that CBFs play an important role in the trade‐off between cold tolerance and plant growth through the precise regulation of COR genes in the complicated transcriptional network.
Effects of Orchidectomy and Testosterone Replacement on Numbers of Kisspeptin‐, Neurokinin B‐, and Dynorphin A‐Immunoreactive Neurones in the Arcuate Nucleus of the Hypothalamus in Obese and Diabetic Rats
Authors: Dudek M. , Kołodziejski P. A. , Pruszyńska‐Oszmałek E. , Ziarniak K. , Sliwowska J. H.
Published: December 2016

Neurones expressing kisspeptin, neurokinin B and dynorphin A, located in the arcuate nucleus of the hypothalamus (ARC), are important regulators of reproduction. Their functions depend on metabolic and hormonal status. We hypothesised that male rats with high‐fat diet‐induced obesity (DIO) and/or streptozotocin‐induced diabetes mellitus type 1 (DM1) and type 2 (DM2) will have alterations in numbers of immunoreactive (‐IR) cells: kisspeptin‐IR and/or neurokinin B‐IR and dynorphin A‐IR neurones in the ARC in the sham condition. In addition, orchidectomy alone (ORX) and with testosterone treatment (ORX+T) will unmask possible deficits in the response of these neurones in DIO, and/or DM1 and DM2 rats. Rats were assigned to four groups: a control (C) and one diabetic group (DM1) were fed a regular chow diet, whereas the obese group (DIO) and the other diabetic group (DM2) were fed a high‐fat diet. To induce diabetes, streptozotocin was injected. After 6 weeks, each group was divided into three subgroups: ORX, ORX+T and sham. After another 2 weeks, metabolic and hormonal profiles were assessed and immunocytochemistry was performed. We found that: (1) under sham conditions: (i) DM1 and DM2 animals had higher numbers of kisspeptin‐IR cells than controls and (ii) DM2 rats had increased numbers of neurokinin B‐IR and dynorphin A‐IR cells compared to C animals; (2) ORX and ORX+T treatments unmasked deficits of the studied neurones in DM1 and DM2 but not in DIO animals; and (3) DIO, DM1 and DM2 rats had altered metabolic and hormonal profiles, in particular decreased levels of testosterone. We concluded that alterations in numbers of kisspeptin‐IR and neurokinin B‐IR neurones in the ARC and their response to ORX and ORX+T may account for disruptions of metabolic and reproductive functions in diabetic but not in obese rats.
Effect of Melanotan‐II on Brain Fos Immunoreactivity and Oxytocin Neuronal Activity and Secretion in Rats
Authors: Paiva L. , Sabatier N. , Leng G. , Ludwig M.
Published: December 2016

Melanocortins stimulate the central oxytocin systems that are involved in regulating social behaviours. Alterations in central oxytocin have been linked to neurological disorders such as autism, and melanocortins have been proposed for therapeutic treatment. In the present study, we investigated how systemic administration of melanotan‐II (MT‐II), a melanocortin agonist, affects oxytocin neuronal activity and secretion in rats. The results obtained show that i.v., but not intranasal, administration of MT‐II markedly induced Fos expression in magnocellular neurones of the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus, and this response was attenuated by prior i.c.v. administration of the melanocortin antagonist, SHU‐9119. Electrophysiological recordings from identified magnocellular neurones of the SON showed that i.v. administration of MT‐II increased the firing rate in oxytocin neurones but did not trigger somatodendritic oxytocin release within the SON as measured by microdialysis. Our data suggest that, after i.v., but not intranasal, administration of MT‐II, the activity of magnocellular neurones of the SON is increased. Because previous studies showed that SON oxytocin neurones are inhibited in response to direct application of melanocortin agonists, the actions of i.v. MT‐II are likely to be mediated at least partly indirectly, possibly by activation of inputs from the caudal brainstem, where MT‐II also increased Fos expression.
Resource Dependence and Network Relations: A Test of Venture Capital Investment Termination in China
Authors: Zheng Yanfeng , Xia Jun
Published: December 2016

This study examines how venture capital (VC) firms terminate investments in an emerging economy context. We contend that due to the weak institutional environment, it is appropriate to draw on insights from power and social relation perspectives for a better understanding of the phenomenon. Specifically, we argue that a termination decision hinges on not only the dependence relationship between a VC firm and its portfolio companies, but also the social relationships among VC firms. Event history analyses of approximately 12,000 VC deals made in China between 2001 and 2012 reveal that when a VC firm has a greater number of investments in an industry, it is more likely to terminate investments on a portfolio company in that industry. Moreover, such effect on termination is moderated by the focal VC's embeddedness with its syndicate partners and collaboration opportunities with other VC firms outside the immediate access of the syndicate partners. Our study sheds light on research on VC decision making in emerging markets by integrating insights from resource dependence relationships and interorganizational network characteristics.
Sonic hedgehog is present in parotid saliva and is decreased in patients with taste dysfunction
Authors: Henkin Robert I. , Knöppel Alexandra B. , Abdelmeguid Mona , Stateman William A. , Hosein Suzanna
Published: December 2016

Purpose

To demonstrate that sonic hedgehog (Shh) is present in human parotid saliva and is decreased in human taste dysfunction.

Methods

Shh was measured in parotid saliva of 27 normal subjects and 81 patients with taste dysfunction of multiple etiologies using a sensitive spectrophotometricELISAassay. Taste dysfunction was defined clinically both by subjective decreases of taste acuity and flavor perception and by impaired gustometry.

Results

Shh was found in parotid saliva of both normal subjects and patients with taste dysfunction. Levels were significantly lower in patients than in normal subjects. Both subjective loss of taste acuity and flavor perception and impaired gustometry was measured in untreated patients.

Conclusions

This is the first demonstration of Shh in human saliva. As Shh has been related to taste bud growth and development, its presence in saliva is consistent with its role as a cell signaling moiety involved with stimulation of taste bud stem cells to generate taste receptors. Decreased saliva Shh secretion can be considered a marker of taste dysfunction in patients with multiple pathologies for their dysfunction.
Drivers of genetic differentiation in a generalist insect‐pollinated herb across spatial scales
Authors: Muñoz‐Pajares A. J. , García C. , Abdelaziz M. , Bosch J. , Perfectti F. , Gómez J. M.
Published: December 2016

The isolation‐by‐distance model (IBD) predicts that genetic differentiation among populations increases with geographic distance. Yet, empirical studies show that a variety of ecological, topographic and historical factors may override the effect of geographic distance on genetic variation. This may particularly apply to species with narrow but highly heterogeneous distribution ranges, such as those occurring along elevational gradients. Using nine SSR markers, we study the genetic differentiation of the montane pollination‐generalist herb, Erysimum mediohispanicum. Because the effects of any given factor may depend on the geographic scale considered, we investigate the contribution of different environmental and historical factors at three different spatial scales. We evaluate five competing models that put forward the role of geographic distance, local environmental factors [biotic interactions (IBEb) and climatic variables (IBEa)], landscape resistance (IBR) and phylogeographic patterns (IBP), respectively. We find significant IBD regardless of the spatial scale and the genetic distance estimator considered. However, IBEa and IBP also play a prominent role in shaping genetic differentiation patterns at the larger spatial scales, and IBR is significant at the fine spatial scale. Overall, our results highlight the importance of combining different estimators, statistical approaches and spatial scales to disentangle the relative importance of the various ecological factors contributing to the shaping of genetic divergence patterns in natural populations.
Widespread selective sweeps throughout the genome of model plant pathogenic fungi and identification of effector candidates
Authors: Badouin H. , Gladieux P. , Gouzy J. , Siguenza S. , Aguileta G. , Snirc A. , Le Prieur S. , Jeziorski C. , Branca A. , Giraud T.
Published: December 2016

Identifying the genes underlying adaptation, their distribution in genomes and the evolutionary forces shaping genomic diversity are key challenges in evolutionary biology. Very few studies have investigated the abundance and distribution of selective sweeps in species with high‐quality reference genomes, outside a handful of model species. Pathogenic fungi are tractable eukaryote models for investigating the genomics of adaptation. By sequencing 53 genomes of two species of anther‐smut fungi and mapping them against a high‐quality reference genome, we showed that selective sweeps were abundant and scattered throughout the genome in one species, affecting near 17% of the genome, but much less numerous and in different genomic regions in its sister species, where they left footprints in only 1% of the genome. Polymorphism was negatively correlated with linkage disequilibrium levels in the genomes, consistent with recurrent positive and/or background selection. Differential expression in planta and in vitro, and functional annotation, suggested that many of the selective sweeps were probably involved in adaptation to the host plant. Examples include glycoside hydrolases, pectin lyases and an extracellular membrane protein with CFEM domain. This study thus provides candidate genes for being involved in plant–pathogen interaction (effectors), which have remained elusive for long in this otherwise well‐studied system. Their identification will foster future functional and evolutionary studies, in the plant and in the anther‐smut pathogens, being model species of natural plant–pathogen associations. In addition, our results suggest that positive selection can have a pervasive impact in shaping genomic variability in pathogens and selfing species, broadening our knowledge of the occurrence and frequency of selective events in natural populations.
Clones or clans: the genetic structure of a deep‐sea sponge,Aphrocallistes vastus,in unique sponge reefs of British Columbia, Canada
Authors: Brown Rachel R. , Davis Corey S. , Leys Sally P.
Published: December 2016

Understanding patterns of reproduction, dispersal and recruitment in deep‐sea communities is increasingly important with the need to manage resource extraction and conserve species diversity. Glass sponges are usually found in deep water (>1000 m) worldwide but form kilometre‐long reefs on the continental shelf of British Columbia and Alaska that are under threat from trawling and resource exploration. Due to their deep‐water habitat, larvae have not yet been found and the level of genetic connectivity between reefs and nonreef communities is unknown. The genetic structure ofAphrocallistes vastus, the primary reef‐building species in the Strait of Georgia (SoG) British Columbia, was studied using single nucleotide polymorphisms (SNPs). Pairwise comparisons of multilocus genotypes were used to assess whether sexual reproduction is common. Structure was examined 1) between individuals in reefs, 2) between reefs and 3) between sites in and outside the SoG. Sixty‐sevenSNPs were genotyped in 91 samples from areas in and around the SoG, including four sponge reefs and nearby nonreef sites. The results show that sponge reefs are formed through sexual reproduction. Within a reef and across the SoG basin, the genetic distance between individuals does not vary with geographic distance (r = −0.005 to 0.014), but populations within the SoG basin are genetically distinct from populations in Barkley Sound, on the west coast of Vancouver Island. Population structure was seen across all sample sites (globalFST = 0.248), especially between SoG and non‐SoG locations (average pairwiseFST = 0.251). Our results suggest that genetic mixing occurs across sponge reefs via larvae that disperse widely.
1,2‐Diacylglycerol choline phosphotransferase catalyzes the final step in the unique Treponema denticola phosphatidylcholine biosynthesis pathway
Authors: Vences‐Guzmán Miguel Ángel , Paula Goetting‐Minesky M. , Guan Ziqiang , Castillo‐Ramirez Santiago , Córdoba‐Castro Luz América , López‐Lara Isabel M. , Geiger Otto , Sohlenkamp Christian , Christopher Fenno J.
Published: December 2016

Treponema denticola synthesizes phosphatidylcholine through a licCA‐dependent CDP‐choline pathway identified only in the genus Treponema. However, the mechanism of conversion of CDP‐choline to phosphatidylcholine remained unclear. We report here characterization of TDE0021 (herein designated cpt) encoding a 1,2‐diacylglycerol choline phosphotransferase homologous to choline phosphotransferases that catalyze the final step of the highly conserved Kennedy pathway for phosphatidylcholine synthesis in eukaryotes. T. denticola Cpt catalyzed in vitro phosphatidylcholine formation from CDP‐choline and diacylglycerol, and full activity required divalent manganese. Allelic replacement mutagenesis of cpt in T. denticola resulted in abrogation of phosphatidylcholine synthesis. T. denticola Cpt complemented a Saccharomyces cerevisiae CPT1 mutant, and expression of the entire T. denticola LicCA‐Cpt pathway in E. coli resulted in phosphatidylcholine biosynthesis. Our findings show that T. denticola possesses a unique phosphatidylcholine synthesis pathway combining conserved prokaryotic choline kinase and CTP:phosphocholine cytidylyltransferase activities with a 1,2‐diacylglycerol choline phosphotransferase that is common in eukaryotes. Other than in a subset of mammalian host‐associated Treponema that includes T. pallidum, this pathway is found in neither bacteria nor Archaea. Molecular dating analysis of the Cpt gene family suggests that a horizontal gene transfer event introduced this gene into an ancestral Treponema well after its divergence from other spirochetes.
Structural basis for rifamycin resistance of bacterial RNA polymerase by the three most clinically important RpoB mutations found in Mycobacterium tuberculosis
Authors: Molodtsov Vadim , Scharf Nathan T. , Stefan Maxwell A. , Garcia George A. , Murakami Katsuhiko S.
Published: December 2016

Since 1967, Rifampin (RMP, a Rifamycin) has been used as a first line antibiotic treatment for tuberculosis (TB), and it remains the cornerstone of current short‐term TB treatment. Increased occurrence of Rifamycin‐resistant (RIFR) TB, ∼41% of which results from the RpoB S531L mutation in RNA polymerase (RNAP), has become a growing problem worldwide. In this study, we determined the X‐ray crystal structures of the Escherichia coli RNAPs containing the most clinically important S531L mutation and two other frequently observed RIFR mutants, RpoB D516V and RpoB H526Y. The structures reveal that the S531L mutation imparts subtle if any structural or functional impact on RNAP in the absence of RIF. However, upon RMP binding, the S531L mutant exhibits a disordering of the RIF binding interface, which effectively reduces the RMP affinity. In contrast, the H526Y mutation reshapes the RIF binding pocket, generating significant steric conflicts that essentially prevent any RIF binding. While the D516V mutant does not exhibit any such gross structural changes, certainly the electrostatic surface of the RIF binding pocket is dramatically changed, likely resulting in the decreased affinity for RIFs. Analysis of interactions of RMP with three common RIFR mutant RNAPs suggests that modifications to RMP may recover its efficacy against RIFR TB.
Several Hfq‐dependent alterations in physiology of Yersinia enterocolitica O:3 are mediated by derepression of the transcriptional regulator RovM
Authors: Leskinen Katarzyna , Pajunen Maria I. , Varjosalo Markku , Fernández‐Carrasco Helena , Bengoechea José A. , Skurnik Mikael
Published: December 2016

In bacteria, the RNA chaperone Hfq enables pairing of small regulatory RNAs with their target mRNAs and therefore is a key player of post‐transcriptional regulation network. As a global regulator, Hfq is engaged in the adaptation to external environment, regulation of metabolism and bacterial virulence. In this study we used RNA‐sequencing and quantitative proteomics (LC‐MS/MS) to elucidate the role of this chaperone in the physiology and virulence of Yersinia enterocolitica serotype O:3. This global approach revealed the profound impact of Hfq on gene and protein expression. Furthermore, the role of Hfq in the cell morphology, metabolism, cell wall integrity, resistance to external stresses and pathogenicity was evaluated. Importantly, our results revealed that several alterations typical for the hfq‐negative phenotype were due to derepression of the transcriptional factor RovM. The overexpression of RovM caused by the loss of Hfq chaperone resulted in extended growth defect, alterations in the lipid A structure, motility and biofilm formation defects, as well as changes in mannitol utilization. Furthermore, in Y. enterocolitica RovM only in the presence of Hfq affected the abundance of RpoS. Finally, the impact of hfq and rovM mutations on the virulence was assessed in the mouse infection model.
Suppression and synthetic‐lethal genetic relationships of ΔgpsB mutations indicate that GpsB mediates protein phosphorylation and penicillin‐binding protein interactions in Streptococcus pneumoniaeD39
Authors: Rued Britta E. , Zheng Jiaqi J. , Mura Andrea , Tsui Ho‐Ching T. , Boersma Michael J. , Mazny Jeffrey L. , Corona Federico , Perez Amilcar J. , Fadda Daniela , Doubravová Linda , Buriánková Karolína , Branny Pavel , Massidda Orietta , Winkler Malcolm E.
Published: December 2016

GpsB regulatory protein and StkP protein kinase have been proposed as molecular switches that balance septal and peripheral (side‐wall like) peptidoglycan (PG) synthesis in Streptococcus pneumoniae (pneumococcus); yet, mechanisms of this switching remain unknown. We report that ΔdivIVA mutations are not epistatic to ΔgpsB division‐protein mutations in progenitor D39 and related genetic backgrounds; nor is GpsB required for StkP localization or FDAA labeling at septal division rings. However, we confirm that reduction of GpsB amount leads to decreased protein phosphorylation by StkP and report that the essentiality of ΔgpsB mutations is suppressed by inactivation of PhpP protein phosphatase, which concomitantly restores protein phosphorylation levels. ΔgpsB mutations are also suppressed by other classes of mutations, including one that eliminates protein phosphorylation and may alter division. Moreover, ΔgpsB mutations are synthetically lethal with Δpbp1a, but not Δpbp2a or Δpbp1b mutations, suggesting GpsB activation of PBP2a activity. Consistent with this result, co‐IP experiments showed that GpsB complexes with EzrA, StkP, PBP2a, PBP2b and MreC in pneumococcal cells. Furthermore, depletion of GpsB prevents PBP2x migration to septal centers. These results support a model in which GpsB negatively regulates peripheral PG synthesis by PBP2b and positively regulates septal ring closure through its interactions with StkP‐PBP2x.
Sudan black: a fast, easy and non‐toxic method to assess myelin repair in demyelinating diseases
Authors: Ineichen Benjamin V. , Weinmann Oliver , Good Nicolas , Plattner Patricia S. , Wicki Carla , Rushing Elisabeth J. , Linnebank Michael , Schwab Martin E.
Published: December 2016

Aims

The search for novel drugs that enhance myelin repair in entities such as multiple sclerosis has top priority in neurological research, not least because remyelination can hinder further neurodegeneration in neuro‐inflammatory conditions. Recently, several new compounds with the potential to boost remyelination have been identified using high‐throughput in vitro screening methods. However, assessing their potential to enhance remyelination in vivo using plastic embedded semi‐thin sections or electron microscopy, even though being the gold standard for assessing remyelination, is toxic, extremely time‐consuming and expensive.

Methods

We screened available myelin dyes for a staining candidate which offers a faster and easier alternative to visualize remyelination in cryo‐sections.

Results

We identified sudan black as a candidate with excellent myelin resolution and we show that our adapted sudan black staining can demonstrate myelin repair in rodent spinal cord cryosections as reliable as in semithin sections, but much faster, easier, less toxic and less expensive. Besides that, it can resolve the small myelinated axons in the corpus callosum. The staining can yet readily be combined with immunostainings which can be challenging in semithin sections. We validated the method in human spinal cord tissue as well as in experimental demyelination of the rat spinal cord by a lysolecithin time course experiment. As proof‐of‐principle, we demonstrate that sudan black is able to reliably detect the remyelination enhancing properties of benztropine.

Conclusion

Our adapted sudan black staining can be used to rapidly and non‐toxically screen for remyelinating therapies in demyelinating diseases.
Myopathology in the times of modern genetics
Authors: Schuelke M. , Øien N. C. , Oldfors A.
Published: December 2016

The advent of Next Generation Sequencing (NGS) technologies has accelerated the rate of novel disease gene discovery. Analysis of the large datasets generated by whole exome sequencing, whole genome sequencing, and other NGS approaches poses a challenge to physicians and pathologists searching for disease causing variants amongst the 50 000—3 million polymorphisms typically seen in these datasets. This review describes strategies that successfully combine classical neuropathological investigation (e.g. histology, immunostaining and electron microscopy) with modern NGS technologies to pinpoint the underlying genetic cause of a disease. We describe filtering techniques and free online bioinformatic tools that can help physicians and researchers establish a molecular diagnosis from NGS data. The ethical issues raised by NGS data are outlined. We provide specific examples that illustrate how traditional and contemporary approaches integrate to solve a difficult diagnosis or to correct initially wrong assumptions based on data generated from one method alone.
Peritonitis as a risk factor for long‐term cardiovascular mortality in peritoneal dialysis patients: The case of a friendly fire?
Authors: Pecoits‐Filho Roberto , Yabumoto Franciele M , Campos Ludimila G , Moraes Thyago P , Figueiredo Ana E , Olandoski Márcia , Shimakura Silvia E , Barretti Pasqual ,   on behalf of the BRAZPD Investigators
Published: December 2016

Aim

Since the impact of peritonitis on long‐term non‐infectious mortality has not been investigated until the present, the aim of this study was to analyze the impact of peritonitis on long‐term cardiovascular (CV) mortality in a large peritoneal dialysis (PD) cohort.

Methods

The analysis was based on BRAZPD II, a national prospective cohort study that recruited patients in Brazilian centres from December 2004 to January 2011. Incident adult PD patients with at least 90 days on treatment were included in the analysis. Cardiovascular death occurring after a minimum of 30 days after a peritonitis episode was considered the primary endpoint. Cox regression analysis for time‐dependent variables was used for the adjustments.

Results

There were 2405 episodes of peritonitis in 5707 patients (48% males, 44% diabetes, 73% hypertensive). Patients with one episode of peritonitis presented a 22% increase in the hazard ratio of late CV mortality compared to those who never experienced peritonitis (HR1.22; CI95%1.01–1.47). Adjusted hazard for CV mortality showed a stepwise negative effect on survival for each additional peritonitis episode of infection: two episodes (HR1.78; CI95%1.31–2.42), three episodes (HR2.81; CI95%1.83–4.32) and four episodes (HR3.84; CI95%2.01–7.32).

Conclusion

Peritonitis was an independent predictor of CV mortality and the frequency of peritonitis was strongly associated with an increase in this risk. This is the first study to demonstrate the impact of peritonitis on late cardiovascular mortality of PD patients, suggesting a link between acute inflammation and cardiovascular outcomes.
Tense and Relativity
Authors: Bacon Andrew
Published: December 2016

Those inclined to positions in the philosophy of time that take tense seriously have typically assumed that not all regions of space‐time are equal: one special region of space‐time corresponds to what is presently happening. When combined with assumptions from modern physics this has the unsettling consequence that the shape of this favored region distinguishes people in certain places or people traveling at certain velocities. In this paper I shall attempt to avoid this result by developing a tensed picture of reality that is nonetheless consistent with ‘hypersurface egalitarianism’—the view that all hypersurfaces are equal.
Factors influencing micronutrient bioavailability in biofortified crops
Authors: Bechoff Aurélie , Dhuique‐Mayer Claudie
Published: December 2016

Dietary and human factors have been found to be the major factors influencing the bioavailability of micronutrients, such as provitamin A carotenoid (pVAC), iron, and zinc, in biofortified crops. Dietary factors are related to food matrix structure and composition. Processing can improve pVAC bioavailability by disrupting the food matrix but can also result in carotenoid losses. By degrading antinutrients, such as phytate, processing can also enhance mineral bioavailability. In in vivo interventions, biofortified crops have been shown to be overall efficacious in reducing micronutrient deficiency, with bioconversion factors varying between 2.3:1 and 10.4:1 for trans‐β‐carotene and amounts of iron and zinc absorbed varying between 0.7 and 1.1 mg/day and 1.1 and 2.1 mg/day, respectively. Micronutrient bioavailability was dependent on the crop type and the presence of fat for pVACs and on antinutrients for minerals. In addition to dietary factors, human factors, such as inflammation and disease, can affect micronutrient status. Understanding the interactions between micronutrients is also essential, for example, the synergic effect of iron and pVACs or the competitive effect of iron and zinc. Future efficacy trials should consider human status and genetic polymorphisms linked to interindividual variations.
High‐resolution DNA content analysis of microbiopsy samples in oral lichen planus
Authors: Pentenero M , Monticone M , Marino R , Aiello C , Marchitto G , Malacarne D , Giaretti W , Gandolfo S , Castagnola P
Published: December 2016

Objectives

DNA aneuploidy has been reported to be a predictor of poor prognosis in both premalignant and malignant lesions. In oral lichen planus (OLP), this hypothesis remains to be proved. This study aimed to determine the rate of occurrence of DNA aneuploidy in patients with OLP by high‐resolution DNA flow cytometry.

Methods

Patients with OLP were consecutively enrolled. Tissue samples were subdivided for formalin fixation and routine histological assessment and for immediate storage at −20°C for later DNA ploidy analysis, which was performed by DAPI staining of the extracted nuclei and excitation with a UV lamp. The DNA aneuploid sublines were characterized by the DNA Index.

Results

A DNA aneuploid status was observed in two of 77 patients with OLP (2.6%). When considering the clinical aspect of the OLP lesions, both DNA aneuploid cases had a reticular clinical aspect.

Conclusions

DNA aneuploidy is an uncommon event in OLP and less frequent compared to other non‐dysplastic and non‐OLP oral potentially malignant disorders. The extremely low rate of DNA aneuploidy could represent an occasional finding or reflect the low rate of malignant transformation observed in patients with OLP even if the real prognostic value of DNA ploidy analysis in patients with OLP remains to be confirmed.
Immune reconstitution inflammatory syndrome in HIV infection: taking the bad with the good
Authors: Wong C‐S , Richards ES , Pei L , Sereti I
Published: December 2016

In this review, we will describe the immunopathogies of immune reconstitution inflammatory syndrome, IRIS. IRIS occurs in a small subset of HIV patient, initiating combination antiretroviral therapy (ART), where immune reconstitution becomes dysregulated, resulting in an overly robust antigen‐specific inflammatory reaction. We will discuss IRIS in terms of the associated coinfections: mycobacteria, cryptococci, and viruses.
Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting “Catecholamine‐Sensitive Area”: A Dominant‐Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions
Authors: SHIRAI YASUHIRO , GOYA MASAHIKO , OHNO SEIKO , HORIE MINORU , DOI SHOZABURO , ISOBE MITSUAKI , HIRAO KENZO
Published: December 2016

We report on a patient diagnosed with catechoaminergic polymorphic ventricular tachycardia (CPVT) who underwent catheter ablation of ventricular premature contractions (VPCs) induced by epinephrine. VPCs were classified roughly into three types. Type 1 and Type 2 VPCs (right bundle branch block [RBBB] configuration and inferior axis) were eliminated by radiofrequency applications at the left aortic sinus of Valsalva and the anterolateral papillary muscle (APM), respectively. Although no spontaneous VPCs were seen after the elimination of Type 1 and 2 VPCs, pacing resulting in capture at the APM induced Type 3 VPC (RBBB configuration and superior axis) reproducibly. The electrophysiological findings observed in our representative case have important implications both for understanding the pathophysiology of CPVT and for considering therapeutic strategies.
Thorax Percutaneous Approach for Epicardial Ventricular Ablation in a Patient with Electrical Storm
Authors: BARBATO GAETANO , CARINCI VALERIA , FORTIPARRI SERGIO , PAVESI PIERCAMILLO , PERGOLINI FRANCESCO , DI PASQUALE GIUSEPPE
Published: December 2016

Subxiphoid puncture is considered the standard approach for epicardial ablation of ventricular arrhythmia, but in some cases this access is impracticable due to the patient's anatomy. We describe the case of a patient with electrical storm and abnormal subdiaphragmatic anatomy that precluded the usual subxiphoid approach. In this patient the pericardial space was gained through a direct thorax puncture at the fifth intercostals space close to the mammary line. The tools and technique utilized in this case were similar to what is usually used for traditional subxiphoid puncture. The thorax percutaneous puncture was successfully carried out without complication.