bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible causes for rippling in a multivacancy graphene system
Authors: Mombrú Dominique , Faccio Ricardo , Mombrú Alvaro W.
Published: October 2017

The occurrence of ripples in an eight‐atom vacancy graphene system was analyzed through first principles calculations based on density functional theory. The study focuses on the conditions that should be considered in order that ripples could occur in the single layer defected graphene. The vacancies concentration, especially the pentagonal figures formed after relaxation of the vacant system, and the distances between neighbor pentagons, are found to be key aspects for rippling occurrence, with no charge distribution consequence. Two different configurations of rippling have been found where the position of the pentagonal figures is discussed as the driving force for any of them to occur.
Finite‐time boundary stabilization of reaction‐diffusion systems
Authors: Wu Kai‐Ning , Sun Han‐Xiao , Shi Peng , Lim Cheng‐Chew
Published: October 2017

In this paper, the problem of boundary finite‐time stabilization is considered for reaction‐diffusion systems (RDSs). First, a full‐domain controller is designed, and sufficient conditions are given to ensure finite‐time stability of RDSs under the designed controller. Then, for practical applications, a boundary controller is designed to obtain finite‐time stability. By virtue of the finite‐time stability lemma, criteria are presented to guarantee the finite‐time stability of RDSs for the Neumann boundary conditions and the mixed boundary conditions. As an extension to uncertain RDSs, robust finite‐time stabilization is studied, and criterion is obtained under the boundary control. Numerical simulations verify the effectiveness of the proposed design techniques.
Immunity to CRISPR Cas9 and Cas12a therapeutics
Authors: Chew Wei Leong
Published: October 2017

Genome‐editing therapeutics are poised to treat human diseases. As we enter clinical trials with the most promising CRISPR‐Cas9 and CRISPR‐Cas12a (Cpf1) modalities, the risks associated with administering these foreign biomolecules into human patients become increasingly salient. Preclinical discovery with CRISPR‐Cas9 and CRISPR‐Cas12a systems and foundational gene therapy studies indicate that the host immune system can mount undesired responses against the administered proteins and nucleic acids, the gene‐edited cells, and the host itself. These host defenses include inflammation via activation of innate immunity, antibody induction in humoral immunity, and cell death by T‐cell‐mediated cytotoxicity. If left unchecked, these immunological reactions can curtail therapeutic benefits and potentially lead to mortality. Ways to assay and reduce the immunogenicity of Cas9 and Cas12a proteins are therefore critical for ensuring patient safety and treatment efficacy, and for bringing us closer to realizing the vision of permanent genetic cures. WIREs Syst Biol Med 2018, 10:e1408. doi: 10.1002/wsbm.1408

This article is categorized under:

Laboratory Methods and Technologies > Genetic/Genomic Methods

Translational, Genomic, and Systems Medicine > Translational Medicine

Translational, Genomic, and Systems Medicine > Therapeutic Methods
Legal Skills
Authors: Cherkassky Lisa , Cressey Julia , Gale Christopher , Guth Jessica , Kapsis Ilias , Lister Robin , Onzivu William , Rook Steve
Published: October 2017

A comprehensive and accessible guide to the academic and practical skills needed in the study of law, including essential techniques for legal research, reasoning, writing, advocacy, negotiation, interviewing and advising. Also features an extensive section on career development.
Towards next-to-next-to-leading-log accuracy for the width difference in the $$ {B}_s-{\overline{B}}_s $$ system: fermionic contributions to order (m

c

/m

b
)0 and (m

c

/m

b
)1
Authors: Asatrian H. M. , Hovhannisyan A. , Nierste U. , Yeghiazaryan A.
Published: October 2017

Abstract

We calculate a class of three-loop Feynman diagrams which contribute to the next-to-next-to-leading logarithmic approximation for the width difference ΔΓ
s
in the $$ {B}_s-{\overline{B}}_s $$

B
s

−

B
¯

s

system. The considered diagrams contain a closed fermion loop in a gluon propagator and constitute the order α

s

2
N
f
, where N
f
is the number of light quarks. Our results entail a considerable correction in that order, if ΔΓ
s
is expressed in terms of the pole mass of the bottom quark. If the $$ \overline{\mathrm{MS}} $$

M
S

¯

scheme is used instead, the correction is much smaller. As a result, we find a decrease of the scheme dependence. Our result also indicates that the usually quoted value of the NLO renormalization scale dependence underestimates the perturbative error.
Landscape genomics analysis of Achyranthes bidentata reveal adaptive genetic variations are driven by environmental variations relating to ecological habit
Authors: Yang Jie , Li Yong , Miao Cai‐Yun , Mao Run‐Li
Published: October 2017

Knowledge on adaptive genetic variation in response to environmental variation is the key to understanding the adaptive evolution potential of species. China's warm‐temperate zone is an important climatic zone, but only a few landscape genomics studies have been conducted to understand the adaptive evolution of regional vegetation. In this study, natural populations of Achyranthes bidentata Blume were sampled in China's warm‐temperate zone to infer its adaptive evolution using landscape genomics methods. Four SCoT primers were used to investigate the adaptive evolution of A. bidentata in response to environmental variation across the warm‐temperate zone of China. A total of 126 individuals from fifteen natural populations were successfully scored, and 202 unambiguous fragments were obtained. Twenty‐three outlier loci were identified, eighteen outlier loci were significantly associated with environmental variables. Redundancy analytical results suggested that four environmental variables related to temperature and precipitation remarkably influenced the distribution of loci. The results provide empirical evidence that molecular markers with bias toward candidate functional genes might be suitable for landscape genomics studies. Temperature and precipitation jointly drive the adaptive evolution of A. bidentata. The key driving environmental factors identified in this study are mostly related to the ecological habit of A. bidentata. The species personality, i.e., ecological habit, seems to play an important role in the adaptive differentiation on A. bidentata.
Quantitative trait loci affecting intensity of violet flower colour in potato
Authors: Śliwka Jadwiga , Brylińska Marta , Stefańczyk Emil , Jakuczun Henryka , Wasilewicz-Flis Iwona , Sołtys-Kalina Dorota , Strzelczyk-Żyta Danuta , Szajko Katarzyna , Marczewski Waldemar
Published: October 2017

Anthocyanins occur in potato tuber skin and flesh, sprouts, leaves, stems and flowers. The goal of this study was to identify genomic regions and candidate gene alleles key for accumulation of anthocyanins in potato corolla in various quantities. QTL analyses were performed in two mapping populations segregating for flower colour intensity and candidate genes were identified on the basis of function and location (chalcone isomerase, chi; chalcone synthase, chs) or location (RNA-dependent RNA polymerase 1, RDR1). We detected three and four QTL affecting the violet flower colour intensity using the two mapping populations, respectively. In both populations a locus F, necessary for violet flower colour, segregated and we used different approaches to differentiate the qualitative effect of this locus and to detect the genetic factors affecting the quantitative flower colour intensity. The strongest QTL and the only one common for the two mapping populations was located on chromosome V. The role of all three candidate genes, chi, chs and RDR1, in control of flower colour intensity is supported to different extents by the performed genetic analyses. The most important QTL on chromosome V is most likely in the same position as the QTL for anthocyanin tuber flesh coloration described previously, which indicates that the natural variation in some biosynthetic and/or regulatory genes may influence anthocyanin levels in multiple tissues.
Educational Pairings, Motherhood, and Women’s Relative Earnings in Europe
Authors: Van Bavel Jan , Klesment Martin
Published: October 2017

As a consequence of the reversal of the gender gap in education, the female partner in a couple now typically has as much as or more education compared with the male partner in most Western countries. This study addresses the implications for the earnings of women relative to their male partners in 16 European countries. Using the 2007 and 2011 rounds of the European Union Statistics on Income and Living Conditions (N = 58,292), we investigate the extent to which international differences in women’s relative earnings can be explained by educational pairings and their interaction with the motherhood penalty on women’s earnings, by international differences in male unemployment, or by cultural gender norms. We find that the newly emerged pattern of hypogamy is associated with higher relative earnings for women in all countries and that the motherhood penalty on relative earnings is considerably lower in hypogamous couples, but neither of these findings can explain away international country differences. Similarly, male unemployment is associated with higher relative earnings for women but cannot explain away the country differences. Against expectations, we find that the hypogamy bonus on women’s relative earnings, if anything, tends to be stronger rather than weaker in countries that exhibit more conservative gender norms.
Correlation of medial temporal lobe atrophy with seizures in Alzheimer’s disease and mild cognitive impairment: A case control study
Authors: Dhikav Vikas , Duraisawmy Sharmila , Anand Kuljeet
Published: October 2017

Background Seizures are common accompaniment of neurodegenerative disease. Though, Alzheimer’s disease (AD) is the most common cause, but seizures also occasionally occur in mild cognitive impairment (MCI).

Material & methods We studied patients of Subjective Memory Complaints coming to the Department of Neurology of a Tertiary Care Hospital in Northern India from July 2012 to July 2015. A total of 171 patients were studied. Those with a diagnosis of AD/MCI with seizures were taken for the current study. A total of 30 controls with chronic diseases were taken for comparison. Medial Temporal Lobe Atrophy (MTA) Rating was done using Sheleten’s Visual Rating Scale.

Results A total of 256 patients were screened and 171 had dementia of Alzheimer’s type (n = 75; M:F = 60:15) and 96 patients had MCI (M:F = 76:20). The mean MMSE of those with AD was 18.5 ± 3.3 was and that of the MCI was 26.6 ± 2.4. A total of 9 cases with AD had seizures and 6 had seizures in MCI group (total n = 15). Moderately strong correlation was obtained between MMSE of AD patients having seizures and MTA scoring.

Conclusions Seizures are common in dementia of Alzheimer’s type and not uncommon in MCI. They have the potential to worsen the cognitive profile of the patient and need attention in these patients.
Participant‐Reported Benefits of Involvement in an Adaptive Sports Program: A Qualitative Study
Authors: Lape Emma C. , Katz Jeffrey N. , Losina Elena , Kerman Hannah M. , Gedman Marissa A. , Blauwet Cheri A.
Published: October 2017

Background

Although participation in adaptive sports offers numerous benefits for persons with disabilities, a substantial number of eligible persons do not take part. Previous studies have identified personal and environmental factors that promote or inhibit adaptive sports participation. However, these studies have considered a relatively narrow range of factors.

Objective

To use qualitative research techniques to identify novel factors that influence participation in a community‐based adaptive sports program.

Design

Qualitative focus group study.

Setting

Community‐based adaptive sports programs affiliated with a rehabilitation hospital network.

Participants

Participants were recruited from among 134 adults who registered for the sports program in 2013‐2014. Participants with mobility or sensory impairment, absence of cognitive impairment, and English proficiency were included. The 90 former participants with adequate contact information were contacted, and 17 participated in the focus groups.

Methods

Two moderators led each of 3 audio‐recorded focus groups using a moderator's guide. We conducted a thematic analysis of transcript data to identify perceived benefits, barriers, and facilitators of participation.

Results

Our analysis identified 5 themes: physical well‐being and health/safety; interpersonal and social relationships; intrapersonal and beliefs/attitudes; physical environment; and access. Participants experienced participation both as physically beneficial and as transformative in terms of how they view themselves. However, programs drew on limited personal resources and sometimes presented a perceived risk of injury. Finding information about and transportation to programs was a challenge. Participants formed an informal community that modeled what athletes with disabilities are capable of, helping to overcome initial doubts.

Conclusions

To gain the benefits of participation, athletes overcame significant barriers, several of which may be modifiable, including transportation and difficult‐to‐find information about program offerings. The importance of community and raising awareness of athletes' own abilities suggests a key role for mentorship. Our study contributes to the understanding of experiential aspects that motivate participation in adaptive sports.

Level of Evidence

IV
Reverse Shoulder Arthroplasty in Weight‐Bearing Shoulders of Wheelchair‐Dependent Patients: Outcomes and Complications at 2 to 5 years
Authors: Alentorn‐Geli Eduard , Wanderman Nathan R. , Assenmacher Andrew T. , Sánchez‐Sotelo Joaquín , Cofield Robert H. , Sperling John W.
Published: October 2017

Background

Wheelchair‐dependent patients rely on their upper extremities for mobility and transfers. This entails the heavy use of upper extremities as weight‐bearing joints, leading to shoulder overuse with increased prevalence of rotator cuff–related disorders and ultimately to challenging cases for shoulder surgeons when a joint replacement is needed.

Objective

To report the outcomes of reverse shoulder arthroplasty (RSA) in wheelchair‐dependent patients with arthritis and rotator cuff tears.

Design

Retrospective case series/cross‐sectional study.

Setting

Tertiary university hospital.

Patient (participants)

All wheelchair‐dependent patients undergoing RSA between 2004 and 2013.

Methods/Interventions

Of the 22 wheelchair‐dependent patients undergoing RSA, 18 of them had a minimum follow‐up of 2 years. There were 9 men and 9 women, with a mean (standard deviation) age and length of follow‐up of 68 (8.5) years and 36 (24‐63) months. A retrospective chart review and cross‐sectional phone calls were conducted to obtain all data.

Outcomes

Pain, range of motion, functional scores (Neer scale, simple shoulder test, and American Shoulder and Elbow Society), satisfaction, complications/reoperations, radiographic loosening, and 90‐day mortality/morbidity.

Results

RSA resulted in a significant improvement in pain (P = .02) and nonsignificant improvements in forward flexion (P = .3) and external rotation (P = .07). There were 3 (16%) excellent, 12 (63%) satisfactory, and 4 (21%) unsatisfactory results. The mean (standard deviation) postoperative American Shoulder and Elbow Society score was 56.5 (16.5). All patients stated that they would undergo RSA again. There were no surgically related complications or reoperations. The 90‐day mortality and morbidity rates were 0% and 26%, respectively.

Conclusions

RSA is a safe and effective procedure in wheelchair‐dependent patients who use their shoulders for weight‐bearing purposes. Although functional scores are not optimal and medical complications are not uncommon, 79% of patients had an excellent or satisfactory result.

Level of Evidence

III
Antimicrobial Stewardship Practices Reported by California Hospitals Following New Legislative Requirements: Analysis of National Healthcare Safety Network Annual Survey Data, 2014-2015
Authors: Rizzo Kyle , Kealey Melissa , Epson Erin
Published: October 2017

We analyzed California hospitals’ National Healthcare Safety Network Annual Surveys to describe antimicrobial stewardship program (ASP) implementation progress following new state ASP legislation. The proportion of hospitals with all 7 Core Elements of Hospital ASP rose from 59.3% in 2014 to 69.2% in 2015 (P<.001).

Infect Control Hosp Epidemiol 2017;38:1503–1505
LOCAL BORCHERDS PRODUCTS FOR UNITARY GROUPS
Authors: HOFMANN ERIC
Published: October 2017

For the modular variety attached to an arithmetic subgroup of an indefinite unitary group of signature $(1,n+1)$, with $n\geqslant 1$, we study Heegner divisors in the local Picard group over a boundary component of a compactification. For this purpose, we introduce local Borcherds products. We obtain a precise criterion for local Heegner divisors to be torsion elements in the Picard group, and further, as an application, we show that the obstructions to a local Heegner divisor being a torsion element can be described by certain spaces of vector-valued elliptic cusp forms, transforming under a Weil representation.
MAXIMUM GENUS EMBEDDINGS OF LATIN SQUARES
Authors: GRIGGS TERRY S. , PSOMAS CONSTANTINOS , ŠIRÁŇ JOZEF
Published: October 2017

It is proved that every non-trivial Latin square has an upper embedding in a non-orientable surface and every Latin square of odd order has an upper embedding in an orientable surface. In the latter case, detailed results about the possible automorphisms and their actions are also obtained.
Can existing mobile apps support healthier food purchasing behaviour? Content analysis of nutrition content, behaviour change theory and user quality integration
Authors: Flaherty Sarah-Jane , McCarthy Mary , Collins Alan , McAuliffe Fionnuala
Published: October 2017

Objective

To assess the quality of nutrition content and the integration of user quality components and behaviour change theory relevant to food purchasing behaviour in a sample of existing mobile apps.

Design

Descriptive comparative analysis of eleven mobile apps comprising an assessment of their alignment with existing evidence on nutrition, behaviour change and user quality, and their potential ability to support healthier food purchasing behaviour.

Setting

Mobile apps freely available for public use in GoogePlay were assessed and scored according to agreed criteria to assess nutrition content quality and integration of behaviour change theory and user quality components.

Subjects

A sample of eleven mobile apps that met predefined inclusion criteria to ensure relevance and good quality.

Results

The quality of the nutrition content varied. Improvements to the accuracy and appropriateness of nutrition content are needed to ensure mobile apps support a healthy behaviour change process and are accessible to a wider population. There appears to be a narrow focus towards behaviour change with an overemphasis on behavioural outcomes and a small number of behaviour change techniques, which may limit effectiveness. A significant effort from the user was required to use the mobile apps appropriately which may negatively influence user acceptability and subsequent utilisation.

Conclusions

Existing mobile apps may offer a potentially effective approach to supporting healthier food purchasing behaviour but improvements in mobile app design are required to maximise their potential effectiveness. Engagement of mobile app users and nutrition professionals is recommended to support effective design.
Unchained Succubus: A Queer New Institutional Analysis of U.S. Supreme Court Nomination Hearings
Authors: McMahon Adam M.
Published: October 2017

Modern Supreme Court nomination hearings are contentious political events, as evidenced by the four held during the 109th and 111th Congresses to confirm John Roberts, Samuel Alito, Sonia Sotomayor, and Elena Kagan. Senators appear to raise suspicion of nominees purposefully through their questioning during Judiciary Committee hearings, connecting the label of “judicial restraint” with candidates who are male, white, straight, and prone to “reason.” Appointees thought to embody the feminine, nonwhite, queer, and emotional practices of “judicial activism” to offer a contrast. This dichotomous construction has made debates during the nomination process destructively reductive. A paradox thus emerges: by ignoring the importance of descriptive representation, the identity of potential justices to the Supreme Court becomes one of the most salient issues during the hearings; subsequently, this has resulted in senators using cues to create a caricature or “straw man” of nominees belonging to one or more minority groups in order to weaken and discredit otherwise qualified jurists and achieve a party “win” against the White House.
Überblick über interventionelle Therapieverfahren bei spezifischen und unspezifischen Rückenschmerzen
Authors: Bremerich Friedrich
Published: October 2017

Zusammenfassung. Die Behandlung spezifischer und unspezifischer Rückenschmerzen gelingt nur mit gutem Wissen der Anamnese eines Patienten, seiner aktuellen Beschwerden und nach gründlicher körperlicher Untersuchung. Die meisten Patienten leiden an nicht spezifischem Rückenschmerz. Diese profitieren von interdisziplinärer Behandlung unter Berücksichtigung der individuellen Gegebenheiten. Opiate sollten nur mit Vorsicht eingesetzt werden. Bildgebung und apparative Untersuchungen sind wertvolle Bestandteile zur Identifikation der Schmerzursachen, oft aber nicht allein wegweisend. Diagnostische spinale Infiltrationen sind nützlich, um den Schmerzursprung zu lokalisieren und weisen so den Weg für das Management der Therapie. Die Infiltrationen müssen mit aller medizinischen Vorsicht und reproduzierbar erfolgen. Sie sind Teil des interdisziplinären Behandlungspfades. Versagen der konservativen interdisziplinären Therapie kann zur Evaluation hinsichtlich der spinalen Neurostimulation führen. Von dieser profitieren viele Patienten. Substantielle und schnelle Schmerzlinderung ist wichtig, um die Funktion zu erhalten und dem Patienten die Rückkehr zur Berufstätigkeit wie auch zu Freizeitaktivitäten zu ermöglichen.
Ultraschall – eine Revolution in der Schmerztherapie?
Authors: Lorenzana David , Eichenberger Urs
Published: October 2017

Zusammenfassung. Der Ultraschall ist ein mobiles bildgebendes Verfahren ohne Strahlenbelastung für Patient und Therapeut. Die Vielzahl von Publikationen zu ultraschallkontrollierten schmerztherapeutischen Interventionen unterstreicht die zunehmende Bedeutung des Ultraschalls in der interventionellen Schmerzmedizin. Der Ultraschall kann aber nicht nur zur Kontrolle von Interventionen, sondern auch zur Diagnostik von Pathologien peripherer Nerven eingesetzt werden. Ultraschallgestützte Nervendiagnostik hat in den letzten Jahren bei Neurologen zunehmend an Bedeutung gewonnen und wird in Zukunft auch für den im Ultraschall versierten Schmerztherapeuten von Interesse sein. Eine präzise, vielseitige, innovative und sichere Schmerztherapie ist ohne Ultraschall kaum mehr denkbar.
Erratum: An intrinsic mechanism controls reactivation of neural stem cells by spindle matrix proteins
Authors: Li Song , Koe Chwee Tat , Tay Su Ting , Tan Angie Lay Keng , Zhang Shenli , Zhang Yingjie , Tan Patrick , Sung Wing-Kin , Wang Hongyan
Published: October 2017

A correction to this article has been published and is linked from the HTML version of this article.
Monitoring and manipulating cellular crosstalk during kidney fibrosis inside a 3D in vitro co-culture
Authors: Nugraha Bramasta , Mohr Manuel A. , Ponti Aaron , Emmert Maximilian Y. , Weibel Franziska , Hoerstrup Simon P. , Moll Solange , Certa Ulrich , Prunotto Marco , Pantazis Periklis
Published: October 2017

In pharmacological research the development of promising lead compounds requires a detailed understanding of the dynamics of disease progression. However, for many diseases, such as kidney fibrosis, gaining such understanding requires complex real-time, multi-dimensional analysis of diseased and healthy tissue. To allow for such studies with increased throughput we established a dextran hydrogel-based in vitro 3D co-culture as a disease model for kidney fibrosis aimed at the discovery of compounds modulating the epithelial/mesenchymal crosstalk. This platform mimics a simplified pathological renal microenvironment at the interface between tubular epithelial cells and surrounding quiescent fibroblasts. We combined this 3D technology with epithelial reporter cell lines expressing fluorescent biomarkers in order to visualize pathophysiological cell state changes resulting from toxin-mediated chemical injury. Epithelial cell damage onset was robustly detected by image-based monitoring, and injured epithelial spheroids induced myofibroblast differentiation of co-cultured quiescent human fibroblasts. The presented 3D co-culture system therefore provides a unique model system for screening of novel therapeutic molecules capable to interfere and modulate the dialogue between epithelial and mesenchymal cells.
Acute Psychological Stress Disrupts Attentional Bias to Threat-Related Stimuli
Authors: Jiang Caihong , Buchanan Tony W. , Yao Zhuxi , Zhang Kan , Wu Jianhui , Zhang Liang
Published: October 2017

The present study investigated the effect of acute stress on attentional bias to threat using behavioral and ERP methods. Sixty-two male participants were randomly assigned to a stress condition (Trier Social Stress Test) or a control condition. To examine the impact of stress-induced cortisol on attentional bias to threat, participants in the stress group were split into Low- and High cortisol responders. All participants were then administered a modified dot probe task in which the cues were neutral and angry faces. Behavioral results showed a pattern of attentional bias toward threat in the Control group but not in the stress group. For the ERPs, the P100 peaked earlier for the angry-cued targets than the neutral-cued targets in the Control group, which suggests a rapid, adaptive response toward threat. However, this effect was not observed in the stress group, suggesting a suppressed attentional bias under stress. In addition, the stress group (including both Low and High cortisol responders) showed reduced P300 amplitude to target onset than the Control group. These results suggest that acute stress disrupts attentional bias to threat including a reduction in early bias to threat in addition to a subsequent change of attention allocation.
Influence of facial feedback during a cooperative human-robot task in schizophrenia
Authors: Cohen Laura , Khoramshahi Mahdi , Salesse Robin N. , Bortolon Catherine , Słowiński Piotr , Zhai Chao , Tsaneva-Atanasova Krasimira , Di Bernardo Mario , Capdevielle Delphine , Marin Ludovic , Schmidt Richard C. , Bardy Benoit G. , Billard Aude , Raffard Stéphane
Published: October 2017

Rapid progress in the area of humanoid robots offers tremendous possibilities for investigating and improving social competences in people with social deficits, but remains yet unexplored in schizophrenia. In this study, we examined the influence of social feedbacks elicited by a humanoid robot on motor coordination during a human-robot interaction. Twenty-two schizophrenia patients and twenty-two matched healthy controls underwent a collaborative motor synchrony task with the iCub humanoid robot. Results revealed that positive social feedback had a facilitatory effect on motor coordination in the control participants compared to non-social positive feedback. This facilitatory effect was not present in schizophrenia patients, whose social-motor coordination was similarly impaired in social and non-social feedback conditions. Furthermore, patients’ cognitive flexibility impairment and antipsychotic dosing were negatively correlated with patients’ ability to synchronize hand movements with iCub. Overall, our findings reveal that patients have marked difficulties to exploit facial social cues elicited by a humanoid robot to modulate their motor coordination during human-robot interaction, partly accounted for by cognitive deficits and medication. This study opens new perspectives for comprehension of social deficits in this mental disorder.
Cyclophilin D regulates the dynamic assembly of mitochondrial ATP synthase into synthasomes
Authors: Beutner Gisela , Alanzalon Ryan E. , Porter George A.
Published: October 2017

Mitochondrial electron transport is essential for oxidative phosphorylation (OXPHOS). Electron transport chain (ETC) activity generates an electrochemical gradient that is used by the ATP synthase to make ATP. ATP synthase is organized into supramolecular units called synthasomes that increase the efficiency of ATP production, while within ATP synthase is the cyclophilin D (CypD) regulated mitochondrial permeability transition pore (PTP). We investigated whether synthasomes are dynamic structures that respond to metabolic demands and whether CypD regulates this dynamic. Isolated heart mitochondria from wild-type (WT) and CypD knockout (KO) mice were treated to either stimulate OXPHOS or open the PTP. The presence and dynamics of mitochondrial synthasomes were investigated by native electrophoresis, immunoprecipitation, and sucrose density centrifugation. We show that stimulation of OXPHOS, inhibition of the PTP, or deletion of CypD increased high order synthasome assembly. In contrast, OXPHOS inhibition or PTP opening increased synthasome disassembly in WT, but not in CypD KO heart mitochondria. CypD activity also correlated with synthasome assembly in other tissues, such as liver and brain. We conclude that CypD not only regulates the PTP, but also regulates the dynamics of synthasome assembly depending on the bioenergetic state of the mitochondria.
Observation of photobleaching in Ge-deficient Ge16.8Se83.2 chalcogenide thin film with prolonged irradiation
Authors: Zhang Sen , Chen Yimin , Wang Rongping , Shen Xiang , Dai Shixun
Published: October 2017

We presented the unusual result of photobleaching (PB) in Ge-deficient Ge16.8Se83.2 thin films with continuous irradiation with 560 nm laser for 12000 s, which is contradicted with the previous reports that the PB only occurs in GexSe100-x films with x > 30. Observation of the dynamics variations of the photo-induced effects indicated that, photodarkening (PD) appears almost instantaneously upon light irradiation, saturates faster in a shorter time scale, and then photobleaching (PB) becomes dominant. Moreover, both PD and PB process accelerates with increasing irradiation power density. Raman spectra provided the evidence on the change of the photostructure of the samples, e.g. the structural transformation from Ge(Se1/2)4 edge-sharing (ES) to corner-sharing (CS) tetrahedral and homopolar Ge-Ge and Se-Se bonds to heteropolar Ge-Se bonds.
Modular endolysin of Burkholderia AP3 phage has the largest lysozyme-like catalytic subunit discovered to date and no catalytic aspartate residue
Authors: Maciejewska Barbara , Źrubek Karol , Espaillat Akbar , Wiśniewska Magdalena , Rembacz Krzysztof P. , Cava Felipe , Dubin Grzegorz , Drulis-Kawa Zuzanna
Published: October 2017

Endolysins are peptidoglycan-degrading enzymes utilized by bacteriophages to release the progeny from bacterial cells. The lytic properties of phage endolysins make them potential antibacterial agents for medical and industrial applications. Here, we present a comprehensive characterization of phage AP3 modular endolysin (AP3gp15) containing cell wall binding domain and an enzymatic domain (DUF3380 by BLASTP), both widespread and conservative. Our structural analysis demonstrates the low similarity of an enzymatic domain to known lysozymes and an unusual catalytic centre characterized by only a single glutamic acid residue and no aspartic acid. Thus, our findings suggest distinguishing a novel class of muralytic enzymes having the activity and catalytic centre organization of DUF3380. The lack of amino acid sequence homology between AP3gp15 and other known muralytic enzymes may reflect the evolutionary convergence of analogous glycosidases. Moreover, the broad antibacterial spectrum, lack of cytotoxic effect on human cells and the stability characteristics of AP3 endolysin advocate for its future application development.
Disease-relevant signalling-pathways in head and neck cancer: Taspase1’s proteolytic activity fine-tunes TFIIA function
Authors: Gribko Alena , Hahlbrock Angelina , Strieth Sebastian , Becker Sven , Hagemann Jan , Deichelbohrer Max , Hildebrandt Andreas , Habtemichael Negusse , Wünsch D.
Published: October 2017

Head and neck cancer (HNC) is the seventh most common malignancy in the world and its prevailing form, the head and neck squamous cell carcinoma (HNSCC), is characterized as aggressive and invasive cancer type. The transcription factor II A (TFIIA), initially described as general regulator of RNA polymerase II-dependent transcription, is part of complex transcriptional networks also controlling mammalian head morphogenesis. Posttranslational cleavage of the TFIIA precursor by the oncologically relevant protease Taspase1 is crucial in this process. In contrast, the relevance of Taspase1-mediated TFIIA cleavage during oncogenesis of HNSCC is not characterized yet. Here, we performed genome-wide expression profiling of HNSCC which revealed significant downregulation of the TFIIA downstream target CDKN2A. To identify potential regulatory mechanisms of TFIIA on cellular level, we characterized nuclear-cytoplasmic transport and Taspase1-mediated cleavage of TFIIA variants. Unexpectedly, we identified an evolutionary conserved nuclear export signal (NES) counteracting nuclear localization and thus, transcriptional activity of TFIIA. Notably, proteolytic processing of TFIIA by Taspase1 was found to mask the NES, thereby promoting nuclear localization and transcriptional activation of TFIIA target genes, such as CDKN2A. Collectively, we here describe a hitherto unknown mechanism how cellular localization and Taspase1 cleavage fine-tunes transcriptional activity of TFIIA in HNSCC.
Sex differentiation in grayling (Salmonidae) goes through an all-male stage and is delayed in genetic males who instead grow faster
Authors: Maitre Diane , Selmoni Oliver M. , Uppal Anshu , Marques da Cunha Lucas , Wilkins Laetitia G. E. , Roux Julien , Mobley Kenyon B. , Castro Isabelle , Knörr Susanne , Robinson-Rechavi Marc , Wedekind Claus
Published: October 2017

Fish populations can be threatened by distorted sex ratios that arise during sex differentiation. Here we describe sex differentiation in a wild grayling (Thymallus thymallus) population that suffers from distorted sex ratios. We verified that sex determination is linked to the sex determining locus (sdY) of salmonids. This allowed us to study sex-specific gene expression and gonadal development. Sex-specific gene expression could be observed during embryogenesis and was strong around hatching. About half of the fish showed immature testes around eleven weeks after fertilization. This phenotype was mostly replaced by the “testis-to-ovary” or “ovaries” phenotypes during development. The gonads of the remaining fish stayed undifferentiated until six months after fertilization. Genetic sexing revealed that fish with undifferentiated gonads were all males, who grew larger than the genetic females during the observational period. Only 12% of the genetic males showed testicular tissue six months after fertilization. We conclude that sex differentiation starts before hatching, goes through an all-male stage for both sexes (which represents a rare case of “undifferentiated” gonochoristic species that usually go through an all-female stage), and is delayed in males. During these juvenile stages males grow faster than females instead of developing their gonads.
Changes in GABAergic markers accompany degradation of neuronal function in the primary visual cortex of senescent rats
Authors: Ding Yanxia , Zheng Yuan , Liu Tao , Chen Ting , Wang Changhua , Sun Qiushuang , Hua Mutian , Hua Tianmiao
Published: October 2017

Numerous studies have reported age-dependent degradation of neuronal function in the visual cortex and have attributed this functional decline to weakened intracortical inhibition, especially GABAergic inhibition. However, whether this type of functional decline is linked to compromised GABAergic inhibition has not been fully confirmed. Here, we compared the neuronal response properties and markers of GABAergic inhibition in the primary visual cortex (V1) of young adult and senescent rats. Compared with those of young adult rats, old rats’ V1 neurons exhibited significantly increased visually evoked responses and spontaneous activity, a decreased signal-to-noise ratio and reduced response selectivity for the stimulus orientation and motion direction. Additionally, the ratio of GABA-positive neurons to total cortical neurons in old rats was significantly decreased compared with that in young rats. Expression of the key GABA-synthesizing enzyme GAD67 was significantly lower in old rats than in young rats, although GAD65 expression showed a marginal difference between the two age groups. Further, expression of an important GABAA receptor subunit, GABAAR α1, was significantly attenuated in old rats relative to young ones. These results demonstrate that ageing may result in decreased GABAergic inhibition in the visual cortex and that this decrease in GABAergic inhibition accompanies neuronal function degradation.
The burden and challenges of tuberculosis in China: findings from the Global Burden of Disease Study 2015
Authors: Zhu Sui , Xia Lan , Yu Shicheng , Chen Saobing , Zhang Juying
Published: October 2017

To achieve the End Tuberculosis (TB) Strategy, it is important to understand the characteristics of TB in China, which may provide the government with important clues for controlling TB by 2030. Data from the Global Burden of Disease Study 2015 (GBD 2015) and Institute for Health Metrics and Evaluation (IHME) were reviewed and analysed. The age-standardized death rate decreased by 83.79% [95% uncertainty interval (UI) 73.06–87.10] from 1990 to 2015. The age-standardized prevalence of TB in males decreased steadily by 33.88% (95% UI 29.35–37.67) but nearly increased by 6.24% (95% UI -2.02–15.07) in females from 1990 to 2015. Disability-adjusted life years (DALYs) were higher in males than in females, and the highest TB burden was found in the elderly (70+ years of age). Over the period 1990–2015, the attributable age-standardized DALY rates for smoking decreased by 12.98% (95% UI 2.40–24.27), but increased for alcohol use and high fasting plasma glucose (HFPG). Greater attention should be paid to females especially in the under 5 years of age group, and more latent reasons explaining TB DALYs should be explored in future studies.
Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux
Authors: Darlow John M. , Darlay Rebecca , Dobson Mark G. , Stewart Aisling , Charoen Pimphen , Southgate Jennifer , Baker Simon C. , Xu Yaobo , Hunziker Manuela , Lambert Heather J. , Green Andrew J. , Santibanez-Koref Mauro , Sayer John A. , Goodship Timothy H. J. , Puri Prem , Woolf Adrian S. , Kenda Rajko B. , Barton David E. , Cordell Heather J.
Published: October 2017

Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions – congenital dysplasia, acquired scarring or both – are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene butFOXI2,FANK1andGLRX3remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.
A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro
Authors: Maggi Maristella , Mittelman Steven D. , Parmentier Jean Hugues , Colombo Giorgio , Meli Massimiliano , Whitmire Jeannette Marie , Merrell D. Scott , Whitelegge Julian , Scotti Claudia
Published: October 2017

L-Asparaginases (ASNases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment for more than 40 years. Both the Escherichia coli (EcAII) and Erwinia chrysanthemi (ErAII) type II ASNases currently used in the clinics are characterized by high in vivo instability, short half-life and the requirement of several administrations to obtain a pharmacologically active concentration. Moreover, they are sensitive to proteases (cathepsin B and asparagine endopeptidase) that are over-expressed by resistant leukaemia lymphoblasts, thereby impairing drug activity and pharmacokinetics. Herein, we present the biochemical, structural and in vitro antiproliferative characterization of a new EcAII variant, N24S. The mutant shows completely preserved asparaginase and glutaminase activities, long-term storage stability, improved thermal parameters, and outstanding resistance to proteases derived from leukaemia cells. Structural analysis demonstrates a modification in the hydrogen bond network related to residue 24, while Normal Mode-based geometric Simulation and Molecular Dynamics predict a general rigidification of the monomer as compared to wild-type. These improved features render N24S a potential alternative treatment to reduce the number of drug administrations in vivo and to successfully address one of the major current challenges of ALL treatment: spontaneous, protease-dependent and immunological inactivation of ASNase.
Shotgun Glycomics Identifies Tumor-Associated Glycan Ligands Bound by an Ovarian Carcinoma-Specific Monoclonal Antibody
Authors: Liau B. , Tan B. , Teo G. , Zhang P. , Choo A. , Rudd P. M.
Published: October 2017

Cancers display distinctive carbohydrate molecules (glycans) on their surface proteins and lipids. mAb A4, an in-house generated monoclonal IgM antibody, is capable of distinguishing malignant ovarian carcinoma cells from benign ovarian epithelia by binding specifically to cancer cell-associated glycans. However, the structural details of the glycan targets of mAb A4 have been elusive. Here we developed a novel approach of isolating and fractionating glycan molecules released from glycoproteins in cancer cell lysates using HILIC-UPLC, and used them as probes on a microarray for affinity-based identification of the binding targets, allowing full-size, difficult to synthesize, cancer-associated glycans to be directly studied. As a result of this “shotgun” glycomics approach, we corroborate the previously assigned specificity of mAb A4 by showing that mAb A4 binds primarily to large (>15 glucose units), sialylated N-glycans containing the H-type 1 antigen (Fuc-α1,2-Gal-β1,3-GlcNAc). Although mAb A4 was also capable of directly binding to type 1 N-acetyl-lactosamine, this epitope was mostly shielded by sialylation and thus relatively inaccessible to binding. Knowledge of the structure of mAb A4 antigen will facilitate its clinical development as well as its use as a diagnostic biomarker.
L290P/V mutations increase ERK3’s cytoplasmic localization and migration/invasion-promoting capability in cancer cells
Authors: Alsaran Hadel , Elkhadragy Lobna , Shakya Astha , Long Weiwen
Published: October 2017

Protein kinases are frequently mutated in human cancers, which leads to altered signaling pathways and contributes to tumor growth and progression. ERK3 is an atypical mitogen-activated protein kinase (MAPK) containing an S-E-G activation motif rather than the conserved T-X-Y motif in conventional MAPKs such as ERK1/2. Recent studies have revealed important roles for ERK3 in cancers. ERK3 promotes cancer cell migration/invasion and tumor metastasis, and its expression is upregulated in multiple cancers. Little is known, however, regarding ERK3 mutations in cancers. In the present study, we functionally and mechanistically characterized ERK3 L290P/V mutations, which are located within ERK3’s kinase domain, and are shown to exist in several cancers including lung cancer and colon cancer. We found that in comparison with wild type ERK3, both L290P and L290V mutants have greatly increased activity in promoting cancer cell migration and invasion, but have little impact on ERK3’s role in cell proliferation. Mechanistically, while they have no clear effect on kinase activity, L290P/V mutations enhance ERK3’s cytoplasmic localization by increasing the interaction with the nuclear export factor CRM1. Our findings suggest that L290P/V mutations of ERK3 may confer increased invasiveness to cancers.
Dynamic coupling between slow waves and sleep spindles during slow wave sleep in humans is modulated by functional pre-sleep activation
Authors: Yordanova Juliana , Kirov Roumen , Verleger Rolf , Kolev Vasil
Published: October 2017

Co-existent sleep spindles and slow waves have been viewed as a mechanism for offline information processing. Here we explored if the temporal synchronization between slow waves and spindle activity during slow wave sleep (SWS) in humans was modulated by preceding functional activations during pre-sleep learning. We activated differentially the left and right hemisphere before sleep by using a lateralized variant of serial response time task (SRTT) and verified these inter-hemispheric differences by analysing alpha and beta electroencephalographic (EEG) activities during learning. The stability and timing of coupling between positive and negative phases of slow waves and sleep spindle activity during SWS were quantified. Spindle activity was temporally synchronized with both positive (up-state) and negative (down-state) slow half waves. Synchronization of only the fast spindle activity was laterally asymmetric after learning, corresponding to hemisphere-specific activations before sleep. However, the down state was associated with decoupling, whereas the up-state was associated with increased coupling of fast spindle activity over the pre-activated hemisphere. These observations provide original evidence that (1) the temporal grouping of fast spindles by slow waves is a dynamic property of human SWS modulated by functional pre-sleep activation patterns, and (2) fast spindles synchronized by slow waves are functionally distinct.