bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting‐state functional connectivity and cognitive dysfunction correlations in spinocerebelellar ataxia type 6 (SCA6)
Authors: Pereira Licia , Airan Raag D. , Fishman Ann , Pillai Jay J. , Kansal Kalyani , Onyike Chiadi U. , Prince Jerry L. , Ying Sarah H. , Sair Haris I.
Published: March 2017

Objective

The aim of this study is to evaluate the correlation between resting state functional MRI (RS‐fMRI) activity and motor and cognitive impairment in spinocerebellar ataxia type 6 (SCA6).

Methods

Twelve patients with genetically confirmed SCA6 and 14 age matched healthy controls were imaged with RS‐fMRI. Whole brain gray matter was automatically parcellated into 1000 regions of interest (ROIs). For each ROI, the first eigenvariate of voxel time courses was extracted. For each patient, Pearson correlation coefficients between each pair of ROI time courses were calculated across the 1000 ROIs. The set of average control correlation coefficients were fed as an undirected weighted adjacency matrix into the Rubinov and Sporns (2010) modularity algorithm. The intranetwork global efficiency of the thresholded adjacency sub‐matrix was calculated and correlated with ataxia scores and cognitive performance.

Results

SCA6 patients showed mild cognitive impairments in executive function and visual‐motor processing compared to control subjects. These neuropsychological impairments were correlated with decreased RS functional connectivity (FC) in the attention network.

Conclusions

Mild cognitive executive functions and visual‐motor coordination impairments seen in SCA6 patients correlate with decreased resting‐state connectivity in the attention network, suggesting a possible metric for the study of cognitive dysfunction in cerebellar disease. Hum Brain Mapp 38:3001–3010, 2017. © 2017 Wiley Periodicals, Inc.
Three‐dimensional culture of buffalo granulosa cells in hanging drop mimics the preovulatory follicle stage
Authors: Yadav Monica , Agrawal Himanshu , Pandey Mamta , Singh Dheer , Onteru Suneel K.
Published: March 2017

Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three‐dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 hr in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly‐([2‐hydroxyethyl methacrylate]) (polyHEMA) methods in the DMEM media containing 1 ng/ml FSH and 10 ng/ml IGF‐1 for 144 hr. The expression profile of nine GC‐specific transcripts; CYP19, TNFAIP6, AMH, PTI, NR4A1, FSHR, RUNX, LHR, and COX2/PTGS2; revealed that 3D‐spheroids developed in hanging drop method maintained the GC phenotype of preovulatory follicles. Therefore, hanging drop method is a best method for culturing GCs to mimic the intrafollicular environment.
Elucidating the interaction of clofazimine with bovine liver catalase; a comprehensive spectroscopic and molecular docking approach
Authors: Zaman Masihuz , Nusrat Saima , Zakariya Syed Mohammad , Khan Mohsin Vahid , Ajmal Mohammad Rehan , Khan Rizwan Hasan
Published: March 2017

Nowadays, understanding of interface between protein and drugs has become an active research area of interest. These types of interactions provide structural guidelines in drug design with greater clinical efficacy. Thus, structural changes in catalase induced by clofazimine were monitored by various biophysical techniques including UV‐visible spectrometer, fluorescence spectroscopy, circular dichroism, and dynamic light scattering techniques. Increase in absorption spectra (UV‐visible spectrum) confers the complex formation between drug and protein. Fluorescence quenching with a binding constants of 2.47 × 104 M−1 revealed that clofazimine binds with protein. Using fluorescence resonance energy transfer, the distance (r) between the protein (donor) and drug (acceptor) was found to be 2.89 nm. Negative Gibbs free energy change (ΔG°) revealed that binding process is spontaneous. In addition, an increase in α‐helicity was observed by far‐UV circular dichroism spectra by adding clofazimine to protein. Dynamic light scattering results indicate that topology of bovine liver catalase was slightly altered in the presence of clofazimine. Hydrophobic interactions are the main forces between clofazimine and catalase interaction as depicted by molecular docking studies. Apart from hydrophobic interactions, some hydrogen bonding was also observed during docking method. The results obtained from the present study may establish abundant in optimizing the properties of ligand‐protein mixtures relevant for numerous formulations.
Comparing chamber and eddy covariance based net ecosystem CO2 exchange of fen soils
Authors: Poyda Arne , Reinsch Thorsten , Skinner R. Howard , Kluß Christof , Loges Ralf , Taube Friedhelm
Published: March 2017

Due to their high emission potential, the reporting of CO2 emissions from peatlands requires exact emission factors for different land use categories. Recently used emission factors are mainly based on CO2 flux measurements by chamber techniques or the micrometeorological eddy covariance (EC) method. However, evidence about the reliability and comparability of annual CO2 balances based on these methods is scarce. Therefore, manual chamber measurements of ecosystem respiration (RECO) and net ecosystem exchange (NEE) were conducted for two years (March 2012–April 2014) to model annual balances of two sites on fen soils with different land use intensity in northern Germany: an unutilized and rewetted grassland (UG) and an intensively utilized wet grassland (GW). Simultaneously, EC measurements of NEE were conducted on the sites. Two reasons for occasionally great deviations in NEE between the methods could be observed: (1) the accordance of both methods was most hampered during transition periods such as the beginning of the growing season and the onset of regrowth after a grassland defoliation due to different spatial scales of EC and chamber measurements and (2) RECO and gross primary production (GPP) partitioned from EC NEE measurements were systematically lower than those from the chamber‐based model, which could be a result of the EC energy balance gap. Differences were more pronounced for the managed site GW as a result of more frequent regrowth periods. It is concluded that the EC and chamber method can show comparable results for the CO2 exchange of grasslands on fen soils when the limitations of both methods are known and considered for the reporting of emission factors. These limitations are due to energy balance closure and potentially biased footprints for EC and a restricted representativeness especially during early stages of plant development for the chamber method.
Mutifunctional Electrospun Nonwoven Mats with Two‐Way Shape Memory Behavior Prepared from Sol–Gel Crosslinked Poly(ε‐Caprolactone)
Authors: Pandini Stefano , Agnelli Silvia , Merlettini Andrea , Chiellini Federica , Gualandi Chiara , Paderni Katia , Focarete Maria Letizia , Messori Massimo , Toselli Maurizio
Published: March 2017

Nonwoven fibrous mats based on semicrystalline networks are prepared starting from poly(ε‐caprolactone) and properly combining electrospinning and sol–gel reactions. The mats are obtained as continuous, randomly oriented micrometric fibers with different network densities. The systems are subjected to thermomechanical cycles to investigate their one‐way and two‐way shape memory behavior. One‐way tests aim at exploring the effects of the deformation temperature on the materials response, with particular interest to the less investigated cold‐working conditions (i.e., deformation temperature below T
m). The materials display two‐way shape memory capabilities (i.e., the ability to change between two distinguished shapes upon heating and cooling under a fixed nonzero stress) and the effect of the applied stress is explored. The shape memory characterization is accompanied by an ex situ SEM analysis, to describe the concurrent microstructural evolution during the macroscopic shape variation, and by the assessment of their biocompatibility, to explore the suitability of the nonwovens for biomedical applications.

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A bicriterion approach to common flow allowances due window assignment and scheduling with controllable processing times
Authors: Wang Dujuan , Yin Yunqiang , Cheng T.C.E.
Published: March 2017

We investigate a single‐machine scheduling problem for which both the job processing times and due windows are decision variables to be determined by the decision maker. The job processing times are controllable as a linear or convex function of the amount of a common continuously divisible resource allocated to the jobs, where the resource allocated to the jobs can be used in discrete or continuous quantities. We use the common flow allowances due window assignment method to assign due windows to the jobs. We consider two performance criteria: (i) the total weighted number of early and tardy jobs plus the weighted due window assignment cost, and (ii) the resource consumption cost. For each resource consumption function, the objective is to minimize the first criterion, while keeping the value of the second criterion no greater than a given limit. We analyze the computational complexity, devise pseudo‐polynomial dynamic programming solution algorithms, and provide fully polynomial‐time approximation schemes and an enhanced volume algorithm to find high‐quality solutions quickly for the considered problems. We conduct extensive numerical studies to assess the performance of the algorithms. The computational results show that the proposed algorithms are very efficient in finding optimal or near‐optimal solutions. © 2017 Wiley Periodicals, Inc. Naval Research Logistics, 64: 41–63, 2017
Comparative transcriptome analysis of isogenic cell line models and primary cancers links capicua (CIC) loss to activation of the MAPK signalling cascade
Authors: LeBlanc Veronique G , Firme Marlo , Song Jungeun , Chan Susanna Y , Lee Min Hye , Yip Stephen , Chittaranjan Suganthi , Marra Marco A
Published: March 2017

CIC encodes a transcriptional repressor, capicua (CIC), whose disrupted activity appears to be involved in several cancer types, including type I low‐grade gliomas (LGGs) and stomach adenocarcinomas (STADs). To explore human CIC's transcriptional network in an isogenic background, we developed novel isogenic CIC knockout cell lines as model systems, and used these in transcriptome analyses to study the consequences of CIC loss. We also compared our results with analyses of transcriptome data from TCGA for type I LGGs and STADs. We identified 39 candidate targets of CIC transcriptional regulation, and confirmed seven of these as direct targets. We showed that, although many CIC targets appear to be context‐specific, the effects of CIC loss converge on the dysregulation of similar biological processes in different cancer types. For example, we found that CIC deficiency was associated with disruptions in the expression of genes involved in cell–cell adhesion, and in the development of several cell and tissue types. We also showed that loss of CIC leads to overexpression of downstream members of the mitogen‐activated protein kinase (MAPK) signalling cascade, indicating that CIC deficiency may present a novel mechanism for activation of this oncogenic pathway. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Four‐state memory based on ferroelectric tunnel junctions with double ferroelectric layers
Authors: Chen Geng , Ma Zhijun , Zhou Peng , Mei Zhiheng , Liang Kun , Zhang Tianjin
Published: March 2017

Adding logic states to a memory cell helps to increase storage density. In this paper, ferroelectric tunnel junctions (FTJs) with double ferroelectric layers (Pt/BaTiO3/SrTiO3/BaTiO3/Pt) were proposed to realize multiple storage. Calculations showed that up to four resistance states could be clearly distinguished over a wide range of parameters. Our results reveal the exciting prospects of FTJs for high density non‐volatile memory.
Advancing Social Justice Work at the Intersections of Multiple Privileged Identities
Authors: Kendall Frances E. , Wijeyesinghe Charmaine L.
Published: March 2017

The authors discuss how the concept of social location and tenets of intersectionality inform the understanding of power and privilege, our work with people with multiple privileged identities, and the preparation of social justice educators.
Measuring perceived morphological relatedness
Authors: Hall Kathleen Currie , Allen Claire , Fairburn Tess , Fry Michael , McAuliffe Michael , McMullin Kevin
Published: March 2017

This paper provides a metric for determining whether a given pair of English words is perceived to be morphologically related, based on objective measurements of the words’ orthographic, phonetic, and semantic similarity to each other. The metric is developed on the basis of results from a behavioural study in which participants were asked to judge the relative similarity of pairs of words. The metric is intended to help researchers determine which forms in a language plausibly have segments that alternate; as an example, it is applied to the lexicon of English to illustrate its utility in calculating the frequency of alternation of [s] and [ʃ].
THE EXPECTED JAGGEDNESS OF ORDER IDEALS
Authors: CHAN MELODY , HADDADAN SHAHRZAD , HOPKINS SAM , MOCI LUCA
Published: March 2017

Thejaggednessof an order ideal$I$in a poset$P$is the number of maximal elements in$I$plus the number of minimal elements of$P$not in$I$. A probability distribution on the set of order ideals of$P$istoggle-symmetricif for every$p\in P$, the probability that$p$is maximal in$I$equals the probability that$p$is minimal not in$I$. In this paper, we prove a formula for the expected jaggedness of an order ideal of $P$under any toggle-symmetric probability distribution when$P$is the poset of boxes in a skew Young diagram. Our result extends the main combinatorial theorem of Chan–López–Pflueger–Teixidor [Trans. Amer. Math. Soc., forthcoming. 2015,arXiv:1506.00516], who used an expected jaggedness computation as a key ingredient to prove an algebro-geometric formula; and it has applications to homomesies, in the sense of Propp–Roby, of the antichain cardinality statistic for order ideals in partially ordered sets.
Evaluation of Staphylococcus aureus Bacteremia: Academic and Community-Based Management Within the Same Health System
Authors: Ased Sumaya , Rayes Hamza , Dhami Jaspreet , Amosson Nick , Fordjour Akua , Macaraeg Jeff , Vivekanandan Renuga , Wilson Josh , Cabri Annie , Davids Michele , Anthone Jennifer , Cavalieri Stephen , Destache Christopher J.
Published: March 2017

A nonrandomized, retrospective comparison of Staphylococcus aureus bacteremia between an academic hospital setting (n=53) and a community hospital setting (n=245) within a single healthcare system was performed. Despite infectious disease consultations, S. aureus bacteremia management recommendations based on Infectious Diseases Society of America (IDSA) guidelines were not followed as closely in the community hospital setting. The community hospital setting requires management standardization for patients with S. aureus bacteremia.

Infect Control Hosp Epidemiol 2017;38:740–742
Tensor veli palatini electromyography for monitoring Eustachian tube rehabilitation in otitis media
Authors: Picciotti P M , Della Marca G , D'Alatri L , Lucidi D , Rigante M , Scarano E
Published: March 2017

Background:

The pathogenesis of otitis media is related to Eustachian tube dysfunction. The tensor veli palatini muscle actively opens the Eustachian tube and promotes middle-ear ventilation. This study describes a technique for paratubal electromyography that uses a surface, non-invasive electrode able to record tensor veli palatini muscle activity during swallowing.

Methods:

Twenty otitis media patients and 10 healthy patients underwent tensor veli palatini electromyography. Activity of this muscle before and after Eustachian tube rehabilitation was also assessed.

Results:

In 78.5 per cent of patients, the electromyography duration phase and/or amplitude were reduced in the affected side. The muscle action potential was impaired in all patients who underwent Eustachian tube rehabilitation.

Conclusion:

This study confirmed that Eustachian tube muscle dysfunction has a role in otitis media pathogenesis and showed that muscle activity increases after Eustachian tube rehabilitation therapy.
A Discussion of Alexander Cooley and Jack Snyder's Ranking the World: Grading States as a Tool for Global Governance
Authors: Kurki Milja
Published: March 2017

Ranking the World: Grading States as a Tool of Global Governance, edited by Alexander Cooley and Jack Snyder, assembles an impressive group of political scientists to critically discuss “the important analytical, normative, and policy issues associated with the contemporary practice of ‘grading states.’” The volume addresses a topic of importance to a wide range of political scientists in comparative politics, international relations, and political theory, and raises some fundamental questions about the role of political science at the nexus of theory and practice. We have thus invited a number of colleagues to discuss the volume and its broader implications for political science inquiry.
Interventionen psychiatrisch Pflegender beim Übergang in die Gemeinde
Authors: Kiereck Maximilian , Heinrichs Daniel
Published: March 2017

Zusammenfassung. Der Übergang ehemals forensisch untergebrachter Menschen in die Gemeinde ist mit vielen Schwierigkeiten verbunden. Psychiatrisch Pflegenden in der forensischen Klinik wie in gemeindepsychiatrischen Einrichtungen kommt eine Schlüsselrolle beim Übergang in die Gemeinde zu. Schlüssige Konzepte zur Realisierung gibt es kaum. Umso wichtiger, dass über Möglichkeiten nachgedacht wird.
Vom Mut, die Seins-Angst auf sich zu nehmen
Authors: Herzog Esther
Published: March 2017

Zusammenfassung. Existentielle Angst gehört wesenhaft zum Menschsein, aber sie ist auch gleichzeitig die Quelle echten freimachenden Mutes zum Sein. Als ich meinen Mann in seiner schweren lebensbedrohlichen Erkrankung durch viele klinische Einrichtungen begleitete, habe ich die Unsicherheit des Personals im Umgang mit unserer existentiellen Betroffenheit schmerzlich erfahren.
Energy use and carbon footprints differ dramatically for diverse wastewater-derived carbonaceous substrates: An integrated exploration of biokinetics and life-cycle assessment
Authors: Li Yanbo , Wang Xu , Butler David , Liu Junxin , Qu Jiuhui
Published: March 2017

Energy neutrality and reduction of carbon emissions are significant challenges to the enhanced sustainability of wastewater treatment plants (WWTPs). Harvesting energy from wastewater carbonaceous substrates can offset energy demands and enable net power generation; yet, there is limited research about how carbonaceous substrates influence energy and carbon implications of WWTPs with integrated energy recovery at systems-level. Consequently, this research uses biokinetics modelling and life cycle assessment philology to explore this notion, by tracing and assessing the quantitative flows of energy embodied or captured, and by exploring the carbon footprint throughout an energy-intensive activated sludge process with integrated energy recovery facilities. The results indicate that energy use and carbon footprint per cubic meter of wastewater treated, varies markedly with the carbon substrate. Compared with systems driven with proteins, carbohydrates or other short-chain fatty acids, systems fed with acetic acid realized energy neutrality with maximal net gain of power from methane combustion (0.198 kWh) and incineration of residual biosolids (0.153 kWh); and also achieved a negative carbon footprint (72.6 g CO2). The findings from this work help us to better understand and develop new technical schemes for improving the energy efficiency of WWTPs by repurposing the stream of carbon substrates across systems.
NMR monitoring of the SELEX process to confirm enrichment of structured RNA
Authors: Amano Ryo , Aoki Kazuteru , Miyakawa Shin , Nakamura Yoshikazu , Kozu Tomoko , Kawai Gota , Sakamoto Taiichi
Published: March 2017

RNA aptamers are RNA molecules that bind to a target molecule with high affinity and specificity using uniquely-folded tertiary structures. RNA aptamers are selected from an RNA pool typically comprising up to 1015 different sequences generated by iterative steps of selection and amplification known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Over several rounds of SELEX, the diversity of the RNA pool decreases and the aptamers are enriched. Hence, monitoring of the enrichment of these RNA pools is critical for the successful selection of aptamers, and several methods for monitoring them have been developed. In this study, we measured one-dimensional imino proton NMR spectra of RNA pools during SELEX. The spectrum of the initial RNA pool indicates that the RNAs adopt tertiary structures. The structural diversity of the RNA pools was shown to depend highly on the design of the primer-binding sequence. Furthermore, we demonstrate that enrichment of RNA aptamers can be monitored using NMR. The RNA pools can be recovered from the NMR tube after measurement of NMR spectra. We also can monitor target binding in the NMR tubes. Thus, we propose using NMR to monitor the enrichment of structured aptamers during the SELEX process.
Complete Genomic and Ultrastructural Analysis of a Nam Dinh Virus Isolated from Culex pipiens quinquefasciatus in China*
Authors: Zhou Jianming , Jin Yujuan , Chen Yingjian , Li Jingmei , Zhang Qiwen , Xie Xianqing , Gan Liping , Liu Qu
Published: March 2017

The Nam Dinh virus (NDiV) was isolated from Culex quinquefasciatus in Shenzhen, China, for the first time, in 2011. In this study, we characterized the ultrastructure of NDiV, determined its complete genome sequence and made comparisons with other known nidoviruses. Electron microscopic observation revealed that the NDiV strain isolated in China produced viral nucleocapsid-like particles and vesicles in host cells. The extracellular virions were enveloped and were spherical with short spikes. The complete genome sequence of the newly isolated NDiV was submitted to the GenBank database (GenBank accession number KF522691). Sequencing of the viral genome showed that the homologies of NDiV isolated in China and Vietnam were greater than 94.0% and 89.0% at the nucleotide and amino acid sequence levels, respectively. Moreover, gene substitution was detected, whereas insertions and deletions were not. A phylogenetic tree analysis showed that these viruses belong to the genus Alphamesonivirus1 of the family Mesoniviridae. The similarity between the two viruses regarding morphological and molecular biological characteristics indicates that the molecular genetics of NDiV are conservative and that the regional differences are unlikely to have a significant effect. This is the first report of the isolation and complete sequencing of a mesonivirus in mainland China.
Electric-field-driven magnetic domain wall as a microscale magneto-optical shutter
Authors: Khokhlov Nikolai E. , Khramova Anastasiya E. , Nikolaeva Elena P. , Kosykh Tatyana B. , Nikolaev Alexey V. , Zvezdin Anatoly K. , Pyatakov Alexander P. , Belotelov Vladimir I.
Published: March 2017

Nowadays, spintronics considers magnetic domain walls as a kind of nanodeviсe that demands for switching much less energy in comparison to homogeneous process. We propose and demonstrate a new concept for the light control via electric field applied locally to a magnetic domain wall playing the role of nanodevice. In detail, we charged a 15-μm-thick metallic tip to generate strong non-uniform electric field in the vicinity of the domain wall in the iron garnet film. The electric field influences the domain wall due to flexomagnetoelectric effect and causes the domain wall shift. The resulting displacement of the domain wall is up to 1/3 of domain width and allows to demonstrate a novel type of the electrically controlled magneto-optical shutter. Polarized laser beam focused on the electric-field-driven domain wall was used to demonstrate the concept of a microscale Faraday modulator. We obtained different regimes of the light modulation – linear, nonlinear and tri-stable – for the same domain wall with corresponding controllable displacement features. Such variability to control of domain wall’s displacement with spatial scale of about 10 μm makes the proposed concept very promising for nanophotonics and spintronics.
Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood
Authors: Cardenas Andres , Rifas-Shiman Sheryl L. , Agha Golareh , Hivert Marie-France , Litonjua Augusto A. , DeMeo Dawn L. , Lin Xihong , Amarasiriwardena Chitra J. , Oken Emily , Gillman Matthew W. , Baccarelli Andrea A.
Published: March 2017

Prenatal exposure to mercury, a known neurotoxic metal, is associated with lower cognitive performance during childhood. Disruption of fetal epigenetic programming could explain mercury’s neurodevelopmental effects. We screened for epigenome-wide methylation differences associated with maternal prenatal blood mercury levels in 321 cord blood DNA samples and examined the persistence of these alterations during early (n = 75; 2.9–4.9 years) and mid-childhood (n = 291; 6.7–10.5 years). Among males, prenatal mercury levels were associated with lower regional cord blood DNA methylation at the Paraoxonase 1 gene (PON1) that persisted in early childhood and was attenuated in mid-childhood blood. Cord blood methylation at thePON1locus predicted lower cognitive test scores measured during early childhood. Methylation at thePON1locus was associated with PON1 expression in an independent set of cord blood samples. The observed persistent epigenetic disruption of thePON1gene may modulate mercury toxicity in humans and might serve as a biomarker of exposure and disease susceptibility.
Inosine attenuates spontaneous activity in the rat neurogenic bladder through an A2B pathway
Authors: Doyle Claire , Cristofaro Vivian , Sack Bryan S. , Lukianov Stefan N. , Schäfer Mattias , Chung Yeun Goo , Sullivan Maryrose P. , Adam Rosalyn M.
Published: March 2017

Neurogenic detrusor overactivity (NDO) is among the most challenging complications of spinal cord injury (SCI). A recent report by us demonstrated an improvement in NDO in SCI rats following chronic systemic treatment with the purine nucleoside inosine. The objective of this study was to investigate the mechanism of action of inosine underlying improvement of NDO. Male Sprague-Dawley rats underwent complete spinal cord transection at T8. Inosine (1 mM) delivered intravesically to SCI rats during conscious cystometry significantly decreased the frequency of spontaneous non-voiding contractions. In isolated tissue assays, inosine (1 mM) significantly decreased the amplitude of spontaneous activity (SA) in SCI bladder muscle strips. This effect was prevented by a pan-adenosine receptor antagonist CGS15943, but not by A1 or A3 receptor antagonists. The A2A antagonist ZM241385 and A2B antagonist PSB603 prevented the effect of inosine. The effect of inosine was mimicked by the adenosine receptor agonist NECA and the A2B receptor agonist BAY60-6583. The inhibition of SA by inosine was not observed in the presence of the BK antagonist, iberiotoxin, but persisted in the presence of KATP and SK antagonists. These findings demonstrate that inosine acts via an A2B receptor-mediated pathway that impinges on specific potassium channel effectors.
Immune complexes in chronic Chagas disease patients are formed by exovesicles from Trypanosoma cruzi carrying the conserved MASP N-terminal region
Authors: Díaz Lozano Isabel María , De Pablos Luis Miguel , Longhi Silvia Andrea , Zago María Paola , Schijman Alejandro Gabriel , Osuna Antonio
Published: March 2017

The exovesicles (EVs) are involved in pathologic host-parasite immune associations and have been recently used as biomarkers for diagnosis of infectious diseases. The release of EVs byTrypanosoma cruzi, the causative agent of Chagas disease, has recently been described, with different protein cargoes including the MASP multigene family of proteins MASPs are specific to this parasite and characterized by a conserved C-terminal (C-term) region and an N-terminal codifying for a signal peptide (SP). In this investigation, we identified immature MASP proteins containing the MASP SP in EVs secreted by the infective forms of the parasite. Those EVs are responsible for the formation of immune complexes (ICs) containing anti-MASP SP IgGs in patients with different (cardiac, digestive and asymptomatic) chronic Chagas disease manifestations. Moreover, purified EVs as well as the MASP SP inhibit the action of the complement system and also show a significant association with the humoral response in patients with digestive pathologies. These findings reveal a new route for the secretion of MASP proteins inT. cruzi, which uses EVs as vehicles for immature and misfolded proteins, forming circulating immune complexes. Such complexes could be used in the prognosis of digestive pathologies of clinical forms of Chagas disease.
Improved shear wave motion detection using coded excitation for transient elastography
Authors: He Xiao-Nian , Diao Xian-Fen , Lin Hao-Ming , Zhang Xin-Yu , Shen Yuan-Yuan , Chen Si-Ping , Qin Zheng-Di , Chen Xin
Published: March 2017

Transient elastography (TE) is well adapted for use in studying liver elasticity. However, because the shear wave motion signal is extracted from the ultrasound signal, the weak ultrasound signal can significantly deteriorate the shear wave motion tracking process and make it challenging to detect the shear wave motion in a severe noise environment, such as within deep tissues and within obese patients. This paper, therefore, investigated the feasibility of implementing coded excitation in TE for shear wave detection, with the hypothesis that coded ultrasound signals can provide robustness to weak ultrasound signals compared with traditional short pulse. The Barker 7, Barker 13, and short pulse were used for detecting the shear wave in the TE application. Two phantom experiments and one in vitro liver experiment were done to explore the performances of the coded excitation in TE measurement. The results show that both coded pulses outperform the short pulse by providing superior shear wave signal-to-noise ratios (SNR), robust shear wave speed measurement, and higher penetration intensity. In conclusion, this study proved the feasibility of applying coded excitation in shear wave detection for TE application. The proposed method has the potential to facilitate robust shear elasticity measurements of tissue.
Structural insights into the γ-lactamase activity and substrate enantioselectivity of an isochorismatase-like hydrolase from Microbacterium hydrocarbonoxydans
Authors: Gao Shuaihua , Zhou Yu , Zhang Weiwei , Wang Wenhe , Yu You , Mu Yajuan , Wang Hao , Gong Xinqi , Zheng Guojun , Feng Yue
Published: March 2017

(+)-γ-lactamase catalyzes the specific hydrolysis of (+)-γ-lactam out of the racemic γ-lactam (2-Azabicyclo[2.2.1]hept-5-en-3-one) to leave optically pure (−)-γ-lactam, which is the key building block of antiviral drugs such as carbovir and abacavir. However, no structural data has been reported on how the enzymes bind the γ-lactams and achieve their enantioselectivities. We previously identified an isochorismatase-like hydrolase (IHL, Mh33H4-5540) with (+)-γ-lactamase activity, which constitutes a novel family of γ-lactamase. Here, we first discovered that this enzyme actually hydrolyzed both (+)- and (−)-γ-lactam, but with apparently different specificities. We determined the crystal structures of the apo-form, (+)-γ-lactam bound, and (−)-γ-lactam bound forms of the enzyme. The structures showed that the binding sites of both (+) and (−)-γ-lactam resemble those of IHLs, but the “cover” loop conserved in IHLs is lacking in the enzyme, probably resulting in its incomplete enantioselectivity. Structural, biochemical, and molecular dynamics simulation studies demonstrated that the steric clash caused by the binding-site residues, especially the side-chain of Cys111 would reduce the binding affinity of (−)-γ-lactam and possibly the catalytic efficiency, which might explain the different catalytic specificities of the enantiomers of γ-lactam. Our results would facilitate the directed evolution and application of Mh33H4-5540 in antiviral drug synthesis.
Rational Design of Protein C Activators
Authors: Barranco-Medina Sergio , Murphy Mary , Pelc Leslie , Chen Zhiwei , Di Cera Enrico , Pozzi Nicola
Published: March 2017

In addition to its procoagulant and proinflammatory functions mediated by cleavage of fibrinogen and PAR1, the trypsin-like protease thrombin activates the anticoagulant protein C in a reaction that requires the cofactor thrombomodulin and the endothelial protein C receptor. Once in the circulation, activated protein C functions as an anticoagulant, anti-inflammatory and regenerative factor. Hence, availability of a protein C activator would afford a therapeutic for patients suffering from thrombotic disorders and a diagnostic tool for monitoring the level of protein C in plasma. Here, we present a fusion protein where thrombin and the EGF456 domain of thrombomodulin are connected through a peptide linker. The fusion protein recapitulates the functional and structural properties of the thrombin-thrombomodulin complex, prolongs the clotting time by generating pharmacological quantities of activated protein C and effectively diagnoses protein C deficiency in human plasma. Notably, these functions do not require exogenous thrombomodulin, unlike other anticoagulant thrombin derivatives engineered to date. These features make the fusion protein an innovative step toward the development of protein C activators of clinical and diagnostic relevance.
Mitigation Effect of Proanthocyanidin on Secondary Heart Injury in Rats Caused by Mechanical Trauma
Authors: Ma Shuo , Chen Chong , Cao Tingting , Bi Yue , Zhou Jicheng , Li Xintao , Yu Deqin , Li Shuzhuang
Published: March 2017

Multiple organ dysfunctional syndrome secondary to mechanical trauma (MT) has attracted considerable research attention. The heart is one of the most important organs of the body, and secondary cardiac insufficiency caused by MT seriously affects the quality of life. This study aims to investigate whether proanthocyanidin can alleviate myocardial injury and improve heart function in the process of MT leading to secondary cardiac insufficiency. Noble-Collip drum wasused to prepare MT model in rats. And myocardial apoptosis index was calculated after TUNEL staining. Ventricular intubation was employed to detect heart function. Changes in myocardial ultrastructure were observed using an electron microscope. ELISA was used to detect the content of TNF-α and reactive oxygen species generated from monocytes and cardiomyocytes. The changes in Ca2+ concentration in cardiomyocyte were observed by confocal microscope. Compared with trauma group, the administration group had a decreased apoptosis index of cardiomyocytes, and increased ±dp/dtmax. Meanwhile, proanthocyanidin can inhibit monocytes’ TNF-α production, and reduce plasma TNF-α concentration. Moreover, proanthocyanidin can attenuate the excessive oxidative stress reaction of cardiomyocyte, and inhibit calcium overload in cardiomyocytes. In conclusion, proanthocyanidin can effectively ease myocardial damage and improve cardiac function, through anti-inflammatory and antioxidant effects in secondary cardiac insufficiency caused by MT.
Microstructural changes are coincident with the improvement of clinical symptoms in surgically treated compressed nerve roots
Authors: Wu Weifei , Liang Jie , Chen Ying , Chen Aihua , Wu Yongde , Yang Zong
Published: March 2017

Diffusion tensor imaging (DTI) has been widely used to visualize peripheral nerves, but the microstructure of compressed nerve roots can be assessed using DTI. However, there are no data regarding the association among microstructural changes evaluated using DTI, the symptoms assessed using the Oswestry Disability Index (ODI) and the duration of symptoms after surgery in patients with lumbar disc herniation (LDH). Thirty patients with unilateral radiculopathy were investigated using DTI. The changes in the mean fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) values as well as the correlation between these changes and the severity and duration of the clinical symptoms were investigated before and at least one month after surgery. The FA values were significantly increased after surgical treatment (p < 0.0001). Both the ADC and ODI values were noticeably decreased (p < 0.0001). A strong positive correlation between the preoperative and postoperative DTI parameters (p < 0.0001) as well as between the preoperative ODI and postoperative ODI/ODI changes (p < 0.0001) were found. In addition, there was a significant positive correlation between the changes in the DTI parameters and changes in the ODI (p < 0.0001). This preliminary study suggests it may be possible to use DTI to diagnose, quantitatively evaluate and follow-up patients with LDH.
Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis
Authors: Zhou Shaoli , Zhu Qianqian , Li Xiang , Chen Chaojin , Liu Jiping , Ye Yuping , Ruan Ying , Hei Ziqing
Published: March 2017

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox’s proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20–1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19–1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16–1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13–1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker.
3D proteochemometrics: using three-dimensional information of proteins and ligands to address aspects of the selectivity of serine proteases
Authors: Subramanian Vigneshwari , Ain Qurrat Ul , Henno Helena , Pietilä Lars-Olof , Fuchs Julian E. , Prusis Peteris , Bender Andreas , Wohlfahrt Gerd
Published: March 2017

Field-based proteochemometric modelling predicts activities and visualizes features, which can support the design of more selective protease inhibitors.
Amiloride as a new RNA-binding scaffold with activity against HIV-1 TAR
Authors: Patwardhan Neeraj N. , Ganser Laura R. , Kapral Gary J. , Eubanks Christopher S. , Lee Janghyun , Sathyamoorthy Bharathwaj , Al-Hashimi Hashim M. , Hargrove Amanda E.
Published: March 2017

NMR-guided evolution of the pyrazine C(5)- and C(6)-positions of amiloride reveals a tunable scaffold for selective RNA interactions.
Complexes between cationic pyridylphenylene dendrimers and ovine prion protein: do hydrophobic interactions matter?
Authors: Sorokina S. , Semenyuk P. , Stroylova Yu. , Muronetz V. , Shifrina Z.
Published: March 2017

MD simulation predicted the possible binding sites for the dendrimer interactions with protein while ITC data revealed both electrostatic and hydrophobic driving forces for the complexation.
Graphene/cellulose nanocrystals hybrid aerogel with tunable mechanical strength and hydrophilicity fabricated by ambient pressure drying technique
Authors: Zhang Xiaofang , Liu Ping , Duan Yongxin , Jiang Min , Zhang Jianming
Published: March 2017

An amphiphilic graphene/cellulose nanocrystal hybrid aerogel with tunable mechanical strength was fabricated by a facile ambient pressure drying technique.
Real 3D microsphere lasers by femtosecond laser processing
Authors: Hou Zhi-Shan , Huang Qiu-Lan , Zhan Xue-Peng , Li Ai-Wu , Xu Huai-Liang
Published: March 2017

Real 3D microspheres are fabricated using femtosecond laser processing and might be applicable for use as single-mode microlasers with controlled resonance wavelengths.
Improved performance of Schiff based ionophore modified with MWCNT for Fe(ii) sensing by potentiometry and voltammetry supported with DFT studies
Authors: Kumar Sanjeev , Mittal Susheel K. , Kaur Navneet , Kaur Ravneet
Published: March 2017

A novel potentiometric and voltammetric sensor for creating a cationic response for Fe(ii) is introduced.
Feasibility study of simultaneous azo dye decolorization and bioelectricity generation by microbial fuel cell-coupled constructed wetland: substrate effects
Authors: Fang Zhou , Cheng Sichao , Wang Hui , Cao Xian , Li Xianning
Published: March 2017

Microbial fuel cells (MFCs) were embedded into constructed wetlands to form microbial fuel cell coupled constructed wetlands (CW-MFCs) and were used for simultaneous azo dye wastewater treatment and bioelectricity generation.
Protein-derived carbon nanodots with an ethylenediamine-modulated structure as sensitive fluorescent probes for Cu2+detection
Authors: Sai Liman , Chen Jun , Chang Quanhong , Shi Wangzhou , Chen Qi , Huang Lei
Published: March 2017

The increasing use of fluorescent carbon nanodots (CNDs) demonstrates their advantages for sensing applications; these include superior photostability, absence of toxicity, and rapid analytical capability.
Incorporating a silicon unit into a polyether backbone—an effective approach to enhance polyether solubility in CO2
Authors: Zhang Yongfei , Zhu Zewen , Bai Zhenguo , Jiang Wei , Liu Fengqi , Tang Jun
Published: March 2017

A series of poly(silyl ether)s were prepared by condensation polymerization and hydrosilation polymerization through incorporating a silicon unit into a polyether backbone.
Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes controlled by monophosphine ligands
Authors: Kondo Hiroki , Itami Kenichiro , Yamaguchi Junichiro
Published: March 2017

A Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes has been developed.
Denitrogenative Suzuki and carbonylative Suzuki coupling reactions of benzotriazoles with boronic acids
Authors: Wang Yuanhao , Wu Yunfei , Li Yuanhe , Tang Yefeng
Published: March 2017

Palladium-catalyzed denitrogenative Suzuki and carbonylative Suzuki reactions of benzotriazoles with boronic acids have been achieved through thein situgeneration ofortho-amino-arenediazonium species.
Tutte’s invariant approach for Brownian motion reflected in the quadrant
Authors: Franceschi S. , Raschel Kilian
Published: March 2017

We consider a Brownian motion with negative drift in the quarter plane with orthogonal reflection on the axes. The Laplace transform of its stationary distribution satisfies a functional equation, which is reminiscent from equations arising in the enumeration of (discrete) quadrant walks. We develop a Tutte’s invariant approach to this continuous setting, and we obtain an explicit formula for the Laplace transform in terms of generalized Chebyshev polynomials.
Copper Triflate Catalyzed Oxidative α-Allylation of Glycine Derivatives
Authors: Cai Chun , Chen Ting-Ting
Published: March 2017

Copper triflate catalyzed oxidative C–H functionalization of glycine derivatives with allyltributyltin has been established using oxygen or tert-butyl hydroperoxide as oxidant. Various glycine esters and glycine amides were suitable substrates for this oxidative allylation reaction and afforded the desired homoallylic amines in moderate to good yields.
Concise Total Syntheses of Paullone and Kenpaullone via Cyanide-Catalyzed Intramolecular Imino-Stetter Reaction
Authors: Cheon Cheol-Hong , Lee Sang , Lee Seong
Published: March 2017

Highly concise total syntheses of paullone and kenpaullone were developed. Cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines derived from methyl 2-aminocinnamate derivatives and 2-nitrobenzaldehyde provided 2-(2′-nitrophenyl)indole-3-acetic acid derivatives. Subsequent reduction of the nitro group with zinc under acidic conditions to an amino group followed by spontaneous lactam formation allowed for the total syntheses of paullone and kenpaullone to be completed in two steps starting from commercially available materials. The direct use of a nitro group as the precursor of an amino group present in the phenyl ring at the 2-position in the indole ring significantly streamlined the total syntheses of these target molecules.
Does the Access to Sun Exposure Ensure Adequate Levels of 25-Hydroxyvitamin D?
Authors: Paula Francisco José Albuquerque de , Franceschini Silvio Antônio , Vieira Carolina Sales , Ferriani Rui Alberto , Silva de Sá Marcos Felipe , Lara Lucia Alves da Silva , Damaso Ênio Luis
Published: March 2017

Objectives To assess the prevalence of hypovitaminosis D, altered arterial blood pressure, and serum levels of glucose and lipids in community-dwelling women in the city of Ribeirão Preto, in the southeast of Brazil.

Methods This was a cross-sectional study of women aged 40–70 years old. Calcium intake and level of sun exposure were assessed by means of a questionnaire. A blood sample was used to determine glucose, lipid profile and 25-hydroxyvitamin D (25[OH]D) concentration.

Results Ninety-one women were enrolled (age = 54.2 ± 7.1 years). The mean serum 25(OH)D concentration was 25.7 ± 8.9 ng/mL. A total of 24 (26.4%) women had 25(OH)D levels < 20 ng/mL. Seventy women (76.9%) had 25(OH)D levels < 30 ng/mL. Seventy-five women (90.4%) had inadequate calcium intake, and 61 women (67%) had appropriate sun exposure, 49 of whom (80.3%) had serum 25(OH)D levels < 30 ng/mL.

Conclusion This study indicates that even in community-dwelling women, living in a city with high sun exposure, serum levels of 25(OH)D > 30 ng/ml are hardly reached. Thus, it is probable that other intrinsic factors besides sun exposure may regulate the levels of vitamin D.