bluuebunny/crossref_metadata_2025 huggingface dataset:
Low‐dose curcumin stimulates proliferation of rat embryonic neural stem cells through glucocorticoid receptor and STAT3
Authors: Ma Xiao‐Xiao , Liu Jin , Wang Chun‐Man , Zhou Jiang‐Ping , He Zhen‐Zhou , Lin Han
Published: March 2018

Aims

This study was to determine whether curcumin had any effect on the proliferation of neural stem cell (NSC), analyze the expression of glucocorticoid receptor (GR), signal transducer and activator of transcription 3 (STAT3), and Notch1 at transcription and protein level, and discuss the related mechanisms.

Methods and results

NSCs were harvested from E15 SD rat brain and cultured. All experiments were performed at the second passage. Cell cytotoxicity, cell viability, and proliferation assays were used to figure out the optimal concentration of curcumin, which can be used for the protein and mRNA studies. The results showed that by downregulation of GR and STAT3 expression, 0.5 μmol L−1 curcumin exhibited the most pronounced effect in promoting the proliferation of NSCs, which were also induced by antagonists of GR and STAT3, but was inhibited by GR agonist.

Conclusion

This study shows that low‐dose curcumin stimulates the proliferation of NSCs, which is probably by inhibiting the mRNA and protein expressions of GR and directly or indirectly regulating the STAT3 via the synergistic effect of GR and STAT3 pathways and its related signal pathways.
A framework for investigating illegal wildlife trade on social media with machine learning
Authors: Di Minin Enrico , Fink Christoph , Hiippala Tuomo , Tenkanen Henrikki
Published: March 2018

Article impact statement: Machine learning can be used to automatically monitor and assess illegal wildlife trade on social media platforms.
Survival after lung transplantation of cystic fibrosis patients infected with Burkholderia dolosa (genomovar VI)
Authors: Wang Ruobing , Welsh Sebastian K. , Budev Marie , Goldberg Hilary , Noone Peadar G. , Gray Alice , Zaas David , Boyer Debra
Published: March 2018

Cystic fibrosis (CF) with severe lung disease is a well‐recognized indication for lung transplantation. Colonization with various organisms in CF patients may impact post‐transplant morbidity and mortality. Burkholderia cepacia complex (BCC) is made up of distinct genomovars with significant morbidity and mortality associated with B. cenocepacia (genomovar III) following lung transplant. The outcomes of patients infected with genomovar B. dolosa (genomovar VI) have yet to be described in the literature. We performed a retrospective chart review of all cystic fibrosis patients colonized with B. dolosa from our center who underwent lung transplantation (n = 11) at various medical centers across the US between 2000 and 2014. Survival rates were 73%, 53%, and 30% for 1, 3, and 5 years, respectively. Median survival was 44 months (95% CI = 11.1‐76.8). CF patients with B. dolosa that have undergone lung transplantation have decreased one‐year survival when compared to all patients transplanted with cystic fibrosis. Conditional 5‐year survival for B. dolosa‐infected patients was 43% in patients that survived the first year post‐transplant, suggesting that this first year is crucial in managing the infection. Importantly, the survival of the B. dolosa patients was higher than compared to previously reported survival rates of B. cenocepacia patients post‐transplant.
Cover Image, Volume 20, Issue 4
Authors: Ruz‐Maldonado Inmaculada , Pingitore Attilio , Liu Bo , Atanes Patricio , Huang Guo Cai , Baker David , Alonso Francisco José , Bermúdez‐Silva Francisco Javier , Persaud Shanta J.
Published: March 2018

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180.

image
Walk, swim or fly? Locomotor mode predicts genetic differentiation in vertebrates
Authors: Medina Iliana , Cooke Georgina M. , Ord Terry J.
Published: March 2018

Limited dispersal is commonly used to explain differences in diversification rates. An obvious but unexplored factor affecting dispersal is the mode of locomotion used by animals. Whether individuals walk, swim or fly can dictate the type and severity of geographical barriers to dispersal, and determine the general range over which genetic differentiation might occur. We collated information on locomotion mode and genetic differentiation (FST) among vertebrate populations from over 400 published articles. Our results showed that vertebrate species that walk tend to have higher genetic differentiation among populations than species that swim or fly. Within species that swim, vertebrates in freshwater systems have higher genetic differentiation than those in marine systems, which is consistent with the higher number of species in freshwater environments. These results show that locomotion mode can impact gene flow among populations, supporting at a broad‐scale what has previously been proposed at smaller taxonomical scales.
Bioenergetic theory predicts infection dynamics of human schistosomes in intermediate host snails across ecological gradients
Authors: Civitello David J. , Fatima Hiba , Johnson Leah R. , Nisbet Roger M. , Rohr Jason R.
Published: March 2018

Epidemiological dynamics depend on the traits of hosts and parasites, but hosts and parasites are heterogeneous entities that exist in dynamic environments. Resource availability is a particularly dynamic and potent environmental driver of within‐host infection dynamics (temporal patterns of growth, reproduction, parasite production and survival). We developed, parameterised and validated a model for resource‐explicit infection dynamics by incorporating a parasitism module into dynamic energy budget theory. The model mechanistically explained the dynamic multivariate responses of the human parasite Schistosoma mansoni and its intermediate host snail to variation in resources and host density. At the population level, feedbacks mediated by resource competition could create a unimodal relationship between snail density and human risk of exposure to schistosomes. Consequently, weak snail control could backfire if reductions in snail density release remaining hosts from resource competition. If resource competition is strong and relevant to schistosome production in nature, it could inform control strategies.
Low cytomegalovirus seroprevalence in early multiple sclerosis: a case for the ‘hygiene hypothesis’?
Authors: Alari‐Pahissa E. , Moreira A. , Zabalza A. , Alvarez‐Lafuente R. , Munteis E. , Vera A. , Arroyo R. , Alvarez‐Cermeño J. C. , Villar L. M. , López‐Botet M. , Martínez‐Rodríguez J. E.
Published: March 2018

Background and purpose

Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early‐life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non‐early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses.

Methods

Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus‐6, as well as T‐cell and natural killer (NK)‐cell immunophenotypes.

Results

Cytomegalovirus seroprevalence in early MS was lower than in non‐early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T‐cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK‐cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age‐related decline in serum anti‐EBNA‐1 antibodies (P < 0.01), but no CMV‐related differences in anti‐human herpesvirus‐6 humoral responses.

Conclusions

Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T‐cell and NK‐cell subsets and/or modulation of Epstein–Barr virus‐specific immune responses at early stages of the disease.
Effect of non‐uniform reactor cooling on fracture and constraint of a reactor pressure vessel
Authors: Qian Guian , Niffenegger Markus , Sharabi Medhat , Lafferty Nathan
Published: March 2018

In the lifetime prediction and extension of a nuclear power plant, a reactor pressure vessel (RPV) has to demonstrate the exclusion of brittle fracture. This paper aims to apply fracture mechanics to analyse the non‐uniform cooling effect in case of a loss‐of‐coolant accident on the RPV integrity.

A comprehensive framework coupling reactor system, fluid dynamics, fracture mechanics, and probabilistic analyses for the RPVs integrity analysis is proposed. The safety margin of the allowed RTNDT is increased by more than 16°C if a probabilistic method is applied. Considering the non‐uniform plume cooling effect increases KI more than 30%, increases the failure frequency by more than 1 order of magnitude, and increases the crack tip constraint due to the resulting higher stress. Thus, in order to be more realistic and not to be nonconservative, 3D computational fluid dynamics may be required to provide input for the fracture mechanics analysis of the RPV.
The “Dirty Ice” of the McMurdo Ice Shelf: Analogues for biological oases during the Cryogenian
Authors: Hawes I. , Jungblut A. D. , Matys E. D. , Summons R. E.
Published: March 2018

The Cryogenian (~717–636 Ma) is characterized by widespread glaciation and dramatic fluctuations in biogeochemical cycling during the Sturtian and Marinoan glaciations. The Snowball Earth hypothesis posits that during this period, ice‐covered oceans of more or less global extent shut down or greatly diminished photosynthesis in the marine realm. However, rather than suffering a catastrophic loss of biodiversity, fossil evidence suggests that major eukaryotic lineages survived and, indeed, the end of the Cryogenian marks the onset of a rapid diversification of eukaryotic life. Persistence of diverse life forms through glaciations is thought to have occurred in supraglacial refugia although the exact nature and full extent of such habitats remain uncertain. We present further evidence for the diversity and characteristics of supraglacial ecosystems on the McMurdo Ice Shelf in Antarctica and suggest that refugia analogous to “dirty ice,” that is debris‐covered ice shelf ecosystems, potentially provided nutrient‐rich and long‐lasting biological Cryogenian oases. We also discuss how features of the McMurdo Ice Shelf indicate that mechanisms exist whereby material can be exchanged between the shallow sea floor and the surfaces of ice shelves along continental margins, providing vectors whereby ice shelf ecosystems can nourish underlying seafloor communities and vice versa.
‘EVERYBODY GETS FRAGEBOGENED SOONER OR LATER’: THE DENAZIFICATION QUESTIONNAIRE AS CULTURAL TEXT*
Authors: Sollors Werner
Published: March 2018

Disseminated in millions of copies to post‐war Germans, the Allied denazification questionnaire, in its best‐known version, asked 131 questions not only about membership of the NSDAP, SS, SA, and fifty other affiliated associations, but also about individuals’ pre‐Nazi voting record, implicated relatives, and such data as weight, height, and foreign‐language expertise. Erich Kästner and Ina Seidel filled in such a questionnaire in 1945. While its massive circulation made it a site of German cultural memory, it also became a bureaucratic nightmare for those who had to evaluate the piles of these forms in the Allied armies and the German ‘Spruchkammern’. The ʻFragebogenʼ provoked writers on both sides of the Atlantic to represent it in fiction and non‐fiction. Just Scheu composed a song about it, and Wolfgang Borchert, Margret Boveri, Stig Dagerman, David Davidson, Alan Marcus, John Dos Passos, Zelda Popkin, and Ernst von Salomon commented on it in prose, often critically, calling it a merciless catechism of 131 questions or an ideological equivalent of tax returns. Though often perceived as an embodiment of American culture, it had emerged with the help of Franz Neumann and Herbert Marcuse, German Marxist intellectuals in exile, who hoped that denazification would bring about revolutionary change in Germany.
Atomic force microscopy analysis of SasA‐KaiC complex formation involved in information transfer from the KaiABC clock machinery to the output pathway in cyanobacteria
Authors: Murakami Reiko , Hokonohara Hitomi , Che Dock‐Chil , Kawai Tomoji , Matsumoto Takuya , Ishiura Masahiro
Published: March 2018

The cyanobacterial clock oscillator is composed of three clock proteins: KaiA, KaiB and KaiC. SasA, a KaiC‐binding EnvZ‐like orthodox histidine kinase involved in the main clock output pathway, exists mainly as a trimer (SasA3mer) and occasionally as a hexamer (SasA6mer) in vitro. Previously, the molecular mass of the SasA‐KaiCDD complex, where KaiCDD is a mutant KaiC with two Asp substitutions at the two phosphorylation sites, has been estimated by gel‐filtration chromatography to be larger than 670 kDa. This value disagrees with the theoretical estimation of 480 kDa for a SasA3mer‐KaiC hexamer (KaiC6mer) complex with a 1:1 molecular ratio. To clarify the structure of the SasA‐KaiC complex, we analyzed KaiCDD with 0.1 mmol/L ATP and 5 mmol/L MgCl2 (Mg‐ATP), SasA and a mixture containing SasA and KaiCDD6mer with Mg‐ATP by atomic force microscopy (AFM). KaiCDD images were classified into two types with height distribution corresponding to KaiCDD monomer (KaiCDD1mer) and KaiCDD6mer, respectively. SasA images were classified into two types with height corresponding to SasA3mer and SasA6mer, respectively. The AFM images of the SasA‐KaiCDD mixture indicated not only KaiCDD1mer, KaiCDD6mer, SasA3mer and SasA6mer, but also wider area “islands,” suggesting the presence of a polymerized form of the SasA‐KaiCDD complex.
Mechanical and thermal conductive properties of fiber‐reinforced silica‐alumina aerogels
Authors: Yu Yuxi , Peng Kunhuang , Fang Jiyu , Zhang Ruiqian , Wang Guanchun , Peng Xiaoming
Published: March 2018

We report the formation of Al2O3‐SiO2 fiber‐reinforced Al2O3‐SiO2 aerogels with the content of fibers in the range from 40 wt% to 55 wt% by sol‐gel reaction, followed by supercritical drying. The structure and physical properties of fiber‐reinforced Al2O3‐SiO2 aerogels are studied. We find that the fiber‐reinforced Al2O3‐SiO2 aerogels can be resistant to the temperature of 1200°C. The integration of fibers significantly improves the mechanical properties of Al2O3‐SiO2 aerogels. We find that the bending strength of fiber‐reinforced Al2O3‐SiO2 aerogels increases 0.431 MPa to 0.755 MPa and the elastic modulus increases from 0.679 MPa to 1.153 MPa, when the content of fibers increases from 40 wt% to 50 wt%. The thermal conductivity of the fiber‐reinforced Al2O3‐SiO2 aerogels is in the range from 0.0403 W/mK to 0.0545 W/mK, depending on the content of fibers.
Thioester‐containing proteins in the tsetse fly (Glossina) and their response to trypanosome infection
Authors: Matetovici I. , Van Den Abbeele J.
Published: March 2018

Thioester‐containing proteins (TEPs) are conserved proteins with a role in innate immune immunity. In the current study, we characterized the TEP family in the genome of six tsetse fly species (Glossina spp.). Tsetse flies are the biological vectors of several African trypanosomes, which cause sleeping sickness in humans or nagana in livestock. The analysis of the tsetse TEP sequences revealed information about their structure, evolutionary relationships and expression profiles under both normal and trypanosome infection conditions. Phylogenetic analysis of the family showed that tsetse flies harbour a genomic expansion of specific TEPs that are not found in other dipterans. We found a general expression of all TEP genes in the alimentary tract, mouthparts and salivary glands. Glossina morsitans and Glossina palpalis TEP genes display a tissue‐specific expression pattern with some that are markedly up‐regulated when the fly is infected with the trypanosome parasite. A different TEP response was observed to infection with Trypanosoma brucei compared to Trypanosoma congolense, indicating that the tsetse TEP response is trypanosome‐specific. These findings are suggestive for the involvement of the TEP family in tsetse innate immunity, with a possible role in the control of the trypanosome parasite.
Spoils from the Spoiled: Strategies for Entering Stigmatized Markets
Authors: Slade Shantz Angelique , Fischer Eileen , Liu Aurora , Lévesque Moren
Published: March 2018

Stigmatized markets are those where either the products/services, or the consumers, or both, have been collectively, negatively stereotyped and devalued by one or more stakeholder audiences in ways that discredit the overall market. Many stigmatized markets exist, and many flourish, yet little systematic attention has focused on entry into such markets. Our article addresses this gap by conceptualizing various strategies for entering stigmatized markets. We further present propositions regarding the market‐level factors that can influence which of these strategies firms will choose to employ. The contributions include: conceptually clarifying the nature of stigmatized markets; identifying additional types of entry strategies relevant for entering stigmatized markets; theorizing the conditions under which firms would choose one entry strategy over another; and opening up for consideration the effects that market entry may have on stigmatized actors in targeted markets.
Impact of food retailer branding on expectation generation and liking
Authors: Morris Cecile , Beresford Paul , Hirst Craig
Published: March 2018

Branding can influence sensory evaluation, however, the impact of food retailers from different tiers (premium, everyday, and discount) remains undocumented. The aim of this project was to test whether food retailers generated different quality expectations and establish whether these impacted on sensory evaluation. Expected liking of four chocolate samples (private brand, premium, everyday, and discount food retailer brands) was measured using a survey (n = 199) and hedonic ratings (n = 152) were obtained in blind and informed conditions. Seventy‐one of the 152 panelists were required to rate their expected liking prior to the informed hedonic test to assess whether stating expectations could influence subsequent liking. The premium food retailer and private brand generated similarly high quality expectations which resulted in significant disconfirmation although a significant response shift was only observed for the private brand when expectations were measured. In contrast, the everyday and discount food retailers generated lower expectations which aligned well with the sensory experience.

Practical applications

Although established private brands are still perceived as the gold standard; premium food retailers can also generate high expectations and there is a clear hierarchy of expectations between food retailers' tiers. In spite of this, branding had a modest impact on sensory evaluation compared to actual product quality with partial assimilation observed only for the private brand. Food retailers should continue to develop their product quality to carry on improving their brand image. Asking panelists to state their expectations just prior to the informed hedonic testing could result in self‐induced suggestion error. It is recommended that expectations and informed liking are captured sufficiently far apart when using the same panelists.
Molecular Cloning, Expression, and In Situ Hybridization Analysis of Forkhead Box Protein L2 during Development in Macrobrachium nipponense
Authors: Jin Shubo , Fu Hongtuo , Jiang Sufei , Xiong Yiwei , Sun Shengming , Qiao Hui , Zhang Wenyi , Gong Yongsheng , Wu Yan
Published: March 2018

Forkhead box protein L2 (Foxl2) has dramatic effects on early differentiation and development of the female gonad in mammals and fish through the repression of SOX9 expression. In this study, we aimed to isolate a full‐length cDNA sequence encoding Foxl2 from the Macrobrachium nipponense (Mn‐Foxl2) and investigated its gene function. The full‐length cDNA sequence of Mn‐Foxl2 was 2097 bp with an open reading frame of 1740 bp, encoding 579 amino acids. Phylogenetic analysis revealed considerable evolutionary divergence between Mn‐Foxl2 and Foxl2 from fish. Mn‐Foxl2 may be involved in gonadal sex differentiation, based on its dramatically high expression during the sex‐differentiation sensitive period. Tissue distributions indicated that Mn‐Foxl2 mRNA expression was higher in the testis than that in the ovary and higher in males than in females in the same tissues, implying that Foxl2 may promote both male and female sexual development in M. nipponense. In situ hybridization analysis and quantitative polymerase chain reaction analysis in the gonad during the reproductive cycle further confirmed the important roles of Foxl2 in early gonad development in M. nipponense. This study advances our understanding of the role of Foxl2 in M. nipponense and provides the basis for further studies of Foxl2 in crustaceans.
Efficacy of a Live‐attenuated Edwardsiella ictaluri Oral Vaccine in Channel and Hybrid Catfish
Authors: Chatakondi Nagaraj , Peterson Brian C. , Greenway Terrence E. , Byars Todd S. , Wise David J.
Published: March 2018

This study evaluated the efficacy of an oral live‐attenuated Edwardsiella ictaluri vaccine against enteric septicemia of catfish (ESC) in channel and hybrid catfish. The vaccine was delivered one time orally by feeding fish a diet coated with an attenuated E. ictaluri isolate at four doses to deliver between 4 × 106 to 3.2 × 107 viable vaccine cells/g wet feed. Thirty‐five days postvaccination, control and vaccinated fish were challenged with virulent E. ictaluri and mortality was examined for 30 d postchallenge. Mortality of nonvaccinated hybrids (85%) and nonvaccinated channel catfish (73%) was similar but significantly greater than all groups of vaccinated fish. In channel catfish, a trend toward increasing mortality with decreasing dose was observed. Mortality of channel catfish vaccinated with the lowest dose (26.6%) was significantly higher than fish vaccinated with the highest dose (14.1%) but similar to fish vaccinated at the intermediate doses (17.5 and 19.4%). In contrast, mortality of four doses of vaccinated hybrid catfish was similar and ranged between 10.4 and 14.0%. The data demonstrate that the attenuated E. ictaluri vaccine at all four doses tested is effective at reducing ESC‐related mortalities in hybrid and channel catfish.
Mesozooplankton spatial distribution and community structure in the South Adriatic Sea during two winters (2015, 2016)
Authors: Hure Marijana , Mihanović Hrvoje , Lučić Davor , Ljubešić Zrinka , Kružić Petar
Published: March 2018

Whereas the data on mesozooplankton in the epipelagic offshore Mediterranean Sea are extensive, less information is available about plankton in the deeper layers. The present study aims to describe the vertical and horizontal structure and distribution of mesozooplankton species and their associations down to 1,200 m in the water of the Southern Adriatic Sea. Zooplankton were sampled using a Nansen net of 200‐μm mesh size during two cruises in the winters of 2015 and 2016, extending from the coast to the open sea. In total, 203 zooplankton taxa were identified. The community was dominated by copepods, representing between 67% and 91% of the total abundance. The highest total densities were recorded in the upper layers where a high proportion (up to 36%) of appendicularians was also observed in the first sampled year. Five groups of samples were determined based on their community structure. In 2015 communities were distinct between the 0 and 50 m layer and the underlying one (50–100 m), whereas in 2016 epipelagic waters were inhabited by a more uniform mesozooplankton community. The mesopelagic and deep‐water fauna, especially copepods, showed a relatively stable composition in both sampling years Overall, our study confirms the oligotrophic character of the Southern Adriatic, with occasional density outbreaks of appendicularians under favourable conditions.
Ethylene signaling induces gelatinous layers with typical features of tension wood in hybrid aspen
Authors: Felten Judith , Vahala Jorma , Love Jonathan , Gorzsás András , Rüggeberg Markus , Delhomme Nicolas , Leśniewska Joanna , Kangasjärvi Jaakko , Hvidsten Torgeir R. , Mellerowicz Ewa J. , Sundberg Björn
Published: March 2018

The phytohormone ethylene impacts secondary stem growth in plants by stimulating cambial activity, xylem development and fiber over vessel formation. We report the effect of ethylene on secondary cell wall formation and the molecular connection between ethylene signaling and wood formation.

We applied exogenous ethylene or its precursor 1‐aminocyclopropane‐1‐carboxylic acid (ACC) to wild‐type and ethylene‐insensitive hybrid aspen trees (Populus tremula × tremuloides) and studied secondary cell wall anatomy, chemistry and ultrastructure. We furthermore analyzed the transcriptome (RNASeq) afterACCapplication to wild‐type and ethylene‐insensitive trees.

We demonstrate thatACCand ethylene induce gelatinous layers (G‐layers) and alter the fiber cell wall cellulose microfibril angle. G‐layers are tertiary wall layers rich in cellulose, typically found in tension wood of aspen trees. A vast majority of transcripts affected byACCare downstream of ethylene perception and include a large number of transcription factors (TFs). Motif‐analyses reveal potential connections between ethyleneTFs (Ethylene Response Factors (ERFs),ETHYLENE INSENSITIVE3/ETHYLENE INSENSITIVE3‐LIKE1 (EIN3/EIL1)) and wood formation.

G‐layer formation upon ethylene application suggests that the increase in ethylene biosynthesis observed during tension wood formation is important for its formation. Ethylene‐regulatedTFs of theERFandEIN3/EIL1 type could transmit the ethylene signal.
Finding a needle in a haystack: Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor
Authors: Erturk‐Hasdemir Deniz , Kasper Dennis L.
Published: March 2018

Starting from birth, all animals develop a symbiotic relationship with their resident microorganisms that benefits both the microbe and the host. Recent advances in technology have substantially improved our ability to direct research toward the identification of important microbial species that affect host physiology. The identification of specific commensal molecules from these microbes and their mechanisms of action is still in its early stages. Polysaccharide A (PSA) of Bacteroides fragilis is the archetypical example of a commensal molecule that can modulate the host immune system in health and disease. This zwitterionic polysaccharide has a critical impact on the development of the mammalian immune system and also on the stimulation of interleukin 10–producing CD4+ T cells; consequently, PSA confers benefits to the host with regard to experimental autoimmune, inflammatory, and infectious diseases. In this review, we summarize the current understanding of the immunomodulatory effects of B. fragilis PSA and discuss these effects as a novel immunological paradigm. In particular, we discuss recent advances in our understanding of the unique functional mechanisms of this molecule and its therapeutic potential, and we review the recent literature in the field of microbiome research aimed at discovering new commensal products and their immunomodulatory potential.
Identification of a novel QTL for the number of spikelets per panicle using a cross between indica‐ and japonica‐type high‐yielding rice cultivars in Japan
Authors: Takai Toshiyuki , Nakano Hiroshi , Yoshinaga Satoshi , Kondo Motohiko
Published: March 2018

Yield is a complex trait. To improve it, the accumulation of the favourable alleles of valuable genes is required for each yield‐related trait. In this study, we used two high‐yielding rice cultivars developed in Japan, indica‐type ‘Takanari’ and japonica‐type ‘Momiroman’, for a genetic analysis of the sink capacity‐related traits. An F2 population showed transgressive segregation for the number of spikelets per panicle. Quantitative trait locus (QTL) analysis detected four QTLs for the trait. Two of the QTLs were most likely identical to previously cloned GN1a and APO1, and their Takanari alleles had positive effects. The Momiroman alleles of the other two QTLs had positive effects, and one of these QTLs was most likely identical to SPIKE/GPS. The QTL on the long arm of chromosome 3 appeared to be novel; it clustered with QTLs for grain length and days‐to‐heading. Substitution mapping revealed that the close linkage of QTLs caused the clustering. These results suggest that the combination of the favourable alleles of detected QTLs could lead to greater sink capacity than that of the parental cultivars.
Corticosteroids in acute exacerbations of idiopathic interstitial pneumonias: Time to debate – Reply
Authors: Arai Toru , Inoue Yoshikazu
Published: March 2018

See Letter
Social Security and Old Age Unemployment Risk with Efficient Wage Bargaining
Authors: Reichlin Pietro
Published: March 2018

I analyze a life‐cycle economy with old age productivity risk where wages, employment, and severance payments are set through efficient bargaining between risk averse unions and risk neutral firms. Allocations with limited union membership are second‐best inefficient as they generate too little labor supply in young age, too much consumption before retirement, too little employment of older workers (early retirement), and too little insurance against old age unemployment. Providing public transfers to early retirees (disability benefits or early pensions) might help to increase the degree of risk sharing at the cost of lower old age employment. Depending on whether absolute risk aversion is increasing or decreasing in consumption, these policies might or might not produce efficiency gains at equilibrium.
A geopolitics of trauma: Refugee administration and protracted uncertainty in Turkey
Authors: Loyd Jenna M. , Ehrkamp Patricia , Secor Anna J.
Published: March 2018

In this paper we map out what we are calling a “geopolitics of trauma” by examining the role of trauma in transnational refugee regimes and the individualisation of geopolitical relations through mental health diagnosis and service provision. Focusing on one site of entry into the international regime of refugee administration, we present findings from fieldwork that we conducted in August, 2015 in Turkey with NGOs and IGOs involved in the protection, mental health and psychosocial service provision, and resettlement of refugees. The findings that we present demonstrate the challenges of refugee care and management on the front lines in Turkey and the significance of mental health diagnosis, treatment and documentation in the early stages of refugee administration. We suggest that practices of refugee screening and resettlement are imbued with traumatic stressors and trace how trauma intersects with the administration of refugees in different sites and at different times. We argue that the protracted situation of refugees in Turkey (many of whom will wait eight years for their Refugee Status Determination interview) and the multiple interviews and demands for documentation through which a displaced person applies for refugee status and third‐country resettlement become sites of ongoing traumatisation for the refugee subject. Further, in the practices of screening and documentation, we can trace the medicalisation of the refugee subject as not only a question of care but also a practice of legibility on which the state and international organisations base their decisions about inclusion and exclusion. The geopolitics of trauma thus emerges not only in cartographies of war, displacement and resettlement, but also in the minute details and performative demands of the refugee determination and resettlement process.
Survey of the prevalence and methodology of quality assurance for B‐mode ultrasound image quality among veterinary sonographers
Authors: Hoscheit Larry P. , Heng Hock Gan , Lim Chee Kin , Weng Hsin‐Yi
Published: March 2018

Image quality in B‐mode ultrasound is important as it reflects the diagnostic accuracy and diagnostic information provided during clinical scanning. Quality assurance programs for B‐mode ultrasound systems/components are comprised of initial quality acceptance testing and subsequent regularly scheduled quality control testing. The importance of quality assurance programs for B‐mode ultrasound image quality using ultrasound phantoms is well documented in the human medical and medical physics literature. The purpose of this prospective, cross‐sectional, survey study was to determine the prevalence and methodology of quality acceptance testing and quality control testing of image quality for ultrasound system/components among veterinary sonographers. An online electronic survey was sent to 1497 members of veterinary imaging organizations: the American College of Veterinary Radiology, the Veterinary Ultrasound Society, and the European Association of Veterinary Diagnostic Imaging, and a total of 167 responses were received. The results showed that the percentages of veterinary sonographers performing quality acceptance testing and quality control testing are 42% (64/151; 95% confidence interval 34–52%) and 26% (40/156: 95% confidence interval 19–33%) respectively. Of the respondents who claimed to have quality acceptance testing or quality control testing of image quality in place for their ultrasound system/components, 0% have performed quality acceptance testing or quality control testing correctly (quality acceptance testing 95% confidence interval: 0–6%, quality control testing 95% confidence interval: 0–11%). Further education and guidelines are recommended for veterinary sonographers in the area of quality acceptance testing and quality control testing for B‐mode ultrasound equipment/components.
Approximation forte pour les variétés avec une action d’un groupe linéaire
Authors: Cao Yang
Published: March 2018

Let$G$be a connected linear algebraic group over a number field$k$. Let$U{\hookrightarrow}X$be a$G$-equivariant open embedding of a$G$-homogeneous space$U$with connected stabilizers into a smooth$G$-variety$X$. We prove that$X$satisfies strong approximation with Brauer–Manin condition off a set$S$of places of$k$under either of the following hypotheses:

(i)

$S$is the set of archimedean places;

(ii)

$S$is a non-empty finite set and$\bar{k}^{\times }=\bar{k}[X]^{\times }$.

The proof builds upon the case$X=U$, which has been the object of several works.
Exploiting energy sequencing of low energy SIMS to determine intrinsic chemical profiles with sub-nm precision
Authors: Morris Richard J. H. , Hase Thomas P. A.
Published: March 2018

In the past, it has been proposed that secondary ion mass spectrometry (SIMS) depth profiling of a sample using a range of beam energies could be used as a means of estimating the intrinsic sample profile by extrapolating the measured profile parameters back to zero beam energy. In this paper, the authors address some of the issues that have hindered this approach and demonstrate a new metrology that exploits the idea of energy sequencing to yield intrinsic sample features with subnanometer precision. A significant reason why energy sequencing has not been exploited fully to date is because previous attempts failed to consider the convolution between the sample feature and response function parameters. Their new metrology overcomes this by utilizing a simultaneous fitting approach for which the sample feature is shared across all the profile fits and only the energy dependent response function parameters are varied between profiles using a power law dependence. The authors demonstrate how this approach now allows the intrinsic sample feature to be resolved robustly and with high precision. Additionally, the authors also show that once a specific matrix response function power law dependence has been established, as few as two SIMS profile energies would be sufficient to accurately determine the intrinsic sample feature. This new metrology approach is demonstrated using an atomically sharp SiGe/Si interface and was benchmarked against atomic resolution high angle annular dark field-scanning transmission electron microscopy.
Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy
Authors: Vossen M. G. , Ehmann L. , Pferschy S. , Maier-Salamon A. , Haidinger M. , Weiser C. , Wenisch J. M. , Saria K. , Kajahn C. , Jilch S. , Lemmerer R. , Bécède M. , Zeitlinger M. , Kloft C. , Jäger W. , Thalhammer F.
Published: March 2018

Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against
Pseudomonas aeruginosa
and
Enterobacteriaceae
. Current dosing regimens recommend the administration of 0.25 to 0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investigate a 1-g posthemodialysis regimen, thus reducing treatment costs and enhancing patient compliance. A second objective of this trial was to describe the pharmacokinetics of intradialytic doripenem. Ten oliguric or anuric patients in need of intermittent renal replacement therapy were included in this trial. All patients suffered from a septic episode. The mean hemofilter clearance was 123.46 ± 42.03 ml/min, and the total body clearance between hemodialysis sessions was 16.79 ± 6.02 ml/min. The average prehemodialysis trough concentration was 2.4 ± 1.3 mg/liter, while the EUCAST resistance breakpoint for
Enterobacteriaceae
is set at 2 mg/liter. The interpatient variability was considerably higher than the intrapatient variability. Apart from one patient who suffered an allergic reaction, doripenem was tolerated well by all patients. Our data indicate that posthemodialysis administration of 1 g of doripenem results in sufficient plasma levels in anuric but not oliguric patients during the entire dosing interval. (This trial was registered with EudraCT under registration no. 2009-018010-18 and at ClinicalTrials.gov under registration no. NCT02018939.)
The Lysine 299 Residue Endows the Multisubunit Mrp1 Antiporter with Dominant Roles in Na
+
Resistance and pH Homeostasis in Corynebacterium glutamicum
Authors: Xu Ning , Zheng Yingying , Wang Xiaochen , Krulwich Terry A. , Ma Yanhe , Liu Jun
Published: March 2018

Corynebacterium glutamicum
is generally regarded as a moderately salt- and alkali-tolerant industrial organism. However, relatively little is known about the molecular mechanisms underlying these specific adaptations. Here, we found that the Mrp1 antiporter played crucial roles in conferring both environmental Na
+
resistance and alkali tolerance whereas the Mrp2 antiporter was necessary in coping with high-KCl stress at alkaline pH. Furthermore, the Δ
mrp1
Δ
mrp2
double mutant showed the most-severe growth retardation and failed to grow under high-salt or alkaline conditions. Consistent with growth properties, the Na
+
/H
+
antiporters of
C. glutamicum
were differentially expressed in response to specific salt or alkaline stress, and an alkaline stimulus particularly induced transcript levels of the Mrp-type antiporters. When the major Mrp1 antiporter was overwhelmed,
C. glutamicum
might employ alternative coordinate strategies to regulate antiport activities. Site-directed mutagenesis demonstrated that several conserved residues were required for optimal Na
+
resistance, such as Mrp1A K
299
, Mrp1C I
76
, Mrp1A H
230
, and Mrp1D E
136
. Moreover, the chromosomal replacement of lysine 299 in the Mrp1A subunit resulted in a higher intracellular Na
+
level and a more alkaline intracellular pH value, thereby causing a remarkable growth attenuation. Homology modeling of the Mrp1 subcomplex suggested two possible ion translocation pathways, and lysine 299 might exert its effect by affecting the stability and flexibility of the cytoplasm-facing channel in the Mrp1A subunit. Overall, these findings will provide new clues to the understanding of salt-alkali adaptation during
C. glutamicum
stress acclimatization.

IMPORTANCE
The capacity to adapt to harsh environments is crucial for bacterial survival and product yields, including industrially useful
Corynebacterium glutamicum
. Although
C. glutamicum
exhibits a marked resistance to salt-alkaline stress, the possible mechanism for these adaptations is still unclear. Here, we present the physiological functions and expression patterns of
C. glutamicum
putative Na
+
/H
+
antiporters and conserved residues of Mrp1 subunits, which respond to different salt and alkaline stresses. We found that the Mrp-type antiporters, particularly the Mrp1 antiporter, played a predominant role in maintaining intracellular nontoxic Na
+
levels and alkaline pH homeostasis. Loss of the major Mrp1 antiporter had a profound effect on gene expression of other antiporters under salt or alkaline conditions. The lysine 299 residue may play its essential roles in conferring salt and alkaline tolerance by affecting the ion translocation channel of the Mrp1A subunit. These findings will contribute to a better understanding of Na
+
/H
+
antiporters in sodium antiport and pH regulation.
Reconstituting the History of Cronobacter Evolution Driven by Differentiated CRISPR Activity
Authors: Zeng Haiyan , Zhang Jumei , Wu Qingping , He Wenjing , Wu Haoming , Ye Yingwang , Li Chengsi , Ling Na , Chen Moutong , Wang Juan , Cai Shuzhen , Lei Tao , Ding Yu , Xue Liang
Published: March 2018

Cronobacter
strains harboring the CRISPR-Cas system are important foodborne pathogens causing serious neonatal infections. However, the specific role of the CRISPR-Cas system in bacterial evolution remains relatively unexplored. In this study, we investigated the impact of the CRISPR-Cas system on
Cronobacter
evolution and obtained 137 new whole-genome
Cronobacter
sequences by next-generation sequencing technology. Among the strains examined (
n
= 240), 90.6% (193/213) of prevalent species
Cronobacter sakazakii
,
Cronobacter
malonaticus
, and
Cronobacter
dublinensis
strains had intact CRISPR-Cas systems. Two rare species,
Cronobacter
condimenti
(
n
= 2) and
Cronobacter
universalis
(
n
= 6), lacked and preserved the CRISPR-Cas system at a low frequency (1/6), respectively. These results suggest that the presence of one CRISPR-Cas system is important for a
Cronobacter
species to maintain genome homeostasis for survival. The
Cronobacter
ancestral strain is likely to have harbored both subtype I-E and I-F CRISPR-Cas systems; during the long evolutionary process, subtype I-E was retained while subtype I-F selectively degenerated in
Cronobacter
species and was even lost by the major
Cronobacter
pathovars. Moreover, significantly higher CRISPR activity was observed in the plant-associated species
C
.
dublinensis
than in the virulence-related species
C. sakazakii
and
C
.
malonaticus
. Similar spacers of CRISPR arrays were rarely found among species, suggesting intensive change through adaptive acquisition and loss. Differentiated CRISPR activity appears to be the product of environmental selective pressure and might contribute to the bidirectional divergence and speciation of
Cronobacter
.

IMPORTANCE
This study reports the evolutionary history of
Cronobacter
under the selective pressure of the CRISPR-Cas system. One CRISPR-Cas system in
Cronobacter
is important for maintaining genome homeostasis, whereas two types of systems may be redundant and not conducive to acquiring beneficial DNA for environmental adaptation and pathogenicity. Differentiated CRISPR activity has contributed to the bidirectional divergence and genetic diversity of
Cronobacter
. This perspective makes a significant contribution to the literature by providing new insights into CRISPR-Cas systems in general, while further expanding the roles of CRISPR beyond conferring adaptive immunity and demonstrating a link to adaptation and species divergence in a genus. Moreover, our study provides new insights into the balance between genome homeostasis and the uptake of beneficial DNA related to CRISPR-based activity in the evolution of
Cronobacter
.
Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections
Authors: Patel Mira C. , Shirey Kari Ann , Boukhvalova Marina S. , Vogel Stefanie N. , Blanco Jorge C. G.
Published: March 2018

Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI.

IMPORTANCE
Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.