bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of TIE2‐expressing monocytes in hilar cholangiocarcinoma
Authors: Atanasov Georgi , Hau Hans‐Michael , Dietel Corinna , Benzing Christian , Krenzien Felix , Brandl Andreas , Englisch Julianna P. , Wiltberger Georg , Schierle Katrin , Robson Simon C. , Reutzel‐Selke Anja , Jonas Sven , Pascher Andreas , Pratschke Johann , Schmelzle Moritz
Published: April 2016

Background and Objectives

Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang‐receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2‐expressing monocytes (TEMs) in cholangiocarcinoma.

Methods

We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co‐expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival.

Results

High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang‐receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05).

Conclusions

High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91–98. © 2016 Wiley Periodicals, Inc.
Outcomes of one‐side versus two‐sides recipient vessels for bilateral breast reconstructions with bilateral DIEP flaps
Authors: Qiu Shan Shan , Huang Jung‐Ju , Wu Chih‐Wei , Kolios Georgios , Cheng Ming‐Huei
Published: April 2016

Background

This study was to compare the use of one‐side versus two‐sides recipient vessels in either bilateral breast reconstructions or unilateral breast reconstruction with contralateral augmentation using bilateral DIEP flaps.

Patients and Methods

A retrospective review including all cases of bilateral breast reconstructions and unilateral reconstruction with contralateral augmentation with DIEP flaps was performed. Patient's demographics, surgical variables, and outcome were collected. Two distinct cohorts based on the recipient vessel techniques, one‐side versus two‐sides, were compared.

Results

A total of 25 patients with 50 split‐DIEP flaps were included, with one‐side recipient vessels used in 19 patients and two‐sides recipient vessels in 6 patients. Ischemia time was significantly reduced in one‐side recipient group compared to two‐sides recipient vessels group (62.4 ± 21.3 vs. 105.9 ± 32.5, P < 0.001). There was no statistic difference in venous congestion, partial flap loss, or fat necrosis in both groups.

Conclusions

Using one‐side recipient vessels for bilateral breast reconstructions with unilateral breast reconstruction with contralateral augmentation using differentially split DIEP flaps presents a high success rate, acceptable ischemia time, and minimal complications for small to medium volume breast reconstructions. Utilizing this method can reduce the ischemia time and spare one side internal mammary vessels. J. Surg. Oncol. 2016;114:5–10. © 2016 Wiley Periodicals, Inc.
Out of the blue: semiconductor laser pumped visible rare‐earth doped lasers
Authors: Kränkel Christian , Marzahl Daniel‐Timo , Moglia Francesca , Huber Günter , Metz Philip Werner
Published: April 2016

The rise of semiconductor‐based pump sources such as InxGa1‐xN‐laser diodes or frequency‐doubled optically pumped semiconductor lasers with emission wavelengths in the blue encourages a revisitation of the rare‐earth ions Pr3+, Sm3+, Tb3+, Dy3+, Ho3+ and Er3+ with respect to their properties as active ions in crystalline solid‐state laser materials with direct emission in the visible spectral range. Nowadays, some of these blue‐pumped visible lasers compete with Nd3+‐lasers in terms of efficiency and direct lasing at various colors from the cyan‐blue to the deep red can be addressed in very simple and compact laser setups. This paper highlights the spectroscopic properties of suitable rare‐earth ions for visible lasing and reviews the latest progress in the field of blue‐pumped visible rare‐earth doped solid‐state lasers.

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Single mode lasing in transversely multi‐moded PT‐symmetric microring resonators
Authors: Hodaei Hossein , Miri Mohammad‐Ali , Hassan Absar U. , Hayenga William E. , Heinrich Matthias , Christodoulides Demetrios N. , Khajavikhan Mercedeh
Published: April 2016

Conventional techniques for transverse mode discrimination rely on introducing differential external losses to the different competing mode sets, enforcing single‐mode operation at the expense of additional losses to the desirable mode. We show how a parity‐time (PT) symmetric design approach can be employed to achieve single mode lasing in transversely multi‐moded microring resonators. In this type of system, mode selectivity is attained by judiciously utilizing the exceptional point dynamics arising from a complex interplay of gain and loss. The proposed scheme is versatile, robust to deviations from PT symmetry such as caused by fabrication inaccuracies or pump inhomogeneities, and enables a stable operation considerably above threshold while maintaining spatial and spectral purity. The experimental results presented here were obtained in InP‐based semiconductor microring arrangements and pave the way towards an entirely new class of chip‐scale semiconductor lasers that harness gain/loss contrast as a primary mechanism of mode selectivity.

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Economic MPC with a contractive constraint for nonlinear systems
Authors: He Defeng , Sun Jing , Yu Li
Published: April 2016

In this paper, we consider the stability issue of economic model predictive control (EMPC) for constrained nonlinear systems and propose a new contractive constraint formulation of nonlinear EMPC schemes. This formulation is one of Lyapunov‐based approaches in which the contractive function chosen a priori can be used as a Lyapunov function. Some conditions are given to guarantee recursive feasibility and asymptotic stability of the EMPC. Moreover, we analyze the transient economic performance of the EMPC closed‐loop system in some finite‐time intervals. The proposed EMPC scheme is applied to a chemical reactor model to illustrate its utility and benefits. Copyright © 2016 John Wiley & Sons, Ltd.
Natural Objects
Authors: BROWN JOSHUA D. K.
Published: April 2016

This paper introduces a framework for thinking about ontological questions—in particular, the Special Composition Question—and shows how the framework might help support something like an account of restricted composition. The framework takes the form of an account of natural objects, in analogy with David Lewis's account of natural properties. Objects, like properties, come in various metaphysical grades, from the fundamental, fully objective, perfectly natural objects to the nomologically otiose, maximally gerrymandered, perfectly non-natural objects. The perfectly natural objects, I argue, are the mereological simples, and (roughly) a collection composes an object of degree-n naturalness if and only if its members are arranged F-wise, for some property F that appears in the degree-n natural laws. Arbitrary composites turn out to be perfectly non-natural objects and are metaphysical bystanders. Ordinary composite objects fall in between. Some—e.g., atoms—are very (though not perfectly) natural; others—e.g., tables—are highly non-natural.
School-Based Support for Students with a Parent on Military Deployment
Authors: Macdonald Gail
Published: April 2016

Parental deployment to a war zone brings many changes to family life. Changes in family roles and routines unsettle children and interfere with their educational engagement. Defence School Transition Aides (DSTAs) are employed in qualifying Australian schools to assist students from Australian Defence Force (ADF) families to manage transitions associated with a parental deployment to a war zone. Reported here are findings from a study that explored parents’, teachers’ and DSTAs’ perspectives of school-based support designed to assist students to cope with their changed circumstances when a parent is deployed. Results indicate that an appreciation of students’ worries by school personnel eased their distress. DSTAs facilitated processes whereby peers with deployed parents supported each other. Alerting teachers to an intended deployment was also found to be important as it allowed them to be alert to student behaviour changes and prepare ahead for possible student support needs. DSTAs reminded parents through school newsletters to pass on pertinent deployment-related information to the school so that a coordinated school–family approach for supporting students could be enacted. Further research is required to investigate the educational significance of student support offered by culturally aware key adults and student peers during major life transitions.
Nosocomial Outbreak of a Novel Extended-Spectrum β-Lactamase Salmonella enterica Serotype Isangi Among Surgical Patients
Authors: Suleyman Geehan , Tibbetts Robert , Perri Mary Beth , Vager Dora , Xin Yuan , Reyes Katherine , Samuel Linoj , Chami Eman , Starr Patricia , Pietsch Jennifer , Zervos Marcus J. , Alangaden George
Published: April 2016

OBJECTIVE

Nosocomial outbreaks caused by Salmonella are rare. We describe the investigation and control of a cluster of novel extended-spectrum β-lactamase (ESBL) Salmonella enterica serotype Isangi in a hospital in southeastern Michigan.

METHODS

An epidemiologic investigation, including case-control study, assessment of infection control practices and environmental cultures, was performed to identify modes of transmission. Healthcare workers (HCWs) exposed to case patients were screened. Strain relatedness was determined using pulsed-field gel electrophoresis (PFGE); ESBL confirmation was conducted using real-time PCR. Control measures were implemented to prevent further transmission.

RESULTS

Between September 2 and October 22, 2015, 19 surgical patients, including 10 organ transplant recipients and 1 HCW, had positive S. Isangi cultures. Of these case patients and HCW, 13 had gastroenteritis, 2 had bacteremia, 1 had surgical-site infection, and 4 were asymptomatic. Pulsed-field gel electrophoresis (PFGE) showed 89.5% similarity among the isolates in these cases. Isolates with resistant-phenotypes possessed plasmid-mediated CTX-M15 ESBL. A total of 19 case patients were compared with 57 control participants. Case patients had significantly higher odds of exposure to an intraoperative transesophageal (TEE) probe (adjusted odds ratio 9.0; 95% confidence interval, 1.12–72.60; P=.02). Possible cross-transmission occurred in the HCW and 2 patients. Cultures of TEE probes and the environment were negative. The outbreak ended after removal of TEE probes, modification of reprocessing procedures, implementation of strict infection control practices, and enhanced environmental cleaning.

CONCLUSIONS

We report the first nosocomial ESBL S. Isangi outbreak in the United States. Multiple control measures were necessary to interrupt transmission of this gastrointestinal pathogen. Exposure to possibly contaminated TEE probes was associated with transmission. Periodic monitoring of reprocessing procedures of TEE probes may be required to ensure optimal disinfection.

Infect Control Hosp Epidemiol 2016;37:954–961
Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Randomized Controlled Trials
Authors: Anderson Deverick J. , Juthani-Mehta Manisha , Morgan Daniel J.
Published: April 2016

Randomized controlled trials (RCT) produce the strongest level of clinical evidence when comparing interventions. RCTs are technically difficult, costly, and require specific considerations including the use of patient- and cluster-level randomization and outcome selection. In this methods paper, we focus on key considerations for RCT methods in healthcare epidemiology and antimicrobial stewardship (HE&AS) research, including the need for cluster randomization, conduct at multiple sites, behavior modification interventions, and difficulty with identifying appropriate outcomes. We review key RCTs in HE&AS with a focus on advantages and disadvantages of methods used. A checklist is provided to aid in the development of RCTs in HE&AS.

Infect Control Hosp Epidemiol 2016;37:629–634
Robert Bellah's Search for Community and Ethical Modernity in Japan Studies
Authors: Borovoy Amy
Published: April 2016

This article explores Robert Bellah's engagement with Japan in formulating his communitarian critique of American individualism. Bellah's early contribution to post–World War II modernization studies,Tokugawa Religion: The Cultural Roots of Modern Japan, embraced the Weberian framework of social development, but it also described a system that departed from Weber's narrative of liberalization and rationalization in important ways. Bellah argued that in early modern Japan, the profit motive was contained by social obligations and ethical rules. Through his explorations of Japan, Bellah articulated a critique of liberal individualism, drawing on Japanese cultural nationalism in his search for a modern, capitalist system that could be contained by overarching cultural and moral values. One finds a surprising resonance between Bellah's ideal of American “civil religion” and the ideas of interwar philosopher Watsuji Tetsurō and Watsuji's own critique of liberalism and popular democracy as lacking cultural foundations. Bellah's engagement with Watsuji reveals the tensions within Bellah's thought and in his subsequent call for community in America as a means of overcoming the excesses of American individualism. This article considers both the contributions and the limits of Bellah's attempt to invoke Japan as an alternative modernity in Japan studies.
The set-shifting profiles of anorexia nervosa and autism spectrum disorder using the Wisconsin Card Sorting Test: a systematic review and meta-analysis
Authors: Westwood H. , Stahl D. , Mandy W. , Tchanturia K.
Published: April 2016

Difficulties in set-shifting are commonly reported in both autism spectrum disorder (ASD) and anorexia nervosa (AN) populations. Despite this, it is not known whether this cognitive profile persists across different ages, or whether the profiles seen in ASD and AN are comparable. This systematic review and meta-analyses aimed to compare the set-shifting profiles, as measured by the Wisconsin Card Sorting Test (WCST) in adults and younger people with either ASD or AN, relative to healthy controls (HCs) and to statistically compare performance on the WCST between ASD and AN. In all, 24 studies on ASD and 22 studies on AN were identified. In ASD, there were significant differences between the clinical group and HCs, with the ASD group making significantly more perseverative errors, indicating greater difficulty in set-shifting [pooled effect size ofd= 0.67, 95% confidence interval (CI) 0.53–0.81,p⩽ 0.001]. This effect was consistent across the age span. For AN studies, there was a significant difference between adults with AN and HCs (d= 0.52, 95% CI 0.36–0.68,p⩽ 0.001) but a non-significant effect in child studies (d= 0.25, 95% CI −0.05 to 0.55,z= 1.66,p= 0.096). Meta-regression indicated no effect of diagnosis (AN or ASD) on performance in adult studies but there was a non-significant trend (p= 0.053) towards children with ASD performing worse than children with AN. While difficulties with set-shifting appear to be stable in ASD, there may be differences between children and adults with AN, which warrant further investigation.
Theory of the formation of a collisionless Weibel shock: pair vs. electron/proton plasmas
Authors: Bret A. , Stockem Novo A. , Narayan R. , Ruyer C. , Dieckmann M. E. , Silva L. O.
Published: April 2016

Collisionless shocks are shocks in which the mean-free path is much larger than the shock front. They are ubiquitous in astrophysics and the object of much current attention as they are known to be excellent particle accelerators that could be the key to the cosmic rays enigma. While the scenario leading to the formation of a fluid shock is well known, less is known about the formation of a collisionless shock. We present theoretical and numerical results on the formation of such shocks when two relativistic and symmetric plasma shells (pair or electron/proton) collide. As the two shells start to interpenetrate, the overlapping region turns Weibel unstable. A key concept is the one of trapping time τp, which is the time when the turbulence in the central region has grown enough to trap the incoming flow. For the pair case, this time is simply the saturation time of the Weibel instability. For the electron/proton case, the filaments resulting from the growth of the electronic and protonic Weibel instabilities, need to grow further for the trapping time to be reached. In either case, the shock formation time is 2τp in two-dimensional (2D), and 3τp in 3D. Our results are successfully checked by particle-in-cell simulations and may help designing experiments aiming at producing such shocks in the laboratory.
The Role of Personality in Predicting (Change in) Students’	Academic Success Across Four Years of Secondary School
Authors: Spengler Marion , Brunner Martin , Martin Romain , Lüdtke Oliver
Published: April 2016

Abstract. Little longitudinal research has addressed the question of whether the Big Five personality traits (i.e., O, C, E, A, N) predict educational outcomes and whether the Big Five provide incremental predictive validity for educational outcomes when prior achievement, intelligence, and academic self-concept are controlled for. Also, little is known about whether noncognitive factors are related to change in academic success, especially grades, after controlling for its stability. To address these research questions, we used data from the Luxembourg longitudinal extension of the 2009 cycle of the Program for International Student Assessment (PISA). We included data from two student cohorts that were followed across 4 years: The first cohort was in ninth grade when they participated in PISA (N = 240); the second cohort in 10th grade (N = 276). Correlational results showed that Conscientiousness and Openness were substantially related to subject-specific grades in Mathematics, French, and German across several school years. There was evidence for incremental predictive validity beyond intelligence and academic self-concepts. When controlling for the stability of grades, there were only small effects of all predictors on later grades. In summary, students’ personality (but also intelligence and academic self-concepts) predicted the stable part of grades rather than change.
Anchoring Vignettes
Authors: Primi Ricardo , Zanon Cristian , Santos Daniel , De Fruyt Filip , John Oliver P.
Published: April 2016

Abstract. Individuals differ in the way they use rating scales to describe themselves, and these differences are particularly pronounced in children and early adolescents. One promising remedy is to correct (or “anchor”) an individual’s responses according to the way they use the scale when they rate an anchoring vignette (a set of hypothetical targets differing on the attribute of interest). Studying adolescents’ self-reports of their socio-emotional attributes, we compared traditional self-report scores with vignette-corrected scores in terms of reliability (internal consistency), discriminant validity (scale intercorrelations), and criterion validity (predicting achievement test scores in language and math). A large and representative sample of 12th grade Brazilian students (N = 8,582, 62% female, mean age 18.2) were administered a Portuguese-language self-report inventory assessing social-emotional skills related to the Big Five personality dimensions. Correcting scores according to vignette ratings led to increases in the reliability of scales measuring Conscientiousness and Openness, but discriminant validity and criterion validity increased only when each scale was corrected using its own corresponding vignette set. Moreover, accuracy in rating the vignettes was correlated with language achievement test scores, suggesting that verbal factors play a role in providing both normative vignette ratings of others and self-reports that are reliable and valid.
Development of an Inventory Assessing Social and Emotional Skills in	Brazilian Youth
Authors: Primi Ricardo , Santos Daniel , John Oliver P. , Fruyt Filip De
Published: April 2016

Abstract. Whereas the structure of individual differences in personal attributes is well understood in adults, much less work has been done in children and adolescents. On the assessment side, numerous instruments are in use for children but they measure discordant attributes, ranging from one single factor (self-esteem; grit) to three factors (social, emotional, and academic self-efficacy) to five factors (strength and difficulties; Big Five traits). To construct a comprehensive measure for large-scale studies in Brazilian schools, we selected the eight most promising instruments and studied their structure at the item level (Study 1; N = 3,023). The resulting six-factor structure captures the major domains of child differences represented in these instruments and resembles the well-known Big Five personality dimensions plus a negative self-evaluation factor. In a large representative sample in Rio de Janeiro State (Study 2; N = 24,605), we tested a self-report inventory (SENNA1.0) assessing these six dimensions of socio-emotional skills with less than 100 items and found a robust and replicable structure and measurement invariance across grades, demonstrating feasibility for large-scale assessments across diverse student groups in Brazil. Discussion focuses on the contribution to socio-emotional research in education and its measurement as well as on limitations and suggestions for future research.
Enhanced nonlinear interactions in quantum optomechanics via mechanical amplification
Authors: Lemonde Marc-Antoine , Didier Nicolas , Clerk Aashish A.
Published: April 2016

The quantum nonlinear regime of optomechanics is reached when nonlinear effects of the radiation pressure interaction are observed at the single-photon level. This requires couplings larger than the mechanical frequency and cavity-damping rate, and is difficult to achieve experimentally. Here we show how to exponentially enhance the single-photon optomechanical coupling strength using only additional linear resources. Our method is based on using a large-amplitude, strongly detuned mechanical parametric drive to amplify mechanical zero-point fluctuations and hence enhance the radiation pressure interaction. It has the further benefit of allowing time-dependent control, enabling pulsed schemes. For a two-cavity optomechanical set-up, we show that our scheme generates photon blockade for experimentally accessible parameters, and even makes the production of photonic states with negative Wigner functions possible. We discuss how our method is an example of a more general strategy for enhancing boson-mediated two-particle interactions and nonlinearities.
Contrasting effects of defaunation on aboveground carbon storage across the global tropics
Authors: Osuri Anand M. , Ratnam Jayashree , Varma Varun , Alvarez-Loayza Patricia , Hurtado Astaiza Johanna , Bradford Matt , Fletcher Christine , Ndoundou-Hockemba Mireille , Jansen Patrick A. , Kenfack David , Marshall Andrew R. , Ramesh B. R. , Rovero Francesco , Sankaran Mahesh
Published: April 2016

Defaunation is causing declines of large-seeded animal-dispersed trees in tropical forests worldwide, but whether and how these declines will affect carbon storage across this biome is unclear. Here we show, using a pan-tropical data set, that simulated declines of large-seeded animal-dispersed trees have contrasting effects on aboveground carbon stocks across Earth’s tropical forests. In our simulations, African, American and South Asian forests, which have high proportions of animal-dispersed species, consistently show carbon losses (2–12%), but Southeast Asian and Australian forests, where there are more abiotically dispersed species, show little to no carbon losses or marginal gains (±1%). These patterns result primarily from changes in wood volume, and are underlain by consistent relationships in our empirical data (∼2,100 species), wherein, large-seeded animal-dispersed species are larger as adults than small-seeded animal-dispersed species, but are smaller than abiotically dispersed species. Thus, floristic differences and distinct dispersal mode–seed size–adult size combinations can drive contrasting regional responses to defaunation.
Mechanical cell competition kills cells via induction of lethal p53 levels
Authors: Wagstaff Laura , Goschorska Maja , Kozyrska Kasia , Duclos Guillaume , Kucinski Iwo , Chessel Anatole , Hampton-O’Neil Lea , Bradshaw Charles R. , Allen George E. , Rawlins Emma L. , Silberzan Pascal , Carazo Salas Rafael E. , Piddini Eugenia
Published: April 2016

Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults. We show that MDCK cells silenced for the polarity gene scribble (scribKD) are hypersensitive to compaction, that interaction with wild-type cells causes their compaction and that crowding is sufficient for scribKD cell elimination. Importantly, we show that elevation of the tumour suppressor p53 is necessary and sufficient for crowding hypersensitivity. Compaction, via activation of Rho-associated kinase (ROCK) and the stress kinase p38, leads to further p53 elevation, causing cell death. Thus, in addition to molecules, cells use mechanical means to compete. Given the involvement of p53, compaction hypersensitivity may be widespread among damaged cells and offers an additional route to eliminate unfit cells.
Foldamer-mediated manipulation of a pre-amyloid toxin
Authors: Kumar Sunil , Birol Melissa , Schlamadinger Diana E. , Wojcik Slawomir P. , Rhoades Elizabeth , Miranker Andrew D.
Published: April 2016

Disordered proteins, such as those central to Alzheimer’s and Parkinson’s, are particularly intractable for structure-targeted therapeutic design. Here we demonstrate the capacity of a synthetic foldamer to capture structure in a disease relevant peptide. Oligoquinoline amides have a defined fold with a solvent-excluded core that is independent of its outwardly projected, derivatizable moieties. Islet amyloid polypeptide (IAPP) is a peptide central to β-cell pathology in type II diabetes. A tetraquinoline is presented that stabilizes a pre-amyloid, α-helical conformation of IAPP. This charged, dianionic compound is readily soluble in aqueous buffer, yet crosses biological membranes without cellular assistance: an unexpected capability that is a consequence of its ability to reversibly fold. The tetraquinoline docks specifically with intracellular IAPP and rescues β-cells from toxicity. Taken together, our work here supports the thesis that stabilizing non-toxic conformers of a plastic protein is a viable strategy for cytotoxic rescue addressable using oligoquinoline amides.
Hypothalamus proteomics from mouse models with obesity and anorexia reveals therapeutic targets of appetite regulation
Authors: Manousopoulou A , Koutmani Y , Karaliota S , Woelk C H , Manolakos E S , Karalis K , Garbis S D
Published: April 2016

Objective:

This study examined the proteomic profile of the hypothalamus in mice exposed to a high-fat diet (HFD) or with the anorexia of acute illness. This comparison could provide insight on the effects of these two opposite states of energy balance on appetite regulation.

Methods:

Four to six-week-old male C56BL/6J mice were fed a normal (control 1 group;n=7) or a HFD (HFD group;n=10) for 8 weeks. The control 2 (n=7) and lipopolysaccharide (LPS) groups (n=10) were fed a normal diet for 8 weeks before receiving an injection of saline and LPS, respectively. Hypothalamic regions were analysed using a quantitative proteomics method based on a combination of techniques including iTRAQ stable isotope labeling, orthogonal two-dimensional liquid chromatography hyphenated with nanospray ionization and high-resolution mass spectrometry. Key proteins were validated with quantitative PCR.

Results:

Quantitative proteomics of the hypothalamous regions profiled a total of 9249 protein groups (q<0.05). Of these, 7718 protein groups were profiled with a minimum of two unique peptides for each. Hierachical clustering of the differentiated proteome revealed distinct proteomic signatures for the hypothalamus under the HFD and LPS nutritional conditions. Literature research with in silico bioinformatics interpretation of the differentiated proteome identified key biological relevant proteins and implicated pathways. Furthermore, the study identified potential pharmacologic targets. In the LPS groups, the anorexigen pro-opiomelanocortin was downregulated. In mice with obesity, nuclear factor-κB, glycine receptor subunit alpha-4 (GlyR) and neuropeptide Y levels were elevated, whereas serotonin receptor 1B levels decreased.

Conclusions:

High-precision quantitative proteomics revealed that under acute systemic inflammation in the hypothalamus as a response to LPS, homeostatic mechanisms mediating loss of appetite take effect. Conversely, under chronic inflammation in the hypothalamus as a response to HFD, mechanisms mediating a sustained ‘perpetual cycle’ of appetite enhancement were observed. The GlyR protein may constitute a novel treatment target for the reduction of central orexigenic signals in obesity.
Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice
Authors: Weisberg S , Leibel R , Tortoriello D V
Published: April 2016

Background:

Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background).

Results:

In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity.

Conclusions:

These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.
Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486
Authors: Nagasawa K , Matsuura N , Takeshita Y , Ito S , Sano Y , Yamada Y , Uchinaka A , Murohara T , Nagata K
Published: April 2016

Objectives:

Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model.

Methods:

DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1–2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg−1day−1) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr+/Lepr+) littermates served as a control.

Results:

Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats.

Conclusions:

Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS.
A novel lineage restricted, pericyte-like cell line isolated from human embryonic stem cells
Authors: Greenwood-Goodwin Midori , Yang Jiwei , Hassanipour Mohammad , Larocca David
Published: April 2016

Pericytes (PCs) are endothelium-associated cells that play an important role in normal vascular function and maintenance. We developed a method comparable to GMP quality protocols for deriving self-renewing perivascular progenitors from the human embryonic stem cell (hESC), line ESI-017. We identified a highly scalable, perivascular progenitor cell line that we termed PC-A, which expressed surface markers common to mesenchymal stromal cells. PC-A cells were not osteogenic or adipogenic under standard differentiation conditions and showed minimal angiogenic support function in vitro. PC-A cells were capable of further differentiation to perivascular progenitors with limited differentiation capacity, having osteogenic potential (PC-O) or angiogenic support function (PC-M), while lacking adipogenic potential. Importantly, PC-M cells expressed surface markers associated with pericytes. Moreover, PC-M cells had pericyte-like functionality being capable of co-localizing with human umbilical vein endothelial cells (HUVECs) and enhancing tube stability up to 6 days in vitro. We have thus identified a self-renewing perivascular progenitor cell line that lacks osteogenic, adipogenic and angiogenic potential but is capable of differentiation toward progenitor cell lines with either osteogenic potential or pericyte-like angiogenic function. The hESC-derived perivascular progenitors described here have potential applications in vascular research, drug development and cell therapy.
PSD95 nanoclusters are postsynaptic building blocks in hippocampus circuits
Authors: Broadhead Matthew J. , Horrocks Mathew H. , Zhu Fei , Muresan Leila , Benavides-Piccione Ruth , DeFelipe Javier , Fricker David , Kopanitsa Maksym V. , Duncan Rory R. , Klenerman David , Komiyama Noboru H. , Lee Steven F. , Grant Seth G. N.
Published: April 2016

The molecular features of synapses in the hippocampus underpin current models of learning and cognition. Although synapse ultra-structural diversity has been described in the canonical hippocampal circuitry, our knowledge of sub-synaptic organisation of synaptic molecules remains largely unknown. To address this, mice were engineered to express Post Synaptic Density 95 protein (PSD95) fused to either eGFP or mEos2 and imaged with two orthogonal super-resolution methods: gated stimulated emission depletion (g-STED) microscopy and photoactivated localisation microscopy (PALM). Large-scale analysis of ~100,000 synapses in 7 hippocampal sub-regions revealed they comprised discrete PSD95 nanoclusters that were spatially organised into single and multi-nanocluster PSDs. Synapses in different sub-regions, cell-types and locations along the dendritic tree of CA1 pyramidal neurons, showed diversity characterised by the number of nanoclusters per synapse. Multi-nanocluster synapses were frequently found in the CA3 and dentate gyrus sub-regions, corresponding to large thorny excrescence synapses. Although the structure of individual nanoclusters remained relatively conserved across all sub-regions, PSD95 packing into nanoclusters also varied between sub-regions determined from nanocluster fluorescence intensity. These data identify PSD95 nanoclusters as a basic structural unit, or building block, of excitatory synapses and their number characterizes synapse size and structural diversity.
Exercise capacity and cardiac hemodynamic response in female ApoE/LDLR−/− mice: a paradox of preserved V’O2max and exercise capacity despite coronary atherosclerosis
Authors: Wojewoda M. , Tyrankiewicz U. , Gwozdz P. , Skorka T. , Jablonska M. , Orzylowska A. , Jasinski K. , Jasztal A. , Przyborowski K. , Kostogrys R. B. , Zoladz J. A. , Chlopicki S.
Published: April 2016

We assessed exercise performance, coronary blood flow and cardiac reserve of female ApoE/LDLR−/− mice with advanced atherosclerosis compared with age-matched, wild-type C57BL6/J mice. Exercise capacity was assessed as whole body maximal oxygen consumption (V’O2max), maximum running velocity (vmax) and maximum distance (DISTmax) during treadmill exercise. Cardiac systolic and diastolic function in basal conditions and in response to dobutamine (mimicking exercise-induced cardiac stress) were assessed by Magnetic Resonance Imaging (MRI) in vivo. Function of coronary circulation was assessed in isolated perfused hearts. In female ApoE/LDLR−/− mice V’O2max, vmax and DISTmax were not impaired as compared with C57BL6/J mice. Cardiac function at rest and systolic and diastolic cardiac reserve were also preserved in female ApoE/LDLR−/− mice as evidenced by preserved fractional area change and similar fall in systolic and end diastolic area after dobutamine. Moreover, endothelium-dependent responses of coronary circulation induced by bradykinin (Bk) and acetylcholine (ACh) were preserved, while endothelium-independent responses induced by NO-donors were augmented in female ApoE/LDLR−/− mice. Basal COX-2-dependent production of 6-keto-PGF1α was increased. Concluding, we suggest that robust compensatory mechanisms in coronary circulation involving PGI2- and NO-pathways may efficiently counterbalance coronary atherosclerosis-induced impairment in V’O2max and exercise capacity.
A comprehensive simulation framework for imaging single particles and biomolecules at the European X-ray Free-Electron Laser
Authors: Yoon Chun Hong , Yurkov Mikhail V. , Schneidmiller Evgeny A. , Samoylova Liubov , Buzmakov Alexey , Jurek Zoltan , Ziaja Beata , Santra Robin , Loh N. Duane , Tschentscher Thomas , Mancuso Adrian P.
Published: April 2016

The advent of newer, brighter, and more coherent X-ray sources, such as X-ray Free-Electron Lasers (XFELs), represents a tremendous growth in the potential to apply coherent X-rays to determine the structure of materials from the micron-scale down to the Angstrom-scale. There is a significant need for a multi-physics simulation framework to perform source-to-detector simulations for a single particle imaging experiment, including (i) the multidimensional simulation of the X-ray source; (ii) simulation of the wave-optics propagation of the coherent XFEL beams; (iii) atomistic modelling of photon-material interactions; (iv) simulation of the time-dependent diffraction process, including incoherent scattering; (v) assembling noisy and incomplete diffraction intensities into a three-dimensional data set using the Expansion-Maximisation-Compression (EMC) algorithm and (vi) phase retrieval to obtain structural information. We demonstrate the framework by simulating a single-particle experiment for a nitrogenase iron protein using parameters of the SPB/SFX instrument of the European XFEL. This exercise demonstrably yields interpretable consequences for structure determination that are crucial yet currently unavailable for experiment design.
Electronic and chemical structure of the H2O/GaN(0001) interface under ambient conditions
Authors: Zhang Xueqiang , Ptasinska Sylwia
Published: April 2016

We employed ambient pressure X-ray photoelectron spectroscopy to investigate the electronic and chemical properties of the H2O/GaN(0001) interface under elevated pressures and/or temperatures. A pristine GaN(0001) surface exhibited upward band bending, which was partially flattened when exposed to H2O at room temperature. However, the GaN surface work function was slightly reduced due to the adsorption of molecular H2O and its dissociation products. At elevated temperatures, a negative charge generated on the surface by a vigorous H2O/GaN interfacial chemistry induced an increase in both the surface work function and upward band bending. We tracked the dissociative adsorption of H2O onto the GaN(0001) surface by recording the core-level photoemission spectra and obtained the electronic and chemical properties at the H2O/GaN interface under operando conditions. Our results suggest a strong correlation between the electronic and chemical properties of the material surface and we expect that their evolutions lead to significantly different properties at the electrolyte/electrode interface in a photoelectrochemical solar cell.
Large gap electron-hole superfluidity and shape resonances in coupled graphene nanoribbons
Authors: Zarenia M. , Perali A. , Peeters F. M. , Neilson D.
Published: April 2016

We predict enhanced electron-hole superfluidity in two coupled electron-hole armchair-edge terminated graphene nanoribbons separated by a thin insulating barrier. In contrast to graphene monolayers, the multiple subbands of the nanoribbons are parabolic at low energy with a gap between the conduction and valence bands and with lifted valley degeneracy. These properties make screening of the electron-hole interaction much weaker than for coupled electron-hole monolayers, thus boosting the pairing strength and enhancing the superfluid properties. The pairing strength is further boosted by the quasi one-dimensional quantum confinement of the carriers, as well as by the large density of states near the bottom of each subband. The latter magnifies superfluid shape resonances caused by the quantum confinement. Several superfluid partial condensates are present for finite-width nanoribbons with multiple subbands. We find that superfluidity is predominately in the strongly-coupled BEC and BCS-BEC crossover regimes, with large superfluid gaps up to 100 meV and beyond. When the gaps exceed the subband spacing, there is significant mixing of the subbands, a rounding of the shape resonances and a resulting reduction in the one-dimensional nature of the system.
Generation of transgenic cynomolgus monkeys that express green fluorescent protein throughout the whole body
Authors: Seita Yasunari , Tsukiyama Tomoyuki , Iwatani Chizuru , Tsuchiya Hideaki , Matsushita Jun , Azami Takuya , Okahara Junko , Nakamura Shinichiro , Hayashi Yoshitaka , Hitoshi Seiji , Itoh Yasushi , Imamura Takeshi , Nishimura Masaki , Tooyama Ikuo , Miyoshi Hiroyuki , Saitou Mitinori , Ogasawara Kazumasa , Sasaki Erika , Ema Masatsugu
Published: April 2016

Nonhuman primates are valuable for human disease modelling, because rodents poorly recapitulate some human diseases such as Parkinson’s disease and Alzheimer’s disease amongst others. Here, we report for the first time, the generation of green fluorescent protein (GFP) transgenic cynomolgus monkeys by lentivirus infection. Our data show that the use of a human cytomegalovirus immediate-early enhancer and chicken beta actin promoter (CAG) directed the ubiquitous expression of the transgene in cynomolgus monkeys. We also found that injection into mature oocytes before fertilization achieved homogenous expression of GFP in each tissue, including the amnion and fibroblasts, whereas injection into fertilized oocytes generated a transgenic cynomolgus monkey with mosaic GFP expression. Thus, the injection timing was important to create transgenic cynomolgus monkeys that expressed GFP homogenously in each of the various tissues. The strategy established in this work will be useful for the generation of transgenic cynomolgus monkeys for transplantation studies as well as biomedical research.
Bare and boron-doped cubic silicon carbide nanowires for electrochemical detection of nitrite sensitively
Authors: Yang Tao , Zhang Liqin , Hou Xinmei , Chen Junhong , Chou Kuo-Chih
Published: April 2016

Fabrication of eletrochemical sensors based on wide bandgap compound semiconductors has attracted increasing interest in recent years. Here we report for the first time electrochemical nitrite sensors based on cubic silicon carbide (SiC) nanowires (NWs) with smooth surface and boron-doped cubic SiC NWs with fin-like structure. Multiple techniques including scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and electron energy loss spectroscopy (EELS) were used to characterize SiC and boron-doped SiC NWs. As for the electrochemical behavior of both SiC NWs electrode, the cyclic voltammetric results show that both SiC electrodes exhibit wide potential window and excellent electrocatalytic activity toward nitrite oxidation. Differential pulse voltammetry (DPV) determination reveals that there exists a good linear relationship between the oxidation peak current and the concentration in the range of 50–15000 μmoL L−1 (cubic SiC NWs) and 5–8000 μmoL L−1 (B-doped cubic SiC NWs) with the detection limitation of 5 and 0.5 μmoL L−1 respectively. Compared with previously reported results, both as-prepared nitrite sensors exhibit wider linear response range with comparable high sensitivity, high stability and reproducibility.