bluuebunny/crossref_metadata_2025 huggingface dataset:
Niacin promotes revascularization and recovery of limb function in diet‐induced obese mice with peripheral ischemia
Authors: Pang Dominic K. T. , Nong Zengxuan , Sutherland Brian G. , Sawyez Cynthia G. , Robson Debra L. , Toma Jelena , Pickering J. Geoffrey , Borradaile Nica M.
Published: May 2016

Niacin can reduce vascular disease risk in individuals with metabolic syndrome, but in light of recent large randomized controlled trials outcomes, its biological actions and clinical utility remain controversial. Niacin can improve endothelial function, vascular inflammation, and vascular regeneration, independent of correcting dyslipidemia, in various lean rodent models of vascular injury. Here, we tested whether niacin could directly improve endothelial cell angiogenic function during combined exposure to excess fatty acids and hypoxia, and whether intervention with niacin during continued feeding of western diet could improve revascularization and functional recovery in obese, hyperlipidemic mice with peripheral ischemia. Treatment with niacin (10 μmol/L) increased human microvascular endothelial cell angiogenic function during exposure to high fatty acids and hypoxia (2% oxygen), as determined by tube formation on Matrigel. To assess revascularization in vivo, we used western diet‐induced obese mice with unilateral hind limb femoral artery ligation and excision. Treatment for 14 days postinjury with once daily i.p. injections of a low dose of niacin (50 mg/kg) improved recovery of hind limb use, in association with enhanced revascularization and decreased inflammation of the tibialis anterior muscle. These effects were concomitant with decreased plasma triglycerides, but not increased plasma apoAI. Thus, niacin improves endothelial tube formation under lipotoxic and hypoxic conditions, and moreover, promotes revascularization and functional hind limb recovery following ischemic injury in diet‐induced obese mice with hyperlipidemia. These data may have implications for niacin therapy in the treatment of peripheral ischemic vascular disease associated with metabolic syndrome.
Snapshot of the prescribing practice for the clopidogrel and esomeprazole coprescription and cost evaluation of the application guidelines
Authors: Vernaz Nathalie , Rollason Victoria , Adlere Liene , Combescure Christophe , Poncet Antoine , Bonnabry Pascal , Desmeules Jules
Published: May 2016

The antiplatelet clopidogrel and the proton pump inhibitor esomeprazole demonstrate a pharmacokinetic interaction through CYP2C19 that could translate into clinical inefficacy of clopidogrel. No medical consensus as to their coprescription has been reached, and different guidelines are available. We evaluated the prescribing practices at the Geneva University Hospitals (HUG) by measuring whether the coprescription was staggered as suggested by experts. We estimated the financial impact of different implementation guidelines. We used the HUG electronic patient records to follow the physicians' prescriptions and the administration by nurses from January 2013 to April 2014. We performed a time series analysis to assess 15 years of proton pump inhibitors (PPIs) and antiplatelet drug use. “Extra costs” were calculated assuming that clopidogrel or esomeprazole would replace prasugrel or ticagrelor and pantoprazole or ranitidine, respectively. Only 10.8% of the patient medical orders for the clopidogrel and esomeprazole coprescription specified to stagger the administration, 12.6% specified a concomitant coprescription, and 76.6% had no clear information. A high rate of 49.6% of the nurses staggered the clopidogrel and esomeprazole coprescription when no clear information was given. We found a statistically significant decrease in clopidogrel use after the publication of the OCLA (Omeprazole–CLopidogrel–Aspirin) study and a significant increase in the trend of esomeprazole. Alternative treatments to avoid this interaction are cost ineffective or offer therapeutic options of lesser quality. We observed a high rate of 56.2% of the clopidogrel and esomeprazole coprescription in our hospital and can therefore not ignore the PK/PD interaction. The most common prescription practice was to not specify the time frame of administration, which was translated by nurses in 49.6% of the cases to a scheduled staggered coprescription of clopidogrel and esomeprazole. As long as no consensus has been reached, the medical orders time frame information should be mandatory to allow a clear and harmonious staggering strategy.
RNAi as a management tool for the western corn rootworm, Diabrotica virgifera virgifera
Authors: Fishilevich Elane , Vélez Ana M , Storer Nicholas P , Li Huarong , Bowling Andrew J , Rangasamy Murugesan , Worden Sarah E , Narva Kenneth E , Siegfried Blair D
Published: May 2016

The western corn rootworm (WCR), Diabrotica virgifera virgifera, is the most important pest of corn in the US Corn Belt. Economic estimates indicate that costs of control and yield loss associated with WCR damage exceed $US 1 billion annually. Historically, corn rootworm management has been extremely difficult because of its ability to evolve resistance to both chemical insecticides and cultural control practices. Since 2003, the only novel commercialized developments in rootworm management have been transgenic plants expressing Bt insecticidal proteins. Four transgenic insecticidal proteins are currently registered for rootworm management, and field resistance to proteins from the Cry3 family highlights the importance of developing traits with new modes of action. One of the newest approaches for controlling rootworm pests involves RNA interference (RNAi). This review describes the current understanding of the RNAi mechanisms in WCR and the use of this technology for WCR management. Further, the review addresses ecological risk assessment of RNAi and insect resistance management of RNAi for corn rootworm. © 2016 Society of Chemical Industry
A Systematic Approach for Developing Decision Aids: From Cognitive Work Analysis to Prototype Design and Development
Authors: Dhukaram Anandhi Vivekanandan , Baber Chris
Published: May 2016

Cognitive Work Analysis (CWA) has proved successful in supporting Human Factors analysis, providing a system‐level view of operations that can be used to understand how systems achieve their missions. However, a critical gap exists in the transition from CWA to prototype design and implementation. The aim of this paper is to fill this gap between CWA and implementation. This paper describes an approach for the design of software system in which CWA descriptions are converted to Unified Modeling Language (UML) models. The approach presented in this paper is intended to be minimalistic and streamlined, to focus on the design of a prototype. Following the design process, a Decision Aid prototype was developed. This prototype is evaluated against the original CWA to check that the translation has been effective. This paper shows how CWA can be integrated with UML for prototype design and implementation. We believe that this paper should prove useful to a range of practitioners concerned about maintaining a user's cognitive perspective during specification and analysis of a system.
Synthesis, Surface Activities and Toluene Solubilization by Amine‐oxide Gemini Surfactants
Authors: Liu Hongqin , Hu Jun , Xu Baocai , Zhao Tingting , Shi Guoying , Zhang Guiju
Published: May 2016

A series of amine‐oxide gemini surfactants featuring amide groups [N, N’‐dimethyl‐N, N’‐bis(2‐alkylamideethyl)‐ethylenediamine oxide (alkyl = C11H23, C13H27, C15H31, C17H35)] have been synthesized via a three‐step synthetic route, and their chemical structures were confirmed by mass spectra, FTIR and 1H‐NMR spectra. The surface activities of these compounds have been measured. The results show that these synthesized amine‐oxide gemini surfactants reduced the surface tension of water to a minimum value of approximately 26.91 mN m−1 at a concentration of 2.92 × 10−5mol L−1. Furthermore, their critical micelle concentration (CMC) values and solubilization of toluene decrease with an increase of the hydrophobic chain length from 12 to 18. Isoelectric point measurements revealed that their pI values range from 4.0 to 10.5.
Establishing a scholarly culture requires a conceptual framework for leveraging change
Authors: O’Brien Jennifer Marie
Published: May 2016

None
DNA Damage Response in Hematopoietic Stem Cell Ageing
Authors: Li Tangliang , Zhou Zhong-Wei , Ju Zhenyu , Wang Zhao-Qi
Published: May 2016

Maintenance of tissue-specific stem cells is vital for organ homeostasis and organismal longevity. Hematopoietic stem cells (HSCs) are the most primitive cell type in the hematopoietic system. They divide asymmetrically and give rise to daughter cells with HSC identity (self-renewal) and progenitor progenies (differentiation), which further proliferate and differentiate into full hematopoietic lineages. Mammalian ageing process is accompanied with abnormalities in the HSC self-renewal and differentiation. Transcriptional changes and epigenetic modulations have been implicated as the key regulators in HSC ageing process. The DNA damage response (DDR) in the cells involves an orchestrated signaling pathway, consisting of cell cycle regulation, cell death and senescence, transcriptional regulation, as well as chromatin remodeling. Recent studies employing DNA repair-deficient mouse models indicate that DDR could intrinsically and extrinsically regulate HSC maintenance and play important roles in tissue homeostasis of the hematopoietic system. In this review, we summarize the current understanding of how the DDR determines the HSC fates and finally contributes to organismal ageing.
Predictive value of serum β‐hCG for early pregnancy outcomes among women with recurrent spontaneous abortion
Authors: Liu Yinglin , Liu Yukun , Li Xuejiao , Jiao Xuedan , Zhang Rui , Zhang Jianping
Published: May 2016

Objective

To examine peak serum levels of the β‐subunit of human chorionic gonadotropin (β‐hCG) for prediction of early pregnancy outcomes among women with recurrent spontaneous abortion (RSA).

Methods

In a retrospective study, the medical records of pregnant women with a history of RSA treated at Sun Yat‐sen Memorial Hospital, China, between January 2011 and July 2013 were reviewed. Serum β‐hCG had been measured twice weekly from 5 to 13 weeks of pregnancy, and pregnancy was monitored by transvaginal ultrasonography to 13+ 6 weeks. Optimal cutoff for peak β‐hCG level was determined by receiver operator characteristic curve analysis and Youden index. Women were divided into four groups on the basis of optimal peak β‐hCG cutoff and pregnancy outcome (pregnancy at 13 weeks or spontaneous abortion). Peak β‐hCG levels and length of pregnancy at this peak were examined.

Results

Overall, 1240 patients were included. The optimal cutoff value of peak β‐hCG was 88 468 IU/L, with a sensitivity, specificity, positive predictive value, and negative predictive value for successful pregnancy of 95.6%, 88.0%, 95.6%, and 89.0%, respectively. A faster rise in β‐hCG, higher peak β‐hCG, and longer pregnancy length at peak β‐hCG were associated with successful early pregnancy.

Conclusion

A cutoff value of serum β‐hCG of 88 000 IU/L could be used to predict early pregnancy outcomes for women with a history of RSA.
Viscous and viscoelastic stress states at the calving front of Antarctic ice shelves
Authors: Christmann Julia , Plate Carolin , Müller Ralf , Humbert Angelika
Published: May 2016

Calving mechanisms are still poorly understood and stress states in the vicinity of ice-shelf fronts are insufficiently known for the development of physically motivated calving laws that match observations. A calving model requires the knowledge of maximum tensile stresses. These stresses depend on different simulation approaches and material models. Therefore, this study compares results of a two-dimensional (2-D) continuum approach using finite elements with results of a one-dimensional (1-D) beam model elaborated in Reeh (1968). A purely viscous model, as well as a viscoelastic Maxwell model, is applied for the 2-D case. The maximum tensile stress usually appears at the top surface of an ice shelf. Its location and magnitude are predominantly influenced by the thickness of the ice shelf and the height of the freeboard, the traction-free part at the ice front. More precisely, doubling the thickness leads to twice the stress maximum, while doubling the freeboard, based on changes of the ice density, results in an increase of the stress maximum by 61%. Poisson's ratio controls the evolution of the maximum stress with time. The viscosity and Young's modulus define the characteristic time of the Maxwell model and thus the time to reach the maximum principal stress.
Design of deformable mirrors for high power lasers
Authors: Bonora Stefano , Pilar Jan , Lucianetti Antonio , Mocek Tomas
Published: May 2016

We present the workflow of the design, realization and testing of deformable mirrors suitable for high power diode pumped solid-state lasers. It starts with the study of the aberration to be corrected, and then it continues with the design of the actuators position and characteristic. In this paper, we present and compare three deformable mirrors realized for multi-J level laser facilities. We show that with the same design concept it is possible to realize deformable mirrors for other types of lasers. As an example, we report the realization of a deformable mirror for femtosecond lasers and for a CW

$\text{CO}_{2}$

laser.
Visions of Europe: emerging challenges for the European project in the aftermath of the 2014 European Parliament elections
Authors: Giovannini Arianna , Polverari Laura , Seddone Antonella
Published: May 2016

The European Union (EU) is facing a profound political crisis of leadership, legitimacy, and purpose. This article provides an analysis of these key dimensions of crisis. It does so by examining the way in which they intersect and their impact on the EU’s institutional architecture, on the politicization of the European public sphere, on the wider dynamics of representation that underpin these processes, and on the political systems and polities of the member states. Drawing on such analysis, we assess the 2014 European Parliament election with reference to the findings of the six articles included in this collection. We conclude with a critical reflection on the competing and often piecemeal ‘visions of Europe’ that emerge from the studies in this volume and the challenges they pose to the EU project.
Connections between the Ozmidov scale and mean velocity profile in stably stratified atmospheric surface layers
Authors: Li Dan , Salesky Scott T. , Banerjee Tirtha
Published: May 2016

The mean velocity profile (MVP) in thermally stratified atmospheric surface layers (ASLs) deviates from the classic logarithmic form. A theoretical framework was recently proposed (Katulet al.Phys. Rev. Lett., vol. 107, 2011, 268502) to link the MVP to the spectrum of turbulence and was found to successfully predict the MVP for unstable stratification. However, the theory failed to reproduce the MVP in stable conditions (Saleskyet al.Phys. Fluids, vol. 25, 2013, 105101), especially when${\it\zeta}>0.2$(where${\it\zeta}$is the atmospheric stability parameter). In the present study, it is demonstrated that this shortcoming is due to the failure to identify the appropriate length scale that characterizes the size of momentum transporting eddies in the stable ASL. Beyond${\it\zeta}\approx 0.2$(near where the original theory fails), the Ozmidov length scale becomes smaller than the distance from the wall$z$and hence is a more stringent constraint for characterizing the size of turbulent eddies. An expression is derived to connect the Ozmidov length scale to the normalized MVP (${\it\phi}_{m}$), allowing${\it\phi}_{m}$to be solved numerically. It is found that the revised theory produces a prediction of${\it\phi}_{m}$in good agreement with the widely used empirical Businger–Dyer relation and two experimental datasets in the stable ASL. The results here demonstrate that the behaviour of${\it\phi}_{m}$in the stable ASL is closely linked to the size of momentum transporting eddies, which can be characterized by the Ozmidov scale under mildly to moderately stable conditions ($0.2<{\it\zeta}<1-2$).
Selection by mating competitiveness improves the performance ofAnastrepha ludensmales of the genetic sexing strain Tapachula-7
Authors: Quintero-Fong L. , Toledo J. , Ruiz L. , Rendón P. , Orozco-Dávila D. , Cruz L. , Liedo P.
Published: May 2016

The sexual performance ofAnastrepha ludensmales of the Tapachula-7 genetic sexing strain, produced via selection based on mating success, was compared with that of males produced without selection in competition with wild males. Mating competition, development time, survival, mass-rearing quality parameters and pheromone production were compared. The results showed that selection based on mating competitiveness significantly improved the sexual performance of offspring. Development time, survival of larvae, pupae and adults, and weights of larvae and pupae increased with each selection cycle. Differences in the relative quantity of the pheromone compounds (Z)-3-nonenol and anastrephin were observed when comparing the parental males with the F4 and wild males. The implications of this colony management method on the sterile insect technique are discussed.
Effects of dairy factory, milk casein content and titratable acidity on coagulation properties in Trentingrana dairy industry
Authors: Penasa Mauro , Toffanin Valentina , Cologna Nicola , Cassandro Martino , De Marchi Massimo
Published: May 2016

The objective of the present study was to investigate the effect of environmental factors, milk casein content and titratable acidity on milk coagulation properties (MCP) of samples routinely collected in the Trento province (northeast Italy) under field conditions. Rennet coagulation time (RCT, min), curd-firming time (k20, min) and curd firmness (a30, mm) were determined by Formagraph on 14 971 samples from 635 herds associated to 17 dairy factories. Besides MCP, fat, protein, and casein percentages, titratable acidity (TA), and somatic cell and bacterial counts were available. A standardised index of milk aptitude to coagulate (IAC) was derived using information of RCT and a30. An analysis of variance was conducted on MCP and IAC using a fixed effects linear model. Approximately 3% of milk samples did not form a curd within the testing time (30 min) and k20 was missing for 26% of milks. The percentage of samples without information on k20 largely differed among dairy factories (1·7–20·9%). Significant differences were estimated between the best and the worst dairy factory for RCT (−2 min), k20 (−1·2 min), a30 (+3·4 mm) and IAC (+2·6 points). Milk casein content and TA were important factors in explaining the variation of MCP and IAC, supporting the central role of these two traits on technological properties. The Trento province is heterogeneous in terms of dairy systems and this could explain the differences among dairy factories.
African Penguin tolerance to humans depends on historical exposure at colony level
Authors: PICHEGRU LORIEN , EDWARDS TREVOR B. , DILLEY BEN J. , FLOWER TOM P. , RYAN PETER G.
Published: May 2016

Sustainable ecotourism requires careful management of human impacts on wildlife. Contrasting responses to the disturbance caused by ecotourism are observed across taxa and within species, because species and populations can differ in their tolerance to humans. However, the mechanisms by which tolerance develops remain unclear. Penguin colonies are popular tourist attractions. Although ecotourism increases public awareness and generates conservation income, it can also disturb penguins, raising concerns for threatened species such as the African PenguinSpheniscus demersus, whose populations are in rapid decline. We compared the tolerance of African Penguins to human disturbance across four colonies with contrasting histories of human exposure. Human approaches invoked the least response at colonies where human exposure was highest, suggesting increased human tolerance with increased exposure. The response to humans close to the nest also decreased more rapidly in highly exposed individuals within colonies. These results were consistent independent of breeding stage, and were repeated among colonies. Because the impacts of human disturbance, including temporary nest desertion, were greatest at the colony with least human exposure, human disturbance of breeding African Penguins potentially may be mitigated through increased levels of tolerance to humans, or displacement of shyer individuals, although this could not be assessed in the present study.

However, human exposure could significantly increase stress, impair reproduction and even reduce genetic diversity. Consequently, ecotourism must be managed carefully to minimize population level impacts, potentially by facilitating habituation in populations subject to non-threatening human disturbance, and maintaining some areas free of disturbance to allow shy individuals to breed.
A sustained decline in Cyprus Warbler Sylvia melanothorax numbers in western Cyprus, coinciding with the colonisation of its breeding range by the Sardinian Warbler S. melanocephala
Authors: POMEROY DEREK , WALSH FRANK , FLINT PETER , HELLICAR MARTIN , SHAW PHIL
Published: May 2016

During 1998–2011, in an area of western Cyprus spanning about one-quarter of the global breeding range of the endemic Cyprus Warbler Sylvia melanothorax, the species declined at a rate of c.59% decade-1, suggesting that there is an urgent need to review its global conservation status. This decline has coincided with the recent, rapid colonisation of western Cyprus by the Sardinian Warbler S. melanocephala, whose numbers have increased substantially within the study area, as might be expected of a newly colonising breeding species. To identify possible causes of the Cyprus Warbler’s decline we compared its rate of change with measures of land-cover, vegetation density, altitude, rainfall and the presence of Sardinian Warblers at survey sites. The rate of decline in the Cyprus Warbler’s abundance was strongly correlated with land-cover and with the duration of site occupancy by Sardinian Warbler; Cyprus Warbler abundance had declined more steeply on sites colonised by Sardinian Warblers early in the survey period than on sites colonised later. Furthermore, on sites surveyed by BirdLife Cyprus in 2006–2014, Cyprus Warbler abundance had continued to decline significantly (also by c.59% decade-1) in western Cyprus, while Sardinian Warbler abundance had continued to increase. In contrast, Cyprus Warbler abundance showed no significant change in central and eastern Cyprus, where Sardinian Warblers were sparse or absent during the breeding season. These findings are consistent with at least two contrasting scenarios: that changes have occurred in land-cover or climatic conditions in Cyprus, to the detriment of Cyprus Warbler and to the benefit of Sardinian Warbler; or that in western Cyprus at least, the two species may compete for similar resources, despite a lack of evidence of this in an earlier, more detailed study. In either case, we suggest the need for a thorough, nationwide breeding survey of the two species.
Beliefs about Emotions, Depression, Anxiety and Fatigue: A Mediational Analysis
Authors: Sydenham Mia , Beardwood Jennifer , Rimes Katharine A.
Published: May 2016

Background: Beliefs that it is unacceptable to experience or express negative emotions have been found to be associated with various clinical problems. It is unclear how such beliefs, which could be viewed as a form of unhelpful perfectionism about emotions, may contribute to symptomatology. Aims: This study investigated two hypotheses: a) greater endorsement of beliefs about the unacceptability of negative emotions will be associated with greater emotional avoidance and lower levels of support-seeking and self-compassion; b) these beliefs about emotions will be associated with higher levels of symptoms of depression, anxiety and fatigue and that this relationship will be mediated by social support-seeking, emotional avoidance and self-compassion. Method: Online questionnaires were completed by 451 community participants. Mediational analyses were undertaken to investigate emotional avoidance, social support-seeking and self-compassion as mediators of the relationship between beliefs about emotions and symptoms of depression, anxiety and fatigue. Results: Beliefs about the unacceptability of negative emotions were significantly associated with more emotional avoidance and less self-compassion and support-seeking. The relationships between beliefs about emotions and depression, anxiety and fatigue were significantly mediated by self-compassion and emotional avoidance but not social support-seeking. Conclusions: Future research should investigate whether interventions that pay particular attention to emotional avoidance and self-compassion, such as mindfulness-based therapy or modified forms of CBT, may be beneficial in reducing distress and fatigue associated with beliefs about the unacceptability of negative emotions.
The fin-to-limb transition as the re-organization of a Turing pattern
Authors: Onimaru Koh , Marcon Luciano , Musy Marco , Tanaka Mikiko , Sharpe James
Published: May 2016

A Turing mechanism implemented by BMP, SOX9 and WNT has been proposed to control mouse digit patterning. However, its generality and contribution to the morphological diversity of fins and limbs has not been explored. Here we provide evidence that the skeletal patterning of the catshark Scyliorhinus canicula pectoral fin is likely driven by a deeply conserved Bmp–Sox9–Wnt Turing network. In catshark fins, the distal nodular elements arise from a periodic spot pattern of Sox9 expression, in contrast to the stripe pattern in mouse digit patterning. However, our computer model shows that the Bmp–Sox9–Wnt network with altered spatial modulation can explain the Sox9 expression in catshark fins. Finally, experimental perturbation of Bmp or Wnt signalling in catshark embryos produces skeletal alterations which match in silico predictions. Together, our results suggest that the broad morphological diversity of the distal fin and limb elements arose from the spatial re-organization of a deeply conserved Turing mechanism.
Conservation of uORF repressiveness and sequence features in mouse, human and zebrafish
Authors: Chew Guo-Liang , Pauli Andrea , Schier Alexander F.
Published: May 2016

Upstream open reading frames (uORFs) are ubiquitous repressive genetic elements in vertebrate mRNAs. While much is known about the regulation of individual genes by their uORFs, the range of uORF-mediated translational repression in vertebrate genomes is largely unexplored. Moreover, it is unclear whether the repressive effects of uORFs are conserved across species. To address these questions, we analyse transcript sequences and ribosome profiling data from human, mouse and zebrafish. We find that uORFs are depleted near coding sequences (CDSes) and have initiation contexts that diminish their translation. Linear modelling reveals that sequence features at both uORFs and CDSes modulate the translation of CDSes. Moreover, the ratio of translation over 5′ leaders and CDSes is conserved between human and mouse, and correlates with the number of uORFs. These observations suggest that the prevalence of vertebrate uORFs may be explained by their conserved role in repressing CDS translation.
TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells
Authors: Ra Eun A. , Lee Taeyun A. , Won Kim Seung , Park Areum , Choi Hyun jin , Jang Insook , Kang Sujin , Hee Cheon Jae , Cho Jin Won , Eun Lee Ji , Lee Sungwook , Park Boyoun
Published: May 2016

Autophagy is responsible for the bulk degradation of cytosolic constituents and plays an essential role in the intestinal epithelium by controlling beneficial host–bacterial relationships. Atg5 and Atg7 are thought to be critical for autophagy. However, Atg5- or Atg7-deficient cells still form autophagosomes and autolysosomes, and are capable of removing proteins or bacteria. Here, we report that human TRIM31 (tripartite motif), an intestine-specific protein localized in mitochondria, is essential for promoting lipopolysaccharide-induced Atg5/Atg7-independent autophagy. TRIM31 directly interacts with phosphatidylethanolamine in a palmitoylation-dependent manner, leading to induction of autolysosome formation. Depletion of endogenous TRIM31 significantly increases the number of intestinal epithelial cells containing invasive bacteria. Crohn’s disease patients display TRIM31 downregulation. Human cytomegalovirus-infected intestinal cells show a decrease in TRIM31 expression as well as a significant increase in bacterial load, reversible by the introduction of wild-type TRIM31. We provide insight into an alternative autophagy pathway that protects against intestinal pathogenic bacterial infection.
Interrupting peptidoglycan deacetylation during Bdellovibrio predator-prey interaction prevents ultimate destruction of prey wall, liberating bacterial-ghosts
Authors: Lambert Carey , Lerner Thomas R. , Bui Nhat Khai , Somers Hannah , Aizawa Shin-Ichi , Liddell Susan , Clark Ana , Vollmer Waldemar , Lovering Andrew L. , Sockett R. Elizabeth
Published: May 2016

The peptidoglycan wall, located in the periplasm between the inner and outer membranes of the cell envelope in Gram-negative bacteria, maintains cell shape and endows osmotic robustness. Predatory Bdellovibrio bacteria invade the periplasm of other bacterial prey cells, usually crossing the peptidoglycan layer, forming transient structures called bdelloplasts within which the predators replicate. Prey peptidoglycan remains intact for several hours, but is modified and then degraded by escaping predators. Here we show predation is altered by deleting two Bdellovibrio N-acetylglucosamine (GlcNAc) deacetylases, one of which we show to have a unique two domain structure with a novel regulatory”plug”. Deleting the deacetylases limits peptidoglycan degradation and rounded prey cell “ghosts” persist after mutant-predator exit. Mutant predators can replicate unusually in the periplasmic region between the peptidoglycan wall and the outer membrane rather than between wall and inner-membrane, yet still obtain nutrients from the prey cytoplasm. Deleting two further genes encoding DacB/PBP4 family proteins, known to decrosslink and round prey peptidoglycan, results in a quadruple mutant Bdellovibrio which leaves prey-shaped ghosts upon predation. The resultant bacterial ghosts contain cytoplasmic membrane within bacteria-shaped peptidoglycan surrounded by outer membrane material which could have promise as “bacterial skeletons” for housing artificial chromosomes.
Conductive Paper with Antibody-Like Film for Electrical Readings of Biomolecules
Authors: Tavares Ana P. M. , Ferreira Nádia S. , Truta Liliana A. A. N. A. , Sales M. Goreti F.
Published: May 2016

This work reports a novel way of producing an inexpensive substrate support to assemble a sensing film, designed for the electrical transduction of an intended biomolecule. The support uses cellulose paper as substrate, made hydrophobic with solid wax and covered by a home-made conductive ink having graphite as core material. The hydrophobicity of the paper was confirmed by contact angle measurements and the conductive ink composition was optimized with regard to its adhesion, conductivity and thermal stability. This support was further modified targeting its application in quantitative analysis. Carnitine (CRT) was selected as target compound, a cancer biomarker. The recognition material consisted of an antibody-like receptor film for CRT, tailored on the support and prepared by electrically-sustained polymerization of 3,4-ethylenedioxythiophene (EDOT) or dodecylbenzenesulfonic acid (DBS). Fourier transform infrared spectroscopy (FTIR) and Raman spectroscopy analysis confirmed the presence of the polymeric film on the support and the performance of the devices was extensively evaluated with regard to linear response ranges, selectivity, applicability and reusability. Overall, the paper-based sensors offer simplicity of fabrication, low cost and excellent reusability features. The design could also be extended to other applications in electrical-based approaches to be used in point-of-care (POC).
Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a
Authors: Hou Zhaohua , Zhang Jian , Han Qiuju , Su Chenhe , Qu Jing , Xu Dongqing , Zhang Cai , Tian Zhigang
Published: May 2016

Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV+ hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression.
CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver
Authors: Stegmann Kerstin A. , Robertson Francis , Hansi Navjyot , Gill Upkar , Pallant Celeste , Christophides Theodoros , Pallett Laura J. , Peppa Dimitra , Dunn Claire , Fusai Giuseppe , Male Victoria , Davidson Brian R. , Kennedy Patrick , Maini Mala K.
Published: May 2016

Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56brightCD16−CD57−), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6− fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bethiEomeslo(CXCR6−) and T-betloEomeshi(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bethiEomeslo, suggesting its lineage was closer to CXCR6− peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-betloEomeshi NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.
A large aberrant stem ichthyosauriform indicating early rise and demise of ichthyosauromorphs in the wake of the end-Permian extinction
Authors: Jiang Da-Yong , Motani Ryosuke , Huang Jian-Dong , Tintori Andrea , Hu Yuan-Chao , Rieppel Olivier , Fraser Nicholas C. , Ji Cheng , Kelley Neil P. , Fu Wan-Lu , Zhang Rong
Published: May 2016

Contrary to the fast radiation of most metazoans after the end-Permian mass extinction, it is believed that early marine reptiles evolved slowly during the same time interval. However, emerging discoveries of Early Triassic marine reptiles are questioning this traditional view. Here we present an aberrant basal ichthyosauriform with a hitherto unknown body design that suggests a fast radiation of early marine reptiles. The new species is larger than coeval marine reptiles and has an extremely small head and a long tail without a fluke. Its heavily-built body bears flattened and overlapping gastral elements reminiscent of hupehsuchians. A phylogenetic analysis places the new species at the base of ichthyosauriforms, as the sister taxon of Cartorhynchus with which it shares a short snout with rostrally extended nasals. It now appears that ichthyosauriforms evolved rapidly within the first one million years of their evolution, in the Spathian (Early Triassic), and their true diversity has yet to be fully uncovered. Early ichthyosauromorphs quickly became extinct near the Early-Middle Triassic boundary, during the last large environmental perturbation after the end-Permian extinction involving redox fluctuations, sea level changes and volcanism. Marine reptile faunas shifted from ichthyosauromorph-dominated to sauropterygian-dominated composition after the perturbation.
Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis
Authors: Litjens Geert , Sánchez Clara I. , Timofeeva Nadya , Hermsen Meyke , Nagtegaal Iris , Kovacs Iringo , Hulsbergen - van de Kaa Christina , Bult Peter , van Ginneken Bram , van der Laak Jeroen
Published: May 2016

Pathologists face a substantial increase in workload and complexity of histopathologic cancer diagnosis due to the advent of personalized medicine. Therefore, diagnostic protocols have to focus equally on efficiency and accuracy. In this paper we introduce ‘deep learning’ as a technique to improve the objectivity and efficiency of histopathologic slide analysis. Through two examples, prostate cancer identification in biopsy specimens and breast cancer metastasis detection in sentinel lymph nodes, we show the potential of this new methodology to reduce the workload for pathologists, while at the same time increasing objectivity of diagnoses. We found that all slides containing prostate cancer and micro- and macro-metastases of breast cancer could be identified automatically while 30–40% of the slides containing benign and normal tissue could be excluded without the use of any additional immunohistochemical markers or human intervention. We conclude that ‘deep learning’ holds great promise to improve the efficacy of prostate cancer diagnosis and breast cancer staging.
Using Network Dynamical Influence to Drive Consensus
Authors: Punzo Giuliano , Young George F. , Macdonald Malcolm , Leonard Naomi E.
Published: May 2016

Consensus and decision-making are often analysed in the context of networks, with many studies focusing attention on ranking the nodes of a network depending on their relative importance to information routing. Dynamical influence ranks the nodes with respect to their ability to influence the evolution of the associated network dynamical system. In this study it is shown that dynamical influence not only ranks the nodes, but also provides a naturally optimised distribution of effort to steer a network from one state to another. An example is provided where the “steering” refers to the physical change in velocity of self-propelled agents interacting through a network. Distinct from other works on this subject, this study looks at directed and hence more general graphs. The findings are presented with a theoretical angle, without targeting particular applications or networked systems; however, the framework and results offer parallels with biological flocks and swarms and opportunities for design of technological networks.
Inapparent Streptococcus agalactiae infection in adult/commercial tilapia
Authors: Sun Jiufeng , Fang Wei , Ke Bixia , He Dongmei , Liang Yuheng , Ning Dan , Tan Hailing , Peng Hualin , Wang Yunxin , Ma Yazhou , Ke Changwen , Deng Xiaoling
Published: May 2016

We report on inapparent infections in adult/commercial tilapia in major tilapia fish farms in Guangdong. A total of 146 suspected isolates were confirmed to be S. agalactiae using an API 20 Strep system and specific PCR amplification. All isolates were identified as serotype Ia using multiplex serotyping PCR. An MLST assay showed single alleles of adhP (10), atr (2), glcK (2), glnA (1), pheS (1), sdhA (3) and tkt (2) and this profile was designated ‘unique ST 7’. The analysis of virulence genes resulted in 10 clusters, of which dltr-bca-sodA-spb1-cfb-bac (62, 42.47%) was the predominant virulence gene profile. The PFGE analysis of S. agalactiae yielded 6 distinct PFGE types (A, B, C, D, F and G), of which Pattern C (103) was the predominant type, accounting for approximately 70.55% (103/146) of the total S. agalactiae strains. Therefore, unlike what has been found in juvenile tilapia, in which PFGE pattern D/F is the major prevalent pattern, we found that pattern C was the major prevalent pattern in inapparent infected adult/commercial tilapia in Guangdong, China. In conclusion, we close a gap in the current understanding of S. agalactiae epidemiology and propose that researchers should be alert for inapparent S. agalactiae infections in adult/commercial tilapia to prevent a potential threat to food safety.
Human papillomavirus DNA positivity and seropositivity in rural Chinese men and women: a population-based cross-sectional study
Authors: Liu Fangfang , Deng Qiuju , Zhang Chanyuan , Pan Yaqi , Liu Ying , He Zhonghu , Sun Min , Liu Mengfei , Li Jingjing , Li Xiang , Zhang Chaoting , Hang Dong , Ning Tao , Guo Chuanhai , Liang Yongmei , Xu Ruiping , Zhang Lixin , Cai Hong , Ke Yang
Published: May 2016

Data on simultaneous analysis of human papillomavirus (HPV) DNA and serology and the correlations within a single general population are limited. Among 1603 men and 2187 women enrolled from rural China, serum antibodies against bacterially derived GST-L1 fusion proteins of HPV were assessed with multiplexed serology and HPV DNA was evaluated with PCR-based sequencing. Few subjects were dually positive to HPV DNA and serum antibodies for any HPV (6.6% of men and 3.1% of women). The proportion of men ever having been infected with any HPV (DNA and/or antibody positive) was higher than that of women (71.0% vs. 65.2%, P < 0.001). Type-specific association was observed for genital HPV infection and HPV seropositivity among women but not among men. A positive correlation between the number of lifetime sexual partners and positivity for oncogenic HPV DNA and/or antibodies was found in men but was absent in women. Among 762 couples, the presence of HPV DNA and/or antibodies in one partner was positively associated with the identical HPV type in the other partner. These findings may reflect a site-specific natural course of HPV infection and further understanding of the epidemiology of HPV.
LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma
Authors: Kong Cheng , Zhu Xiang-zhi , Lee Tsair-Fwu , Feng Ping-bo , Xu Jian-hua , Qian Pu-dong , Zhang Lan-fang , He Xia , Huang Sheng-fu , Zhang Yi-qin
Published: May 2016

We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax(the maximum point dose) and the D1cc(the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmaxand the D1ccwere the most significant predictors of TLI development. We drew dose-response curves for Dmaxand D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmaxand 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.
The microbiomes and metagenomes of forest biochars
Authors: Noyce Genevieve L. , Winsborough Carolyn , Fulthorpe Roberta , Basiliko Nathan
Published: May 2016

Biochar particles have been hypothesized to provide unique microhabitats for a portion of the soil microbial community, but few studies have systematically compared biochar communities to bulk soil communities. Here, we used a combination of sequencing techniques to assess the taxonomic and functional characteristics of microbial communities in four-year-old biochar particles and in adjacent soils across three forest environments. Though effects varied between sites, the microbial community living in and around the biochar particles had significantly lower prokaryotic diversity and higher eukaryotic diversity than the surrounding soil. In particular, the biochar bacterial community had proportionally lower abundance of Acidobacteria, Planctomycetes, and β-Proteobacteria taxa, compared to the soil, while the eukaryotic biochar community had an 11% higher contribution of protists belonging to the Aveolata superphylum. Additionally, we were unable to detect a consistent biochar effect on the genetic functional potential of these microbial communities for the subset of the genetic data for which we were able to assign functions through MG-RAST. Overall, these results show that while biochar particles did select for a unique subset of the biota found in adjacent soils, effects on the microbial genetic functional potential appeared to be specific to contrasting forest soil environments.
Raised HIF1α during normoxia in high altitude pulmonary edema susceptible non-mountaineers
Authors: Soree Poonam , Gupta Rajinder K. , Singh Krishan , Desiraju Koundinya , Agrawal Anurag , Vats Praveen , Bharadwaj Abhishek , Baburaj T. P. , Chaudhary Pooja , Singh Vijay K. , Verma Saroj , Bajaj Amir Chand , Singh Shashi Bala
Published: May 2016

High altitude pulmonary edema (HAPE) susceptibility is associated with EGLN1 polymorphisms, we hypothesized that HAPE-susceptible (HAPE-S, had HAPE episode in past) subjects may exhibit abnormal HIF1α levels in normoxic conditions. We measured HIF1α levels in HAPE-S and HAPE resistant (HAPE-R, no HAPE episode) individuals with similar pulmonary functions. Hemodynamic responses were also measured before and after normobaric hypoxia (Fi02 = 0.12 for 30 min duration at sea level) in both groups. . HIF1α was higher in HAPE-S (320.3 ± 267.5 vs 58.75 ± 33.88 pg/ml, P < 0.05) than HAPE-R, at baseline, despite no significant difference in baseline oxygen saturations (97.7 ± 1.7% and 98.8 ± 0.7). As expected, HAPE-S showed an exaggerated increase in pulmonary artery pressure (27.9 ± 6 vs 19.3 ± 3.7 mm Hg, P < 0.05) and a fall in peripheral oxygen saturation (66.9 ± 11.7 vs 78.7 ± 3.8%, P < 0.05), when exposed to hypoxia. HIF1α levels at baseline could accurately classify members of the two groups (AUC = 0.87). In a subset of the groups where hemoglobin fractions were additionally measured to understand the cause of elevated hypoxic response at baseline, two of four HAPE-S subjects showed reduced HbA. In conclusion, HIF 1 α levels during normoxia may represent an important marker for determination of HAPE susceptibility.