bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of reducing energy supply during the finishing of Belgian Blue double-muscled cull cows
Authors: Cabaraux J. F. , Dotreppe O. , Dufrasne I. , Clinquart A. , Istasse L. , Hornick J. -L.
Published: February 2017

A 4-year experiment has been conducted on finishing Belgian Blue cull cows of double-muscled type in order to study the effects of diets containing adequate levels of metabolizable protein, but either normal (NENP), low (LENP) or medium (MENP) levels of metabolizable energy, on animal performance, carcass and meat characteristics, and plasma metabolites and hormones. The LENP diet was offered during the whole (LENP group) or second half of the finishing (NENP-LENP groups), and the MENP diet during the whole finishing (MENP group). The degree of fatness required for the slaughter of animals from NENP groups was close to 4-5 (scale from 0 (very lean) to 5 (very fat)). In each underfed group, the slaughter of the animals was synchronized to that of NENP cows, by degressive degree of fatness. The same duration of finishing was thus obtained for all groups.

The experimental feeding strategies reduced the amounts of fat deposited in the carcass and the meat while muscle deposition was remarkably preserved. The proportions of saturated and monounsaturated fatty acids in intramuscular fat were also decreased while their proportions increased in plasma free fatty acids. Plasma insulin levels were also reduced and those ofIGF-1 were, surprisingly, maintained. The low energy diet promoted thus the settlement of a discrete lipolytic state while high levels ofIGF-1 preserved muscle deposition. This feeding strategy should be evaluated in other breeds of cattle.
Effect of rumen-protected supplements of fish oil on intake, digestibility and nitrogen balance of growing goats
Authors: Fernández J. R. , Rodríguez Osorio M. , Ramos E. , de la Torre G. , Gil Extremera F. , Sanz Sampelayo M. R.
Published: February 2017

Two groups of six male goats were used to assess the effects of rumen-protected supplements offish oil on intake, digestibility and nitrogen (N) balance. The animals were offered a diet consisting of forage and concentrate, the latter fraction supplemented with 0 (control) or lOOg/kg of rumen-protected fish oil supplement (PFO), containing a high proportion of the n-3 series (whole diet contained 0 or 60 g PFO per kg dry matter). No significant differences (P > 0.05) were found between the two groups concerning live-weight gain, food intake, digestibility of DM, organic matter, N, neutral-detergent fibre and energy. In contrast, there were differences (P < 0.05) regarding the digestibility of fat and of acid-detergent fibre, which were higher among the animals given the PFO diet. With respect to the individual fatty acids, we observed higher digestibility (P < 0.05) of C14:0, C16:0, C18:0 and C20:0 among the animals given the PFO diet. The digestibility of C14:0, C18:0 and C20:0 was found to be negative among the animals given the control diet. No significant differences (P > 0-05) were found regarding digestibility of total C18:1. In contrast, the coefficients for C18:2 (n-6) and C18:3 (n-3) were higher (P < 0.05) among the non-supplemented animals. The intake and faecal flow values of C18:0 suggest that the mono- and polyunsaturated fatty acids with 18 atoms of carbon may, in both cases, undergo partial hydrogenation, which would be greater among the control group. The utilization of C20:5 (n-3) and, especially, of C22 : 6 (n-3), which were consumed only by the animals given the PFO diet, was estimated at 1-000. The PFO diet also produced lower levels ofurinary-N excretion (P < 0.05), giving rise to higher N balances (P < 0.05).
Socio-economic differences in diet, physical activity and leisure-time screen use among Scottish children in 2006 and 2010: are we closing the gap?
Authors: McNeill Geraldine , Masson Lindsey F , Macdiarmid Jennie I , Craig Leone CA , Wills Wendy J , Bromley Catherine
Published: February 2017

Objective

To investigate socio-economic differences in children’s diet, activity and inactivity and changes in these differences over 4 years during which new policies on food in schools were introduced.

Design

Two cross-sectional surveys in which diet was assessed by FFQ and physical activity and inactivity were assessed by interviewer-administered questionnaire. Socio-economic status was assessed by the area-based Scottish Index of Multiple Deprivation.

Setting

Scotland, 2006 and 2010.

Subjects

Children aged 3–17 years (n 1700 in 2006, n 1906 in 2010).

Results

In both surveys there were significant linear associations between socio-economic deprivation and intakes of energy, non-milk extrinsic sugars (NMES) as a percentage of food energy, sugar-sweetened beverages, confectionery, crisps and savoury snacks and leisure-time screen use (all higher among children in more deprived areas), while intakes of fruit, fruit juice and vegetables showed the opposite trend. In 2010 children in more deprived areas engaged in more physical activity out of school than those in more affluent areas, but between 2006 and 2010 there was an overall reduction in physical activity out of school. There were also small but statistically significant overall reductions in intakes of confectionery, crisps and savoury snacks, energy and NMES and saturated fat as a percentage of food energy, but no statistically significant change in socio-economic gradients in diet or activity between the two surveys.

Conclusions

Interventions to improve diet and physical activity in children in Scotland need to be designed so as to be effective in all socio-economic groups.
Correlating Atom Probe Tomography with Atomic-Resolved Scanning Transmission Electron Microscopy: Example of Segregation at Silicon Grain Boundaries
Authors: Stoffers Andreas , Barthel Juri , Liebscher Christian H. , Gault Baptiste , Cojocaru-Mirédin Oana , Scheu Christina , Raabe Dierk
Published: February 2017

In the course of a thorough investigation of the performance-structure-chemistry interdependency at silicon grain boundaries, we successfully developed a method to systematically correlate aberration-corrected scanning transmission electron microscopy and atom probe tomography. The correlative approach is conducted on individual APT and TEM specimens, with the option to perform both investigations on the same specimen in the future. In the present case of a Σ9 grain boundary, joint mapping of the atomistic details of the grain boundary topology, in conjunction with chemical decoration, enables a deeper understanding of the segregation of impurities observed at such grain boundaries.
Understanding of Capping Effects on the Tip Shape Evolution and on the Atom Probe Data of Bulk LaAlO3 Using Transmission Electron Microscopy
Authors: Kwak Chang-Min , Kim Young-Tae , Park Chan-Gyung , Seol Jae-Bok
Published: February 2017

Two challenges exist in laser-assisted atom probe tomography (APT). First, a drastic decline in mass-resolving power is caused, not only by laser-induced thermal effects on the APT tips of bulk oxide materials, but also the associated asymmetric evaporation behavior; second, the field evaporation mechanisms of bulk oxide tips under laser illumination are still unclear due to the complex relations between laser pulse and oxide materials. In this study, both phenomena were investigated by depositing Ni- and Co-capping layers onto the bulk LaAlO3 tips, and using stepwise APT analysis with transmission electron microscopy (TEM) observation of the tip shapes. By employing the metallic capping, the heating at the surface of the oxide tips during APT analysis became more symmetrical, thereby enabling a high mass-resolving power in the mass spectrum. In addition, the stepwise microscopy technique visualized tip shape evolution during APT analysis, thereby accounting for evaporation sequences at the tip surface. The combination of “capping” and “stepwise APT with TEM,” is applicable to any nonconductors; it provides a direct observation of tip shape evolution, allows determination of the field evaporation strength of oxides, and facilitates understanding of the effects of ultrafast laser illumination on an oxide tip.
THE REGULAR PART OF A SEMIGROUP OF LINEAR TRANSFORMATIONS WITH RESTRICTED RANGE
Authors: SOMMANEE WORACHEAD , SANGKHANAN KRITSADA
Published: February 2017

Let$V$be a vector space and let$T(V)$denote the semigroup (under composition) of all linear transformations from$V$into$V$. For a fixed subspace$W$of$V$, let$T(V,W)$be the semigroup consisting of all linear transformations from$V$into$W$. In 2008, Sullivan [‘Semigroups of linear transformations with restricted range’,Bull. Aust. Math. Soc.77(3) (2008), 441–453] proved that$$\begin{eqnarray}\displaystyle Q=\{\unicode[STIX]{x1D6FC}\in T(V,W):V\unicode[STIX]{x1D6FC}\subseteq W\unicode[STIX]{x1D6FC}\} & & \displaystyle \nonumber\end{eqnarray}$$is the largest regular subsemigroup of$T(V,W)$and characterized Green’s relations on$T(V,W)$. In this paper, we determine all the maximal regular subsemigroups of$Q$when$W$is a finite-dimensional subspace of$V$over a finite field. Moreover, we compute the rank and idempotent rank of$Q$when$W$is an$n$-dimensional subspace of an$m$-dimensional vector space$V$over a finite field$F$.
Expert patient perspectives on radiotherapy: a phenomenological comparison
Authors: Carmichael M. , Bridge P.
Published: February 2017

Background

Patient involvement in health profession student training is becoming more common and includes clinical case studies, informing curriculum development and active teaching in dedicated patient experience sessions. Despite a growing evidence base supporting patient involvement, there is little published data concerning motivation for involvement. A qualitative study was performed to provide narrative relating to patient experiences in expert patient sessions on an undergraduate radiation therapy course.

Methods

A phenomenological approach utilised semi-structured interviews with two expert patients from different backgrounds. A common set of questions were used for each participant. Interviews were digitally recorded and transcribed before thematic coding.

Results

Both participants identified areas of similarity as well as key difference in their experiences. Both had different levels of public speaking experience as well as different levels of knowledge relating to radiation therapy treatment. Both found the initial session emotional but ultimately enjoyed the process and found it cathartic.

Conclusion

The patients enjoyed this experience and identified clear value of the teaching for themselves and the students. Previous public speaking or clinical experience seemed to have limited impact on patient experience and suggested the vulnerability of the situation. Both had different perspectives of their fellow patients and their role in the healthcare partnership. These findings indicate the value of ensuring students have access to a range of perspectives from different patients.
Evaluating organic bread wheat as a rotation crop for organic dairy farms
Authors: Roche Erin H. , Mallory Ellen B. , Molloy Thomas , Kersbergen Richard J.
Published: February 2017

The rising demand for local, organic bread wheat (Triticum aestivum L.) in the northeastern USA may be an economic and agronomic opportunity for organic dairy producers. Bread wheat must produce adequate grain yields and crude protein (CP) levels to be profitable as a food crop and must complement the on-farm production of high-quality dairy feed. A field study evaluated bread wheat and perennial forage performance in five 3-year crop sequences all ending in a perennial legume/grass forage. The sequences differed by wheat type (winter or spring) and the crop prior to wheat: (1) corn silage (Zea mays L.), (2) soybean (Glycine max L.) or (3) one-year-old perennial forage. Wheat sequences were compared with a sequence of two years of corn silage followed by a new perennial forage seeding and with a continuous perennial forage control. Winter wheat spike density, wheat aboveground biomass and nitrogen uptake were always greater than spring wheat. Wheat grain yield and CP were strongly affected by wheat type, with winter wheat having greater yield but lower CP than spring wheat. At one site-year, winter wheat CP was 15 g kg−1 higher following perennial forage than following corn. Only spring wheat met the bread flour industry standard for CP. Newly established perennial forage following wheat had higher yields and legume composition in both years, along with higher projected milk yields in one year, than the continuous perennial forage. Three-year net revenue based on off-farm sales were on average US$ 741 ha−1 higher for sequences with winter wheat than those with spring wheat, and were equal to the perennial forage control. Rotations that included wheat would likely be more competitive if straw were sold or used on the farm, or, if topdressing practices or varietal choice were used to increase grain protein levels of winter wheat.
Historical institutional determinants of financial system development in Africa
Authors: EMENALO CHUKWUNONYE O. , GAGLIARDI FRANCESCA , HODGSON GEOFFREY M.
Published: February 2017

The literature on the determinants of cross-country variation in financial system development identifies historical institutional factors, mostly rooted in colonial effects, as key causes. Using a sample of 39 African former European colonies for 2006–11, this paper investigates the extent to which the historical institutional determinants identified by legal origins, disease endowment, religion-based and ethnic fractionalisation theories explain current differences in financial system development across Africa. While most existing research focuses only on one financial system development dimension, namely financial system depth, this article considers also financial system access. The results do not support any of the above theories when depth measures are used, while three of them (legal origins, disease endowment and ethnic fractionalisation theories) are validated when using access measures. This suggests that in Africa financial system depth and access do not have common historical institutional determinants, pointing to the need for greater fine tuning of prevalent theories and empirical measures.
An analysis of operational risk events in US and European Banks 2008–2014
Authors: Li Yifei , Allan Neil , Evans John
Published: February 2017

This paper explores the characteristics of 2,141 operational risk events amongst European (EU) and US banks over the period 2008–2014. We have analysed the operational risk events using a method originating in biology for the study of interrelatedness of characteristics in a complex adaptive system. The methodology, called cladistics, provides insights into the relationships between characteristics of operational risk events in banks that is not available from the traditional statistical analysis. We have used cladistics to explore if there are consistent patterns of operational risk characteristics across banks in single and different geographic zones. One significant pattern emerged which indicates there are key, stable characteristics across both geographic zones and across banks in each zone. The results identify the characteristics that could then be managed by the banks to reduce operational risk losses. We also have analysed separately the characteristics of operational risk events for “big” banks and extreme events and these results indicate that big banks and small banks have similar key operational risk characteristics, but the characteristics of extreme operational risk events are different to those for the non-extreme events.
Psychometric Evaluation of Somatic and Psychological Health Report: A Sample from Chinese Adolescents
Authors: Shi Ling , Wu Fuxiang , Ye Lin , Zhu Gu , Lu Zuhong , Liu Yangyang
Published: February 2017

The purpose of the present study was to do a psychometric evaluation of the somatic and psychological health report (SPHERE) among Chinese adolescents. Our participants were 116 twins (50 females). Psychometric evaluation indicated that the reliability and validity of this scale were good. The internal consistencies and split-half reliabilities of all subscales were above 0.80. Furthermore, the item-total correlations were acceptable for all the subscales (all the values were higher than 0.20). The present findings suggest that the SPHERE can be well used to measure Chinese adolescents’ somatic and psychological health.
NOS1 S-nitrosylates PTEN and inhibits autophagy in nasopharyngeal carcinoma cells
Authors: Zhu Lingqun , Li Linlin , Zhang Qianbing , Yang Xiao , Zou Zhiwei , Hao Bingtao , Marincola Francesco M , Liu Zhengjun , Zhong Zhuo , Wang Meng , Li Xiaoxuan , Wang Qianli , Li Keyi , Gao Wenwen , Yao Kaitai , Liu Qiuzhen
Published: February 2017

Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during periods of metabolic stress, and when overly stimulated, commonly contributes to cell death. Nitric oxide (NO), a potent cellular messenger, participates in a complex mechanism which assists in controlling autophagy. However, the mechanism by which endogenous NO formed by distinct isoforms of nitric oxide synthase (NOS) helps to regulate autophagy in cancer cells remains unclear. Here we report that NOS1 reduces excessive levels of autophagy and promotes the survival of nasopharyngeal carcinoma cells. We found that inhibition of NOS1 increased cell death resulting from siRNA or the use of pharmacologic agents; and this effect was reversed by the autophagy inhibitor, chloroquine. The role of NOS1 in the autophagy process depended on the activation of AKT/mTOR signaling by S-nitrosylation of phosphatase and tensin homolog (PTEN) proteins. The mechanism by which NOS1 modifies PTEN protein might involve a direct interaction between these two molecules. Moreover, in an in vivo study, the NOS1 inhibitor N(G)-nitro-L-arginine methyl ester activated AKT/mTOR signaling and promoted autophagy in xenograph tumors. Our studies demonstrated that NOS1 prevents excessive autophagy via S-nitrosylation of PTEN, and activation of the AKT/mTOR signaling pathway. PTEN and the AKT/mTOR signaling pathway are promising targets for improving the chemotherapeutic treatment of cancer.
Environmental conditions regulate the impact of plants on cloud formation
Authors: Zhao D. F. , Buchholz A. , Tillmann R. , Kleist E. , Wu C. , Rubach F. , Kiendler-Scharr A. , Rudich Y. , Wildt J. , Mentel Th. F.
Published: February 2017

The terrestrial vegetation emits large amounts of volatile organic compounds (VOC) into the atmosphere, which on oxidation produce secondary organic aerosol (SOA). By acting as cloud condensation nuclei (CCN), SOA influences cloud formation and climate. In a warming climate, changes in environmental factors can cause stresses to plants, inducing changes of the emitted VOC. These can modify particle size and composition. Here we report how induced emissions eventually affect CCN activity of SOA, a key parameter in cloud formation. For boreal forest tree species, insect infestation by aphids causes additional VOC emissions which modifies SOA composition thus hygroscopicity and CCN activity. Moderate heat increases the total amount of constitutive VOC, which has a minor effect on hygroscopicity, but affects CCN activity by increasing the particles’ size. The coupling of plant stresses, VOC composition and CCN activity points to an important impact of induced plant emissions on cloud formation and climate.
Protein disulfide isomerase secretion following vascular injury initiates a regulatory pathway for thrombus formation
Authors: Bowley Sheryl R. , Fang Chao , Merrill-Skoloff Glenn , Furie Barbara C. , Furie Bruce
Published: February 2017

Protein disulfide isomerase (PDI), secreted by platelets and endothelial cells on vascular injury, is required for thrombus formation. Using PDI variants that form mixed disulfide complexes with their substrates, we identify by kinetic trapping multiple substrate proteins, including vitronectin. Plasma vitronectin does not bind to αvβ3 or αIIbβ3 integrins on endothelial cells and platelets. The released PDI reduces disulfide bonds on plasma vitronectin, enabling vitronectin to bind to αVβ3 and αIIbβ3.In vivostudies of thrombus generation in mice demonstrate that vitronectin rapidly accumulates on the endothelium and the platelet thrombus following injury. This process requires PDI activity and promotes platelet accumulation and fibrin generation. We hypothesize that under physiologic conditions in the absence of secreted PDI, thrombus formation is suppressed and maintains a quiescent, patent vasculature. The release of PDI during vascular injury may serve as a regulatory switch that allows activation of proteins, among them vitronectin, critical for thrombus formation.
Iron isotopic fractionation between silicate mantle and metallic core at high pressure
Authors: Liu Jin , Dauphas Nicolas , Roskosz Mathieu , Hu Michael Y. , Yang Hong , Bi Wenli , Zhao Jiyong , Alp Esen E. , Hu Justin Y. , Lin Jung-Fu
Published: February 2017

The +0.1‰ elevated 56Fe/54Fe ratio of terrestrial basalts relative to chondrites was proposed to be a fingerprint of core-mantle segregation. However, the extent of iron isotopic fractionation between molten metal and silicate under high pressure–temperature conditions is poorly known. Here we show that iron forms chemical bonds of similar strengths in basaltic glasses and iron-rich alloys, even at high pressure. From the measured mean force constants of iron bonds, we calculate an equilibrium iron isotope fractionation between silicate and iron under core formation conditions in Earth of ∼0–0.02‰, which is small relative to the +0.1‰ shift of terrestrial basalts. This result is unaffected by small amounts of nickel and candidate core-forming light elements, as the isotopic shifts associated with such alloying are small. This study suggests that the variability in iron isotopic composition in planetary objects cannot be due to core formation.
Liquid-like cationic sub-lattice in copper selenide clusters
Authors: White Sarah L. , Banerjee Progna , Jain Prashant K.
Published: February 2017

Super-ionic solids, which exhibit ion mobilities as high as those in liquids or molten salts, have been employed as solid-state electrolytes in batteries, improved thermoelectrics and fast-ion conductors in super-capacitors and fuel cells. Fast-ion transport in many of these solids is supported by a disordered, ‘liquid-like’ sub-lattice of cations mobile within a rigid anionic sub-lattice, often achieved at high temperatures or pressures via a phase transition. Here we show that ultrasmall clusters of copper selenide exhibit a disordered cationic sub-lattice under ambient conditions unlike larger nanocrystals, where Cu+ ions and vacancies form an ordered super-structure similar to the bulk solid. The clusters exhibit an unusual cationic sub-lattice arrangement wherein octahedral sites, which serve as bridges for cation migration, are stabilized by compressive strain. The room-temperature liquid-like nature of the Cu+ sub-lattice combined with the actively tunable plasmonic properties of the Cu2Se clusters make them suitable as fast electro-optic switches.
Room temperature organic magnets derived from sp3 functionalized graphene
Authors: Tuček Jiří , Holá Kateřina , Bourlinos Athanasios B. , Błoński Piotr , Bakandritsos Aristides , Ugolotti Juri , Dubecký Matúš , Karlický František , Ranc Václav , Čépe Klára , Otyepka Michal , Zbořil Radek
Published: February 2017

Materials based on metallic elements that have d orbitals and exhibit room temperature magnetism have been known for centuries and applied in a huge range of technologies. Development of room temperature carbon magnets containing exclusively sp orbitals is viewed as great challenge in chemistry, physics, spintronics and materials science. Here we describe a series of room temperature organic magnets prepared by a simple and controllable route based on the substitution of fluorine atoms in fluorographene with hydroxyl groups. Depending on the chemical composition (an F/OH ratio) and sp3 coverage, these new graphene derivatives show room temperature antiferromagnetic ordering, which has never been observed for any sp-based materials. Such 2D magnets undergo a transition to a ferromagnetic state at low temperatures, showing an extraordinarily high magnetic moment. The developed theoretical model addresses the origin of the room temperature magnetism in terms of sp2-conjugated diradical motifs embedded in an sp3 matrix and superexchange interactions via –OH functionalization.
SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts
Authors: Xu Zhan , Greenblatt Matthew B. , Yan Guang , Feng Heng , Sun Jun , Lotinun Sutada , Brady Nicholas , Baron Roland , Glimcher Laurie H. , Zou Weiguo
Published: February 2017

Coordination between osteoblasts and osteoclasts is required for bone health and homeostasis. Here we show that mice deficient in SMURF2 have severe osteoporosis in vivo. This low bone mass phenotype is accompanied by a pronounced increase in osteoclast numbers, although Smurf2-deficient osteoclasts have no intrinsic alterations in activity. Smurf2-deficient osteoblasts display increased expression of RANKL, the central osteoclastogenic cytokine. Mechanistically, SMURF2 regulates RANKL expression by disrupting the interaction between SMAD3 and vitamin D receptor by altering SMAD3 ubiquitination. Selective deletion of Smurf2 in the osteoblast lineage recapitulates the phenotype of germline Smurf2-deficient mice, indicating that SMURF2 regulates osteoblast-dependent osteoclast activity rather than directly affecting the osteoclast. Our results reveal SMURF2 as an important regulator of the critical communication between osteoblasts and osteoclasts. Furthermore, the bone mass phenotype in Smurf2- and Smurf1-deficient mice is opposite, indicating that SMURF2 has a non-overlapping and, in some respects, opposite function to SMURF1.
Correction: Corrigendum: THZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors
Authors: Cayrol Florencia , Praditsuktavorn Pannee , Fernando Tharu M. , Kwiatkowski Nicholas , Marullo Rossella , Calvo-Vidal M. Nieves , Phillip Jude , Pera Benet , Yang Shao Ning , Takpradit Kaipol , Roman Lidia , Gaudiano Marcello , Crescenzo Ramona , Ruan Jia , Inghirami Giorgio , Zhang Tinghu , Cremaschi Graciela , Gray Nathanael S , Cerchietti Leandro
Published: February 2017

Nature Communications 8: Article number: 14290 (2017); Published: 30 January 2017; Updated: 20 February 2017 The original version of this Article contained an error in the spelling of the author Rossella Marullo, which was incorrectly given as Rosella Marullo. This has now been corrected in both thePDF and HTML versions of the Article.
Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis
Authors: Kamran M , Long Z-J , Xu D , Lv S-S , Liu B , Wang C-L , Xu J , Lam E W-F , Liu Q
Published: February 2017

Aurora kinase A (AURKA) has been implicated in the regulation of cell cycle progression, mitosis and a key number of oncogenic signaling pathways in various malignancies. However, little is known about its role in gastric cancer prognosis and genotoxic resistance. Here we found that AURKA was highly overexpressed in gastric cancer and inversely correlated with disease prognosis. Overexpression of AURKA exacerbated gastric cancer drug resistance through upregulating the expression of the anti-apoptotic protein Survivin. Conversely, we demonstrated that AURKA depletion caused a decrease in Survivin protein levels by increasing its ubiquitylation and degradation. Mass spectrometric analysis revealed that upon AURKA depletion, Survivin bound to the FBXL7 E3 ubiquitin ligase, which induced ubiquitin-proteasome degradation of Survivin. In addition, we showed that AURKA regulated FBXL7 both at the levels of transcription and translation. Moreover, proteomic analysis of nuclear AURKA-interacting proteins identified Forkhead box protein P1 (FOXP1). We next showed that AURKA was required for FBXL7 transcription and that AURKA negatively regulated FOXP1-mediated FBXL7 expression. The physiological relevance of the regulation of Survivin by AURKA through the FOXP1–FBXL7 axis was further underscored by the significant positive correlations between AURKA and Survivin expression in gastric cancer patient samples. Moreover, the AURKA depletion or kinase inhibition-induced apoptotic cell death could be reversed by Survivin ectopic overexpression, further supporting that AURKA regulated Survivin to enhance drug resistance. In agreement, inhibition of AURKA synergistically enhanced the cytotoxic effect of DNA-damaging agents in cancer cells by suppressing Survivin expression. Taken together, our data suggest that AURKA restricts Survivin ubiquitylation and degradation in gastric cancer to promote drug resistance and hence the AURKA–Survivin axis can be targeted to promote the efficacy of DNA-damaging agents in gastric cancer.
Computational modeling sheds light on structural evolution in metallic glasses and supercooled liquids
Authors: Ding Jun , Ma En
Published: February 2017

This article presents an overview of three challenging issues that are currently being debated in the community researching on the evolution of amorphous structures in metallic glasses and their parent supercooled liquids. Our emphasis is on the valuable insights acquired in recent computational analyses that have supplemented experimental investigations. The first idea is to use the local structural order developed, and in particular its evolution during undercooling, as a signature indicator to rationalize the experimentally observed temperature-dependence of viscosity, hence suggesting a possible structural origin of liquid fragility. The second issue concerns with the claim that the average nearest-neighbor distance in metallic melts contracts rather than expands upon heating, concurrent with a reduced coordination number. This postulate is, however, based on the shift of the first peak maximum in the pair distribution function and an average bond length determined from nearest neighbors designated using a distance cutoff. These can instead be a result of increasing skewness of the broad first peak, upon thermally exacerbated asymmetric distribution of neighboring atoms activated to shorter and longer distances under the anharmonic interatomic interaction potential. The third topic deals with crystal-like peak positions in the pair distribution function of metallic glasses. These peak locations can be explained using various connection schemes of coordination polyhedra, and found to be present already in high-temperature liquids without hidden crystal order. We also present an outlook to invite more in-depth computational research to fully settle these issues in future, and to establish more robust structure-property relations in amorphous alloys.
Seismic Hazards Implications of Uplifted Pleistocene Coral Terraces in the Gulf of Aqaba
Authors: Bosworth W. , Montagna P. , Pons-Branchu E. , Rasul N. , Taviani M.
Published: February 2017

The Gulf of Aqaba transform plate boundary is a source of destructive teleseismic earthquakes. Seismicity is concentrated in the central sub-basin and decreases to both the north and south. Although principally a strike-slip plate boundary, the faulted margins of the Gulf display largely dip-slip extensional movement and accompanying footwall uplift. We have constrained rates of this uplift by measurements of elevated Pleistocene coral terraces. In particular the terrace that formed during the last interglacial (~125 ka) is found discontinuously along the length of the Gulf at elevations of 3 to 26 m. Global sea level was ~7 m higher than today at 125 ka indicating net maximum tectonic uplift of ~19 m with an average rate of ~0.015 cm/yr. Uplift has been greatest adjacent to the central sub-basin and like the seismicity decreases to the north and south. We suggest that the present pattern of a seismically active central region linked to more aseismic areas in the north and south has therefore persisted for at least the past 125 kyr. Consequently the potential for future destructive earthquakes in the central Gulf is greater than in the sub-basins to the north and south.
Roles of Serum Calcium, Phosphorus, PTH and ALP on Mortality in Peritoneal Dialysis Patients: A Nationwide, Population-based Longitudinal Study Using TWRDS 2005–2012
Authors: Liu Chung-Te , Lin Yen-Chung , Lin Yi-Chun , Kao Chih-Chin , Chen Hsi-Hsien , Hsu Chih-Cheng , Wu Mai-Szu
Published: February 2017

Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) correlate with morbidity and mortality in dialysis patients. However, the comparative roles of each CKD-MBD biomarker remained undetermined on long-term peritoneal dialysis (PD) patients. This retrospective study, employing a population-based database, aimed to evaluate the performance and provide the best evidence of each biomarker of CKD-MBD as predictor of all-cause mortality. Throughout the 8-year study period, total 12,116 PD patients were included in this study. Cox proportional regression and Kaplan-Meier method were used for survival analysis. For Cox regression model, baseline measurements and time-varying covariates were used for analysis. In Cox regression model using time-dependent covariates, serum calcium level of ≧9.5 mg/dL was associated with increased mortality. For phosphorus, serum levels of either ≧6.5 mg/dL or <3.5 mg/dL were associated with increased mortality. For parathyroid hormone (PTH), higher serum levels were not associated increased mortality. For alkaline phosphatase (ALP), mortality increased at levels ≧100 IU/L. Our findings suggested that the detrimental effect of ALP on survival was more consistent, while serum calcium, phosphorus and PTH may have a less prominent effect on mortality. This study provided additional information for manipulating CKD-MBD biomarkers in PD patients.
Plin5 alleviates myocardial ischaemia/reperfusion injury by reducing oxidative stress through inhibiting the lipolysis of lipid droplets
Authors: Zheng Pengfei , Xie Zhonglin , Yuan Yuan , Sui Wen , Wang Chao , Gao Xing , Zhao Yuanlin , Zhang Feng , Gu Yu , Hu Peizhen , Ye Jing , Feng Xuyang , Zhang Lijun
Published: February 2017

Myocardial ischaemia-reperfusion (I/R) injury is a complex pathophysiological process. Current research has suggested that energy metabolism disorders, of which the abnormal consumption of fatty acids is closely related, compose the main pathological basis for myocardial I/R injury. Lipid droplets (LD) are critical regulators of lipid metabolism by LD-associated proteins. Among the lipid droplet proteins, the perilipin family members regulate lipolysis and lipogenesis through different mechanisms. Plin5, an important perilipin protein, promotes LD generation and lowers fatty acid oxidation, thus protecting the myocardium from lipotoxicity. This study investigated the protective effects of Plin5 in I/R myocardium. Our results indicated that Plin5 deficiency exacerbated the myocardial infarct area, aggravated left ventricular systolic dysfunction, reduced lipid storage, and elevated free fatty acids. Plin5-deficient myocardium exhibited severely damaged mitochondria, elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity. Furthermore, the decreased phosphorylation of PI3K/Akt in Plin5-null cardiomyocytes might contribute to I/R injury aggravation. In conclusion, Plin5, a new regulator of myocardial lipid metabolism, decreases free fatty acid peroxidation by inhibiting the lipolysis of intracellular lipid droplets, thus providing cardioprotection against I/R injury and shedding new light on therapeutic solutions for I/R diseases.
The interaction between the proliferating macroalga Asparagopsis taxiformis and the coral Astroides calycularis induces changes in microbiome and metabolomic fingerprints
Authors: Greff Stéphane , Aires Tânia , Serrão Ester A. , Engelen Aschwin H. , Thomas Olivier P. , Pérez Thierry
Published: February 2017

Mediterranean Sea ecosystems are considered as hotspots of biological introductions, exposed to possible negative effects of non–indigenous species. In such temperate marine ecosystems, macroalgae may be dominant, with a great percentage of their diversity represented by introduced species. Their interaction with temperate indigenous benthic organisms have been poorly investigated. To provide new insights, we performed an experimental study on the interaction between the introduced proliferative red alga Asparagopsis taxiformis and the indigenous Mediterranean coral Astroides calycularis. The biological response measurements included meta–barcoding of the associated microbial communities and metabolomic fingerprinting of both species. Significant changes were detected among both associated microbial communities, the interspecific differences decreasing with stronger host interaction. No short term effects of the macroalga on the coral health, neither on its polyp activity or its metabolism, were detected. In contrast, the contact interaction with the coral induced a change in the macroalgal metabolomic fingerprint with a significant increase of its bioactivity against the marine bacteria Aliivibrio fischeri. This induction was related to the expression of bioactive metabolites located on the macroalgal surface, a phenomenon which might represent an immediate defensive response of the macroalga or an allelopathic offense against coral.
Natural and laboratory mutations in kuzbanian are associated with zinc stress phenotypes in Drosophila melanogaster
Authors: Le Manh Hung , Guio Lain , Merenciano Miriam , Rovira Quirze , Barrón Maite G. , González Josefa
Published: February 2017

Organisms must cope with altered environmental conditions such as high concentrations of heavy metals. Stress response to heavy metals is mediated by the metal-responsive transcription factor 1 (MTF-1), which is conserved from Drosophila to humans. MTF-1 binds to metal response elements (MREs) and changes the expression of target genes.kuzbanian (kuz), a metalloendopeptidase that activates the evolutionary conservedNotchsignaling pathway, has been identified as an MTF-1 target gene. We have previously identified a putatively adaptive transposable element in theDrosophila melanogastergenome, namedFBti0019170,inserted in akuzintron. In this work, we investigated whether a laboratory mutant stock overexpressingkuzis associated with zinc stress phenotypes. We found that both embryos and adult flies overexpressingkuzare more tolerant to zinc compared with wild-type flies. On the other hand, we found that the effect ofFBti0019170on zinc stress tolerance depends on developmental stage and genetic background. Moreover, in the majority of the genetic backgrounds analyzed,FBti0019170has a deleterious effect in unpolluted environments in pre-adult stages. These results highlight the complexity of natural mutations and suggest that besides laboratory mutations, natural mutations should be studied in order to accurately characterize gene function and evolution.
Ubiquitination and dynactin regulate TMEPAI lysosomal trafficking
Authors: Luo Shenheng , Jing Lei , Zhao Tian , Li Yuyin , Liu Zhenxing , Diao Aipo
Published: February 2017

The transmembrane prostate androgen-induced protein (TMEPAI) has been reported to be elevated in various tumor cells, is localized to the lysosome and promotes lysosome stability. The molecular mechanism of TMEPAI trafficking however to the lysosome is unknown. Here we report that clathrin and CI-M6PR mediate TMEPAI transport from the Golgi directly into the endo-lysosomal pathway. TMEPAI is ubiquitinated at its C-terminal region and ubiquitination modification of TMEPAI is a signal for its lysosomal trafficking. Moreover, TMEPAI binds the ubiquitin binding proteins Hrs and STAM which is required for its lysosomal transport. In addition, TMEPAI interacts with the dynactin pointed-end complex subunits dynactin 5 and dynactin 6. The aa 132–155 domain is essential for specific TMEPAI binding and deletion of this binding site leads to mis-trafficking of TMEPAI to the plasma membrane. These results reveal the pathway and mechanism regulating transport of TMEPAI to the lysosome, which helps to further understand the role of TMEPAI in tumorigenesis.
miR-203 enhances let-7 biogenesis by targeting LIN28B to suppress tumor growth in lung cancer
Authors: Zhou Yong , Liang Hongwei , Liao Zhicong , Wang Yanbo , Hu Xiuting , Chen Xi , Xu Lin , Hu Zhibin
Published: February 2017

Human cancers often exhibit increased microRNA (miRNA) biogenesis and global aberrant expression of miRNAs; thus, targeting the miRNA biogenesis pathway represents a novel strategy for cancer therapy. Here, we report that miR-203 enhances the biogenesis of tumor suppressor let-7 in lung cancer by directly targeting LIN28B. Specially, we found that the LIN28B protein levels were dramatically increased in lung cancer tissues, but its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism is involved in LIN28B regulation. Interestingly, miR-203 overexpression was accompanied by massive upregulation of a group of miRNAs, especially let-7, and the let-7 expression level was concordant with the miR-203 expression in lung cancer tissues, implying its biological relevance. Furthermore, we showed that miR-203 played a critical role in inhibiting the proliferation and promoting the apoptosis of lung cancer cells by suppressing LIN28B and enhancing let-7 biogenesis. In summary, our results establish a novel mechanism by which miR-203, LIN28B and let-7 are tightly linked to form a regulatory network in lung cancer cells. The findings shed light on the role of a specific miRNA as a modulator of miRNA biogenesis and provide basis for developing new strategies for lung cancer therapy.
Graphene-Induced Pore Formation on Cell Membranes
Authors: Duan Guangxin , Zhang Yuanzhao , Luan Binquan , Weber Jeffrey K. , Zhou Royce W. , Yang Zaixing , Zhao Lin , Xu Jiaying , Luo Judong , Zhou Ruhong
Published: February 2017

Examining interactions between nanomaterials and cell membranes can expose underlying mechanisms of nanomaterial cytotoxicity and guide the design of safer nanomedical technologies. Recently, graphene has been shown to exhibit potential toxicity to cells; however, the molecular processes driving its lethal properties have yet to be fully characterized. We here demonstrate that graphene nanosheets (both pristine and oxidized) can produce holes (pores) in the membranes of A549 and Raw264.7 cells, substantially reducing cell viability. Electron micrographs offer clear evidence of pores created on cell membranes. Our molecular dynamics simulations reveal that multiple graphene nanosheets can cooperate to extract large numbers of phospholipids from the membrane bilayer. Strong dispersion interactions between graphene and lipid-tail carbons result in greatly depleted lipid density within confined regions of the membrane, ultimately leading to the formation of water-permeable pores. This cooperative lipid extraction mechanism for membrane perforation represents another distinct process that contributes to the molecular basis of graphene cytotoxicity.
Gate-tunable electron interaction in high-κ dielectric films
Authors: Kondovych Svitlana , Luk’yanchuk Igor , Baturina Tatyana I. , Vinokur Valerii M.
Published: February 2017

The two-dimensional (2D) logarithmic character of Coulomb interaction between charges and the resulting logarithmic confinement is a remarkable inherent property of high dielectric constant (high-κ) thin films with far reaching implications. Most and foremost, this is the charge Berezinskii-Kosterlitz-Thouless transition with the notable manifestation, low-temperature superinsulating topological phase. Here we show that the range of the confinement can be tuned by the external gate electrode and unravel a variety of electrostatic interactions in high-k films. We find that by reducing the distance from the gate to the film, we decrease the spatial range of the 2D long-range logarithmic interaction, changing it to predominantly dipolar or even to exponential one at lateral distances exceeding the dimension of the film-gate separation. Our findings offer a unique laboratory for the in-depth study of topological phase transitions and related phenomena that range from criticality of quantum metal- and superconductor-insulator transitions to the effects of charge-trapping and Coulomb scalability in memory nanodevices.
Hyperthermia and chemotherapy using Fe(Salen) nanoparticles might impact glioblastoma treatment
Authors: Ohtake Makoto , Umemura Masanari , Sato Itaru , Akimoto Taisuke , Oda Kayoko , Nagasako Akane , Kim Jeong-Hwan , Fujita Takayuki , Yokoyama Utako , Nakayama Tomohiro , Hoshino Yujiro , Ishiba Mai , Tokura Susumu , Hara Masakazu , Muramoto Tomoya , Yamada Sotoshi , Masuda Takatsugu , Aoki Ichio , Takemura Yasushi , Murata Hidetoshi , Eguchi Haruki , Kawahara Nobutaka , Ishikawa Yoshihiro
Published: February 2017

We previously reported that μ-oxo N,N’-bis(salicylidene)ethylenediamine iron [Fe(Salen)], a magnetic organic compound, has direct anti-tumor activity, and generates heat in an alternating magnetic field (AMF). We showed that Fe(Salen) nanoparticles are useful for combined hyperthermia-chemotherapy of tongue cancer. Here, we have examined the effect of Fe(Salen) on human glioblastoma (GB). Fe(Salen) showed in vitro anti-tumor activity towards several human GB cell lines. It inhibited cell proliferation, and its apoptosis-inducing activity was greater than that of clinically used drugs. Fe(Salen) also showed in vivo anti-tumor activity in the mouse brain. We evaluated the drug distribution and systemic side effects of intracerebrally injected Fe(Salen) nanoparticles in rats. Further, to examine whether hyperthermia, which was induced by exposing Fe(Salen) nanoparticles to AMF, enhanced the intrinsic anti-tumor effect of Fe(Salen), we used a mouse model grafted with U251 cells on the left leg. Fe(Salen), BCNU, or normal saline was injected into the tumor in the presence or absence of AMF exposure. The combination of Fe(Salen) injection and AMF exposure showed a greater anti-tumor effect than did either Fe(Salen) or BCNU alone. Our results indicate that hyperthermia and chemotherapy with single-drug nanoparticles could be done for GB treatment.
Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei
Authors: Kessler Bianca , Rinchai Darawan , Kewcharoenwong Chidchamai , Nithichanon Arnone , Biggart Rachael , Hawrylowicz Catherine M. , Bancroft Gregory J. , Lertmemongkolchai Ganjana
Published: February 2017

Melioidosis, caused byBurkholderia pseudomallei, is endemic in northeastern Thailand and Northern Australia. Severe septicemic melioidosis is associated with high levels of pro-inflammatory cytokines and is correlated with poor clinical outcomes. IL-10 is an immunoregulatory cytokine, which in other infections can control the expression of pro-inflammatory cytokines, but its role in melioidosis has not been addressed. Here, whole blood of healthy seropositive individuals (n = 75), living in N. E. Thailand was co-cultured withB. pseudomalleiand production of IL-10 and IFN-γ detected and the cellular sources identified. CD3−CD14+monocytes were the main source of IL-10. Neutralization of IL-10 increased IFN-γ, IL-6 and TNF-α production and improved bacteria killing. IFN-γ production and microbicidal activity were impaired in individuals with diabetes mellitus (DM). In contrast, IL-10 production was unimpaired in individuals with DM, resulting in an IL-10 dominant cytokine balance. Neutralization of IL-10 restored the IFN-γ response of individuals with DM to similar levels observed in healthy individuals and improved killing ofB. pseudomallei in vitro. These results demonstrate that monocyte derived IL-10 acts to inhibit potentially protective cell mediated immune responses againstB. pseudomallei,but may also moderate the pathological effects of excessive cytokine production during sepsis.