bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Blood in Reasoning’: State Violence, Contested Territories and Black Criminal Agency in Urban Brazil
Authors: ALVES JAIME AMPARO
Published: October 2015

This article examines black criminal agency in the context of drug trafficking and territorial control by the Primeiro Comando da Capital (First Capital Command, PCC), a self-identified criminal organisation in São Paulo's favelas. It argues that black youth's racialised encounters with the police shape their political praxis in the city. Since in the racial imaginary, they are constantly linked to crime and violence, and since their criminalised status justifies mass incarceration and death by the police, criminality appears as a valid category to better understand not only their fate but also their agency. Ethnographic fieldwork carried out in 2009 and 2010 in a hyper-impoverished, predominately black slum community, along with weekly visits to a local detention centre in São Paulo, informs the author's analysis of the PCC's controversial languages of resistance and the gendered and racialised outcomes that emerge from their attempts to fend off the state in such topographies of domination.
Behaviour of runaway electrons in the HL-2A plasmas with LHCD and ECCD
Authors: Zhu J. X. , Yao L. M. , Zhang Y. P. , Yang J. W. ,   HL-2A Team
Published: October 2015

The behaviour of runaway electrons have been investigated in lower hybrid current drive (LHCD) and electron cyclotron current drive (ECCD) plasmas as well as the LHCD only plasmas in the HL-2A tokamak. The fast electrons generated by lower hybrid waves (LHWs) and electron cyclotron waves (ECWs) can act as a seed population for runaway electrons. In the LHCD only discharges, a large number of runaway electrons are produced after the termination of lower hybrid (LH) power by conversion of fast electrons into runaway electrons due to the fast electron tail which extends above the runaway critical energy. However, in contrast to LHCD only discharges, during the simultaneous application of LHCD and ECCD discharges, runaway electrons cannot be created by the termination of LH power when the ECCD is on duty. The runaway production is observed to be enhanced until the EC power termination. The loop voltage increase due to the termination of EC power gives rise to a decline in the critical runaway energy, which leads to some of the energetic fast electrons converting into runaway electrons via the acceleration from the toroidal electric field. That is, the fast electrons created by waves can be accelerated into the runaway regime due to the Dreicer process.
Marine protection targets: an updated assessment of global progress
Authors: Boonzaier Lisa , Pauly Daniel
Published: October 2015

Despite the considerable expansion in the number and extent of marine protected areas during the past century, coverage remains limited amid concerns that many marine protected areas are failing to meet their objectives. New estimates of global marine protected area, based on the database maintained by Sea Around Us, revealed a degree of progress towards protecting at least 10% of the global ocean by 2020. It is estimated that > 6,000 marine protected areas, covering c. 3.27% (12 million km2) of the oceans, had been designated by the end of 2013. However, protection is generally weak, with c. one-sixth (1.9 million km2) of the combined area designated as no-take areas (i.e. fishing and other extractive activities are prohibited). Additional large tracts of ocean will need to be protected to reach the 10% target, and we investigate hypothetical scenarios for such expansion. Such scenarios offer a one-dimensional measure of progress as they do not address aspects of other global targets, such as Aichi Target 11, which will help to ensure that marine protected areas meet their objectives and achieve conservation outcomes.
Transcatheter closure of perimembranous ventricular septal defects with the Amplatzer Vascular Plug-II
Authors: Hua Nancy , Aquino Paolo , Owada Carl Y.
Published: October 2015

Objective

The aim of this study was to evaluate the safety and efficacy of the Amplatzer Vascular Plug-II used for the closure of perimembranous ventricular septal defects.

Background

There are no FDA-approved transcatheter devices for the closure of perimembranous ventricular septal defects. Several studies have reported on the use of various devices either off-label or under clinical trial protocols. However these reports have described significant adverse events including residual shunts, complete heart block, arrhythmia, and new valve regurgitations. Thus far, no study on the Amplatzer Vascular Plug-II has been reported.

Methods

We conducted a 4-year retrospective chart review from August, 2010 to August, 2014, of patients with perimembranous ventricular septal defects associated with ventricular septal aneurysm who underwent transcatheter closure using the Amplatzer Vascular Plug-II.

Results

A total of 16 patients underwent Amplatzer Vascular Plug-II transcatheter closure of their perimembranous ventricular septal defects. The median age was 2.56 years (range: 0.5–27.3). Their median weight was 13.0 kg (range: 6.9–71.6). The left ventricular median defect size was 9.3 mm (range: 5.9–14.4). The right ventricular median defect size was 3.6 mm (range: 2.3–5.8). All the patients underwent successful device implantation with 83% of the patients having complete echocardiographic closure at the 1-year follow-up; however, one procedure was complicated by early device embolisation. The device was successfully retrieved and replaced with a larger device. There were no device-related outflow tract obstructions, rhythm abnormalities, or haemolysis.

Conclusion

Application of the Amplatzer Vascular Plug-II for closure of perimembranous ventricular septal defects appears to be a safe and effective treatment option. Prospective clinical trials and longer follow-up periods are warranted.
The metaphoric dance: co-construction of metaphor in cognitive behaviour therapy
Authors: Mathieson Fiona , Jordan Jennifer , Carter Janet D. , Stubbe Maria
Published: October 2015

Attention to client metaphors has been asserted as a way of enhancing cognitive behaviour therapy. Metaphors can be part of the shared language that is co-constructed between clients and therapists. Recent advances in cognitive linguistics have provided the most clearly operationalized method yet to identify metaphors in conversations, allowing analysis of how shared language develops. This study aims to explore how metaphoric shared language develops in early cognitive behaviour therapy sessions. Based on 12 transcripts of early cognitive behaviour therapy sessions, an iterative process led to the identification of a range of therapist and client responses to each other's metaphors, and identification of whether therapists or clients initiated metaphoric exchanges. Types of responses to therapist or client metaphors within three speaking turns were found to be: repetition, rephrasing, exploration, elaboration/extension, or agreement. Bursts of metaphoric exchange were initiated and taken up by therapists and clients at a similar rate. To conclude, therapists need to attend to the occurrence of metaphors and be aware of the range of potential responses that can engage the client in the ‘metaphoric dance’ (co-construction of shared metaphors). This has the potential to enhance engagement and outcomes though more salient reformulating of the problem for the client.
Interpretative theories as roadmaps to constitutional identity: The case of the United States
Authors: BASSOK OR
Published: October 2015

As long as the American Constitution serves as the focal point of American identity, many constitutional interpretative theories also serve as roadmaps to various visions of American constitutional identity. Using the debate over the constitutionality of the Patient Protection and Affordable Care Act, I expose the identity dimension of various interpretative theories and analyse the differences between the roadmaps offered by them. I argue that according to each of these roadmaps, courts’ authority to review legislation is required in order to protect a certain vision of American constitutional identity even at the price of thwarting Americans’ freedom to pursue their current desires. The conventional framing of interpretative theories as merely techniques to decipher the constitutional text or justifications for the Supreme Court’s countermajoritarian authority to review legislation and the disregard of their identity function is perplexing in view of the centrality of the Constitution to American national identity. I argue that this conventional framing is a result of the current understanding of American constitutional identity in terms of neutrality toward the question of the good. This reading of the Constitution as lacking any form of ideology at its core makes majority preferences the best take of current American identity, leaving constitutional theorists with the mission to justify the Court’s authority to diverge from majority preferences.
Epigenome-Wide Association Study of Tic Disorders
Authors: Zilhão Nuno R. , Padmanabhuni Shanmukha S. , Pagliaroli Luca , Barta Csaba ,   BIOS Consortium, Smit Dirk J. A. , Cath Danielle , Nivard Michel G. , Baselmans Bart M. L. , van Dongen Jenny , Paschou Peristera , Boomsma Dorret I.
Published: October 2015

Tic disorders are moderately heritable common psychiatric disorders that can be highly troubling, both in childhood and in adulthood. In this study, we report results obtained in the first epigenome-wide association study (EWAS) of tic disorders. The subjects are participants in surveys at the Netherlands Twin Register (NTR) and the NTR biobank project. Tic disorders were measured with a self-report version of the Yale Global Tic Severity Scale Abbreviated version (YGTSS-ABBR), included in the 8th wave NTR data collection (2008). DNA methylation data consisted of 411,169 autosomal methylation sites assessed by the Illumina Infinium HumanMethylation450 BeadChip Kit (HM450k array). Phenotype and DNA methylation data were available in 1,678 subjects (mean age = 41.5). No probes reached genome-wide significance (p < 1.2 × 10−7). The strongest associated probe was cg15583738, located in an intergenic region on chromosome 8 (p = 1.98 × 10−6). Several of the top ranking probes (p < 1 × 10−4) were in or nearby genes previously associated with neurological disorders (e.g., GABBRI, BLM, and ADAM10), warranting their further investigation in relation to tic disorders. The top significantly enriched gene ontology (GO) terms among higher ranking methylation sites included anatomical structure morphogenesis (GO:0009653, p = 4.6 × 10−15) developmental process (GO:0032502, p = 2.96 × 10−12), and cellular developmental process (GO:0048869, p = 1.96 × 10−12). Overall, these results provide a first insight into the epigenetic mechanisms of tic disorders. This first study assesses the role of DNA methylation in tic disorders, and it lays the foundations for future work aiming to unravel the biological mechanisms underlying the architecture of this disorder.
Carolyn S. Schroeder Award for Outstanding Clinical Practice: Program Development, Practice Integration, and Early Career Development
Authors: Guilfoyle Shanna M.
Published: October 2015

Clinical program development, practice integration, and early career planning are often key activities for pediatric psychologists entering academia as clinical faculty. As the 2015 recipient of the Division 54 Carolyn S. Schroeder Award for Clinical Practice, I discuss my early career experiences developing an innovative, interdisciplinary epilepsy psychosocial service. I consider shared vision, team feedback, development of a clinical research database, and close professional relationships through collaborations and effective mentorship critical factors to successful program development and academic planning. I discuss barriers encountered, solutions identified for successful practice implementation and integration, and ideas for reaching both professional academic, personal goals and provide recommendations.
Multiradionuclide evidence for the solar origin of the cosmic-ray events of AD 774/5 and 993/4
Authors: Mekhaldi Florian , Muscheler Raimund , Adolphi Florian , Aldahan Ala , Beer Jürg , McConnell Joseph R. , Possnert Göran , Sigl Michael , Svensson Anders , Synal Hans-Arno , Welten Kees C. , Woodruff Thomas E.
Published: October 2015

The origin of two large peaks in the atmospheric radiocarbon (14C) concentration at AD 774/5 and 993/4 is still debated. There is consensus, however, that these features can only be explained by an increase in the atmospheric 14C production rate due to an extraterrestrial event. Here we provide evidence that these peaks were most likely produced by extreme solar events, based on several new annually resolved 10Be measurements from both Arctic and Antarctic ice cores. Using ice core 36Cl data in pair with 10Be, we further show that these solar events were characterized by a very hard energy spectrum with high fluxes of solar protons with energy above 100 MeV. These results imply that the larger of the two events (AD 774/5) was at least five times stronger than any instrumentally recorded solar event. Our findings highlight the importance of studying the possibility of severe solar energetic particle events.
Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity
Authors: Agarwal Shivani , Kim Hyunjin , Chan Robin B. , Agarwal Shivangi , Williamson Rebecca , Cho Wonhwa , Di Paolo Gilbert , Satchell Karla J. F.
Published: October 2015

Vibrio cholerae, responsible for acute gastroenteritis secretes a large multifunctional-autoprocessing repeat-in-toxin (MARTX) toxin linked to evasion of host immune system, facilitating colonization of small intestine. Unlike other effector domains of the multifunctional toxin that target cytoskeleton, the function of alpha-beta hydrolase (ABH) remained elusive. This study demonstrates that ABH is an esterase/lipase with catalytic Ser–His–Asp triad. ABH binds with high affinity to phosphatidylinositol-3-phosphate (PtdIns3P) and cleaves the fatty acid in PtdIns3P at thesn1positionin vitromaking it the first PtdIns3P-specific phospholipase A1 (PLA1). Expression of ABHin vivoreduces intracellular PtdIns3P levels and its PtdIns3P-specific PLA1 activity blocks endosomal and autophagic pathways. In accordance with recent studies acknowledging the potential of extracellular pathogens to evade or exploit autophagy to prevent their clearance and facilitate survival, this is the first report highlighting the role of ABH in inhibiting autophagy and endosomal trafficking induced by extracellularV. cholerae.
Engineering the quantum-classical interface of solid-state qubits
Authors: Reilly David J
Published: October 2015

Spanning a range of hardware platforms, the building-blocks of quantum processors are today sufficiently advanced to begin work on scaling-up these systems into complex quantum machines. A key subsystem of all quantum machinery is the interface between the isolated qubits that encode quantum information and the classical control and readout technology needed to operate them. As few-qubit devices are combined to construct larger, fault-tolerant quantum systems in the near future, the quantum-classical interface will pose new challenges that increasingly require approaches from the engineering disciplines in combination with continued fundamental advances in physics, materials and mathematics. This review describes the subsystems comprising the quantum-classical interface from the viewpoint of an engineer, experimental physicist or student wanting to enter the field of solid-state quantum information technology. The fundamental signalling operations of readout and control are reviewed for a variety of qubit platforms, including spin systems, superconducting implementations and future devices based on topological degrees-of-freedom. New engineering opportunities for technology development at the boundary between qubits and their control hardware are identified, transversing electronics to cryogenics.
High-fidelity resonant gating of a silicon-based quantum dot hybrid qubit
Authors: Kim Dohun , Ward Daniel R , Simmons Christie B , Savage Don E , Lagally Max G , Friesen Mark , Coppersmith Susan N , Eriksson Mark A
Published: October 2015

We implement resonant single qubit operations on a semiconductor hybrid qubit hosted in a three-electron Si/SiGe double quantum dot structure. By resonantly modulating the double dot energy detuning and employing electron tunnelling-based readout, we achieve fast (>100 MHz) Rabi oscillations and purely electrical manipulations of the three-electron spin states. We demonstrate universal single qubit gates using a Ramsey pulse sequence as well as microwave phase control, the latter of which shows control of an arbitrary rotation axis on the X–Y plane of the Bloch sphere. Quantum process tomography yields π rotation gate fidelities higher than 93 (96)% around the X (Z) axis of the Bloch sphere. We further show that the implementation of dynamic decoupling sequences on the hybrid qubit enables coherence times longer than 150 ns.
A multi-source dataset of urban life in the city of Milan and the Province of Trentino
Authors: Barlacchi Gianni , De Nadai Marco , Larcher Roberto , Casella Antonio , Chitic Cristiana , Torrisi Giovanni , Antonelli Fabrizio , Vespignani Alessandro , Pentland Alex , Lepri Bruno
Published: October 2015

The study of socio-technical systems has been revolutionized by the unprecedented amount of digital records that are constantly being produced by human activities such as accessing Internet services, using mobile devices, and consuming energy and knowledge. In this paper, we describe the richest open multi-source dataset ever released on two geographical areas. The dataset is composed of telecommunications, weather, news, social networks and electricity data from the city of Milan and the Province of Trentino. The unique multi-source composition of the dataset makes it an ideal testbed for methodologies and approaches aimed at tackling a wide range of problems including energy consumption, mobility planning, tourist and migrant flows, urban structures and interactions, event detection, urban well-being and many others.
A connectivity-based test-retest dataset of multi-modal magnetic resonance imaging in young healthy adults
Authors: Lin Qixiang , Dai Zhengjia , Xia Mingrui , Han Zaizhu , Huang Ruiwang , Gong Gaolang , Liu Chao , Bi Yanchao , He Yong
Published: October 2015

Recently, magnetic resonance imaging (MRI) has been widely used to investigate the structures and functions of the human brain in health and disease in vivo. However, there are growing concerns about the test-retest reliability of structural and functional measurements derived from MRI data. Here, we present a test-retest dataset of multi-modal MRI including structural MRI (S-MRI), diffusion MRI (D-MRI) and resting-state functional MRI (R-fMRI). Fifty-seven healthy young adults (age range: 19–30 years) were recruited and completed two multi-modal MRI scan sessions at an interval of approximately 6 weeks. Each scan session included R-fMRI, S-MRI and D-MRI data. Additionally, there were two separated R-fMRI scans at the beginning and at the end of the first session (approximately 20 min apart). This multi-modal MRI dataset not only provides excellent opportunities to investigate the short- and long-term test-retest reliability of the brain’s structural and functional measurements at the regional, connectional and network levels, but also allows probing the test-retest reliability of structural-functional couplings in the human brain.
Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo
Authors: Huang Tsung-Teng , Lai Hsin-Chih , Ko Yun-Fei , Ojcius David M. , Lan Ying-Wei , Martel Jan , Young John D. , Chong Kowit-Yu
Published: October 2015

Hirsutella sinensismycelium (HSM), the anamorph ofCordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.
The inverted free energy landscape of an intrinsically disordered peptide by simulations and experiments
Authors: Granata Daniele , Baftizadeh Fahimeh , Habchi Johnny , Galvagnion Celine , De Simone Alfonso , Camilloni Carlo , Laio Alessandro , Vendruscolo Michele
Published: October 2015

The free energy landscape theory has been very successful in rationalizing the folding behaviour of globular proteins, as this representation provides intuitive information on the number of states involved in the folding process, their populations and pathways of interconversion. We extend here this formalism to the case of the Aβ40 peptide, a 40-residue intrinsically disordered protein fragment associated with Alzheimer’s disease. By using an advanced sampling technique that enables free energy calculations to reach convergence also in the case of highly disordered states of proteins, we provide a precise structural characterization of the free energy landscape of this peptide. We find that such landscape has inverted features with respect to those typical of folded proteins. While the global free energy minimum consists of highly disordered structures, higher free energy regions correspond to a large variety of transiently structured conformations with secondary structure elements arranged in several different manners and are not separated from each other by sizeable free energy barriers. From this peculiar structure of the free energy landscape we predict that this peptide should become more structured and not only more compact, with increasing temperatures and we show that this is the case through a series of biophysical measurements.
Grain Boundary Plane Orientation Fundamental Zones and Structure-Property Relationships
Authors: Homer Eric R. , Patala Srikanth , Priedeman Jonathan L.
Published: October 2015

Grain boundary plane orientation is a profoundly important determinant of character in polycrystalline materials that is not well understood. This work demonstrates how boundary plane orientation fundamental zones, which capture the natural crystallographic symmetries of a grain boundary, can be used to establish structure-property relationships. Using the fundamental zone representation, trends in computed energy, excess volume at the grain boundary and temperature-dependent mobility naturally emerge and show a strong dependence on the boundary plane orientation. Analysis of common misorientation axes even suggests broader trends of grain boundary energy as a function of misorientation angle and plane orientation. Due to the strong structure-property relationships that naturally emerge from this work, boundary plane fundamental zones are expected to simplify analysis of both computational and experimental data. This standardized representation has the potential to significantly accelerate research in the topologically complex and vast five-dimensional phase space of grain boundaries.
Screening and Identifying a Novel ssDNA Aptamer against Alpha-fetoprotein Using CE-SELEX
Authors: Dong Lili , Tan Qiwen , Ye Wei , Liu Dongli , Chen Haifeng , Hu Hongwei , Wen Duo , Liu Yang , Cao Ya , Kang Jingwu , Fan Jia , Guo Wei , Wu Weizhong
Published: October 2015

Alpha-fetoprotein (AFP) is a liver cancer associated protein and has long been utilized as a serum tumor biomarker of disease progression. AFP is usually detected in HCC patients by an antibody based system. Recently, however, aptamers generated from systematic evolution of ligands by exponential enrichment (SELEX) were reported to have an alternative potential in targeted imaging, diagnosis and therapy. In this study, AFP-bound ssDNA aptamers were screened and identified using capillary electrophoresis (CE) SELEX technology. After cloning, sequencing and motif analysis, we successfully confirmed an aptamer, named AP273, specifically targeting AFP. The aptamer could be used as a probe in AFP immunofluorescence imaging in HepG2, one AFP positive cancer cell line, but not in A549, an AFP negative cancer cell line. More interesting, the aptamer efficiently inhibited the migration and invasion of HCC cells after in vivo transfection. Motif analysis revealed that AP273 had several stable secondary motifs in its structure. Our results indicate that CE-SELEX technology is an efficient method to screen specific protein-bound ssDNA and AP273 could be used as an agent in AFP-based staining, diagnosis and therapy, although more works are still needed.
Trypsin- and low pH-mediated fusogenicity of avian metapneumovirus fusion proteins is determined by residues at positions 100, 101 and 294
Authors: Yun Bingling , Guan Xiaolu , Liu Yongzhen , Gao Yanni , Wang Yongqiang , Qi Xiaole , Cui Hongyu , Liu Changjun , Zhang Yanping , Gao Li , Li Kai , Gao Honglei , Gao Yulong , Wang Xiaomei
Published: October 2015

Avian metapneumovirus (aMPV) and human metapneumovirus (hMPV) are members of the genus Metapneumovirus in the subfamily Pneumovirinae. Metapneumovirus fusion (F) protein mediates the fusion of host cells with the virus membrane for infection. Trypsin- and/or low pH-induced membrane fusion is a strain-dependent phenomenon for hMPV. Here, we demonstrated that three subtypes of aMPV (aMPV/A, aMPV/B and aMPV/C) F proteins promoted cell-cell fusion in the absence of trypsin. Indeed, in the presence of trypsin, only aMPV/C F protein fusogenicity was enhanced. Mutagenesis of the amino acids at position 100 and/or 101, located at a putative cleavage region in aMPV F proteins, revealed that the trypsin-mediated fusogenicity of aMPV F proteins is regulated by the residues at positions 100 and 101. Moreover, we demonstrated that aMPV/A and aMPV/B F proteins mediated cell-cell fusion independent of low pH, whereas the aMPV/C F protein did not. Mutagenesis of the residue at position 294 in the aMPV/A, aMPV/B and aMPV/C F proteins showed that 294G played a critical role in F protein-mediated fusion under low pH conditions. These findings on aMPV F protein-induced cell-cell fusion provide new insights into the molecular mechanisms underlying membrane fusion and pathogenesis of aMPV.
Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO
Authors: Hwang Do Won , Choi Hongyoon , Jang Su Chul , Yoo Min Young , Park Ji Yong , Choi Na Eun , Oh Hyun Jeong , Ha Seunggyun , Lee Yun-Sang , Jeong Jae Min , Gho Yong Song , Lee Dong Soo
Published: October 2015

Exosomes known as nano-sized extracellular vesicles attracted recent interests due to their potential usefulness in drug delivery. Amid remarkable advances in biomedical applications of exosomes, it is crucial to understand in vivo distribution and behavior of exosomes. Here, we developed a simple method for radiolabeling of macrophage-derived exosome-mimetic nanovesicles (ENVs) with 99mTc-HMPAO under physiologic conditions and monitored in vivo distribution of 99mTc-HMPAO-ENVs using SPECT/CT in living mice. ENVs were produced from the mouse RAW264.7 macrophage cell line and labeled with 99mTc-HMPAO for 1 hr incubation, followed by removal of free 99mTc-HMPAO. SPECT/CT images were serially acquired after intravenous injection to BALB/c mouse. When ENVs were labeled with 99mTc-HMPAO, the radiochemical purity of 99mTc-HMPAO-ENVs was higher than 90% and the expression of exosome specific protein (CD63) did not change in 99mTc-HMPAO-ENVs. 99mTc-HMPAO-ENVs showed high serum stability (90%) which was similar to that in phosphate buffered saline until 5 hr. SPECT/CT images of the mice injected with 99mTc-HMPAO-ENVs exhibited higher uptake in liver and no uptake in brain, whereas mice injected with 99mTc-HMPAO showed high brain uptake until 5 hr. Our noninvasive imaging of radiolabeled-ENVs promises better understanding of the in vivo behavior of exosomes for upcoming biomedical application.
Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles
Authors: Partridge S. C. , Kurland B. F. , Liu C.-L. , Ho R. J. Y. , Ruddell A.
Published: October 2015

Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.
The roles of lithium-philic giant nitrogen-doped graphene in protecting micron-sized silicon anode from fading
Authors: Liu Xiaoxu , Chao Dongliang , Zhang Qiang , Liu Hai , Hu Hailong , Zhao Jiupeng , Li Yao , Huang Yizhong , Lin Jianyi , Shen Ze Xiang
Published: October 2015

A stable Si-based anode with a high initial coulombic efficiency (ICE) for lithium-ion batteries (LIB) is critical for energy storage. In the present paper, a new scalable method is adopted in combination with giant nitrogen-doped graphene and micron-size electrode materials. We first synthesize a new type of freestanding LIB anode composed of micron-sized Si (mSi) particles wrapped by giant nitrogen-doped graphene (mSi@GNG) film. High ICE (>85%) and long cycle life (more than 80 cycles) are obtained. In the mSi@GNG composite, preferential formation of a stable solid electrolyte interphase (SEI) on the surface of graphene sheets is achieved. The formation and components of SEI are identified for the first time by using UV-resonance Raman spectroscopy and Raman mapping, which will revive the study of formation and evolution of SEI by Raman. New mechanism is proposed that the giant graphene sheets protect the mSi particles from over-lithiation and fracture. Such a simple and scalable method may also be applied to other anode systems to boost their energy and power densities for LIB.
Intraspecific diversity among partners drives functional variation in coral symbioses
Authors: Parkinson John Everett , Banaszak Anastazia T. , Altman Naomi S. , LaJeunesse Todd C. , Baums Iliana B.
Published: October 2015

The capacity of coral-dinoflagellate mutualisms to adapt to a changing climate relies in part on standing variation in host and symbiont populations, but rarely have the interactions between symbiotic partners been considered at the level of individuals. Here, we tested the importance of inter-individual variation with respect to the physiology of coral holobionts. We identified six genetically distinct Acropora palmata coral colonies that all shared the same isoclonal Symbiodinium ‘fitti’ dinoflagellate strain. No other Symbiodinium could be detected in host tissues. We exposed fragments of each colony to extreme cold and found that the stress-induced change in symbiont photochemical efficiency varied up to 3.6-fold depending on host genetic background. The S. ‘fitti’ strain was least stressed when associating with hosts that significantly altered the expression of 184 genes under cold shock; it was most stressed in hosts that only adjusted 14 genes. Key expression differences among hosts were related to redox signaling and iron availability pathways. Fine-scale interactions among unique host colonies and symbiont strains provide an underappreciated source of raw material for natural selection in coral symbioses.
Clinical significance of Anoctamin-1 gene at 11q13 in the development and progression of head and neck squamous cell carcinomas
Authors: Rodrigo Juan P. , Menéndez Sofía Tirados , Hermida-Prado Francisco , Álvarez-Teijeiro Saúl , Villaronga M. Ángeles , Alonso-Durán Laura , Vallina Aitana , Martínez-Camblor Pablo , Astudillo Aurora , Suárez Carlos , María García-Pedrero Juana
Published: October 2015

This study investigates the clinical significance of Anoctamin-1 gene mapping at 11q13 amplicon in both the development and progression of head and neck squamous cell carcinomas (HNSCC). ANO1 protein expression was evaluated by immunohistochemistry in a cohort of 372 surgically treated HNSCC patients and also in 35 laryngeal precancerous lesions. ANO1 gene amplification was determined by real-time PCR in all the laryngeal premalignancies and 60 of the HNSCCs and molecular data correlated with clinical outcome. ANO1 gene amplification was frequently detected in both premalignant lesions (63%) and HNSCC tumours (58%), whereas concomitant ANO1 expression occurred at a much lower frequency (20 and 22%). Interestingly, laryngeal dysplasias harbouring ANO1 gene amplification showed a higher risk of malignant transformation (HR = 3.62; 95% CI 0.79–16.57; P = 0.097; Cox regression). ANO1 expression and gene amplification showed no significant associations with clinicopathological parameters in HNSCC. However, remarkably ANO1 expression differentially influenced patient survival depending on the tumour site. Collectively, this study provides original evidence demonstrating the distinctive impact of ANO1 expression on HNSCC prognosis depending on the tumour site.
Rational regional distribution of sugarcane cultivars in China
Authors: Luo Jun , Pan Yong-Bao , Xu Liping , Grisham Michael Paul , Zhang Hua , Que Youxiong
Published: October 2015

Knowing yield potential and yield stability of sugarcane cultivars is of significance in guiding sugarcane breeding and rationalising regional distribution of sugarcane cultivars. In the present study, a heritability-adjusted genotype main effect plus genotype × environment (HA-GGE) biplot program was used to analyze the cane and sucrose yields of 44 newly released sugarcane cultivars at eight pilot test sites. The cane and sucrose yields of nine cultivars were higher than those of the control cultivar ROC22. From the perspective of cane yield, cultivars FN 40 and YZ 06–407 were well adapted to a wider range of conditions and produced relatively high cane yields in several pilot sites. From the perspective of sucrose yield, cultivars LC 03–1137, FN 38, FN 41, MT 01–77 and LC 05–136 were well adapted to a wide range of conditions and produced relatively high sucrose yields. Based on these results, three high yielding and widely adapted cultivars, namely, FN 39, LC 05–136 and YZ 05–51 were recommended for production in three major Chinese sugarcane planting areas. The results will provide a theoretical basis for recommending the effective use and rational regional distribution of sugarcane cultivars in China.
Trans-presentation of IL-15 modulates STAT5 activation and Bcl-6 expression in TH1 cells
Authors: Cooley Ian D. , Read Kaitlin A. , Oestreich Kenneth J.
Published: October 2015

During infection, naïve CD4+ T helper cells differentiate into specialized effector subsets based upon environmental signals propagated by the cytokine milieu. Recently, this paradigm has been complicated by the demonstration that alterations in the cytokine environment can result in varying degrees of plasticity between effector T helper cell populations. Therefore, elucidation of the mechanisms by which cytokines regulate T helper cell differentiation decisions is increasingly important. The gamma common cytokine IL-15 is currently undergoing clinical trials for the treatment of malignancies, due to its well-established role in the regulation of natural killer and CD8+ T cell immune responses. However, the effect of IL-15 signaling on CD4+ T cell activity is incompletely understood. One mechanism by which IL-15 activity is conferred is through trans-presentation via the IL-15 receptor alpha subunit. Here, we demonstrate that differentiated TH1 cells are responsive to trans-presented IL-15. Importantly, while trans-presentation of IL-15 results in STAT5 activation and maintenance of the TH1 gene program, IL-15 treatment alone allows for increased Bcl-6 expression and the upregulation of a TFH-like profile. Collectively, these findings describe a novel role for IL-15 in the modulation of CD4+ T cell responses and provide valuable insight for the use of IL-15 in immunotherapeutic approaches.
First Principles Study on the Electronic Structure and Interface Stability of Hybrid Silicene/Fluorosilicene Nanoribbons
Authors: Jiang Q. G. , Zhang J. F. , Ao Z. M. , Wu Y. P.
Published: October 2015

The interface stability of hybrid silicene/fluorosilicene nanoribbons (SFNRs) has been investigated by using density functional theory calculations, where fluorosilicene is the fully fluorinated silicene. It is found that the diffusion of F atoms at the zigzag and armchair interfaces of SFNRs is endothermic and the corresponding minimum energy barriers are respectively 1.66 and 1.56 eV, which are remarkably higher than the minimum diffusion energy barrier of one F atom and two F atoms on pristine silicene 1.00 and 1.29 eV, respectively. Therefore, the thermal stability of SFNRs can be significantly enhanced by increasing the F diffusion barriers through silicene/fluorosilicene interface engineering. In addition, the electronic and magnetic properties of SFNRs are also investigated. It is found that the armchair SFNRs are nonmagnetic semiconductors and the band gap of armchair SFNRs presents oscillatory behavior when the width of silicene part changing. For the zigzag SFNRs, the antiferromagnetic semiconducting state is the most stable one. This work provides fundamental insights for the applications of SFNRs in electronic devices.
Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome
Authors: Åqvist Johan , Kamerlin Shina C.L.
Published: October 2015

Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (TΔS‡) amounts to more than 7 kcal/mol at 25 °C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s−1. This entropy driven mechanism likely reflects the very high selection pressure on the speed of protein synthesis, which drives the rate of each individual GTPase towards maximal turnover rate of the whole translation cycle.
Self-processing of Peroxidases
Authors: Ortiz de Montellano Paul R.
Published: October 2015

The catalytic species of heme peroxidases is powerful enough to oxidize amino acids such as tyrosine and tryptophan. In some peroxidases, this oxidative ability is utilized to autocatalytically modify protein residues and/or the heme group to tailor the protein for its specific biological function. The transformations that are observed include modification of individual amino acids, crosslinking of amino acids, modification of the heme group, and crosslinking of the protein to the prosthetic heme group. These autocatalytic modifications are found in peroxidases that range from bacteria through humans.
Cytochrome c Peroxidase–Cytochrome c Complexes
Authors: Poulos Thomas L.
Published: October 2015

The yeast cytochrome c peroxidase (CCP)–cytochrome c (cytc) electron transfer system has been critically important in deciphering the molecular level details of protein–protein interactions and electron transfer. The crystal structure of the CCP–cytc together with a number mutagenesis, enzymological, and spectroscopic studies have provided a detailed picture on the overall mechanism and has led to a deeper understanding of how oxidizing equivalents are stored and stabilized in metalloproteins. More recently, a second CCP-like enzyme, Leishmania major peroxidase (LmP), has been characterized. The LmP–cytc structure is very similar to the yeast CCP–cytc structure with respect to the active docking surface although the LmP–cytc complex is dominated by electrostatic interactions while the yeast system relies more heavily on nonpolar interactions. In addition, the LmP system exhibits simpler enzyme kinetics and more straightforward ionic strength dependence, which offers some advantages in correlating kinetic studies with mutagenesis and other biophysical approaches.
Understanding the Reactivity and Interactions of Peroxidases with Substrates
Authors: Kwon Hanna , Moody Peter C. E. , Raven Emma L.
Published: October 2015

The heme peroxidase enzymes catalyze the H2O2-dependent oxidation of a wide variety of substrates. In most cases the substrate is a small organic molecule, but there are famous exceptions, most notably in cytochrome c peroxidase and manganese peroxidase. For many years the location of the substrate binding interactions were not known, but more recent structural information for a number of peroxidases with a wide range of different substrates has meant that a more detailed picture of substrate binding to peroxidases is now available. This chapter examines the nature of these substrate binding interactions across the family of peroxidases, gathering evidence from published structures of peroxidase–substrate complexes. Most substrates are found to bind close to the heme, at a single location either at the δ- or the γ-heme edge. But binding of substrate at multiple locations is also possible, and often at long distances from the heme; it has not yet been fully clarified which of these multiple binding sites are physiogically relevant.
Heme Peroxidase Kinetics
Authors: Dunford H. Brian
Published: October 2015

One of the longest and most intensively studied enzymes is horseradish peroxidase. Its reactions are reviewed from historical, kinetic and mechanistic perspectives. Kinetics studies include steady state, transient state and relaxation kinetics. The methods and reasoning involved are applicable to other peroxidases and indeed to other enzymes. Accumulated evidence from several techniques indicate that distal His 42 plays a key role in its redox reactions. The possible implications of recent low temperature neutron diffraction experiments on oxidized yeast cytochrome c peroxidase are discussed.
Multiheme Peroxidases
Authors: Brausemann Anton , Seidel Julian , Wüst Anja , Einsle Oliver
Published: October 2015

Bacterial diheme peroxidases (bCCP) act in the detoxification of reactive oxygen species by reduction of peroxide to water. The substrate H2O2 is bound to the free axial position of a heme cofactor, and in a first step, one H2O molecule is released, while the remaining oxygen is stabilized as a metastable FeivO intermediate that awaits further reduction. Unlike other peroxidases, however, bCCPs employ two heme cofactors, each of which can provide one electron to form the oxoferryl species, so that the formation of a porphyrin radical cation as in the ‘Compound I’ of other peroxidases is not required. This functionality requires precise coordination of electron transfer and substrate binding, and indeed the bCCP family of enzymes in most cases undergo a complex set of redox-dependent structural changes to ensure that the active site heme group only becomes accessible for a substrate after the second heme group is reduced and able to provide an electron to the reaction. Within the family, unsurprisingly, exceptions to this general rule are found and, moreover, the basic structural core of bCCPs has been evolutionarily modified and adapted in several other enzymes to fulfill entirely different functional roles.
Mechanistic Aspects of Catalase-peroxidase
Authors: Gasselhuber Bernhard , Jakopitsch Christa , Zámocký Marcel , Furtmüller Paul G. , Obinger Christian
Published: October 2015

Catalase-peroxidases (KatGs) belong to the peroxidase-catalase superfamily and are found in bacteria, archaea, and lower eukaryotes including fungi. Despite having sequence and structural homology with monofunctional peroxidases, KatGs are the only bifunctional peroxidases with a dominating hydrogen peroxide dismutating activity which rivals that of typical catalases. Albeit both heme-containing catalases and KatGs catalyse the same reaction (2H2O2→2H2O+O2), the mechanism is clearly different. In KatG the activity is based on two redox cofactors, the iron-containing heme b and in close proximity the unique posttranslationally and endogenously generated Trp-Tyr-Met adduct. This strictly conserved adduct is essential for the pseudocatalytic activity of KatGs without influencing the peroxidase activity. The key element in the proposed reaction mechanism is the formation of an adduct radical during turnover. This review accounts for the available literature for this mechanism and additionally discusses the role of the peroxidase activity with a focus on the activation of the antitubercular pro-drug isoniazid by KatG.