bluuebunny/crossref_metadata_2025_split huggingface dataset:
Up‐regulation of PYK2/PKCα‐dependent haem oxygenase‐1 by CO‐releasing molecule‐2 attenuates TNF‐α‐induced lung inflammation
Authors: Lin Chih‐Chung , Chiang Yu‐Ching , Cho Rou‐Ling , Lin Wei‐Ning , Yang Chien‐Chung , Hsiao Li‐Der , Yang Chuen‐Mao 
Published: November 2017

Background and PurposeHaem oxygenase‐1 (HO‐1) could provide cytoprotection against various inflammatory diseases. However, the mechanisms underlying the protective effect of CO‐releasing molecule‐2 (CORM‐2)‐induced HO‐1 expression against TNF‐α‐induced inflammatory responses in human pulmonary alveolar epithelial cells (HPAEpiCs) remain unknown.Experimental ApproachCORM‐2‐induced HO‐1 protein and mRNA expression, and signalling pathways were determined by Western blot and real‐time PCR, coupled with respective pharmacological inhibitors or transfection with siRNAs. The effect of CORM‐2 on TNF‐α‐induced increase in leukocyte counts in BAL fluid and VCAM‐1 expression in lung was determined by cell counting and Western blot analysis.Key ResultsCORM‐2 attenuated the TNF‐α‐induced pulmonary haematoma, VCAM‐1 expression and increase in leukocytes through an up‐regulation of HO‐1 in mice; this effect of CORM‐2 was reversed by the HO‐1 inhibitor zinc protoporphyrin IX. Furthermore, CORM‐2 increased HO‐1 protein and mRNA expression as well as the phosphorylation of PYK2, PKCα and ERK1/2 (p44/p42 MAPK) in HPAEpiCs; these effects were attenuated by their respective pharmacological inhibitors or transfection with siRNAs. Inhibition of PKCα by Gö6976 or Gö6983 attenuated CORM‐2‐induced stimulation of PKCα and ERK1/2 phosphorylation but had no effect on PYK2 phosphorylation. Moreover, inhibition of PYK2 by PF431396 reduced the phosphorylation of all three protein kinases. Finally, PYK2/PKCα/ERK1/2‐mediated stimulation of activator protein 1 was shown to play a key role in CORM‐2‐induced HO‐1 expression via an up‐regulation of c‐Fos mRNA.Conclusions and ImplicationsCORM‐2 activates a PYK2/PKCα/ERK1/2/AP‐1 pathway leading to HO‐1 expression in HPAEpiCs. This HO‐1/CO system might have potential as a therapeutic target in pulmonary inflammation.
Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non‐alcoholic fatty liver disease
Authors: Wang Weijun , Zhao Jinfang , Gui Wenfang , Sun Dan , Dai Haijiang , Xiao Li , Chu Huikuan , Du Fan , Zhu Qingjing , Schnabl Bernd , Huang Kai , Yang Ling , Hou Xiaohua 
Published: November 2017

Background and PurposeThe gut–liver axis is associated with the progression of non‐alcoholic fatty liver disease (NAFLD). Targeting the gut–liver axis and bile acid‐based pharmaceuticals are potential therapies for NAFLD. The effect of tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD, on intestinal barrier function, intestinal inflammation, gut lipid transport and microbiota composition was analysed in a murine model of NAFLD.Experimental ApproachThe NAFLD mouse model was established by feeding mice a high‐fat diet (HFD) for 16 weeks. TUDCA was administered p.o. during the last 4 weeks. The expression levels of intestinal tight junction genes, lipid metabolic and inflammatory genes were determined by quantitative PCR. Tissue inflammation was evaluated by haematoxylin and eosin staining. The gut microbiota was analysed by 16S rRNA gene sequencing.Key ResultsTUDCA administration attenuated HFD‐induced hepatic steatosis, inflammatory responses, obesity and insulin resistance in mice. Moreover, TUDCA attenuated gut inflammatory responses as manifested by decreased intestinal histopathology scores and inflammatory cytokine levels. In addition, TUDCA improved intestinal barrier function by increasing levels of tight junction molecules and the solid chemical barrier. The components involved in ileum lipid transport were also reduced by TUDCA administration in HFD‐fed mice. Finally, the TUDCA‐treated mice showed a different gut microbiota composition compared with that in HFD‐fed mice but similar to that in normal chow diet‐fed mice.Conclusions and ImplicationsTUDCA attenuates the progression of HFD‐induced NAFLD in mice by ameliorating gut inflammation, improving intestinal barrier function, decreasing intestinal fat transport and modulating intestinal microbiota composition.
Assessing the significance of endemic disease in conservation—koalas, chlamydia, and koala retrovirus as a case study
Authors: McCallum Hamish , Kerlin Douglas H. , Ellis William , Carrick Frank 
Published: November 2017

AbstractIt can be difficult to establish the conservation significance of endemic infectious diseases—those that are well established in a population—in contrast with infectious diseases that are still invading. This difficulty can have important implications for designing policy to address species declines. The infectious diseases of koalas provide an ideal case study to examine issues involved in identifying the role of endemic disease in conservation biology. Koala populations are in decline, amidst claims for many years that infectious diseases, particularly those with chlamydial etiology, play a key role in this loss. However, weak associations between prevalence of infection, clinical signs of disease, and population decline mean that it remains unclear whether infectious disease is a primary driver of koala population decline. There are multiple causes of koala decline including drought, habitat destruction, and disease. Well‐designed experiments, linked to appropriate models, are necessary to determine the true role of infectious disease in the current koala population declines and whether a focus on disease is likely to be a feasible, let alone the most cost‐effective, means of preventing further declines.
Factors Affecting Drug‐Development Strategies in Asian Global Clinical Trials for Drug Approval in Japan
Authors: Asano Kunihito , Uyama Yoshiaki , Tohkin Masahiro 
Published: November 2017

AbstractWe assessed the current status of Asian global clinical trials (GCTs) and factors, such as therapeutic areas, main metabolic enzymes targeted, approval status in the United States or the European Union, development strategies, influencing drug‐development strategies in Asian GCTs and in general GCTs for drug approval in Japan. The findings suggested that region‐specific diseases in Asia, intrinsic and extrinsic ethnic differences between Japanese/Asian and Caucasian populations, and the status of the drugs’ development in the United States or the European Union all affected Asian GCTs. These factors may influence the drug development process in Asian GCTs. Furthermore, we found that pharmacokinetics data in Asian GCTs comparing similarities between Japanese and other Asian populations were mainly obtained from late‐phase trials, which may delay the identification of potential differences in ethnic factors.
Gill development in sympatric morphs of Arctic charr from Loch Awe, Scotland: A hidden physiological cost of macrobenthos feeding?
Authors: Jenjan Hussain B.B. , Garduño‐Paz Monica , Huntingford Felicity A. , Adams Colin E. 
Published: November 2017

AbstractThe development of the respiratory surfaces was compared in two sympatric, lacustrine morphs of Arctic charr. A macrobenthic invertebrate feeding specialist, that forages in the littoral benthic zone, had a gill cavity that was 54% larger in volume and had 31% greater respiratory surface area than that of a zooplankton feeding morph that forages in the pelagic zone. The large respiratory surface area in the benthic‐feeding form was the result of longer gill arches, more and longer gill filaments and more numerous secondary lamellae. The difference in gill cavity volume and filament length appears to be the result of a larger head, but not body size, in the benthic‐feeding form. This suggests that differences in these characteristics may have arisen as a by‐product of the expression of larger head size commonly described in macrobenthos foraging specialist charr. The other differences, particularly the more numerous secondary lamellae and the length of the gill arches, were not the result of head size differences between morphs, and thus, these are most likely an adaptation to greater respiratory requirements. Benthic‐feeding fish may have a greater respiratory capacity to allow them to forage in areas with lower levels of dissolved oxygen and/or engage in a more active lifestyle compared to the pelagic‐feeding form. In any event, the strikingly larger respiratory surface is likely to impose an additional ionoregulatory stress on the benthic‐feeding and thus may represent a hidden physiological cost of specialisation for foraging on benthic prey.
Clostridium difficile infection in hospitalized octogenarian patients
Authors: Trifan Anca , Girleanu Irina , Stanciu Carol , Miftode Egidia , Cojocariu Camelia , Singeap Ana‐Maria , Sfarti Catalin , Chiriac Stefan , Cuciureanu Tudor , Stoica Oana 
Published: November 2017

AimTo evaluate the risk factors and outcome of Clostridium difficile infection in hospitalized octogenarian patients.MethodsA retrospective analysis of risk factors and outcome of C. difficile infection in hospitalized octogenarians was carried out at two academic centers in Romania from January 2014 to September 2016. Demographic, clinical and laboratory characteristics; antibiotics and proton pump inhibitors use in‐hospital and 2 months before admission; comorbidities; length of hospital stay; treatment; and outcome were carefully collected from the patients' medical charts and compared with those from octogenarians hospitalized during the same period.ResultsA total of 286 octogenarians were hospitalized during the study period and among them 79 (27.6%) were diagnosed with C. difficile infection. On multivariate logistic regression analyses, the previous 2 months' hospitalizations (OR 10.231, 95% CI 1.769–58.965, P = 0.009), antibiotic use 2 months before admission (OR 12.596, 95% CI 1.024–15.494, P = 0.048), antibiotic treatment during hospitalization (OR 6.302, 95% CI 3.510–11.316, P < 0.0001), arterial hypertension (OR 11.228, 95% CI 1.917–65.783, P = 0.007), chronic kidney disease (OR 4.474, 95% CI 1.037–19.299, P = 0.045) and chronic cardiac failure (OR 7.328, 95% CI 2.068–25.967, P = 0.002) were independently associated with infection. Patients with infection had longer length of hospital stay than those without (15.3 ± 5.1 vs 11.1 ± 4.3 days, P < 0.0001). None of the patients with infection had severe disease, none required surgery and none died during hospitalization.ConclusionsHospitalized octogenarians with comorbidities, recently hospitalized or receiving antibiotic treatment are at risk for C. difficile infection. Clinicians evaluating such patients should have a high index of suspicion for this infection. Geriatr Gerontol Int 2018; 18: 315–320.
Prospects from systems serology research
Authors: Arnold Kelly B. , Chung Amy W. 
Published: November 2017

SummaryAntibodies are highly functional glycoproteins capable of providing immune protection through multiple mechanisms, including direct pathogen neutralization and the engagement of their Fc portions with surrounding effector immune cells that induce anti‐pathogenic responses. Small modifications to multiple antibody biophysical features induced by vaccines can significantly alter functional immune outcomes, though it is difficult to predict which combinations confer protective immunity. In order to give insight into the highly complex and dynamic processes that drive an effective humoral immune response, here we discuss recent applications of ‘Systems Serology’, a new approach that uses data‐driven (also called ‘machine learning’) computational analysis and high‐throughput experimental data to infer networks of important antibody features associated with protective humoral immunity and/or Fc functional activity. This approach offers the ability to understand humoral immunity beyond single correlates of protection, assessing the relative importance of multiple biophysical modifications to antibody features with multivariate computational approaches. Systems Serology has the exciting potential to help identify novel correlates of protection from infection and may generate a more comprehensive understanding of the mechanisms behind protection, including key relationships between specific Fc functions and antibody biophysical features (e.g. antigen recognition, isotype, subclass and/or glycosylation events). Reviewed here are some of the experimental and computational technologies available for Systems Serology research and evidence that the application has broad relevance to multiple different infectious diseases including viruses, bacteria, fungi and parasites.
Regulatory T‐cells in acute dengue viral infection
Authors: Jayaratne Hemadri Eresha , Wijeratne Dulharie , Fernando Samitha , Kamaladasa Achala , Gomes Laksiri , Wijewickrama Ananda , Ogg Graham Stuart , Malavige Gathsaurie Neelika 
Published: November 2017

SummaryAlthough regulatory T‐cells (Tregs) have been shown to be expanded in acute dengue, their role in pathogenesis and their relationship to clinical disease severity and extent of viraemia have not been fully evaluated. The frequency of Tregs was assessed in 56 adult patients with acute dengue by determining the proportion of forkhead box protein 3 (FoxP3) expressing CD4+ CD25+T‐cells (FoxP3+ cells). Dengue virus (DENV) viral loads were measured by quantitative real‐time polymerase chain reaction (PCR) and DENV‐specific T‐cell responses were measured by ex‐vivo interferon (IFN)‐γ enzyme‐linked immunospot (ELISPOT) assays to overlapping peptide pools of DENV‐NS3, NS1 and NS5. CD45RA and CCR4 were used to phenotype different subsets of T‐cells and their suppressive potential was assessed by their expression of cytotoxic T lymphocyte‐antigen 4 (CTLA‐4) and Fas. While the frequency of FoxP3+ cells in patients was significantly higher (P < 0·0001) when compared to healthy individuals, they did not show any relationship with clinical disease severity or the degree of viraemia. The frequency of FoxP3+ cells did not correlate with either ex‐vivo IFN‐γ DENV‐NS3‐, NS5‐ or NS1‐specific T‐cell responses. FoxP3+ cells of patients with acute dengue were predominantly CD45RA+ FoxP3low, followed by CD45RA‐FoxP3low, with only a small proportion of FoxP3+ cells being of the highly suppressive effector Treg subtype. Expression of CCR4 was also low in the majority of T‐cells, with only CCR4 only being expressed at high levels in the effector Treg population. Therefore, although FoxP3+ cells are expanded in acute dengue, they predominantly consist of naive Tregs, with poor suppressive capacity.
Using horizontal cooperation concepts in integrated routing and facility‐location decisions
Authors: Quintero‐Araujo Carlos L. , Gruler Aljoscha , Juan Angel A. , Faulin Javier 
Published: November 2017

AbstractIn a global and competitive economy, efficient supply networks are essential for modern enterprises. Horizontal cooperation (HC) concepts represent a promising strategy to increase the performance of supply chains. HC is based on sharing resources and making joint decisions among different agents at the same level of the supply chain. This paper analyzes different cooperation scenarios concerning integrated routing and facility‐location decisions in road transportation: (a) a noncooperative scenario in which all decisions are individually taken (each enterprise addresses its own vehicle routing problem [VRP]); (b) a semicooperative scenario in which route‐planning decisions are jointly taken (facilities and fleets are shared and enterprises face a joint multidepot VRP); and (c) a fully cooperative scenario in which route‐planning and facility‐location decisions are jointly taken (also customers are shared, and thus enterprises face a general location routing problem). Our analysis explores how this increasing level of HC leads to a higher flexibility and, therefore, to a lower total distribution cost. A hybrid metaheuristic algorithm, combining biased randomization with a variable neighborhood search framework, is proposed to solve each scenario. This allows us to quantify the differences among these scenarios, both in terms of monetary and environmental costs. Our solving approach is tested on a range of benchmark instances, outperforming previously reported results.
Effects of the sodium‐glucose cotransporter 2 (SGLT2) inhibitor velagliflozin, a new drug with therapeutic potential to treat diabetes in cats
Authors: Hoenig M. , Clark M. , Schaeffer D. J. , Reiche D. 
Published: November 2017

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors are used in the treatment of human diabetics. They increase glucose excretion and correct hyperglycemia. We examined the investigationalSGLT2 inhibitor velagliflozin in two groups of six neutered adult obese cats (equal gender distribution). Placebo (Pl) or drug (D; 1 mg/kg) was administered for 35 days. Routine blood examinations, fructosamine, beta‐hydroxybutyrate (BHB), nonesterified fatty acids (NEFA), glucagon, adiponectin, and leptin were measured before and after treatment, also water intake, and urinary electrolytes, glucose, and volume. Indirect calorimetry, an intravenous glucose tolerance test (IVGTT; 0.8 g/kg) and insulin tolerance test (IVITT) were conducted. All cats tolerated treatment well. Significant changes with D included a decrease in the respiratory exchange ratio, an increase in cholesterol, a small increase in albumin, and a rise inBHBandNEFA. Glucose clearance was unaltered, although less insulin was secreted during theIVGTT(p = .056) suggesting improved insulin sensitivity.IVITTwas unchanged. Treatment did not affect glucagon, leptin, or adiponectin. Water intake, urine output, urinary glucose excretion, and the glucose/creatinine ratio but not urinary electrolytes were significantly higher post‐D. We conclude that velagliflozin is a promising drug, which increases urinary glucose excretion in cats and could thereby be beneficial for the treatment of hyperglycemia.
Long‐run macro drivers of citizens’ mood in European institutions: An empirical assessment
Authors: Bonasia Mariangela , Canale Rosaria Rita 
Published: November 2017

AbstractThe aim of the paper is to detect, through dynamic panel data techniques, the long‐run macro drivers of citizens’ mood toward European institutions and to support the existence of an inverse relationship both in the short and in the long‐run between trust on one side and the rate of unemployment and the discretionary fiscal policy measures on the other. This is valid in the whole Eurozone and in particular in peripheral countries. This outcome gives support to the conclusion that the process of institutional consolidation should pass through a greater political sensibility toward some specific economic variables.
Novel carbohydrate binding modules in the surface anchored α‐amylase of Eubacterium rectale provide a molecular rationale for the range of starches used by this organism in the human gut
Authors: Cockburn Darrell W. , Suh Carolyn , Medina Krizia Perez , Duvall Rebecca M. , Wawrzak Zdzislaw , Henrissat Bernard , Koropatkin Nicole M. 
Published: November 2017

SummaryGut bacteria recognize accessible glycan substrates within a complex environment. Carbohydrate binding modules (CBMs) of cell surface glycoside hydrolases often drive binding to the target substrate. Eubacterium rectale, an important butyrate‐producing organism in the gut, consumes a limited range of substrates, including starch. Host consumption of resistant starch increases the abundance of E. rectale in the intestine, likely because it successfully captures the products of resistant starch degradation by other bacteria. Here, we demonstrate that the cell wall anchored starch‐degrading α‐amylase, Amy13K of E. rectale harbors five CBMs that all target starch with differing specificities. Intriguingly these CBMs efficiently bind to both regular and high amylose corn starch (a type of resistant starch), but have almost no affinity for potato starch (another type of resistant starch). Removal of these CBMs from Amy13K reduces the activity level of the enzyme toward corn starches by ∼40‐fold, down to the level of activity toward potato starch, suggesting that the CBMs facilitate activity on corn starch and allow its utilization in vivo. The specificity of the Amy13K CBMs provides a molecular rationale for why E. rectale is able to only use certain starch types without the aid of other organisms.
Light and temperature cues: multitasking receptors and transcriptional integrators
Authors: Casal Jorge J. , Qüesta Julia I. 
Published: November 2017

Contents

Summary
1029

I.
Introduction
1029

II.
Convergence at the receptor
1030

III.
Convergence at transcriptional hubs
1031

IV.
Convergence involving clock components
1033

V.
Conclusions
1033

Acknowledgements
1033

References
1033

SummaryThe combined information provided by light and temperature cues helps to optimise plant body architecture and physiology. Plants possess elaborate systems to sense and respond to these stimuli. Simultaneous perception of light and temperature by dual receptors such as phytochrome B and phototropin leads to immediate signalling convergence. Conversely, cue asynchronies initiate separate pathways and the information of the earliest cue is stored, awaiting the arrival of the later cue to control transcription. Storage mechanisms can involve changes in the activity of selected clock components or epigenetic modifications, depending on the time delay between cues (hours, days or several months). We propose a conceptual framework in which the mechanisms of integration relate to the timing of cue sensing.
Xyloglucan is released by plants and promotes soil particle aggregation
Authors: Galloway Andrew F. , Pedersen Martin J. , Merry Beverley , Marcus Susan E. , Blacker Joshua , Benning Liane G. , Field Katie J. , Knox J. Paul 
Published: November 2017

Summary

Soil is a crucial component of the biosphere and is a major sink for organic carbon. Plant roots are known to release a wide range of carbon‐based compounds into soils, including polysaccharides, but the functions of these are not known in detail.

Using a monoclonal antibody to plant cell wall xyloglucan, we show that this polysaccharide is secreted by a wide range of angiosperm roots, and relatively abundantly by grasses. It is also released from the rhizoids of liverworts, the earliest diverging lineage of land plants. Using analysis of water‐stable aggregate size, dry dispersion particle analysis and scanning electron microscopy, we show that xyloglucan is effective in increasing soil particle aggregation, a key factor in the formation and function of healthy soils.

To study the possible roles of xyloglucan in the formation of soils, we analysed the xyloglucan contents of mineral soils of known age exposed upon the retreat of glaciers. These glacial forefield soils had significantly higher xyloglucan contents than detected in a UK grassland soil.

We propose that xyloglucan released from plant rhizoids/roots is an effective soil particle aggregator and may, in this role, have been important in the initial colonization of land.