bluuebunny/crossref_metadata_2025 huggingface dataset:
Präimplantationsdiagnostik in den Niederlanden
Authors: Geraedts Joep , Coonen Edith , Dreesen Jos , Paulussen Aimee , Die-Smulders Christine de
Published: November 2016

Im Jahr 1995 wurde die Präimplantationsdiagnostik (PID) auf experimenteller Ebene in Maastricht eingeführt. Seit 2003 ist sie Bestandteil des Erstattungssystems des niederländischen Ministry Public Health, Welfare and Sport.

PID wird nur Paaren ermöglicht, die mit einem Risiko für eine schwerwiegende monogene Erkrankung, strukturellen Chromosomenanomalien oder mitochondrialen Erkrankungen bei ihren Nachkommen rechnen müssen. Ein Aneuploidiescreening zur Verbesserung der Erfolgsraten und assistierte Reproduktionstechnologien wie In-vitro-Fertilisation (IVF) oder Intrazytoplasmatische Spermieninjektion (ICSI) waren nie Gegenstand des PID-Programms.

2008 beschloss die niederländische Regierung, eine „National Indications Commission“ einzurichten, die bei neuen Krankheitsentitäten prüfen soll, ob die Kriterien für die Zulassung einer PID erfüllt sind: 1. die Schwere und Art der Erkrankung, 2. bestehende Möglichkeiten für Prävention und Behandlung, 3. zusätzliche medizinische Kriterien und 4. psychologische und ethische Faktoren.

Geschlechtsbestimmung (aus sozialen Gründen) ist auch in den Niederlanden, wie in den meisten europäischen Ländern, nicht erlaubt. Eine PID für die Diagnose sog. Rettungskinder ist nur dann erlaubt, wenn unabhängig hiervon eine Indikation für eine PID der genetischen Erkrankung besteht. HLA-Typisierung ohne Indikation für eine genetische Erkrankung ist hingegen nicht zulässig.

Das Maastricht University Medical Center (UMC) übernimmt die gesamte genetische Diagnostik und verfügt über die mit den Universitäten von Utrecht, Groningen und Amsterdam abgestimmten (University Medical Centre (UMC) Utrecht, University Medical Centre (UMC) Groningen and the Amsterdam Medical Centre (AMC)) SOPs für die PID-Transporte.

Zwischen 1995 und 2015 wurden insgesamt 2870 Zyklen bei 1430 Paaren durchgeführt. Der häufigste Grund für eine Überweisung zur PID war die Huntington-Krankheit, gefolgt von erblichem Brust- und Eierstockkrebs. Unter den weiteren Indikationen sind weit mehr autosomal-dominante genetisch bedingte Erkrankungen als autosomal-rezessive. Unter den zuletzt genannten stehen an erster Stelle Mukoviszidose und danach die spinale Muskelatrophie (SMA). Die Erfolgsrate liegt bei 20 % pro Zyklusbeginn und bei 25 % pro Embryonentransfer. Die Anzahl der Behandlungszyklen pro Paar liegt fast exakt bei 2,0.
Adult Complex Regional Pain Syndrome Type I: A Narrative Review
Authors: Bussa Martino , Mascaro Adriana , Cuffaro Lorena , Rinaldi Simona
Published: November 2016

Complex regional pain syndrome type I (CRPS I) is a multifactorial painful disorder with a complex pathogenesis. Both peripheral and central mechanisms are involved. Acute CRPS I is considered to be an exaggerated inflammatory disorder; however, over time, because of altered function of the sympathetic nervous system and maladaptive neuroplasticity, CRPS I evolves into a neurological disorder. This review thoroughly describes the pathophysiological aspects of CRPS I and summarizes the potential therapeutic options. The mechanisms and targets of the treatment are different in the early and late stages of the disease. This current review builds on a previous review by this author group by deepening the role of the peripheral classic and neuronal inflammatory component in the acute stage of this painful disorder.

Level of Evidence

Not applicable.
New Talaromyces species from indoor environments in China
Authors: Chen A.J. , Sun B.D. , Houbraken J. , Frisvad J.C. , Yilmaz N. , Zhou Y.G. , Samson R.A.
Published: November 2016

Talaromyces contains both asexual and sexually reproducing species. This genus is divided in seven sections and currently has 105 accepted species. In this study we investigated the Talaromyces isolates that were obtained during a study of indoor air collected in Beijing,
China. These indoor Talaromyces strains are resolved in four sections, seven of them are identified as T. islandicus, T. aurantiacus, T. siamensis and T. albobiverticillius according to BenA sequences, while 14 isolates have divergent
sequences and are described here as nine new species. The new species are placed in four sections, namely sections Helici, Islandici, Talaromyces and Trachyspermi. They are described based on sequence data (ITS, BenA, CaM and RPB2) in combination
with phenotypic and extrolite characters. Morphological descriptions and notes for distinguishing similar species are provided for each new species. The recently described T. rubrifaciens is synonymised with T. albobiverticillius based on presented phylogenetic results.
Chronicles of the Egyptian Revolution and its Aftermath: 2011–2016
Authors: Bassiouni M. Cherif
Published: November 2016

This book is about the Egyptian people's 2011 Revolution for freedom, justice, and human dignity, and its aftermath. The Revolution succeeded in toppling the authoritarian Mubarak regime in less than three weeks. It was then co-opted by the Muslim Brotherhood through Egypt's first free and fair elections in 2012, which was in turn crushed in 2013 by a popularly supported military regime whose practices of repression negatively impacted the justice system and human rights. The problems facing the country and its people are daunting, particularly economic, demographic, and social pressures. The contextual analysis of these and other historic and contemporary issues give the reader a comprehensive understanding of what has occurred in the last five years and an insight into where the country is heading. Even though the Revolution has been suppressed and the promise of democracy shunted aside, the majority of the Egyptian people continue to hope for the unachieved dreams of social justice, human dignity, and freedom. Egypt's geopolitical importance makes it indispensable to the stability of the Middle East, and thus important to the world.
The Mind on Paper
Authors: Olson David R.
Published: November 2016

Although the importance of literacy is widely acknowledged in society and remains at the top of the political agenda, writing has been slow to establish a place in the cognitive sciences. Olson argues that to understand the cognitive implications of literacy, it is necessary to see reading and writing as providing access to and consciousness of aspects of language, such as phonemes, words and sentences, that are implicit and unconscious in speech. Reading and writing create a system of metarepresentational concepts that bring those features of language into consciousness as a subject of discourse. This consciousness of language is essential not only to acquiring literacy but also to the formation of systematic thought and rationality. The Mind on Paper is a compelling exploration of what literacy does for our speech and hence for our thought, and will be of interest to readers in developmental psychology, cognitive science, linguistics, and education.
Representations of the Infinite Symmetric Group
Authors: Borodin Alexei , Olshanski Grigori
Published: November 2016

Representation theory of big groups is an important and quickly developing part of modern mathematics, giving rise to a variety of important applications in probability and mathematical physics. This book provides the first concise and self-contained introduction to the theory on the simplest yet very nontrivial example of the infinite symmetric group, focusing on its deep connections to probability, mathematical physics, and algebraic combinatorics. Following a discussion of the classical Thoma's theorem which describes the characters of the infinite symmetric group, the authors describe explicit constructions of an important class of representations, including both the irreducible and generalized ones. Complete with detailed proofs, as well as numerous examples and exercises which help to summarize recent developments in the field, this book will enable graduates to enhance their understanding of the topic, while also aiding lecturers and researchers in related areas.
Establishing a Standard of Care for Deep Brain Stimulation Centers in Canada
Authors: Panisset Michel , Picillo Marina , Jodoin Nicolas , Poon Yu-Yan , Valencia-Mizrachi Alejandro , Fasano Alfonso , Munhoz Renato , Honey Christopher R.
Published: November 2016

During the “DBS Canada Day” symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to share their knowledge regarding deep brain stimulation (DBS) management of movement disorders in three domains: (1) the programming algorithms, (2) the necessary team to run a neurosurgery program, and (3) the appropriate scales to better define in a more comprehensive fashion the effect of the brain surgery. Each presentation was followed by an open discussion, and this article reports on the conclusions of this meeting on these three questions. Concerning programming, the role of the pulse width and the switching off of the stimulation at night for thalamic stimulation for the control of tremor have been discussed. The algorithms proposed in the literature for programming in Parkinson’s disease (PD) need validation. In dystonia, the use of monopolar vs bipolar parameters, the use of low vs high frequencies and the use of smaller versus larger pulse widths all need to be examined properly. Concerning the necessary team to run a neurosurgical program, recommendations will follow the suggestions for standardized outcome measures. Regarding the outcome measures for DBS in PD, investigations need to focus on the non-motor aspects of PD. Identifying which nonmotor symptoms respond to DBS would allow a better screening before and satisfaction postoperatively. There is an important need for more data to determine the optimal programming protocol and the standard measures that should be performed routinely by all centers.
WANG YANGMING IN BEIJING, 1510–1512: “IF I DO NOT AWAKEN OTHERS, WHO WILL DO SO?”
Authors: Israel George Lawrence
Published: November 2016

After being recalled to Beijing in 1510 for evaluation and reassignment in the wake of his two-year exile to Guizhou and his period of service as a magistrate, Wang Yangming was assigned to a succession of posts at the capital that kept him there through 1512. During that short time, he remained disillusioned with the Ming court and high politics and chose to put his energies into fostering a philosophical movement. He believed that by restoring the “way of master-disciple relations and friendship,” he could help propagate the learning of the sages. To that end, he heldjiangxuegatherings with colleagues and friends and carried on an active correspondence. In those venues, Wang Yangming engaged others with his ideas about the goal of sagehood, the obstacles to attaining it, and the methods for overcoming those obstacles. The following article reconstructs this critical period in Wang Yangming's philosophical development and the intellectual movement he sought to foster, as well as the status of his philosophy as of this point in time.
The Facilitators, Obstacles and Needs of Individuals With Autism Spectrum Conditions Accessing Further and Higher Education: A Systematic Review
Authors: Toor Nicky , Hanley Terry , Hebron Judith
Published: November 2016

Many young adults diagnosed with autism spectrum conditions (ASC) intend to go to college and/or university, yet research suggests that these individuals find aspects of college and university life challenging. To explore the views of individuals directly affected by these challenges, a systematic review of the existing qualitative literature in this area was conducted. Twelve studies met the inclusion criteria. Thematic analysis of these articles identified six superordinate themes: the involvement of professionals; academic, environmental, and social factors; wellbeing; communication; and understanding. The facilitators, obstacles and needs of students pervaded these themes and are discussed alongside implications for counsellors and psychologists working in schools.
If You Mobilize Them, They Will Become Informed: Experimental Evidence that Information Acquisition Is Endogenous to Costs and Incentives to Participate
Authors: Shineman Victoria Anne
Published: November 2016

Because non-voters are less politically informed than voters, some propose that increasing voter turnout would reduce the quality of information among the active voting population, damaging electoral outcomes. However, the proposed tradeoff between increased participation and informed participation is a false dichotomy. This article demonstrates that political information is endogenous to participation. A field experiment integrates an intensive mobilization treatment into a panel survey conducted before and after a city-wide election. Subjects who were mobilized to vote also became more informed about the content of the election. The results suggest institutions that encourage participation not only increase voter turnout – mobilizing electoral participation also motivates citizens to become more politically informed.
Asymmetric hybridization between non-native winter moth,Operophtera brumata(Lepidoptera: Geometridae), and native Bruce spanworm,Operophtera bruceata, in the Northeastern United States, assessed with novel microsatellites and SNPs
Authors: Havill N.P. , Elkinton J. , Andersen J.C. , Hagen S.B. , Broadley Hannah J. , Boettner G.J. , Caccone A.
Published: November 2016

The European winter moth,Operophtera brumata, is a non-native pest in the Northeastern USA causing defoliation of forest trees and crops such as apples and blueberries. This species is known to hybridize withO. bruceata, the Bruce spanworm, a native species across North America, although it is not known if there are hybrid generations beyond F1. To study winter moth population genetics and hybridization with Bruce spanworm, we developed two sets of genetic markers, single nucleotide polymorphisms (SNPs) and microsatellites, using genomic approaches. Both types of markers were validated using samples from the two species and their hybrids. We identified 1216 SNPs and 24 variable microsatellite loci. From them we developed a subset of 95 species-diagnostic SNPs and ten microsatellite loci that could be used for hybrid identification. We further validated the ten microsatellite loci by screening field collected samples of both species and putative hybrids. In addition to confirming the presence of F1 hybrids reported in previous studies, we found evidence for multi-generation asymmetric hybridization, as suggested by the occurrence of hybrid backcrosses with the winter month, but not with the Bruce spanworm. Laboratory crosses between winter moth females and Bruce spanworm males resulted in a higher proportion of viable eggs than the reciprocal cross, supporting this pattern. We discuss the possible roles of population demographics, sex chromosome genetic incompatibility, and bacterial symbionts as causes of this asymmetrical hybridization and the utility of the developed markers for future studies.
THE WORKING METHODS OF THE UNITED NATIONS SECURITY COUNCIL: MAINTAINING THE IMPLEMENTATION OF CHANGE
Authors: Harrington Joanna
Published: November 2016

The United Nations Security Council is often described as an opaque body, closed in both membership and approach, and unaccountable for its conduct. For many years, this view has motivated calls for reform to the Council's working methods. This article aims to shine light on the Council's approach to process matters, recognizing the Council's preference for making change through developments in practice. The article reviews the efforts undertaken by the ‘Small Five’ group of States from 2005 to 2012, followed by the efforts since 2013 of the Accountability, Coherence and Transparency Group, while also acknowledging the contributions made by Japan. With some proposals having received some degree of Council support, the sustained implementation of change is identified as the key priority. The article argues for the contextual application of the key concepts of transparency, engagement and accountability, as well as prevention, to provide a principled basis for both the maintenance and development of working methods reform.
Relay intercropping and mineral fertilizer effects on biomass production, maize productivity and weed dynamics in contrasting soils under conservation agriculture
Authors: MHLANGA B. , CHEESMAN S. , MAASDORP B. , MUPANGWA W. , THIERFELDER C.
Published: November 2016

Cash-constrained farmers who cannot afford herbicides and mineral fertilizers may incorporate green manure cover crops (GMCCs) as relay crops to aid in management of weeds and nitrogen in maize systems under conservation agriculture in cases where rotations are a challenge. An experiment was conducted at two sites with contrasting soil types, University of Zimbabwe farm (clay) and Domboshawa Training Centre (sandy) to investigate the effects of maize/velvet bean intercropping at 8 weeks after planting maize (WAPM), applying different fertilizer rates and exploring their interactive effects on weed composition, maize productivity and biomass production [total maize non-cob biomass (stover) plus GMCC biomass]. The performance of the system depended largely on the amount of rainfall received within and across the seasons, sites and their interaction; also on the amount of fertilizer applied. Generally, biomass yields attained by velvet bean [Mucuna pruriensL. (DC.)] were lower than reported previously. Maize grain yield and weed diversity were higher in treatments with higher fertilizer rates, reaching up to 5·1 t/ha and 1·39, respectively. Generally, the highest weed diversity and highest maize grain yield values were observed in maize/velvet bean combinations and higher fertilizer rates (i.e. 0·27 and 4·8 t/ha, respectively) in the sandy soil. Higher fertilizer rates resulted in greater maize stover yield and this contributed greatly to the biomass productivity of the system in the sandy soil in the 2012/13 season, while the high biomass productivity observed in velvet bean in the clay site in the final season contributed significantly to productivity. Maize productivity was not affected by velvet bean introduced at 8 WAPM in any of the seasons. The present study showed that relay cropping velvet bean as late as 8 WAPM and onwards has potential to increase biomass production without compromising maize yields. However, planting it as late as 8 WAPM results in reduced productivity due to reduced moisture availability.
Face processing in adolescents with positive and negative threat bias
Authors: Sylvester C. M. , Petersen S. E. , Luby J. L. , Barch D. M.
Published: November 2016

Background

Individuals with anxiety disorders exhibit a ‘vigilance-avoidance’ pattern of attention to threatening stimuli when threatening and neutral stimuli are presented simultaneously, a phenomenon referred to as ‘threat bias’. Modifying threat bias through cognitive retraining during adolescence reduces symptoms of anxiety, and so elucidating neural mechanisms of threat bias during adolescence is of high importance. We explored neural mechanisms by testing whether threat bias in adolescents is associated with generalized or threat-specific differences in the neural processing of faces.

Method

Subjects were categorized into those with (n = 25) and without (n = 27) threat avoidance based on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort has previously been shown to index threat bias. Brain response to individually presented angry and neutral faces was assessed in a separate session using functional magnetic resonance imaging.

Results

Adolescents with threat avoidance exhibited lower activity for both angry and neutral faces relative to controls in several regions in the occipital, parietal, and temporal lobes involved in early visual and facial processing. Results generalized to happy, sad, and fearful faces. Adolescents with a prior history of depression and/or an anxiety disorder had lower activity for all faces in these same regions. A subset of results replicated in an independent dataset.

Conclusions

Threat bias is associated with generalized, rather than threat-specific, differences in the neural processing of faces in adolescents. Findings may aid in the development of novel treatments for anxiety disorders that use attention training to modify threat bias.
PhD Abstracts
Authors: HUTTON GRAHAM
Published: November 2016

Many students complete PhDs in functional programming each year. As a service to the community, the Journal of Functional Programming publishes the abstracts from PhD dissertations completed during the previous year.
Increasing life expectancy and NDC pension systems
Authors: KNELL MARKUS
Published: November 2016

In this paper, I study how pay-as-you-go pension systems of the notional defined contribution type can be designed such that they remain financially stable in the presence of increasing life expectancy. For this to happen three crucial parameters must be set in an appropriate way: the notional interest rate, the adjustment rate and the annuity conversion factor. I show that there exist two main approaches to implement a stable system. The first uses period-specific annuitization and indexation rates that correct for labor force increases, which are only due to rises in the retirement age which are necessary to ‘neutralize’ the increase in life expectancy. The second approach uses cohort-specific annuitization and indexation rates that are larger than in a stationary situation. This is due to the fact that a continuously increasing life expectancy leads to higher internal rates of return that can be passed on via the indexation.
THE DEMISE OF INTEGRATION
Authors: Smith Christi M.
Published: November 2016

Racial integration has been a tenet of educational equity for over fifty years. Despite this, U.S. higher education presents staggering rates of segregation. Strikingly, there is little scholarship to answer the question of how integrated colleges segregated? I interrogate the process of segregation over a fifty-year period through a comparative historical analysis of the broader field of higher education and case studies of three nineteenth-century colleges. Through analysis of independently collected archival materials, I show that local-level organization of racial contact fails to account for the success or failure of racial integration in schools. Instead, I show that the interaction between colleges—and the emergence of a competitive field of higher education—undermined even successfully integrated campuses. Mesolevel practices are important for revealing how organizational actors implement rationalized cultural ideas as well as how local-level ideas are negotiated in a situated field. The growth of intercollegiate college competition differentiated not only particular types of education but also consecrated groups of people. Further, this reveals the production of cultural meanings around race as a differentiation strategy in response to interorganizational competition.
Prompt gravity signal induced by the 2011 Tohoku-Oki earthquake
Authors: Montagner Jean-Paul , Juhel Kévin , Barsuglia Matteo , Ampuero Jean Paul , Chassande-Mottin Eric , Harms Jan , Whiting Bernard , Bernard Pascal , Clévédé Eric , Lognonné Philippe
Published: November 2016

Transient gravity changes are expected to occur at all distances during an earthquake rupture, even before the arrival of seismic waves. Here we report on the search of such a prompt gravity signal in data recorded by a superconducting gravimeter and broadband seismometers during the 2011 Mw 9.0 Tohoku-Oki earthquake. During the earthquake rupture, a signal exceeding the background noise is observed with a statistical significance higher than 99% and an amplitude of a fraction of μGal, consistent in sign and order of magnitude with theoretical predictions from a first-order model. While prompt gravity signal detection with state-of-the-art gravimeters and seismometers is challenged by background seismic noise, its robust detection with gravity gradiometers under development could open new directions in earthquake seismology, and overcome fundamental limitations of current earthquake early-warning systems imposed by the propagation speed of seismic waves.
Altered intestinal microbiota–host mitochondria crosstalk in new onset Crohn’s disease
Authors: Mottawea Walid , Chiang Cheng-Kang , Mühlbauer Marcus , Starr Amanda E. , Butcher James , Abujamel Turki , Deeke Shelley A. , Brandel Annette , Zhou Hu , Shokralla Shadi , Hajibabaei Mehrdad , Singleton Ruth , Benchimol Eric I. , Jobin Christian , Mack David R. , Figeys Daniel , Stintzi Alain
Published: November 2016

Intestinal microbial dysbiosis is associated with Crohn’s disease (CD). However, the mechanisms leading to the chronic mucosal inflammation that characterizes this disease remain unclear. In this report, we use systems-level approaches to study the interactions between the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms of disease. We report an altered host proteome in CD patients indicative of impaired mitochondrial functions. In particular, mitochondrial proteins implicated in H2S detoxification are downregulated, while the relative abundance of H2S microbial producers is increased. Network correlation analysis reveals that Atopobium parvulum controls the central hub of H2S producers. A. parvulum induces pancolitis in colitis-susceptible interleukin-10-deficient mice and this phenotype requires the presence of the intestinal microbiota. Administrating the H2S scavenger bismuth mitigates A. parvulum-induced colitis in vivo. This study reveals that host–microbiota interactions are disturbed in CD and thus provides mechanistic insights into CD pathogenesis.
Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide
Authors: Wang Yukun , Chen Charles H. , Hu Dan , Ulmschneider Martin B. , Ulmschneider Jakob P.
Published: November 2016

Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures—formed by a single sequence—may be a key feature in preventing bacterial resistance and could explain why sequence–function relationships in AMPs remain elusive.
Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease
Authors: Dölle Christian , Flønes Irene , Nido Gonzalo S. , Miletic Hrvoje , Osuagwu Nelson , Kristoffersen Stine , Lilleng Peer K. , Larsen Jan Petter , Tysnes Ole-Bjørn , Haugarvoll Kristoffer , Bindoff Laurence A. , Tzoulis Charalampos
Published: November 2016

Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we study the complete spectrum of mtDNA changes, including deletions, copy-number variation and point mutations, in single neurons from the dopaminergic substantia nigra and other brain areas of individuals with Parkinson disease and neurologically healthy controls. We show that in dopaminergic substantia nigra neurons of healthy individuals, mtDNA copy number increases with age, maintaining the pool of wild-type mtDNA population in spite of accumulating deletions. This upregulation fails to occur in individuals with Parkinson disease, however, resulting in depletion of the wild-type mtDNA population. By contrast, neuronal mtDNA point mutational load is not increased in Parkinson disease. Our findings suggest that dysregulation of mtDNA homeostasis is a key process in the pathogenesis of neuronal loss in Parkinson disease.
Atomically resolved phase transition of fullerene cations solvated in helium droplets
Authors: Kuhn M. , Renzler M. , Postler J. , Ralser S. , Spieler S. , Simpson M. , Linnartz H , Tielens A. G. G. M. , Cami J. , Mauracher A. , Wang Y. , Alcamí M. , Martín F. , Beyer M. K. , Wester R. , Lindinger A. , Scheier P.
Published: November 2016

Helium has a unique phase diagram and below 25 bar it does not form a solid even at the lowest temperatures. Electrostriction leads to the formation of a solid layer of helium around charged impurities at much lower pressures in liquid and superfluid helium. These so-called ‘Atkins snowballs’ have been investigated for several simple ions. Here we form HenC60+ complexes with n exceeding 100 via electron ionization of helium nanodroplets doped with C60. Photofragmentation of these complexes is measured by merging a tunable narrow-bandwidth laser beam with the ions. A switch from red- to blueshift of the absorption frequency of HenC60+ on addition of He atoms at n=32 is associated with a phase transition in the attached helium layer from solid to partly liquid (melting of the Atkins snowball). Elaborate molecular dynamics simulations using a realistic force field and including quantum effects support this interpretation.
PEP-19 modulates calcium binding to calmodulin by electrostatic steering
Authors: Wang Xu , Putkey John A.
Published: November 2016

PEP-19 is a small protein that increases the rates of Ca2+ binding to the C-domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca2+ binding and to sensitize HeLa cells to ATP-induced Ca2+ release. Here, we report the NMR solution structure of a complex between PEP-19 and the C-domain of apo CaM. The acidic sequence of PEP-19 associates between helices E and F of CaM via hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend toward the solvent and form a negatively charged surface that resembles a catcher’s mitt near Ca2+ binding loop III of CaM. The topology and gradients of negative electrostatic surface potential support a mechanism by which PEP-19 increases the rate of Ca2+ binding to the C-domain of CaM by ‘catching’ and electrostatically steering Ca2+ to site III.
Pre- and post-weaning diet alters the faecal metagenome in the cat with differences in vitamin and carbohydrate metabolism gene abundances
Authors: Young Wayne , Moon Christina D. , Thomas David G. , Cave Nick J. , Bermingham Emma N.
Published: November 2016

Dietary format, and its role in pet nutrition, is of interest to pet food manufacturers and pet owners alike. The aim of the present study was to investigate the effects of pre- and post-weaning diets (kibbled or canned) on the composition and function of faecal microbiota in the domestic cat by shotgun metagenomic sequencing and gene taxonomic and functional assignment using MG-RAST. Post-weaning diet had a dramatic effect on community composition; 147 of the 195 bacterial species identified had significantly different mean relative abundances between kittens fed kibbled and canned diets. The kittens fed kibbled diets had relatively higher abundances of Lactobacillus (>100-fold), Bifidobacterium (>100-fold), and Collinsella (>9-fold) than kittens fed canned diets. There were relatively few differences in the predicted microbiome functions associated with the pre-weaning diet. Post-weaning diet affected the abundance of functional gene groups. Genes involved in vitamin biosynthesis, metabolism, and transport, were significantly enriched in the metagenomes of kittens fed the canned diet. The impact of post-weaning diet on the metagenome in terms of vitamin biosynthesis functions suggests that modulation of the microbiome function through diet may be an important avenue for improving the nutrition of companion animals.
An anti-TNF-α antibody mimetic to treat ocular inflammation
Authors: Khalili Hanieh , Lee Richard W. , Khaw Peng T. , Brocchini Steve , Dick Andrew D. , Copland David A.
Published: November 2016

Infliximab is an antibody that neutralizes TNF-α and is used principally by systemic administration to treat many inflammatory disorders. We prepared the antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to assess whether such formulations have biological activity and potential utility for ocular use. FpFinfliximab was designed to address side effects caused by antibody degradation and the presence of the Fc region. Surface plasmon resonance analysis indicated that infliximab and FpFinfliximab maintained binding affinity for both human and murine recombinant TNF-α. No Fc mediated RPE cellular uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells in the EAU mice after a single intravitreal injection at the onset of peak disease. These results offer an opportunity to develop and formulate for ocular use, FpF molecules designed for single and potentially multiple targets using bi-specific FpFs.
Ultrasonic spray coating polymer and small molecular organic film for organic light-emitting devices
Authors: Liu Shihao , Zhang Xiang , Zhang Letian , Xie Wenfa
Published: November 2016

Ultrasonic spray coating process (USCP) with high material -utilization, low manufacture costs and compatibility to streamline production has been attractive in researches on photoelectric devices. However, surface tension exists in the solvent is still a huge obstacle to realize smooth organic film for organic light emitting devices (OLEDs) by USCP. Here, high quality polymer anode buffer layer and small molecular emitting layer are successfully realized through USCP by introducing extra-low surface tension diluent and surface tension control method. The introduction of low surface tension methyl alcohol is beneficial to the formation of poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) films and brings obvious phase separation and improved conductivity to PEDOT:PSS film. Besides, a surface tension control method, in which new stable tension equilibrium is built at the border of wetting layer, is proposed to eliminate the effect of surface tension during the solvent evaporation stage of ultrasonic spray coating the film consists of 9,9-Spirobifluoren-2-yl-diphenyl-phosphine oxide doped with 10 wt% tris [2-(p -tolyl) pyridine] iridium (III). A smooth and homogenous small molecular emitting layer without wrinkles is successfully realized. The effectiveness of the ultrasonic spray coating polymer anode buffer layer and small molecular emitting layer are also proved by introducing them in OLEDs.
Hierarchical effects of pro-inflammatory cytokines on the post-influenza susceptibility to pneumococcal coinfection
Authors: Duvigneau Stefanie , Sharma-Chawla Niharika , Boianelli Alessandro , Stegemann-Koniszewski Sabine , Nguyen Van Kinh , Bruder Dunja , Hernandez-Vargas Esteban A.
Published: November 2016

In the course of influenza A virus (IAV) infections, a secondary bacterial infection frequently leads to serious respiratory conditions provoking high hospitalization and death tolls. Although abundant pro-inflammatory responses have been reported as key contributing factors for these severe dual infections, the relative contributions of cytokines remain largely unclear. In the current study, mathematical modelling based on murine experimental data dissects IFN-γ as a cytokine candidate responsible for impaired bacterial clearance, thereby promoting bacterial growth and systemic dissemination during acute IAV infection. We also found a time-dependent detrimental role of IL-6 in curtailing bacterial outgrowth which was not as distinct as for IFN-γ. Our numerical simulations suggested a detrimental effect of IFN-γ alone and in synergism with IL-6 but no conclusive pathogenic effect of IL-6 and TNF-α alone. This work provides a rationale to understand the potential impact of how to manipulate temporal immune components, facilitating the formulation of hypotheses about potential therapeutic strategies to treat coinfections.
Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han Chinese from South China
Authors: Wang Dong , Zhang Deng-Feng , Feng Jia-Qi , Li Guo-Dong , Li Xiao-An , Yu Xiu-Feng , Long Heng , Li Yu-Ye , Yao Yong-Gang
Published: November 2016

Leprosy is a chronic infectious and neurological disease caused by Mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620 individuals with or without leprosy from China. We also sequenced the entire exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by using the next generation sequencing technology (NGS). We found that PARL SNP rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL and PINK1 were associated with leprosy in patients underwent NGS. Furthermore, PARL and PINK1 could physically interact with each other and were involved in the highly connected network formed by reported leprosy susceptibility genes. Together, our results showed that PARL and PINK1 genetic variants are associated with leprosy.
RETRACTED ARTICLE: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism
Authors: Pratheeshkumar Poyil , Son Young-Ok , Divya Sasidharan Padmaja , Wang Lei , Zhang Zhuo , Shi Xianglin
Published: November 2016

Arsenic is a well-documented human carcinogen. The present study explored the role of the onco-miR, miR-21 and its target protein, programmed cell death 4 (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our results showed that treatment of human bronchial epithelial (BEAS-2B) cells with arsenic induces ROS through p47phox, one of the NOX subunits that is the key source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21 expression associated with inhibition of PDCD4, and caused malignant cell transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3 transcriptional activation by IL-6 is crucial for the arsenic induced miR-21 increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4 or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream protein E-cadherin expression and induced β-catenin/TCF-dependent transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21-PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis.
Solid-liquid density and spin crossovers in (Mg, Fe)O system at deep mantle conditions
Authors: Ghosh Dipta B. , Karki Bijaya B.
Published: November 2016

The low/ultralow-velocity zones in the Earth’s mantle can be explained by the presence of partial melting, critically depending on density contrast between the melt and surrounding solid mantle. Here, first-principles molecular dynamics simulations of (Mg, Fe) O ferropericlase in the solid and liquid states show that their densities increasingly approach each other as pressure increases. The isochemical density difference between them diminishes from 0.78 (±0.7) g/cm3 at zero pressure (3000 K) to 0.16 (±0.04) g/cm3 at 135 GPa (4000 K) for pure and alloyed compositions containing up to 25% iron. The simulations also predict a high-spin to low-spin transition of iron in the liquid ferropericlase gradually occurring over a pressure interval centered at 55 GPa (4000 K) accompanied by a density increase of 0.14 (±0.02) g/cm3. Temperature tends to widen the transition to higher pressure. The estimated iron partition coefficient between the solid and liquid ferropericlase varies from 0.3 to 0.6 over the pressure range of 23 to 135 GPa. Based on these results, an excess of as low as 5% iron dissolved in the liquid could cause the solid-liquid density crossover at conditions of the lowermost mantle.
Visualizing epithelial expression of EGFR in vivo with distal scanning side-viewing confocal endomicroscope
Authors: Duan Xiyu , Li Haijun , Zhou Juan , Zhou Quan , Oldham Kenn R. , Wang Thomas D.
Published: November 2016

Confocal endomicroscopy is an emerging imaging technology that has recently been introduced into the clinic to instantaneously collect “optical biopsies” in vivo with histology-like quality. Here, we demonstrate a fast scanner located in the distal end of a side-viewing instrument using a compact lens assembly with numerical aperture of 0.5 to achieve a working distance of 100 μm and field-of-view of 300 × 400 μm2. The microelectromechanical systems (MEMS) mirror was designed based on the principle of parametric resonance and images at 5 frames per second. The instrument has a 4.2 mm outer diameter and 3 cm rigid length, and can pass through the biopsy channel of a medical endoscope. We achieved real time optical sections of NIR fluorescence with 0.87 μm lateral resolution, and were able to visualize in vivo binding of a Cy5.5-labeled peptide specific for EGFR to the cell surface of pre-cancerous colonocytes within the epithelium of dysplastic crypts in mouse colon. By performing targeted imaging with endomicroscopy, we can visualize molecular expression patterns in vivo that provide a biological basis for disease detection.
NF-kappaΒ-inducing kinase regulates stem cell phenotype in breast cancer
Authors: Vazquez-Santillan Karla , Melendez-Zajgla Jorge , Jimenez-Hernandez Luis Enrique , Gaytan-Cervantes Javier , Muñoz-Galindo Laura , Piña-Sanchez Patricia , Martinez-Ruiz Gustavo , Torres Javier , Garcia-Lopez Patricia , Gonzalez-Torres Carolina , Ruiz Victor , Avila-Moreno Federico , Velasco-Velazquez Marco , Perez-Tapia Mayra , Maldonado Vilma
Published: November 2016

Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-κB) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector. The effect of NIK in the cancer stem cell properties was assessed by mammosphere formation, mice xenografts and stem markers expression. BCSCs expressed higher levels of NIK and its inhibition through small hairpin (shRNA), reduced the expression of CSC markers and impaired clonogenicity and tumorigenesis. Genome-wide expression analyses suggested that NIK acts on ERK1/2 pathway to exert its activity. In addition, forced expression of NIK increased the BCSC population and enhanced breast cancer cell tumorigenicity. The in vivo relevance of these results is further supported by a tissue microarray of breast cancer samples in which we observed correlated expression of Aldehyde dehydrogenase (ALDH) and NIK protein. Our results support the essential involvement of NIK in BCSC phenotypic regulation via ERK1/2 and NF-κB.
Knockout of Zebrafish Ovarian Aromatase Gene (cyp19a1a) by TALEN and CRISPR/Cas9 Leads to All-male Offspring Due to Failed Ovarian Differentiation
Authors: Lau Esther Shuk-Wa , Zhang Zhiwei , Qin Mingming , Ge Wei
Published: November 2016

Sexual or gonadal differentiation is a complex event and its mechanism remains elusive in teleosts. Despite its complexity and plasticity, the process of ovarian differentiation is believed to involve gonadal aromatase (cyp19a1a) in nearly all species studied. However, most data concerning the role of aromatase have come from gene expression analysis or studies involving pharmacological approaches. There has been a lack of genetic evidence for the importance of aromatase in gonadal differentiation, especially the timing when the enzyme starts to exert its effect. This is due to the lack of appropriate loss-of-function approaches in fish models for studying gene functions. This situation has changed recently with the development of genome editing technologies, namely TALEN and CRISPR/Cas9. Using both TALEN and CRISPR/Cas9, we successfully established three mutant zebrafish lines lacking the ovarian aromatase. As expected, all mutant fish were males, supporting the view that aromatase plays a critical role in directing ovarian differentiation and development. Further analysis showed that the ovarian aromatase did not seem to affect the formation of so-called juvenile ovary and oocyte-like germ cells; however, it was essential for further differentiation of the juvenile ovary into the true ovary.
Collagen cross-linking: insights on the evolution of metazoan extracellular matrix
Authors: Rodriguez-Pascual Fernando , Slatter David Anthony
Published: November 2016

Collagens constitute a large family of extracellular matrix (ECM) proteins that play a fundamental role in supporting the structure of various tissues in multicellular animals. The mechanical strength of fibrillar collagens is highly dependent on the formation of covalent cross-links between individual fibrils, a process initiated by the enzymatic action of members of the lysyl oxidase (LOX) family. Fibrillar collagens are present in a wide variety of animals, therefore often being associated with metazoan evolution, where the emergence of an ancestral collagen chain has been proposed to lead to the formation of different clades. While LOX-generated collagen cross-linking metabolites have been detected in different metazoan families, there is limited information about when and how collagen acquired this particular modification. By analyzing telopeptide and helical sequences, we identified highly conserved, potential cross-linking sites throughout the metazoan tree of life. Based on this analysis, we propose that they have importantly contributed to the formation and further expansion of fibrillar collagens.