bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization, modeling, in silico analysis of equine pituitary gonadotropin alpha subunit and docking interaction studies with ganirelix
Authors: Bhardwaj Anuradha , Nayan Varij , Sharma Parvati , Kumar Sanjay , Pal Yash , Singh Jitender
Published: July 2017

Equine pituitary gonadotropins (eLH, eFSH, eCG) are heterodimeric glycoprotein hormones with alpha (α) and beta (β) subunits. It is responsible for maintenance of pregnancy in mares during early gestation and fairly valuable for inducing superovulation in animals other than equines. The alpha subunit is common, while beta subunit is species-specific in all glycoprotein hormones. In the present investigation, molecular cloning and in silico characterization including homology modeling and molecular docking analysis of the equine chorionic gonadotropin (eCG) alpha subunit was carried out for gaining structural and functional insights into the eCG alpha subunit and its possible interaction with ganirelix, a gonadotropin-releasing hormone (GnRH) antagonist. The equine chorionic gonadotropin (eCG) alpha subunit expressed in pituitary gland was selected, amplified from total RNA, cloned and sequenced. The in silico analyses were made for homology modelling, structural details, epitope identification and chromosomal localization. Molecular docking studies of eCG alpha were undertaken with a drug ganirelix which is used to control ovulation and has antagonistic activity against GnRH. The protein sequence corresponding to selected open reading frame (ORF) was 99–100% similar with domesticated horse, Przewalski’s horse, and 92–93% with Burchell’s zebra and donkey. Molecular docking studies revealed the possible interaction of eCG alpha with ganirelix. The possible drug-macromolecule interactions were visualized between eCG alpha and ganirelix. The study will provide structural insight into unique sites and an alternate route of gonadotropin suppression applicable to assisted reproductive technologies.
Bilateral Wilms tumour: a review of clinical and molecular features
Authors: Charlton Jocelyn , Irtan Sabine , Bergeron Christophe , Pritchard-Jones Kathy
Published: July 2017

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5–8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features.
The impact of switching to clozapine on psychiatric hospital admissions: a mirror-image study
Authors: Kirwan P. , O’Connor L. , Sharma K. , McDonald C.
Published: July 2017

Background

Clozapine is an atypical antipsychotic agent used primarily in the management of treatment-resistant schizophrenia. Previous studies have demonstrated clozapine’s superior efficacy over other antipsychotic medications in treating this population of patients. The aim of this study was to assess if the number of hospital admissions and days spent in hospital reduced with the initiation of clozapine, compared with when the same sample of patients were prescribed other antipsychotics prior to clozapine initiation.

Method

A mirror-image study design was adopted. In this case the intervention under study was the initiation of clozapine. Information was collected retrospectively from the charts of patients attending the University Hospital Galway clozapine clinic. The number of admissions and number of hospital days were collected for each patient over the 3 years before and after clozapine initiation. Wilcoxon’s signed-rank test was used to test for statistical significance.

Results

The total sample size comprised of 62 patients, of which the majority were male (74.2%) and had a diagnosis of schizophrenia (82.3%). The mean dose of clozapine was 417 mg, and mean age of the sample was 38 years. Mean number of hospital admissions reduced from 2.8 to 0.8 (p<0.0001) following initiation of clozapine. Mean number of days spent in hospital reduced from 116.4 to 17.1 (p<0.0001).

Conclusion

After initiation of clozapine treatment, patients experience a substantial reduction in number of hospital admissions and number of days spent in hospital when compared with a similar period prior to clozapine initiation.
ON VANISHING THEOREMS FOR LOCAL SYSTEMS ASSOCIATED TO LAURENT POLYNOMIALS
Authors: ESTEROV ALEXANDER , TAKEUCHI KIYOSHI
Published: July 2017

We prove some vanishing theorems for the cohomology groups of local systems associated to Laurent polynomials. In particular, we extend one of the results of Gelfand et al.[Generalized Euler integrals and$A$-hypergeometric functions, Adv. Math.84(1990), 255–271] to various directions. In the course of the proof, some properties of vanishing cycles of perverse sheaves and twisted Morse theory are used.
Unifying the Study of Asymmetric Hypotheses
Authors: Rosenberg Andrew S. , Knuppe Austin J. , Braumoeller Bear F.
Published: July 2017

This article presents a conceptual clarification of asymmetric hypotheses and a discussion of methodologies available to test them. Despite the existence of a litany of theories that posit asymmetric hypotheses, most empirical studies fail to capture their core insight: boundaries separating zones of data from areas that lack data are substantively interesting. We discuss existing set-theoretic and large-N approaches to the study of asymmetric hypotheses, introduce new ones from the literatures on stochastic frontier and data envelopment analysis, evaluate their relative merits, and give three examples of how asymmetric hypotheses can be studied with this suite of tools.
Democratic Partisanship: From Theoretical Ideal to Empirical Standard
Authors: HERMAN LISE ESTHER
Published: July 2017

In recent years, a number of scholars have taken parties and partisanship as objects of normative theorizing. They posit partisanship as a fundamentally democratic practice and develop a model of what partisans can do at their best to contribute to liberal democracy. However, the standards the literature puts forth remain insufficiently specified to serve as empirical benchmarks. This article further conceptualizes this model of democratic partisanship and offers a theoretical framework within which to empirically evaluate the democratic merits of partisan discourses. It establishes a series of indicators for assessing the extent to which partisan discourse displays two main qualities: cohesiveness and respect for political pluralism. The article then discusses the implications of using this theoretical framework as a basis for empirical studies and shows how the model can thereby benefit both political scientists and theorists.
Responsibility for “Covering-up” an offence
Authors: Feller S. Z.
Published: July 2017

The following are some reflections on the judgment of the Supreme Court in Abu Khadrah v. Attorney-General. The facts of the case, albeit very simple, enable a number of primary legal problems regarding the offence of “covering-up” a criminal act to be considered.

a. The facts. The appellant was aware from what someone had told him that his informant along with the appellant's brother and other persons had sailed in his brother's boat to Gaza—obviously before the Six Day War—had there met Egyptian intelligence personnel, had handed over a sack and received from them a not inconsiderable sum of Israel money. The appellant was charged under sec. 5 of the Penal Law Revision (State Security—Foreign Relations and Official Secrets) Law, 1957 (hereinafter called the State Security Law) with “covering-up” of an offence committed by his brother and the others contrary to sec. 22 (b) of that Law.
Efficacy of single-dose 500 mg mebendazole in soil-transmitted helminth infections: a review
Authors: Mrus J. , Baeten B. , Engelen M. , Silber S.A.
Published: July 2017

Soil-transmitted helminthiasis (STH) is caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Mebendazole is one of the recommended preventive chemotherapy agents for STH. This review summarizes the efficacy data from 29 studies with single-dose 500 mg mebendazole in STH treatment and compares the results with those of a recently conducted phase 3 study of a 500 mg mebendazole chewable tablet against A. lumbricoides and T. trichiura infections. Studies that reported efficacy results against at least one STH infection were selected from the literature and efficacy data by each STH type were abstracted and pooled. Single-dose 500 mg mebendazole treatment resulted in a cure rate of 92.6% (range: 72.5–100%) for A. lumbricoides, 27.6% (range: 8.4–100%) for T. trichiura and 25.5% (range: 2.9–91.1%) for hookworms. Egg reduction rate for A. lumbricoides was 97.9% (range: 89.8–100%), for T. trichiura it was 72.9% (range: 31.6–93.0%) and for hookworms it was 72.0% (range: −6.5% (denoting an increase in egg count) to 98.3%). Similar results were observed in the studies that were placebo-controlled. In the phase 3 study, the cure rate and egg reduction rate reported was 83.7% and 97.9%, respectively, for A. lumbricoides and 33.9% and 59.7%, respectively, for T. trichiura. In conclusion, single-dose 500 mg mebendazole showed a high cure rate against A. lumbricoides and a substantial reduction in faecal egg count for all STH types. These results are consistent with the recently conducted phase 3 study of a new 500 mg chewable mebendazole tablet.
Taxonomy, ecology and geographic distribution ofGallardoneris iberica(Polychaeta, Lumbrineridae) in southern Europe
Authors: Katsiaras Nikolaos , Rousou Maria , Carrera-Parra Luis F. , Garcia-Gomez Sergio Carlos , Simboura Nomiki , Louizidou Paraskevi , Chintiroglou Chariton Charles , Martins Roberto
Published: July 2017

The polychaeteGallardoneris ibericawas described in soft-bottom benthic habitats from the Atlantic Iberian Peninsula coasts in 2012. Since then, successive studies have found this species in Spain, Italy and Croatia. The present study is the first to reportG. ibericafor Greece and Cyprus (42 new records) confirming its wide geographic distribution on southern European coasts. Taxonomic accounts and ecological preferences based on a large survey and review of available literature are being presented. The species was frequently found in habitats characterized by infralittoral muddy sands with variable organic matter and ‘Moderate’ ecological quality status; nevertheless it was also recorded in coarser and finer sediments, circalittoral mixed sediments, phytal substrates and undisturbed sites. Its relative abundance per sample was always lower than 2%. A review of the available ecological and geographic data of the otherGallardonerisspecies and a worldwide taxonomic key toGallardonerisspecies are provided.
Reconciling Regulatory Space with External Accountability through WTO Adjudication – Trade, Environment and Development
Authors: WEIMER MARIA
Published: July 2017

This article argues in favour of broadening the trade and environment debate in the World Trade Organization (WTO) to include a developmental perspective. WTO litigation involving environmental regulation touches upon the issue of global justice and the power asymmetries structurally embedded in the global economy. The recognition of the WTO as a legitimate global institution, therefore, depends on its ability to reconcile the respect for the right to regulate with the need to give due regard to the interests and concerns of foreign constituencies affected by domestic regulation. By imposing other-regarding obligations, WTO law can act as a mechanism of external accountability of powerful states vis-à-vis affected foreigners, especially where asymmetric relations and different stages of economic development are involved. The article applies this framework to analyze the legal reasoning of the Appellate Body in theUS-Tuna IIdispute between the US and Mexico – a dispute illustrating the complex intertwinement between economic, environmental and developmental issues. It concludes that the use of the concepts of ‘even-handedness’ and ‘calibration’ under Article 2.1 of the Technical Barriers to Trade Agreement and Article XX of the General Agreement on Tariffs and Trade did not enable the Appellate Body to strike an adequate balance between the right to regulate and external accountability. While in the original report the Appellate Body used ‘even-handedness’ to impose only a minimal level of external accountability on the US, in the compliance report, the Appellate Body has gone too far by failing to defer to the US risk assessment amidst scientific controversy and uncertainty.
Europeanisation and Catalonia’s in(ter)dependence
Authors: MORENO LUIS
Published: July 2017

The European Union has transcended many of the old prerogatives of national independence bringing about the very function of interdependence among Member States. Within the latter there are sub-state communities claiming simultaneously both self-government and ‘more Europe’. The future intent of this political process in the Old Continent is to make territorial subsidiarity consistent with home rule within European framework legislation and continental institutions. The first part of this article focuses on the idea of a closer European Union based upon the implementation of territorial subsidiarity, as well as on the challenges posed by democratic accountability, multi-level governance and the preservation of the European Social Model (ESM). The second section illustrates some of these challenges in practice through an analysis of how the meaning of independence has developed in a ‘stateless nation’ such as Catalonia. In Spain, the lack of territorial accommodation, together with a long-standing centre–periphery controversy, has fuelled claims for secession by some Catalan nationalists. The conclusions ponder on how ‘cosmopolitan localism’ can optimise both independence and interdependence of stateless nations like Catalonia in the global context.
Indigenous autonomy in Colombia: State-building processes and multiculturalism
Authors: RUEDA-SAIZ PABLO
Published: July 2017

This article shows a novel facet in the complex relation between multiculturalism, the state and the market. Contrary to conventional theories in political science, sociology and anthropology, it shows that it is not just the success, but also the failure of the state and the market to commoditise nature and turn it into property that can actually help to foster ethnic identity. While state-driven market incentives to expand the agricultural frontier in Colombia during the 1960s and 1970s failed, they did help to foster differentiated indigenous identities and organisations, which converged around the revival of long-forgotten nineteenth century indigenous laws and other political opportunities to reclaim lands that had been taken away from them. Moreover, this article also shows that during a period of institutional openness in the late 1980s and early 1990s, the political emergence of indigenous identities became an important component of Colombia’s state-building processes by helping this country to maintain its territorial integrity through a model of delegated indigenous governance.
The smectic order of wrinkles
Authors: Aharoni Hillel , Todorova Desislava V. , Albarrán Octavio , Goehring Lucas , Kamien Randall D. , Katifori Eleni
Published: July 2017

A thin elastic sheet lying on a soft substrate develops wrinkled patterns when subject to an external forcing or as a result of geometric incompatibility. Thin sheet elasticity and substrate response equip such wrinkles with a global preferred wrinkle spacing length and with resistance to wrinkle curvature. These features are responsible for the liquid crystalline smectic-like behaviour of such systems at intermediate length scales. This insight allows better understanding of the wrinkling patterns seen in such systems, with which we explain pattern breaking into domains, the properties of domain walls and wrinkle undulation. We compare our predictions with numerical simulations and with experimental observations.
Crystalline metamaterials for topological properties at subwavelength scales
Authors: Yves Simon , Fleury Romain , Berthelot Thomas , Fink Mathias , Lemoult Fabrice , Lerosey Geoffroy
Published: July 2017

The exciting discovery of topological condensed matter systems has lately triggered a search for their photonic analogues, motivated by the possibility of robust backscattering-immune light transport. However, topological photonic phases have so far only been observed in photonic crystals and waveguide arrays, which are inherently physically wavelength scaled, hindering their application in compact subwavelength systems. In this letter, we tackle this problem by patterning the deep subwavelength resonant elements of metamaterials onto specific lattices, and create crystalline metamaterials that can develop complex nonlocal properties due to multiple scattering, despite their very subwavelength spatial scale that usually implies to disregard their structure. These spatially dispersive systems can support subwavelength topological phases, as we demonstrate at microwaves by direct field mapping. Our approach gives a straightforward tabletop platform for the study of photonic topological phases, and allows to envision applications benefiting the compactness of metamaterials and the amazing potential of topological insulators.
Pericyte-expressed Tie2 controls angiogenesis and vessel maturation
Authors: Teichert Martin , Milde Laura , Holm Annegret , Stanicek Laura , Gengenbacher Nicolas , Savant Soniya , Ruckdeschel Tina , Hasanov Zulfiyya , Srivastava Kshitij , Hu Junhao , Hertel Stella , Bartol Arne , Schlereth Katharina , Augustin Hellmut G.
Published: July 2017

The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoietin/Tie signalling affects angiogenesis. Here we show that human and murine pericytes express functional Tie2 receptor. Silencing of Tie2 in pericytes results in a pro-migratory phenotype. Pericyte Tie2 controls sprouting angiogenesis in in vitro sprouting and in vivo spheroid assays. Tie2 downstream signalling in pericytes involves Calpain, Akt and FOXO3A. Ng2-Cre-driven deletion of pericyte-expressed Tie2 in mice transiently delays postnatal retinal angiogenesis. Yet, Tie2 deletion in pericytes results in a pronounced pro-angiogenic effect leading to enhanced tumour growth. Together, the data expand and revise the current concepts on vascular Angiopoietin/Tie signalling and propose a bidirectional, reciprocal EC-pericyte model of Tie2 signalling.
Co-option of the cardiac transcription factor Nkx2.5 during development of the emu wing
Authors: Farlie Peter G. , Davidson Nadia M. , Baker Naomi L. , Raabus Mai , Roeszler Kelly N. , Hirst Claire , Major Andrew , Mariette Mylene M. , Lambert David M. , Oshlack Alicia , Smith Craig A.
Published: July 2017

The ratites are a distinctive clade of flightless birds, typified by the emu and ostrich that have acquired a range of unique anatomical characteristics since diverging from basal Aves at least 100 million years ago. The emu possesses a vestigial wing with a single digit and greatly reduced forelimb musculature. However, the embryological basis of wing reduction and other anatomical changes associated with loss of flight are unclear. Here we report a previously unknown co-option of the cardiac transcription factorNkx2.5to the forelimb in the emu embryo, but not in ostrich, or chicken and zebra finch, which have fully developed wings.Nkx2.5is expressed in emu limb bud mesenchyme and maturing wing muscle, and mis-expression ofNkx2.5throughout the limb bud in chick results in wing reductions. We propose thatNkx2.5functions to inhibit early limb bud expansion and later muscle growth during development of the vestigial emu wing.
Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish
Authors: Wehner Daniel , Tsarouchas Themistoklis M. , Michael Andria , Haase Christa , Weidinger Gilbert , Reimer Michell M. , Becker Thomas , Becker Catherina G.
Published: July 2017

The inhibitory extracellular matrix in a spinal lesion site is a major impediment to axonal regeneration in mammals. In contrast, the extracellular matrix in zebrafish allows substantial axon re-growth, leading to recovery of movement. However, little is known about regulation and composition of the growth-promoting extracellular matrix. Here we demonstrate that activity of the Wnt/β-catenin pathway in fibroblast-like cells in the lesion site is pivotal for axon re-growth and functional recovery. Wnt/β-catenin signaling induces expression of col12a1a/b and deposition of Collagen XII, which is necessary for axons to actively navigate the non-neural lesion site environment. Overexpression of col12a1a rescues the effects of Wnt/β-catenin pathway inhibition and is sufficient to accelerate regeneration. We demonstrate that in a vertebrate of high regenerative capacity, Wnt/β-catenin signaling controls the composition of the lesion site extracellular matrix and we identify Collagen XII as a promoter of axonal regeneration. These findings imply that the Wnt/β-catenin pathway and Collagen XII may be targets for extracellular matrix manipulations in non-regenerating species.
An intrinsic mechanism controls reactivation of neural stem cells by spindle matrix proteins
Authors: Li Song , Koe Chwee Tat , Tay Su Ting , Tan Angie Lay Keng , Zhang Shenli , Zhang Yingjie , Tan Patrick , Sung Wing-Kin , Wang Hongyan
Published: July 2017

The switch between quiescence and proliferation is central for neurogenesis and its alteration is linked to neurodevelopmental disorders such as microcephaly. However, intrinsic mechanisms that reactivate Drosophila larval neural stem cells (NSCs) to exit from quiescence are not well established. Here we show that the spindle matrix complex containing Chromator (Chro) functions as a key intrinsic regulator of NSC reactivation downstream of extrinsic insulin/insulin-like growth factor signalling. Chro also prevents NSCs from re-entering quiescence at later stages. NSC-specific in vivo profiling has identified many downstream targets of Chro, including a temporal transcription factor Grainy head (Grh) and a neural stem cell quiescence-inducing factor Prospero (Pros). We show that spindle matrix proteins promote the expression of Grh and repress that of Pros in NSCs to govern their reactivation. Our data demonstrate that nuclear Chro critically regulates gene expression in NSCs at the transition from quiescence to proliferation.
Spin caloritronic nano-oscillator
Authors: Safranski C. , Barsukov I. , Lee H. K. , Schneider T. , Jara A. A. , Smith A. , Chang H. , Lenz K. , Lindner J. , Tserkovnyak Y. , Wu M. , Krivorotov I. N.
Published: July 2017

Energy loss due to ohmic heating is a major bottleneck limiting down-scaling and speed of nano-electronic devices, and harvesting ohmic heat for signal processing is a major challenge in modern electronics. Here, we demonstrate that thermal gradients arising from ohmic heating can be utilized for excitation of coherent auto-oscillations of magnetization and for generation of tunable microwave signals. The heat-driven dynamics is observed in Y3Fe5O12/Pt bilayer nanowires where ohmic heating of the Pt layer results in injection of pure spin current into the Y3Fe5O12 layer. This leads to excitation of auto-oscillations of the Y3Fe5O12 magnetization and generation of coherent microwave radiation. Our work paves the way towards spin caloritronic devices for microwave and magnonic applications.
Structural basis for dolichylphosphate mannose biosynthesis
Authors: Gandini Rosaria , Reichenbach Tom , Tan Tien-Chye , Divne Christina
Published: July 2017

Protein glycosylation is a critical protein modification. In biogenic membranes of eukaryotes and archaea, these reactions require activated mannose in the form of the lipid conjugate dolichylphosphate mannose (Dol-P-Man). The membrane protein dolichylphosphate mannose synthase (DPMS) catalyzes the reaction whereby mannose is transferred from GDP-mannose to the dolichol carrier Dol-P, to yield Dol-P-Man. Failure to produce or utilize Dol-P-Man compromises organism viability, and in humans, several mutations in the human dpm1 gene lead to congenital disorders of glycosylation (CDG). Here, we report three high-resolution crystal structures of archaeal DPMS from Pyrococcus furiosus, in complex with nucleotide, donor, and glycolipid product. The structures offer snapshots along the catalytic cycle, and reveal how lipid binding couples to movements of interface helices, metal binding, and acceptor loop dynamics to control critical events leading to Dol-P-Man synthesis. The structures also rationalize the loss of dolichylphosphate mannose synthase function in dpm1-associated CDG.
Long-term hepatitis B infection in a scalable hepatic co-culture system
Authors: Winer Benjamin Y. , Huang Tiffany S. , Pludwinski Eitan , Heller Brigitte , Wojcik Felix , Lipkowitz Gabriel E. , Parekh Amit , Cho Cheul , Shrirao Anil , Muir Tom W. , Novik Eric , Ploss Alexander
Published: July 2017

Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.
Effects of Transgenic Rice Infected with SRBSDV on Bt expression and the Ecological Fitness of Non-vector Brown Planthopper Nilaparvata lugens
Authors: Xu Hong-Xing , He Xiao-Chan , Zheng Xu-Song , Zhou Xiao-Jun , Lin Yong-Jun , Lu Zhong-Xian
Published: July 2017

The susceptibility of rice lines, T1C-19, T2A-1, and MH63 to SRBSDV infection are similar and the contents of cry protein in T2A-1 and T1C-19 do not change significantly. The survival rates of BPH nymphs feeding on SRBSDV-infected T1C-19, Bt T2A-1, or MH63 rice plants were not significantly different. The developmental stages of female BPH fed on T1C-19 plants infected with SRBSDV were significantly shorter than those fed on uninfected rice, while the males showed no significant difference. The duration of BPH feeding on SRBSDV-infected T2A-1 and MH63 also showed no significant difference in comparison with the respective control groups. Longevities of BPH adults feeding on SRBSDV-infected T1C-19, T2A-1 or MH63 were also not significant. However, the longevity of male adult BPH feeding on un-infected MH63 was significantly reduced in comparison with that of adult males feeding on un-infected T1C-19 and T2A-1 rice. In addition, the different rice lines and the rice plants infected and uninfected with SRBSDV did not significantly affect the sex ratio, female body weight, longevity, fecundity, or egg hatchability of BPH. In general, transgenic Bt rice infected with SRBSDV had little effect on the ecological adaptability of BPH.
Dendritic optical antennas: scattering properties and fluorescence enhancement
Authors: Guo Ke , Antoncecchi Alessandro , Zheng Xuezhi , Sallam Mai , Soliman Ezzeldin A. , Vandenbosch Guy A. E. , Moshchalkov Victor. V. , Koenderink A. Femius
Published: July 2017

With the development of nanotechnologies, researchers have brought the concept of antenna to the optical regime for manipulation of nano-scaled light matter interactions. Most optical nanoantennas optimize optical function, but are not electrically connected. In order to realize functions that require electrical addressing, optical nanoantennas that are electrically continuous are desirable. In this article, we study the optical response of a type of electrically connected nanoantennas, which we propose to call “dendritic” antennas. While they are connected, they follow similar antenna hybridization trends to unconnected plasmon phased array antennas. The optical resonances supported by this type of nanoantennas are mapped both experimentally and theoretically to unravel their optical response. Photoluminescence measurements indicate a potential Purcell enhancement of more than a factor of 58.
Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy
Authors: Ouyang Yabo , Yin Qianqian , Li Wei , Li Zhenpeng , Kong Desheng , Wu Yanling , Hong Kunxue , Xing Hui , Shao Yiming , Jiang Shibo , Ying Tianlei , Ma Liying
Published: July 2017

Interindividual heterogeneity in the disease progression of HIV-1-infected patients receiving long-term antiretroviral therapy suggests that some host-related factors may have limited treatment efficacy. To understand the nature of factors contributing to treatment failure, we performed a retrospective cohort study of 45 chronically HIV-1-infected individuals sharing a similar demographics and route of infection, compared the differences between virologically suppressed (VS) and treatment failure (TF) patients with respect to clinical, immunological and virological characteristics. We found that the baseline diversity of HIV-1 env quasispecies was the major difference between VS and TF group, and higher baseline diversity in TF patients. We further predicted TF-related env mutations using a selection pressure-based approach, followed by an analysis of these mutations based on the available three-dimensional structures of gp120/gp41 or their complexes with neutralizing antibodies. Notably, almost all of the identified residues could be mapped to the epitopes of known HIV-1 neutralizing antibodies, especially the epitopes of broadly neutralizing antibodies, and these mutations tended to compromise antibody-antigen interactions. These results indicate that the escape of HIV-1 from host humoral immunity may play a direct role in TF in long-term antiretroviral-experienced patients and that based on env gene sequence of the viruses in the patients.
Sugar intake from sweet food and beverages, common mental disorder and depression: prospective findings from the Whitehall II study
Authors: Knüppel Anika , Shipley Martin J. , Llewellyn Clare H. , Brunner Eric J.
Published: July 2017

Intake of sweet food, beverages and added sugars has been linked with depressive symptoms in several populations. Aim of this study was to investigate systematically cross-sectional and prospective associations between sweet food/beverage intake, common mental disorder (CMD) and depression and to examine the role of reverse causation (influence of mood on intake) as potential explanation for the observed linkage. We analysed repeated measures (23,245 person-observations) from the Whitehall II study using random effects regression. Diet was assessed using food frequency questionnaires, mood using validated questionnaires. Cross-sectional analyses showed positive associations. In prospective analyses, men in the highest tertile of sugar intake from sweet food/beverages had a 23% increased odds of incident CMD after 5 years (95% CI: 1.02, 1.48) independent of health behaviours, socio-demographic and diet-related factors, adiposity and other diseases. The odds of recurrent depression were increased in the highest tertile for both sexes, but not statistically significant when diet-related factors were included in the model (OR 1.47; 95% CI: 0.98, 2.22). Neither CMD nor depression predicted intake changes. Our research confirms an adverse effect of sugar intake from sweet food/beverage on long-term psychological health and suggests that lower intake of sugar may be associated with better psychological health.
Obesity, adipokines, and C-peptide are associated with distinct plasma phospholipid profiles in adult males, an untargeted lipidomic approach
Authors: Pickens C. Austin , Vazquez Ana I. , Jones A. Daniel , Fenton Jenifer I.
Published: July 2017

Obesity is associated with dysregulated lipid metabolism and adipokine secretion. Our group has previously reported obesity and adipokines are associated with % total fatty acid (FA) differences in plasma phospholipids. The objective of our current study was to identify in which complex lipid species (i.e., phosphatidylcholine, sphingolipids, etc) these FA differences occur. Plasma lipidomic profiling (n = 126, >95% Caucasian, 48–65 years) was performed using chromatographic separation and high resolution tandem mass spectrometry. The responses used in the statistical analyses were body mass index (BMI), waist circumference (WC), serum adipokines, cytokines, and a glycemic marker. High-dimensional statistical analyses were performed, all models were adjusted for age and smoking, and p-values were adjusted for false discovery. In Bayesian models, the lipidomic profiles (over 1,700 lipids) accounted for >60% of the inter-individual variation of BMI, WC, and leptin in our population. Across statistical analyses, we report 51 individual plasma lipids were significantly associated with obesity. Obesity was inversely associated lysophospholipids and ether linked phosphatidylcholines. In addition, we identify several unreported lipids associated with obesity that are not present in lipid databases. Taken together, these results provide new insights into the underlying biology associated with obesity and reveal new potential pathways for therapeutic targeting.
An integrated strategy by using target tissue metabolomics biomarkers as pharmacodynamic surrogate indices to screen antipyretic components of Qingkaikling injection
Authors: Zhang Zhixin , Lu Fang , Liu Haiyu , Zhao Huizhen , Liu Yuehong , Fu Shuang , Wang Meiling , Xie Ziye , Yu Honghong , Huang Zhenghai , Zhang Yanling , Gao Xiaoyan
Published: July 2017

Traditional Chinese medicine (TCM) treatment can be valuable therapeutic strategies. However, the active components and action mechanisms that account for its therapeutic effects remain elusive. Based on the hypothesis that the components of a formula which exert effect would be measurable in target tissue, a target tissue metabolomics-based strategy was proposed for screening of antipyretic components in Qingkaikling injection (QKLI). First, we detected the components of QKLI which could reach its target tissue (hypothalamus) by determining the hypothalamus microdialysate and discovered that only baicalin and geniposide could be detected. Then, by conducting hypothalamus metabolomics studies, 14 metabolites were screened as the potential biomarkers that related to the antipyretic mechanisms of QKLI and were used as its pharmacodynamic surrogate indices. Subsequently, the dynamic concentration of baicalin and geniposide in hypothalamus microdialysates and biomarkers in hypothalamus were measured and correlated with each other. The results indicated that only baicalin shown a good correlation with these biomarkers. Finally, a network pharmacology approach was established to validate the antipyretic activity of baicalin and the results elucidated its antipyretic mechanisms as well. The integrated strategy proposed here provided a powerful means for identifying active components and mechanisms contributing to pharmacological effects of TCM.
Replication of H9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release
Authors: Chan Renee W. Y. , Chan Louisa L. Y. , Mok Chris K. P. , Lai Jimmy , Tao Kin P. , Obadan Adebimpe , Chan Michael C. W. , Perez Daniel R. , Peiris J. S. Malik , Nicholls John M.
Published: July 2017

H9N2 viruses are the most widespread influenza viruses in poultry in Asia. We evaluated the infection and tropism of human and avian H9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. H9 viruses infected the upper and lower respiratory tract and the majority of H9 viruses had a decreased ability to release virus from the bronchus rather than the lung. This may be attributed to a weak neuraminidase (NA) cleavage of carbon-6-linked sialic acid (Sia) rather than carbon-3-linked Sia. The modified cleavage of N-acetlylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) by NA in H9 virus replication was observed by reverse genetics, and recombinant H9N2 viruses with amino acids (38KQ) deleted in the NA stalk, and changing the amino acid at position 431 from Proline-to-Lysine. Using recombinant H9 viruses previously evaluated in the ferret, we found that viruses which replicated well in the ferret did not replicate to the same extent in the human ex vivo cultures. The existing risk assessment models for H9N2 viruses in ferrets may not always have a strong correlation with the replication in the human upper respiratory tract. The inclusion of the human ex vivo cultures would further strengthen the future risk-assessment strategies.
Functional and Transcriptomic Characterization of Peritoneal Immune-Modulation by Addition of Alanyl-Glutamine to Dialysis Fluid
Authors: Herzog Rebecca , Kuster Lilian , Becker Julia , Gluexam Tobias , Pils Dietmar , Spittler Andreas , Bhasin Manoj K. , Alper Seth L. , Vychytil Andreas , Aufricht Christoph , Kratochwill Klaus
Published: July 2017

Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells. Ex-vivo stimulation of PD effluent peritoneal cells increased release of interleukin (IL) 6 and tumor necrosis factor (TNF) α. Both IL-6 and TNF-α were lower at 1 h than at 4 h of the peritoneal equilibration test but the reductions in cytokine release were attenuated in AlaGln-supplemented samples. AlaGln-supplemented samples exhibited priming of IL-6-related pathways and downregulation of TNF-α upstream elements. Results from measurement of cytokine release and transcriptome analysis in this pilot clinical study support the conclusion that suppression of PD effluent cell immune function in human subjects by standard PD fluid is attenuated by AlaGln supplementation.
A new marine-derived sulfoglycolipid triggers dendritic cell activation and immune adjuvant response
Authors: Manzo Emiliano , Cutignano Adele , Pagano Dario , Gallo Carmela , Barra Giusi , Nuzzo Genoveffa , Sansone Clementina , Ianora Adrianna , Urbanek Konrad , Fenoglio Daniela , Ferrera Francesca , Bernardi Cinzia , Parodi Alessia , Pasquale Giuseppe , Leonardi Antonio , Filaci Gilberto , De Palma Raffaele , Fontana Angelo
Published: July 2017

Dendritic Cells (DCs) recognize infectious non-self molecules and engage the adaptive immune system thereby initiating long lasting, antigen-specific responses. As such, the ability to activate DCs is considered a key tool to enhance the efficacy and quality of vaccination. Here we report a novel immunomodulatory sulfolipid named β-SQDG18 that prototypes a class of natural-derived glycolipids able to prime human DCs by a TLR2/TLR4-independent mechanism and trigger an efficient immune responsein vivo. β-SQDG18 induces maturation of DC with the upregulation of MHC II molecules and co-stimulatory proteins (CD83, CD86), as well as pro-inflammatory cytokines (IL-12 and INF-γ). Mice immunized with OVA associated to β-SQDG18 (1:500) produced a titer of anti-OVA Ig comparable to traditional adjuvants. In an experimental model of melanoma, vaccination of C57BL/6 mice with β-SQDG18-adjuvanted hgp10 peptide elicited a protective response with a reduction in tumour growth and increase in survival.
Exploring the binding sites and proton diffusion on insulin amyloid fibril surfaces by naphthol-based photoacid fluorescence and molecular simulations
Authors: Amdursky Nadav , Rashid M. Harunur , Stevens Molly M. , Yarovsky Irene
Published: July 2017

The diffusion of protons along biological surfaces and the interaction of biological structures with water are fundamental areas of interest in biology and chemistry. Here, we examine the surface of insulin amyloid fibrils and follow the binding of small molecules (photoacids) that differ according to the number and location of their sulfonic groups. We use transient fluorescence combined with a spherically-symmetric diffusion theory to show that the binding mode of different photoacids determines the efficiency of proton dissociation from the photoacid and the dimensionality of the proton’s diffusion. We use molecular dynamics simulations to examine the binding mode and mechanism of the photoacids and its influence on the unique kinetic rates and diffusion properties of the photoacid’s dissociated proton, where we also suggest a proton transfer process between one of the photoacids to proximal histidine residues. We show that the photoacids can be used as fluorescent markers for following the progression of amyloidogenic processes. The detailed characterisation of different binding modes to the surface of amyloid fibrils paves the way for better understanding of the binding mechanism of small molecules to amyloid fibrils.
Homeostatic Left Heart integration and disintegration links atrio-ventricular covariation’s dyshomeostasis in Hypertrophic Cardiomyopathy
Authors: Piras Paolo , Torromeo Concetta , Evangelista Antonietta , Gabriele Stefano , Esposito Giuseppe , Nardinocchi Paola , Teresi Luciano , Madeo Andrea , Schiariti Michele , Varano Valerio , Puddu Paolo Emilio
Published: July 2017

Left ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.
Establishing a yeast-based screening system for discovery of human GLUT5 inhibitors and activators
Authors: Tripp Joanna , Essl Christine , Iancu Cristina V. , Boles Eckhard , Choe Jun-yong , Oreb Mislav
Published: July 2017

Human GLUT5 is a fructose-specific transporter in the glucose transporter family (GLUT, SLC2 gene family). Its substrate-specificity and tissue-specific expression make it a promising target for treatment of diabetes, metabolic syndrome and cancer, but few GLUT5 inhibitors are known. To identify and characterize potential GLUT5 ligands, we developed a whole-cell system based on a yeast strain deficient in fructose uptake, in which GLUT5 transport activity is associated with cell growth in fructose-based media or assayed by fructose uptake in whole cells. The former method is convenient for high-throughput screening of potential GLUT5 inhibitors and activators, while the latter enables detailed kinetic characterization of identified GLUT5 ligands. We show that functional expression of GLUT5 in yeast requires mutations at specific positions of the transporter sequence. The mutated proteins exhibit kinetic properties similar to the wild-type transporter and are inhibited by established GLUT5 inhibitors N-[4-(methylsulfonyl)-2-nitrophenyl]-1,3-benzodioxol-5-amine (MSNBA) and (−)-epicatechin-gallate (ECG). Thus, this system has the potential to greatly accelerate the discovery of compounds that modulate the fructose transport activity of GLUT5.
Uncovering Offshore Financial Centers: Conduits and Sinks in the Global Corporate Ownership Network
Authors: Garcia-Bernardo Javier , Fichtner Jan , Takes Frank W. , Heemskerk Eelke M.
Published: July 2017

Multinational corporations use highly complex structures of parents and subsidiaries to organize their operations and ownership. Offshore Financial Centers (OFCs) facilitate these structures through low taxation and lenient regulation, but are increasingly under scrutiny, for instance for enabling tax avoidance. Therefore, the identification of OFC jurisdictions has become a politicized and contested issue. We introduce a novel data-driven approach for identifying OFCs based on the global corporate ownership network, in which over 98 million firms (nodes) are connected through 71 million ownership relations. This granular firm-level network data uniquely allows identifying both sink-OFCs and conduit-OFCs. Sink-OFCs attract and retain foreign capital while conduit-OFCs are attractive intermediate destinations in the routing of international investments and enable the transfer of capital without taxation. We identify 24 sink-OFCs. In addition, a small set of five countries – the Netherlands, the United Kingdom, Ireland, Singapore and Switzerland – canalize the majority of corporate offshore investment as conduit-OFCs. Each conduit jurisdiction is specialized in a geographical area and there is significant specialization based on industrial sectors. Against the idea of OFCs as exotic small islands that cannot be regulated, we show that many sink and conduit-OFCs are highly developed countries.