bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of free or anchored antimicrobial peptides as candidates for the prevention of orthopaedic device‐related infections
Authors: D'Este Francesca , Oro Debora , Boix‐Lemonche Gerard , Tossi Alessandro , Skerlavaj Barbara
Published: July 2017

The prevention of implant‐associated infection, one the most feared complications in orthopaedic surgery, remains a major clinical challenge and urges development of effective methods to prevent bacterial colonization of implanted devices. Alpha‐helical antimicrobial peptides (AMPs) may be promising candidates in this respect due to their potent and broad‐spectrum antimicrobial activity, their low tendency to elicit resistance and possible retention of efficacy in the immobilized state.

The aim of this study was to evaluate the potential of five different helical AMPs, the cathelicidins BMAP‐27 and BMAP‐28, their (1–18) fragments and the rationally designed, artificial P19(9/G7) peptide, for the prevention of orthopaedic implant infections. Peptides were effective at micromolar concentrations against 22 Staphylococcus and Streptococcus isolates from orthopaedic infections, while only BMAP‐28 and to a lesser extent BMAP‐27 were active against Enterococcus faecalis. Peptides in solution showed activities comparable to those of cefazolin and linezolid, on a molar basis, and also a variable capacity to neutralize bacterial lipopolysaccharide, while devoid of adverse effects on MG‐63 osteoblast cells at concentrations corresponding to the MIC. The (1–18) BMAP fragments and P19(9/G7) were selected for further examination, based on better selectivity indices, and showed effectiveness in the presence of hyaluronic acid and in synovial fluid, while human serum affected their activity to variable extents, with BMAP‐27(1–18) best retaining activity. This peptide was immobilized on streptavidin–resin beads and retained activity against reference Staphylococcus epidermidis and Staphylococcus aureus strains, with negligible toxicity towards osteoblasts, underlining its potential for the development of infection‐resistant biomaterials for orthopaedic application. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
Efficacy of a Proprietary Trigonella foenum‐graecum L. De‐Husked Seed Extract in Reducing Menopausal Symptoms in Otherwise Healthy Women: A Double‐Blind, Randomized, Placebo‐Controlled Study
Authors: Steels E. , Steele M.L. , Harold M. , Coulson S.
Published: July 2017

Trigonella foenum‐graecum seed extract has demonstrated hormone modulatory activity, providing biological plausibility for relieving menopausal symptoms. The study aimed to assess efficacy of a standardized T. foenum‐graecum de‐husked seed extract in reducing menopausal symptoms in healthy aging women. The study was a double‐blind, randomized, placebo‐controlled trial that recruited 115 women aged 40 to 65 years of which 59 were allocated to active (n = 54 completed) and 56 to placebo (n = 50 completed). Active treatment was T. foenum‐graecum de‐husked seed extract, 600 mg per day for 12 weeks. Outcome measures included Menopause‐Specific Quality of Life (MENQOL) questionnaire, frequency of hot flushes and night sweats and serum estradiol levels. There was a significant reduction in menopausal symptoms in the active group compared with placebo as assessed by total MENQOL score (p < 0.001); reflected by significant improvements in the vasomotor (p < 0.001), psychosocial (p < 0.001), physical (p < 0.001) and sexual symptoms (p < 0.001) domains. Vasomotor outcomes correlated with hot flushes, the active group reporting significantly less daytime hot flushes and night sweats at 12 weeks (p < 0.001). The average estradiol levels were similar in both the active group and placebo group after treatment. This study demonstrated that this proprietary T. foenum‐graecum de‐husked seed extract may reduce menopausal symptoms in healthy women. Copyright © 2017 John Wiley & Sons, Ltd.
A geometry‐based two‐step method for nonlinear classification using quasi‐linear support vector machine
Authors: Li Weite , Zhou Bo , Chen Benhui , Hu Jinglu
Published: July 2017

This paper proposes a two‐step method to construct a nonlinear classifier consisting of multiple local linear classifiers interpolated with a basis function. In the first step, a geometry‐based approach is first introduced to detect local linear partitions and build local linear classifiers. A coarse nonlinear classifier can then be constructed by interpolating the local linear classifiers. In the second step, a support vector machine (SVM) formulation is used to further implicitly optimize the linear parameters of the nonlinear classifier. In this way, the nonlinear classifier is constructed in exactly the same way as a standard SVM, using a special data‐dependent quasi‐linear kernel composed of the information of the local linear partitions. Numerical experiments on several real‐world datasets demonstrate the effectiveness of the proposed classifier and show that, in cases where traditional nonlinear SVMs run into overfitting problems, the proposed classifier is effective in improving the classification performance. © 2017 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Differences between polydioxanone and poliglactin in intestinal anastomoses – a comparative study of intestinal anastomoses
Authors: Santos Carlos Henrique Marques dos , Santos Filho Kerginaldo Gondim dos , Cassino Pedro Carvalho , Chiquetti Camila Vieira , Mello Alvaro Pereira de , Dourado Doroty Mesquita
Published: July 2017

Introduction Intestinal anastomosis is a surgical practice constantly realized by surgeons worldwide. When the option is to perform manual anastomosis, which is still widely used for its low cost, the question arises as to the best material to be applied.

Objective To compare polydioxanone and polyglactin threads for healing and tensile strength in intestinal anastomosis in rats.

Method We used 25 rats Wistar; after anesthesia, in groups A and B (10 rats each), laparotomy was performed, transection of the ileum at 5 and 10 cm proximally to the ileocecal valve; in group A, anastomosis was performed with 4 separate extra mucosal sutures with polidioxanone; in group B, anastomosis was performed with polyglactin; in group C (5 rats), laparotomy and manipulation of the ileum were performed. After 21 days, the animals were anesthetized and submitted to euthanasia. The specimens were sent for histopathological study and tensile strength analysis. Statistical analysis was performed using the Turkey and Student's t tests, with a significance of p < 0.05.

Results The results showed that in the tensile strength analysis, there were no significant differences between them. The histological analysis showed significant differences between the cicatrization pattern, where polydioxanone caused less fibrosis than polyglactin.

Conclusion Polydioxanone caused less fibrosis than polyglactin in intestinal anastomoses of rats.
A History of Ayutthaya
Authors: Baker Chris , Phongpaichit Pasuk
Published: July 2017

Early European visitors placed Ayutthaya alongside China and India as the great powers of Asia. Yet in 1767 the city was destroyed and its history has been neglected. This book is the first study of Ayutthaya from its emergence in the thirteenth century until its fall. It offers a wide-ranging view of social, political, and cultural history with focus on commerce, kingship, Buddhism, and war. By drawing on a wide range of sources including chronicles, accounts by Europeans, Chinese, Persians, and Japanese, law, literature, art, landscape, and language, the book presents early Siam as a 'commercial' society, not the peasant society usually assumed. Baker and Phongpaichit attribute the fall of the city not to internal conflict or dynastic decline but failure to manage the social and political consequences of prosperity. This book is essential reading for all those interested in the history of Southeast Asia and the early modern world.
Modernity and the English Rural Novel
Authors: Head Dominic
Published: July 2017

This book examines the persistence of the rural tradition in the English novel into the twentieth century. In the shadow of metropolitan literary culture, rural writing can seem to strive for a fantasy version of England with no compelling social or historical relevance. Dominic Head argues that the apparent disconnection is, in itself, a response to modernity rather than a refusal to engage with it, and that the important writers in this tradition have had a significant bearing on the trajectory of English cultural life through the twentieth century. At the heart of the discussion is the English rural regional novel of the 1920s and 1930s, which reveals significant points of overlap with mainstream literary culture and the legacies of modernism. Rural writers refashioned the conventions of the tradition and the effects of literary nostalgia, to produce the swansong of a fading genre with resonances that are still relevant today.
After the Enlightenment
Authors: Guilhot Nicolas
Published: July 2017

After the Enlightenment is the first attempt at understanding modern political realism as a historical phenomenon. Realism is not an eternal wisdom inherited from Thucydides, Machiavelli or Hobbes, but a twentieth-century phenomenon rooted in the interwar years, the collapse of the Weimar Republic, and the transfer of ideas between Continental Europe and the United States. The book provides the first intellectual history of the rise of realism in America, as it informed policy and academic circles after 1945. It breaks through the narrow confines of the discipline of international relations and resituates realism within the crisis of American liberalism. Realism provided a new framework for foreign policy thinking and transformed the nature of American democracy. This book sheds light on the emergence of 'rational choice' as a new paradigm for political decision-making and speaks to the current revival in realism in international affairs.
“Set Them to the Cyphering Schoole”: Reading, Writing, and Arithmetical Education, circa 1540–1700
Authors: Otis Jessica
Published: July 2017

During the late sixteenth and seventeenth centuries, English men and women replaced their existing oral and object-based arithmetical practices with literate practices based on Arabic numerals. While the adoption of Arabic numerals was incentivized by continental commercial developments, this article argues that England's increasing literacy rates and the development of vernacular arithmetic textbooks enabled changing arithmetical practices. By exploring the qualities of printed books, analyzing marginalia in arithmetic textbooks, and examining changing educational advertisements and curricula over time, we can demonstrate the importance of literacy and literature to early modern arithmetical education.
State Formation from the Vantage of Early English Jamaica: The Neglect of Edward Doyley
Authors: Gardina Pestana Carla
Published: July 2017

Edward Doyley led English Jamaica for most of its first decade. Sent as part of a military force intent on conquering the island, he rose to a position of command in the army as a result of his survival and seniority. Eventually he took charge of the navy and civilian affairs as well. Wielding theoretically vast powers he lacked official authorization from any central authority for much of his tenure. His correspondence requesting support for the island reveals the needs of a newly conquered colony, enumerating the requirements that an expanding imperial center must fill as England moved more decisively toward engagement in the wider world. Scholarly debates over state building that emphasize military and naval expansion as a driving force, and debates about state formation focusing on negotiations between central and local authorities, speak to the experience of early Jamaica. Doyley's circumstances place him in a position between the two ideal situations described in that literature.
Fleets of Fodder: The Ecological Orchestration of Agrarian Improvement in New South Wales and the Cape of Good Hope, 1780–1830
Authors: Capps Maura
Published: July 2017

This article challenges the dominant historical paradigms used to analyze imperial plant and animal transfers by examining the role of fodder crops in early colonial development in New South Wales and the Cape of Good Hope. In Alfred Crosby's enduring formulation of ecological imperialism—that is, the ecological transformation of temperate colonies of settlement by European plants, animals, and pathogens—was a largely independent process. To Crosby's critics, his grand narrative fails to acknowledge the technocratic management of plant and animal transfers on the part of increasingly long-armed colonial states from the mid-nineteenth century. Yet neither approach can adequately explain the period between the decline of Britain's Atlantic empire in the 1780s and the rise of its global empire in the 1830s, a period dominated by an aggressive ethos of agrarian improvement but lacking the institutional teeth of a more evolved imperial state. Traveling fodder crops link these embryonic antipodean colonies to the luminaries of the Agricultural Revolution in Britain. The attempt to transfer fodder-centric mixed husbandry to these colonies points to an emerging coalition of imperial ambition and scientific expertise in the late eighteenth-century British Empire.
“In Ten Years There Is an Increase of 450 Priests of Antichrist”: Quantification, Anti-Catholicism, and theBulwark
Authors: Burstein Miriam Elizabeth
Published: July 2017

The Scottish Reformation Society'sThe Bulwark(1851–present) was the Victorian era's most influential anti-Catholic periodical, a reputation based on its self-proclaimed devotion to “facts.” Attempting to counter a unified Catholic Church in a period of pronounced intra-Protestant conflict, theBulwarksought to root religious controversy in the increasingly popular phenomenon of statistical inquiry. TheBulwark’s obsession with collating and interpreting religion-based numbers was unique not for its existence, but for its sheer extent. It thus exemplifies how “official” statistical documents, methods, and conclusions were translated into the concerns of popular religious culture. In particular, theBulwark’s ongoing surveys of Catholicism's “progress,” intended to frighten Protestants into action, weaponized statistical discourses that were used in more measured fashion elsewhere. To that end, theBulwarkargued that only Protestants had the right mindset to put religious statistics into a proper explanatory framework, whereas Catholics manipulated their own data for dishonest rhetorical purposes that theBulwarkdisclaimed. TheBulwark’s statistical turn, which bypassed the sectarianism of its theological articles, positioned it as a voice uniting the interests of all Protestant readers against Parliament's dangerously tolerant brand of liberalism.
Identifying the metabolomic fingerprint of high and low flavonoid consumers
Authors: Ivey Kerry L. , Rimm Eric B. , Kraft Peter , Clish Clary B. , Cassidy Aedin , Hodgson Jonathan , Croft Kevin , Wolpin Brian , Liang Liming
Published: July 2017

High flavonoid consumption can improve vascular health. Exploring flavonoid–metabolome relationships in population-based settings is challenging, as: (i) there are numerous confounders of the flavonoid–metabolome relationship; and (ii) the set of dependent metabolite variables are inter-related, highly variable and multidimensional. The Metabolite Fingerprint Score has been developed as a means of approaching such data. This study aims to compare its performance with that of more traditional methods, in identifying the metabolomic fingerprint of high and low flavonoid consumers. This study did not aim to identify biomarkers of intake, but rather to explore how systemic metabolism differs in high and low flavonoid consumers. Using liquid chromatography–tandem MS, 174 circulating plasma metabolites were profiled in 584 men and women who had complete flavonoid intake assessment. Participants were randomised to one of two datasets: (a) training dataset, to determine the models for the discrimination variables (n 399); and (b) validation dataset, to test the capacity of the variables to differentiate higher from lower total flavonoid consumers (n 185). The stepwise and full canonical variables did not discriminate in the validation dataset. The Metabolite Fingerprint Score successfully identified a unique pattern of metabolites that discriminated high from low flavonoid consumers in the validation dataset in a multivariate-adjusted setting, and provides insight into the relationship of flavonoids with systemic lipid metabolism. Given increasing use of metabolomics data in dietary association studies, and the difficulty in validating findings using untargeted metabolomics, this paper is of timely importance to the field of nutrition. However, further validation studies are required.
Relationships Among Rivals (RAR): A Framework for Analyzing Contending Hypotheses in Process Tracing
Authors: Zaks Sherry
Published: July 2017

Methodologists and substantive scholars alike agree that one of process tracing’s foremost contributions to qualitative research is its capacity to adjudicate among competing explanations of a phenomenon. Existing approaches, however, only provide explicit guidance on dealing with mutually exclusive explanations, which are exceedingly rare in social science research. I develop a tripartite solution to this problem. The Relationships among Rivals (RAR) framework (1) introduces a typology of relationships between alternative hypotheses, (2) develops specific guidelines for identifying which relationship is present between two hypotheses, and (3) maps out the varied implications for evidence collection and inference. I then integrate the RAR framework into each of the main process-tracing approaches and demonstrate how it affects the inferential process. Finally, I illustrate the purchase of the RAR framework by reanalyzing a seminal example of process-tracing research: Schultz’s (2001) analysis of the Fashoda Crisis. I show that the same evidence can yield new and sometimes contradictory inferences once scholars approach comparative hypothesis testing with this more nuanced framework.
The National Health Service at a Critical Moment: when Brexit means Hectic
Authors: COSTA-FONT JOAN
Published: July 2017

Leaving the European Union (so-called ‘Brexit’) is a ‘critical moment’ for health policy reform which can pave the way to different pathways, including, a ‘critical juncture’. Given that Brexit cannot be undone without a second referendum, it opens up opportunities to elude European constraints for reform along the lines of equity, employment rights and patient choice. Brexit deepens the financial crisis of the National Health Service (NHS) by increasing hiring costs and imposing new transaction costs to accommodate patient cross-border mobility and international public health needs. Given the weak sustainability of the NHS, it could lead to major system reform.
Self-reported use of nutrition labels to make food choices is associated with healthier dietary behaviours in adolescents
Authors: Haidar Amier , Carey Felicia R , Ranjit Nalini , Archer Natalie , Hoelscher Deanna
Published: July 2017

Objective

The study aimed to examine nutrition label use and dietary behaviours among ethnically diverse middle- and high-school students, in Texas, USA.

Design

The School Physical Activity and Nutrition (SPAN) survey is a cross-sectional statewide study using a self-administered questionnaire to assess nutrition and physical activity behaviours. Height and weight measurements were used to determine BMI. Multivariable logistic regression was used to determine associations between nutrition label use and dietary behaviours, with gender, grade, ethnicity, BMI, parent education, socio-economic status and nutrition knowledge as covariates.

Setting

Participants from 283 schools, weighted to represent Texas youth.

Subjects

SPAN 2009–2011 included 6716 8th and 11th graders (3465 girls and 3251 boys). The study population consisted of 39·83 % White/Other, 14·61 % African-American and 45·56 % Hispanic adolescents; with a mean age of 14·9 years, and 61·95 % at a healthy weight, 15·71 % having overweight and 22·34 % having obesity.

Results

Adolescents who did not use nutrition labels had 1·69 times greater odds of consuming ≥1 sugary beverages/d (P<0·05). Adolescents who used nutrition labels had 2·13 times greater odds of consuming ≥1 fruits and vegetables/d (P<0·05). Adolescents who used nutrition labels had significantly higher healthy eating scores than those who did not (P<0·001). For every 1-point increase in nutrition knowledge, adolescents had 1·22 greater odds of using nutrition labels.

Conclusions

Nutrition label use is associated with healthier dietary behaviours in adolescents. Intervention strategies for youth should include efforts to teach adolescents to use labels to make healthy food choices.
The unprecedented 2015/16 Tasman Sea marine heatwave
Authors: Oliver Eric C. J. , Benthuysen Jessica A. , Bindoff Nathaniel L. , Hobday Alistair J. , Holbrook Neil J. , Mundy Craig N. , Perkins-Kirkpatrick Sarah E.
Published: July 2017

The Tasman Sea off southeast Australia exhibited its longest and most intense marine heatwave ever recorded in 2015/16. Here we report on several inter-related aspects of this event: observed characteristics, physical drivers, ecological impacts and the role of climate change. This marine heatwave lasted for 251 days reaching a maximum intensity of 2.9 °C above climatology. The anomalous warming is dominated by anomalous convergence of heat linked to the southward flowing East Australian Current. Ecosystem impacts range from new disease outbreaks in farmed shellfish, mortality of wild molluscs and out-of-range species observations. Global climate models indicate it is very likely to be that the occurrence of an extreme warming event of this duration or intensity in this region is respectively ≥330 times and ≥6.8 times as likely to be due to the influence of anthropogenic climate change. Climate projections indicate that event likelihoods will increase in the future, due to increasing anthropogenic influences.
Correction: Corrigendum: Recent pause in the growth rate of atmospheric CO2 due to enhanced terrestrial carbon uptake
Authors: Keenan Trevor F. , Prentice I. Colin , Canadell Josep G. , Williams Christopher A. , Wang Han , Raupach Michael , Collatz G. James
Published: July 2017

Nature Communications 7: Article number:13428 (2017); Published 8 November 2016; Updated 14 July 2017 An earlier publication by Leggett and Ball presented statistical evidence for a relationship between the pause in global temperature, a pause in the global rate of change of CO2 and an increase in global vegetation cover.
Implementing a universal gate set on a logical qubit encoded in an oscillator
Authors: Heeres Reinier W. , Reinhold Philip , Ofek Nissim , Frunzio Luigi , Jiang Liang , Devoret Michel H. , Schoelkopf Robert J.
Published: July 2017

A logical qubit is a two-dimensional subspace of a higher dimensional system, chosen such that it is possible to detect and correct the occurrence of certain errors. Manipulation of the encoded information generally requires arbitrary and precise control over the entire system. Whether based on multiple physical qubits or larger dimensional modes such as oscillators, the individual elements in realistic devices will always have residual interactions, which must be accounted for when designing logical operations. Here we demonstrate a holistic control strategy which exploits accurate knowledge of the Hamiltonian to manipulate a coupled oscillator-transmon system. We use this approach to realize high-fidelity (98.5%, inferred), decoherence-limited operations on a logical qubit encoded in a superconducting cavity resonator using four-component cat states. Our results show the power of applying numerical techniques to control linear oscillators and pave the way for utilizing their large Hilbert space as a resource in quantum information processing.
A 3 °C global RCP8.5 emission trajectory cancels benefits of European emission reductions on air quality
Authors: Fortems-Cheiney A. , Foret G. , Siour G. , Vautard R. , Szopa S. , Dufour G. , Colette A. , Lacressonniere G. , Beekmann M.
Published: July 2017

Despite the international agreement to reduce global warming to below 2 °C, the Intended Nationally Determined Contributions submitted for the COP21 would lead to a global temperature rise of about 3 °C. The relative consequences of such a one-degree additional warming have not yet been investigated for regional air quality. Here we found that a + 3 °C global pollutant emission trajectory with respect to pre-industrial climate (reached along the 2040–2069 period under a RCP8.5 scenario) would significantly increase European ozone levels relative to a 2 °C one (reached along the 2028–2057 period under a RCP4.5 scenario). This increase is particularly high over industrial regions, large urban areas, and over Southern Europe and would annihilate the benefits of emission reduction policies. The regional ozone increase mainly stems from the advection of ozone at Europe’s boundaries, themselves due to high global methane concentrations associated with the RCP8.5 emission scenario. These results make regional emission regulation, combined with emissions-reduction policies for global methane, of crucial importance.
CREATE-X a role for capecitabine in early-stage breast cancer: an analysis of available data
Authors: Zujewski Jo Anne , Rubinstein Lawrence
Published: July 2017

Breast cancer patients with residual disease after neoadjuvant chemotherapy and surgery may benefit from additional anti-cancer therapies. Capecitabine, an oral antimetabolite and prodrug of 5-Flurouracil, has been approved for treating metastatic breast cancer. One randomized clinical trial (CREATE-X) of capecitabine versus no additional therapy has been conducted in women with early stage breast cancer who received standard chemotherapy pre-operative therapy and had residual invasive breast cancer at the time of surgery. Results from CREATE-X, showed that capecitabine had a statistically significant survival advantage compared with no additional therapy. This perspective provides a review and analysis of the available data from CREATEx in the context of results from other adjuvant trials of capecitabine in early stage breast cancer that had disease–free survival as a primary endpoint. We conclude that although the previously published studies of capecitabine in the adjuvant setting did not meet their primary endpoint, the data from these studies are consistent with the hypothesis that capecitabine may offer additional survival benefit in patients with chemo-refractory breast cancer at the time of surgery after receiving standard chemotherapy. In these patients, offering a course of adjuvant capecitabine or enrolling the patient in a clinical trial are appropriate therapeutic options. The patient should be informed about both the increased survival observed in the CREATEx trial and the expected toxicities from capecitabine chemotherapy.
A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA
Authors: Lake Blue B. , Codeluppi Simone , Yung Yun C. , Gao Derek , Chun Jerold , Kharchenko Peter V. , Linnarsson Sten , Zhang Kun
Published: July 2017

Significant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell’s transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.
A positive feedback loop mediated by Sigma X enhances expression of the streptococcal regulator ComR
Authors: Khan Rabia , Junges Roger , Åmdal Heidi A. , Chen Tsute , Morrison Donald A. , Petersen Fernanda C.
Published: July 2017

Natural transformation is used by bacteria to take up DNA from their surroundings and incorporate it into their genomes. Streptococci do so during a transient period of competence, triggered by pheromones that they produce, secrete and sense under conditions influenced by the environment. In Streptococcus mutans, Streptococcus suis, and species of the bovis, salivarius and pyogenic groups of streptococci, the pheromone XIP is sensed by the intra-cellular regulator ComR, that in turn activates the transcription of comS, encoding the XIP precursor, and of sigX, encoding the only known alternative sigma factor in streptococci. Although induction of comR during competence has been known for more than fifteen years, the mechanism regulating its expression remains unidentified. By a combination of directional RNA-sequencing, optimal competence conditions, stepwise deletions and marker-less genome editing, we found that SigX is the missing link in overproduction of ComR. In the absence of comR induction, both sigX expression and transformation were significantly reduced. Placing comR and comS transcripts under the control of different regulators so as to form two interlocked positive feedback circuits may enable S. mutans to fine-tune the kinetics and magnitude of the competence response according to their need.
Superior non-specific motor learning in the blind
Authors: Morin-Parent Florence , de Beaumont Louis , Théoret Hugo , Lepage Jean-Francois
Published: July 2017

It is well established that blindness induces changes in cerebral function and structure, namely affecting the somatomotor regions. However, the behavioural significance of these changes on the motor system, and on motor learning in particular, remains elusive. In this study, we used a modified version of the serial reaction time task (SRTT) with auditory cues to assess sequence specific and non-specific motor learning in blind adults and sighted controls, and compare them with sighted controls performing the classic visual SRTT. Our results show that the auditory SRTT faithfully replicates the typical learning pattern obtained with the visual SRTT. On the auditory SRTT, blind individuals consistently showed faster reaction times than sighted controls, being at par with sighted individuals performing the visual SRTT. On the other hand, blind participants displayed a particular pattern of motor learning in comparison to both sighted groups; while controls improved prominently on sequence specific learning, blind individuals displayed comparable performance on both specific and non-specific learning, markedly outperforming the control groups on non-specific learning. These results show that blindness, in addition to causing long-term changes in cortical organisation, can also influence dynamic neuroplastic mechanisms in systems beyond those typically associated with compensatory sensory processing.
Observation of aggregation triggered by Resonance Energy Transfer (RET) induced intermolecular pairing force
Authors: Pan Xiaoyong , Wang Weizhi , Ke Lin , Zhang Nan
Published: July 2017

In this report, we showed the existence of RET induced intermolecular pairing force by comparing their fluorescence behaviors under room illumination vs standing in dark area for either PFluAnt solution or PFluAnt&PFOBT mixture. Their prominent emission attenuation under room illumination brought out the critical role of photo, i.e. RET induced intermolecular pairing force in induction of polymer aggregation. Constant UV-Vis absorption and fluorescence spectra in terms of both peak shapes and maximum wavelengths implied no chemical decomposition was involved. Recoverable fluorescence intensity, fluorescence lifetime as well as NMR spectra further exclude photo induced decomposition. The controllable on/off state of RET induced intermolecular pairing force was verified by the masking effect of outside PFluAnt solution which function as filter to block the excitation of inside PFluAnt and thus off the RET induced intermolecular pairing force. Theoretical calculation suggest that magnitude of RET induced intermolecular pairing force is on the same scale as that of van der Waals interaction. Although the absolute magnitude of RET induced intermolecular pairing force was not tunable, its effect can be magnified by intentionally turn it “on”, which was achieved by irradiance with 5 W desk lamp in this report.
Superhydrophobic Drag-Reduction Spherical Bearing Fabricated by Laser Ablation and PEI Regulated ZnO Nanowire Growth
Authors: Weng Rui , Zhang Haifeng , Tuo Yanjing , Wang Yang , Liu Xiaowei
Published: July 2017

The resistance of the bearing is a significant factor affecting the performance of the ball-disk rotor gyroscope. The micro and nano combined surface with low surface energy material modifications can be hydrophobic. This can reduce the drag when the bearing is lubricated by deionized water. Laser ablation method is utilized to form micron-scaled structures on the surface of the stainless steel rotor ball. And the nanostructures are formed by PEI (Polyetherimide) regulated ZnO nanowires growth. After low surface energy material modification, the water contact angle of processed surface was 163° and the sliding angle was less than 4°. The maximum rotational speed was enhanced by up to 82.77% at 1.5 W driving power. Experiments show that the superhydrophobic drag-reduction spherical bearing has good short-term reliability. At 5 V drive voltage, the bearing can extend the rotational speed of ball-disk rotor gyroscope to 35000 rpm, and maintain the normal operation for longer than 40 minutes. This is quite meaningful for short-term-work or one-time-use rotor gyroscopes.
Identification of a T cell gene expression clock obtained by exploiting a MZ twin design
Authors: Remondini Daniel , Intrator Nathan , Sala Claudia , Pierini Michela , Garagnani Paolo , Zironi Isabella , Franceschi Claudio , Salvioli Stefano , Castellani Gastone
Published: July 2017

Many studies investigated age-related changes in gene expression of different tissues, with scarce agreement due to the high number of affecting factors. Similarly, no consensus has been reached on which genes change expression as a function of age and not because of environment. In this study we analysed gene expression of T lymphocytes from 27 healthy monozygotic twin couples, with ages ranging over whole adult lifespan (22 to 98 years). This unique experimental design allowed us to identify genes involved in normative aging, which expression changes independently from environmental factors. We obtained a transcriptomic signature with 125 genes, from which chronological age can be estimated. This signature has been tested in two datasets of same cell type hybridized over two different platforms, showing a significantly better performance compared to random signatures. Moreover, the same signature was applied on a dataset from a different cell type (human muscle). A lower performance was obtained, indicating the possibility that the signature is T cell-specific. As a whole our results suggest that this approach can be useful to identify age-modulated genes.
Evidence of selection on splicing-associated loci in human populations and relevance to disease loci mapping
Authors: Gamazon Eric R. , Konkashbaev Anuar , Derks Eske M. , Cox Nancy J. , Lee Younghee
Published: July 2017

We performed a whole-genome scan of genetic variants in splicing regulatory elements (SREs) and evaluated the extent to which natural selection has shaped extant patterns of variation in SREs. We investigated the degree of differentiation of single nucleotide polymorphisms (SNPs) in SREs among human populations and applied long-range haplotype- and multilocus allelic differentiation-based methods to detect selection signatures. We describe an approach, sampling a large number of loci across the genome from functional classes and using the consensus from multiple tests, for identifying candidates for selection signals. SRE SNPs in various SNP functional classes show different patterns of population differentiation compared with their non-SRE counterparts. Intronic regions display a greater enrichment for extreme population differentiation among the potentially tissue-dependent transcript ratio quantitative trait loci (trQTLs) than SRE SNPs in general and includ outlier trQTLs for cross-population composite likelihood ratio, suggesting that incorporation of context annotation for regulatory variation may lead to improved detection of signature of selection on these loci. The proportion of extremely rare SNPs disrupting SREs is significantly higher in European than in African samples. The approach developed here will be broadly useful for studies of function and disease-associated variation in the human genome.
Antifungal treatment of wild amphibian populations caused a transient reduction in the prevalence of the fungal pathogen, Batrachochytrium dendrobatidis
Authors: Geiger Corina C. , Bregnard Cindy , Maluenda Elodie , Voordouw Maarten J. , Schmidt Benedikt R.
Published: July 2017

Emerging infectious diseases can drive host populations to extinction and are a major driver of biodiversity loss. Controlling diseases and mitigating their impacts is therefore a priority for conservation science and practice. Chytridiomycosis is a devastating disease of amphibians that is caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), and for which there is an urgent need to develop mitigation methods. We treated tadpoles of the common midwife toad (Alytes obstetricans) with antifungal agents using a capture-treat-release approach in the field. Antifungal treatment during the spring reduced the prevalence of Bd in the cohort of tadpoles that had overwintered and reduced transmission of Bd from this cohort to the uninfected young-of-the-year cohort. Unfortunately, the mitigation was only transient, and the antifungal treatment was unable to prevent the rapid spread of Bd through the young-of-the year cohort. During the winter, Bd prevalence reached 100% in both the control and treated ponds. In the following spring, no effects of treatment were detectable anymore. We conclude that the sporadic application of antifungal agents in the present study was not sufficient for the long-term and large-scale control of Bd in this amphibian system.
Plasmodium berghei P47 is essential for ookinete protection from the Anopheles gambiae complement-like response
Authors: Ukegbu Chiamaka Valerie , Giorgalli Maria , Yassine Hassan , Ramirez Jose Luis , Taxiarchi Chrysanthi , Barillas-Mury Carolina , Christophides George K. , Vlachou Dina
Published: July 2017

Malaria is a mosquito-borne disease affecting millions of people every year. The rodent parasite Plasmodium berghei has served as a model for human malaria transmission studies and played a pivotal role in dissecting the mosquito immune response against infection. The 6-cysteine protein P47, known to be important for P. berghei female gamete fertility, is shown to serve a different function in Plasmodium falciparum, protecting ookinetes from the mosquito immune response. Here, we investigate the function of P. berghei P47 in Anopheles gambiae mosquito infections. We show that P47 is expressed on the surface of both female gametocytes and ookinetes where it serves distinct functions in promoting gametocyte-to-ookinete development and protecting ookinetes from the mosquito complement-like response, respectively. The latter function is essential, as ookinetes lacking P47 are targeted for killing while traversing the mosquito midgut cells and eliminated upon exposure to hemolymph proteins of the complement-like system. Silencing key factors of the complement-like system restores oocyst development and disease transmission to rodent hosts. Our data establish a dual role of P. berghei P47 in vivo and reinforce the use of this parasite to study the impact of the mosquito immune response on human malaria transmission.
PLD1 promotes dendritic spine development by inhibiting ADAM10-mediated N-cadherin cleavage
Authors: Luo Li-Da , Li Gang , Wang Yun
Published: July 2017

Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer’s disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines. On the contrary, loss of function of PLD1, including overexpression of the catalytically-inactive PLD1 (PLD1ci) or knocking down PLD1 by siRNAs, leads to reduction in the spine density and the spine area. Moreover, we found that PLD1 promotes the dendritic spine development via regulating the membrane level of N-cadherin. Further studies showed that the regulation of surface N-cadherin by PLD1 is related with the cleavage of N-cadherin by a member of the disintegrin and metalloprotease family-ADAM10. Taking together, our results indicate a positive role of PLD1 in synaptogenesis by inhibiting the ADAM10 mediated N-cadherin cleavage and provide new therapeutic clues for some neurological diseases.
3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7
Authors: Alam Sarfaraz , Khan Feroz
Published: July 2017

Global prevalence of breast cancer and its rising frequency makes it a key area of research in drug discovery programs. The research article describes the development of field based 3D-QSAR model based on human breast cancer cell line MCF7 in vitro anticancer activity, which defines the molecular level understanding and regions of structure-activity relationship for triterpene maslinic acid and its analogs. The key features such as average shape, hydrophobic regions and electrostatic patterns of active compounds were mined and mapped to virtually screen potential analogs. Then, field points based descriptors were used to develop a 3D-QSAR model by aligning known active compounds onto identified pharmacophore template. The derived LOO validated PLS regression QSAR model showed acceptable r2 0.92 and q2 0.75. After screening through Lipinski’s rule of five filter for oral bioavailability, ADMET risk filter for drug like features, and synthetic accessibility for chemical synthesis, out of 593 hits, 39 were left top hits. Docking screening was performed through identified potential targets namely, AKR1B10, NR3C1, PTGS2, and HER2. Finally, compound P-902 was identified as best hit. This study, would be of great help in lead identification and optimization for early drug discovery.
Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence
Authors: Zhang Qiong , Nijampatnam Bhavitavya , Hua Zhang , Nguyen Thao , Zou Jing , Cai Xia , Michalek Suzanne M. , Velu Sadanandan E. , Wu Hui
Published: July 2017

Streptococcus mutans employs a key virulence factor, three glucosyltransferase (GtfBCD) enzymes to establish cariogenic biofilms. Therefore, the inhibition of GtfBCD would provide anti-virulence therapeutics. Here a small molecule library of 500,000 small molecule compounds was screened in silico against the available crystal structure of the GtfC catalytic domain. Based on the predicted binding affinities and drug-like properties, small molecules were selected and evaluated for their ability to reduce S. mutans biofilms, as well as inhibit the activity of Gtfs. The most potent inhibitor was further characterized for Gtf binding using OctetRed instrument, which yielded low micromolar KD against GtfB and nanomolar KD against GtfC, demonstrating selectivity towards GtfC. Additionally, the lead compound did not affect the overall growth of S. mutans and commensal oral bacteria, and selectively inhibit the biofilm formation by S. mutans, indicative of its selectivity and non-bactericidal nature. The lead compound also effectively reduced cariogenicity in vivo in a rat model of dental caries. An analog that docked poorly in the GtfC catalytic domain failed to inhibit the activity of Gtfs and S. mutans biofilms, signifying the specificity of the lead compound. This report illustrates the validity and potential of structure-based design of anti-S. mutans virulence inhibitors.
Improved low-rank matrix recovery method for predicting miRNA-disease association
Authors: Peng Li , Peng Manman , Liao Bo , Huang Guohua , Liang Wei , Li Keqin
Published: July 2017

MicroRNAs (miRNAs) performs crucial roles in various human diseases, but miRNA-related pathogenic mechanisms remain incompletely understood. Revealing the potential relationship between miRNAs and diseases is a critical problem in biomedical research. Considering limitation of existing computational approaches, we develop improved low-rank matrix recovery (ILRMR) for miRNA-disease association prediction. ILRMR is a global method that can simultaneously prioritize potential association for all diseases and does not require negative samples. ILRMR can also identify promising miRNAs for investigating diseases without any known related miRNA. By integrating miRNA-miRNA similarity information, disease-disease similarity information, and miRNA family information to matrix recovery, ILRMR performs better than other methods in cross validation and case studies.
Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI
Authors: Radinsky Olga , Edri Avishay , Brusilovsky Michael , Fedida-Metula Shlomit , Sobarzo Ariel , Gershoni-Yahalom Orly , Lutwama Julius , Dye John , Lobel Leslie , Porgador Angel
Published: July 2017

Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors’ sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.