bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cradle of the New Humanitarian System? International Work and European Volunteers at the Cambodian Border Camps, 1979–1993
Authors: TAITHE BERTRAND
Published: April 2016

This article investigates the development of communities of practice in Thai-border Cambodian refugee camps for those international humanitarian workers involved at the frontiers of the Cold War. Under the management of the United Nations Border Relief Operation (UNBRO) and United Nations High Commissioner for Refugees (UNHCR) these camps brought together various NGOs and volunteers. Their prolonged presence at the border of Thailand enabled an epistemic community to emerge which facilitated the production of knowledge on refugees. Using oral histories and the archives of NGOs, this article investigates the development of an international community of practice in which Europeans played a key role, one which centred on the medical and social needs of refugees at a time of acute political instrumental use of humanitarian aid. The focus of humanitarians' work on genocide and associated trauma, resulted in a clear political awareness that humanitarian aid had been used to maintain Khmer Rouge presence at the borders and that, in the peace negotiations of the early 1990s, it might facilitate their territorial and political return to a position of power.
The association between aspects of daily life and quality of life of people with dementia living in long-term care facilities: a momentary assessment study
Authors: Beerens Hanneke C. , de Boer Bram , Zwakhalen Sandra M.G. , Tan Frans E.S. , Ruwaard Dirk , Hamers Jan P.H. , Verbeek Hilde
Published: April 2016

Background:

To improve the quality of life (QoL) of people with dementia (PwD) living in long-term care facilities, insight into the association between QoL and how people spend their daily lives is urgently needed. This study investigated which aspects of daily life are related to QoL in dementia.

Methods:

An observational study was conducted. Daily life was assessed with the tablet-based Maastricht Electronic Daily Life Observation-tool (MEDLO-tool). Aspects included activity, engagement in the activity, social interaction, physical effort, mood, and agitation. QoL was assessed by formal nursing caregivers using the Quality of Life-Alzheimer's Disease scale (QoL-AD). A total of 9,660 momentary assessments were conducted.

Results:

The mean age of the 115 participants was 84 years and most (75%) were women. Bivariate analyses showed that residents with a higher QoL carried out less passive/purposeless activities (25% vs. 38%), were more engaged in active, expressive, and social activities, (40% vs. 27%), had more social interaction (34% vs. 22%), and had better mood scores (scale 1–7, 5.0 vs. 4.8), compared with residents with a lower QoL (allp-values < 0.001). Multivariate analyses showed that having more social interaction and a positive mood are related to a higher QoL.

Conclusions:

The results underline the importance of social interaction and a positive mood for a higher QoL. Future research should investigate the importance of engagement in activities in more detail.
Deep-neural network approaches for speech recognition with heterogeneous groups of speakers including children
Authors: SERIZEL ROMAIN , GIULIANI DIEGO
Published: April 2016

This paper introduces deep neural network (DNN)–hidden Markov model (HMM)-based methods to tackle speech recognition in heterogeneous groups of speakers including children. We target three speaker groups consisting of children, adult males and adult females. Two different kind of approaches are introduced here: approaches based on DNN adaptation and approaches relying on vocal-tract length normalisation (VTLN). First, the recent approach that consists in adapting a general DNN to domain/language specific data is extended to target age/gender groups in the context of DNN–HMM. Then, VTLN is investigated by training a DNN–HMM system by using either mel frequency cepstral coefficients normalised with standard VTLN or mel frequency cepstral coefficients derived acoustic features combined with the posterior probabilities of the VTLN warping factors. In this later, novel, approach the posterior probabilities of the warping factors are obtained with a separate DNN and the decoding can be operated in a single pass when the VTLN approach requires two decoding passes. Finally, the different approaches presented here are combined to take advantage of their complementarity. The combination of several approaches is shown to improve the baseline phone error rate performance by thirty per cent to thirty-five per cent relative and the baseline word error rate performance by about ten per cent relative.
The psychosocial experiences of older palliative patients while participating in a Living with Hope Program
Authors: Duggleby Wendy , Cooper Dan , Nekolaichuk Cheryl , Cottrell Laura , Swindle Jenny , Barkway Kelsi
Published: April 2016

Objective:

Several studies have reported the effectiveness of a variety of psychosocial interventions in increasing levels of hope in palliative care patients. The experience of palliative patients while participating in these interventions is unknown. Understanding these experiences would provide a rich understanding of how the interventions work to foster hope. The purpose of the present study was to describe the psychosocial processes that participants with advanced cancer receiving palliative care experienced when taking part in a Living with Hope Program (LWHP).

Method:

In the context of a study evaluating the LWHP, data were collected from 13 dyads (persons with advanced cancer and their caregivers) at two timepoints (one week apart). A thematic qualitative analysis of 52 open-ended audiotaped interviews was conducted that focused on the psychosocial processes that occurred during the LWHP.

Results:

The average age of palliative participants was 67 (SD = 6.6) and of their family caregivers 61 years of age (SD = 13.9). A thematic analysis suggested that the participants experienced the following psychosocial processes while participating in the LWHP: (1) reminiscing, (2) leaving a legacy, (3) positive reappraisal, and (4) motivational processes. These processes are the mechanisms by which the LWHP fosters the positive outcomes of increasing hope and improving quality of life. As well, the finding of motivational processes suggested that the LWHP may also increase life satisfaction, which is an outcome of motivational processes.

Significance of the results:

The findings from our study underscore the importance of uncovering the psychosocial processes through which the LWHP works to foster hope. They will assist in making revisions to the intervention that will increase its effectiveness, as well as providing a better understanding of hope in persons with advanced cancer.
Reliability and validity of the Turkish version of the EORTC QLQ–C15–PAL for patients with advanced cancer
Authors: Ozcelik Hanife , Guzel Yasemin , Sonmez Esra , Aksoy Fatma , Uslu Ruchan
Published: April 2016

Objective:

Assessing quality of life, which is the main focus of palliative care, is highly important. The number of available, specific, simple, and valid assessment instruments for patients with advanced cancer in Turkey is limited. The aim of our study was to perform a psychometric evaluation of the Turkish version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core 15–PAL (EORTC QLQ–C15–PAL).

Method:

The study was conducted in İzmir with patients who had received treatment in the palliative care unit of a university hospital between November of 2011 and December of 2013. Sociodemographic and disease characteristics forms, the Karnofsky Performance Status (KPS) Scale, and the EORTC QLQ–C15–PAL Scale were employed in order to gather data.

Results:

A total of 150 patients completed the study: 55.3% of participants were female, 80.7% were married, and the average age was 52.76 ± 14.55. The value of Cronbach's α in the analyses ranged from 0.93 to 0.98. Most questionnaire areas had low to moderate correlations with the others. The moderate correlations were between fatigue and physical function (–0.41) and between insomnia and emotional function (–0.53). Conversely, weak correlations were found between nausea/vomiting and appetite loss (0.31) and between insomnia and pain (0.22). KPS scores decreased, patient physical and emotional function were diminished, global QoL declined, and patients' symptoms became more frank.

Significance of results:

We concluded that the EORTC QLQ–C15–PAL is a valid and reliable tool to determine the quality of life of advanced cancer patients who are undergoing palliative treatment in Turkey.
Prevalence and risk of violence and the mental, physical and sexual health problems associated with human trafficking: an updated systematic review
Authors: Ottisova L. , Hemmings S. , Howard L.M. , Zimmerman C. , Oram S.
Published: April 2016

Background.

To update and expand on a 2012 systematic review of the prevalence and risk of violence and the prevalence and risk of physical, mental and sexual health problems among trafficked people.

Method.

Systematic review and meta-analysis. Searches of 15 electronic databases of peer-reviewed articles and doctoral theses were supplemented by reference screening, citation tracking of included articles and expert recommendations. Studies were included if they reported on the prevalence or risk of violence while trafficked, or the prevalence or risk of physical, mental or sexual health outcomes among people who have been trafficked. Two reviewers independently screened papers for eligibility and appraised the quality of included studies.

Results.

Thirty-seven papers reporting on 31 studies were identified. The majority of studies were conducted in low and middle-income countries with women and girls trafficked into the sex industry. There is limited but emerging evidence on the health of trafficked men and the health consequences of trafficking into different forms of exploitation. Studies indicate that trafficked women, men and children experience high levels of violence and report significant levels of physical health symptoms, including headaches, stomach pain and back pain. Most commonly reported mental health problems include depression, anxiety and post-traumatic stress disorder. Although serological data on sexually transmitted infections are limited, women and girls trafficked for sexual exploitation self-report symptoms suggestive of a high prevalence of infections. Limitations of the review include methodological weaknesses of primary studies and some differences in definition and operationalisation of trafficking, which hinder comparability and generalisability of the results.

Conclusions.

There is increasing evidence human trafficking is associated with high prevalence and increased risk of violence and a range of physical and mental health problems. Although more studies have emerged in recent years reporting on the health of trafficked men and people trafficked for forms of exploitation other than in the sex industry, further research is needed in this area. Appropriate interventions and support services to address the multiple and serious medical needs, especially mental health, of trafficked people are urgently needed.
Prejudice, Social Dominance, and Similarity among People who Favor Integration of Minorities
Authors: Martínez Carmen , Saiz José , Angosto Josefa
Published: April 2016

This study examines differences in prejudice, perceived similarity, and social dominance in members of the majority who favor integration as a means of minority acculturation. A total of 342 non-Gypsy Spanish participants filled out a questionnaire about their relationship to one of three outgroups: Maghrebians, Gypsies, and Latin Americans. Hierarchical cluster analysis showed that a three-cluster solution was most fitting for every outgroup. ANOVAs applied to the three clusters indicated significant differences in prejudice, perceived similarity, and social dominance. Referring to Gypsies the largest effect size was observed in manifest prejudice (η2= .63), in Maghrebians, the largest effect size was observed in subtle prejudice (η2=.77), while for Latin Americans, perceived similarity had the largest effect size η2( = .60). The results reveal a need to modify existing measures of integration; we recommend using questionnaires to measure behaviors that members of the majority would be willing to implement.
The Bidirectional Relationship Between Person-Job Fit and Work	Engagement
Authors: de Beer Leon T. , Rothmann Sebastiaan , Mostert Karina
Published: April 2016

Abstract. Although theorized and generally accepted, research on the relationship (specifically the direction of the causal relationship) between person-job fit and work engagement is limited and not yet clear. Theoretical arguments can be presented for both directions, but empirical evidence is scarce. The study reported here explored the bidirectional relationship between person-job fit and work engagement in a longitudinal design. A three-wave cross-lagged panel design was used in a sample of 382 participants from the financial, healthcare, and manufacturing industries in South Africa. The results of Bayesian informative hypothesis testing showed the most support for the hypothesis stating that work engagement is a stronger predictor of person-job fit over time. Conversely, the hypothesis that person-job fit is the predictor of work engagement over time received limited support.
Participative Supervisory Behavior and the Importance of Feeling Safe	and Competent to Voice
Authors: Svendsen Mari , Jønsson Thomas S. , Unterrainer Christine
Published: April 2016

Abstract. In our field study of 147 employees and their supervisors, we tested a moderated mediation model, investigating how participative supervisory behavior relates differently to promotive and prohibitive voice. Overall, we found a significant effect of participative supervisory behavior on promotive and prohibitive voice, and this effect was mediated by psychological safety for prohibitive voice, but not promotive voice. Unexpectedly, we did not find a direct moderation effect of occupational self-efficacy. However, our results suggest that occupational self-efficacy creates a conditional indirect effect for prohibitive voice. Accordingly, our results shed light on the boundary conditions of participative supervisory behavior and illustrate the usefulness of conceptualizing voice as promotive and prohibitive. Implications for theory and practice are discussed.
Salinity Monitoring Gives Insight into the Global Water Cycle
Authors: Stammer Detlef
Published: April 2016

Salinity and Water Cycle over the Oceans: Recent Progress and Future Challenges; Hamburg, Germany, 12–15 October 2015
Controversial Pacts Aim for Dam Removals on Western U.S. River
Authors: Showstack Randy
Published: April 2016

New agreements regarding the Klamath River in Oregon and California would enable the largest U.S. dam removal project ever. Critics say water quality will suffer, decry hydropower loss.
Temperate phages enhance pathogen fitness in chronic lung infection
Authors: Davies Emily V , James Chloe E , Kukavica-Ibrulj Irena , Levesque Roger C , Brockhurst Michael A , Winstanley Craig
Published: April 2016

The Liverpool Epidemic Strain (LES) is a polylysogenic, transmissible strain of Pseudomonas aeruginosa, capable of superinfecting existing P. aeruginosa respiratory infections in individuals with cystic fibrosis (CF). The LES phages are highly active in the CF lung and may have a role in the competitiveness of the LES in vivo. In this study, we tested this by competing isogenic PAO1 strains that differed only by the presence or absence of LES prophages in a rat model of chronic lung infection. Lysogens invaded phage-susceptible populations, both in head-to-head competition and when invading from rare, in the spatially structured, heterogeneous lung environment. Appreciable densities of free phages in lung tissue confirmed active phage lysis in vivo. Moreover, we observed lysogenic conversion of the phage-susceptible competitor. These results suggest that temperate phages may have an important role in the competitiveness of the LES in chronic lung infection by acting as anti-competitor weapons.
Coupling carbon nanomaterials with photochromic molecules for the generation of optically responsive materials
Authors: Zhang Xiaoyan , Hou Lili , Samorì Paolo
Published: April 2016

Multifunctional carbon-based nanomaterials offer routes towards the realization of smart and high-performing (opto)electronic (nano)devices, sensors and logic gates. Meanwhile photochromic molecules exhibit reversible transformation between two forms, induced by the absorption of electromagnetic radiation. By combining carbon-based nanomaterials with photochromic molecules, one can achieve reversible changes in geometrical structure, electronic properties and nanoscale mechanics triggering by light. This thus enables a reversible modulation of numerous physical and chemical properties of the carbon-based nanomaterials towards the fabrication of cognitive devices. This review examines the state of the art with respect to these responsive materials, and seeks to identify future directions for investigation.
Consistent role of weak and strong interactions in high- and low-diversity trophic food webs
Authors: Gellner Gabriel , McCann Kevin S.
Published: April 2016

The growing realization of a looming biodiversity crisis has inspired considerable progress in the quest to link biodiversity, structure and ecosystem function. Here we construct a method that bridges low- and high-diversity approaches to food web theory by elucidating the connection between the stability of the basic building block of food webs and the mean stability properties of large random food web networks. Applying this theoretical framework to common food web models reveals two key findings. First, in almost all cases, high-diversity food web models yield a stability relationship between weak and strong interactions that are compatible in every way to simple low-diversity models. And second, the models that generate the recently discovered phenomena of being purely stabilized by increasing interaction strength correspond to the biologically implausible assumption of perfect interaction strength symmetry.
Local biomass burning is a dominant cause of the observed precipitation reduction in southern Africa
Authors: Hodnebrog Øivind , Myhre Gunnar , Forster Piers M. , Sillmann Jana , Samset Bjørn H.
Published: April 2016

Observations indicate a precipitation decline over large parts of southern Africa since the 1950s. Concurrently, atmospheric concentrations of greenhouse gases and aerosols have increased due to anthropogenic activities. Here we show that local black carbon and organic carbon aerosol emissions from biomass burning activities are a main cause of the observed decline in southern African dry season precipitation over the last century. Near the main biomass burning regions, global and regional modelling indicates precipitation decreases of 20–30%, with large spatial variability. Increasing global CO2 concentrations further contribute to precipitation reductions, somewhat less in magnitude but covering a larger area. Whereas precipitation changes from increased CO2 are driven by large-scale circulation changes, the increase in biomass burning aerosols causes local drying of the atmosphere. This study illustrates that reducing local biomass burning aerosol emissions may be a useful way to mitigate reduced rainfall in the region.
MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
Authors: Papangeli Irinna , Kim Jongmin , Maier Inna , Park Saejeong , Lee Aram , Kang Yujung , Tanaka Keiichiro , Khan Omar F. , Ju Hyekyung , Kojima Yoko , Red-Horse Kristy , Anderson Daniel G. , Siekmann Arndt F. , Chun Hyung J.
Published: April 2016

G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development.
Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation
Authors: Ono Wanida , Sakagami Naoko , Nishimori Shigeki , Ono Noriaki , Kronenberg Henry M.
Published: April 2016

Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP–PPR system during root morphogenesis and tooth eruption.
T-cell activation is an immune correlate of risk in BCG vaccinated infants
Authors: Fletcher Helen A. , Snowden Margaret A. , Landry Bernard , Rida Wasima , Satti Iman , Harris Stephanie A. , Matsumiya Magali , Tanner Rachel , O’Shea Matthew K. , Dheenadhayalan Veerabadran , Bogardus Leah , Stockdale Lisa , Marsay Leanne , Chomka Agnieszka , Harrington-Kandt Rachel , Manjaly-Thomas Zita-Rose , Naranbhai Vivek , Stylianou Elena , Darboe Fatoumatta , Penn-Nicholson Adam , Nemes Elisa , Hatherill Mark , Hussey Gregory , Mahomed Hassan , Tameris Michele , McClain J Bruce , Evans Thomas G. , Hanekom Willem A. , Scriba Thomas J. , McShane Helen
Published: April 2016

Vaccines to protect against tuberculosis (TB) are urgently needed. We performed a case–control analysis to identify immune correlates of TB disease risk in Bacille Calmette–Guerin (BCG) immunized infants from the MVA85A efficacy trial. Among 53 TB case infants and 205 matched controls, the frequency of activated HLA-DR+ CD4+ T cells associates with increased TB disease risk (OR=1.828, 95% CI=1.25–2.68, P=0.002, FDR=0.04, conditional logistic regression). In an independent study of Mycobacterium tuberculosis-infected adolescents, activated HLA-DR+ CD4+ T cells also associate with increased TB disease risk (OR=1.387, 95% CI=1.068–1.801, P=0.014, conditional logistic regression). In infants, BCG-specific T cells secreting IFN-γ associate with reduced risk of TB (OR=0.502, 95% CI=0.29–0.86, P=0.013, FDR=0.14). The causes and impact of T-cell activation on disease risk should be considered when designing and testing TB vaccine candidates for these populations.
Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells
Authors: Meininger Isabel , Griesbach Richard A. , Hu Desheng , Gehring Torben , Seeholzer Thomas , Bertossi Arianna , Kranich Jan , Oeckinghaus Andrea , Eitelhuber Andrea C. , Greczmiel Ute , Gewies Andreas , Schmidt-Supprian Marc , Ruland Jürgen , Brocker Thomas , Heissmeyer Vigo , Heyd Florian , Krappmann Daniel
Published: April 2016

MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4+ T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation.
Neurons in the inferior colliculus of the rat show stimulus-specific adaptation for frequency, but not for intensity
Authors: Duque Daniel , Wang Xin , Nieto-Diego Javier , Krumbholz Katrin , Malmierca Manuel S.
Published: April 2016

Electrophysiological and psychophysical responses to a low-intensity probe sound tend to be suppressed by a preceding high-intensity adaptor sound. Nevertheless, rare low-intensity deviant sounds presented among frequent high-intensity standard sounds in an intensity oddball paradigm can elicit an electroencephalographic mismatch negativity (MMN) response. This has been taken to suggest that the MMN is a correlate of true change or “deviance” detection. A key question is where in the ascending auditory pathway true deviance sensitivity first emerges. Here, we addressed this question by measuring low-intensity deviant responses from single units in the inferior colliculus (IC) of anesthetized rats. If the IC exhibits true deviance sensitivity to intensity, IC neurons should show enhanced responses to low-intensity deviant sounds presented among high-intensity standards. Contrary to this prediction, deviant responses were only enhanced when the standards and deviants differed in frequency. The results could be explained with a model assuming that IC neurons integrate over multiple frequency-tuned channels and that adaptation occurs within each channel independently. We used an adaptation paradigm with multiple repeated adaptors to measure the tuning widths of these adaption channels in relation to the neurons’ overall tuning widths.
Cell surface Glut1 levels distinguish human CD4 and CD8 T lymphocyte subsets with distinct effector functions
Authors: Cretenet Gaspard , Clerc Isabelle , Matias Maria , Loisel Severine , Craveiro Marco , Oburoglu Leal , Kinet Sandrina , Mongellaz Cédric , Dardalhon Valérie , Taylor Naomi
Published: April 2016

CD4 and CD8 T lymphocyte activation requires the generation of sufficient energy to support new biosynthetic demands. Following T cell receptor (TCR) engagement, these requirements are met by an increased glycolysis, due, at least in part, to induction of the Glut1 glucose transporter. As Glut1 is upregulated on tumor cells in response to hypoxia, we assessed whether surface Glut1 levels regulate the antigen responsiveness of human T lymphocytes in both hypoxic and atmospheric oxygen conditions. Notably, Glut1 upregulation in response to TCR stimulation was significantly higher in T lymphocytes activated under hypoxic as compared to atmospheric oxygen conditions. Furthermore, TCR-stimulated human T lymphocytes sorted on the basis of Glut1-Lo and Glut1-Hi profiles maintained distinct characteristics, irrespective of the oxygen tension. While T cells activated in hypoxia divided less than those activated in atmospheric oxygen, Glut1-Hi lymphocytes exhibited increased effector phenotype acquisition, augmented proliferation and an inverted CD4/CD8 ratio in both oxygen conditions. Moreover, Glut1-Hi T lymphocytes exhibited a significantly enhanced ability to produce IFN-γ and this secretion potential was completely dependent on continued glycolysis. Thus, Glut1 surface levels identify human T lymphocytes with distinct effector functions in both hypoxic and atmospheric oxygen tensions.
Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells
Authors: Kok Yik Lim , Vongrad Valentina , Shilaih Mohaned , Di Giallonardo Francesca , Kuster Herbert , Kouyos Roger , Günthard Huldrych F. , Metzner Karin J.
Published: April 2016

The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4+ T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4+ T cells were over-represented in gene hotspots identified in CD4+ T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4+ T cells.
New potential binding determinant for hERG channel inhibitors
Authors: Saxena P. , Zangerl-Plessl E.-M. , Linder T. , Windisch A. , Hohaus A. , Timin E. , Hering S. , Stary-Weinzinger A.
Published: April 2016

Human ether-à-go-go related gene (hERG) 1 channels conduct the rapid delayed rectifier K+ current (IKr) and are essential for the repolarization of the cardiac action potential. hERG1 inhibition by structurally diverse drugs may lead to life threatening arrhythmia. Putative binding determinants of hERG1 channel blockers include T623, S624 and V625 on the pore helix and residues G648, Y652 and F656, located on segment S6. We and others have previously hypothesized that additional binding determinants may be located on helix S5, which is in close contact with the S6 segments. In order to test this hypothesis, we performed a detailed investigation combining ionic current measurements with two-microelectrode voltage clamp and molecular modeling techniques. We identified a novel aromatic high affinity binding determinant for blockers located in helix S5, F557, which is equally potent as Y652. Modeling supports a direct interaction with the outer pore helix.
Colony-Level Differences in the Scaling Rules Governing Wood Ant Compound Eye Structure
Authors: Perl Craig D. , Niven Jeremy E.
Published: April 2016

Differential organ growth during development is essential for adults to maintain the correct proportions and achieve their characteristic shape. Organs scale with body size, a process known as allometry that has been studied extensively in a range of organisms. Such scaling rules, typically studied from a limited sample, are assumed to apply to all members of a population and/or species. Here we study scaling in the compound eyes of workers of the wood ant,Formica rufa, from different colonies within a single population. Workers’ eye area increased with body size in all the colonies showing a negative allometry. However, both the slope and intercept of some allometric scaling relationships differed significantly among colonies. Moreover, though mean facet diameter and facet number increased with body size, some colonies primarily increased facet number whereas others increased facet diameter, showing that the cellular level processes underlying organ scaling differed among colonies. Thus, the rules that govern scaling at the organ and cellular levels can differ even within a single population.
RUNX2 Mutation Impairs 1α,25-Dihydroxyvitamin D3 mediated Osteoclastogenesis in Dental Follicle Cells
Authors: Wang X. Z. , Sun X. Y. , Zhang C. Y. , Yang X. , Yan W. J. , Ge L. H. , Zheng S. G.
Published: April 2016

Cleidocranial dysplasia (CCD), a skeletal disorder characterized by delayed permanent tooth eruption and other dental abnormalities, is caused by heterozygousRUNX2mutations. As an osteoblast-specific transcription factor,RUNX2plays a role in bone remodeling, tooth formation and tooth eruption. To investigate the crosstalk betweenRUNX2and 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2D3) in human dental follicle cells (hDFCs) during osteoclast formation, we established a co-culture system of hDFCs from CCD patient and healthy donors with peripheral blood mononuclear cells (PBMCs). Expression of the osteoclast-associated genes and the number of TRAP+cells were reduced in CCD hDFCs, indicating its suppressed osteoclast-inductive ability, which was reflected by the downregulated RANKL/OPG ratio. In addition, 1α,25-(OH)2D3-stimulation elevated the expression of osteoclast-related genes, as well asRANKLmRNA levels and RANKL/OPG ratios in control hDFCs. Conversely,RUNX2mutation abolished this 1α,25-(OH)2D3-inducedRANKLgene activation and osteoclast formation in CCD hDFCs. Therefore,RUNX2haploinsufficiency impairs dental follicle-induced osteoclast formation capacity through RANKL/OPG signaling, which may be partially responsible for delayed permanent tooth eruption in CCD patients. Furthermore, this abnormality was not rescued by 1α,25-(OH)2D3application because 1α,25-(OH)2D3-induced RANKL activation in hDFCs is mediated principally via theRUNX2-dependent pathway.
Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes
Authors: Hu Shijia , Divaris Kimon , Parker Joel , Padilla Ricardo , Murrah Valerie , Wright John Timothy
Published: April 2016

Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues (“dentome”). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the “dentome” and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.
Optimizing Dynamical Network Structure for Pinning Control
Authors: Orouskhani Yasin , Jalili Mahdi , Yu Xinghuo
Published: April 2016

Controlling dynamics of a network from any initial state to a final desired state has many applications in different disciplines from engineering to biology and social sciences. In this work, we optimize the network structure for pinning control. The problem is formulated as four optimization tasks: i) optimizing the locations of driver nodes, ii) optimizing the feedback gains, iii) optimizing simultaneously the locations of driver nodes and feedback gains and iv) optimizing the connection weights. A newly developed population-based optimization technique (cat swarm optimization) is used as the optimization method. In order to verify the methods, we use both real-world networks and model scale-free and small-world networks. Extensive simulation results show that the optimal placement of driver nodes significantly outperforms heuristic methods including placing drivers based on various centrality measures (degree, betweenness, closeness and clustering coefficient). The pinning controllability is further improved by optimizing the feedback gains. We also show that one can significantly improve the controllability by optimizing the connection weights.
Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells
Authors: Hamanoue Makoto , Morioka Kazuhito , Ohsawa Ikuroh , Ohsawa Keiko , Kobayashi Masaaki , Tsuburaya Kayo , Akasaka Yoshikiyo , Mikami Tetsuo , Ogata Toru , Takamatsu Ken
Published: April 2016

Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38 and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration.
Water orientation and hydrogen-bond structure at the fluorite/water interface
Authors: Khatib Rémi , Backus Ellen H. G. , Bonn Mischa , Perez-Haro María-José , Gaigeot Marie-Pierre , Sulpizi Marialore
Published: April 2016

Water in contact with mineral interfaces is important for a variety of different processes. Here, we present a combined theoretical/experimental study which provides a quantitative, molecular-level understanding of the ubiquitous and important CaF2/water interface. Our results show that, at low pH, the surface is positively charged, causing a substantial degree of water ordering. The surface charge originates primarily from the dissolution of fluoride ions, rather than from adsorption of protons to the surface. At high pH we observe the presence of Ca-OH species pointing into the water. These OH groups interact remarkably weakly with the surrounding water and are responsible for the “free OH” signature in the VSFG spectrum, which can be explained from local electronic structure effects. The quantification of the surface termination, near-surface ion distribution and water arrangement is enabled by a combination of advanced phase-resolved Vibrational Sum Frequency Generation spectra of CaF2/water interfaces and state-of-the-art ab initio molecular dynamics simulations which include electronic structure effects.
Uncertainty assessment of PM2.5 contamination mapping using spatiotemporal sequential indicator simulations and multi-temporal monitoring data
Authors: Yang Yong , Christakos George , Huang Wei , Lin Chengda , Fu Peihong , Mei Yang
Published: April 2016

Because of the rapid economic growth in China, many regions are subjected to severe particulate matter pollution. Thus, improving the methods of determining the spatiotemporal distribution and uncertainty of air pollution can provide considerable benefits when developing risk assessments and environmental policies. The uncertainty assessment methods currently in use include the sequential indicator simulation (SIS) and indicator kriging techniques. However, these methods cannot be employed to assess multi-temporal data. In this work, a spatiotemporal sequential indicator simulation (STSIS) based on a non-separable spatiotemporal semivariogram model was used to assimilate multi-temporal data in the mapping and uncertainty assessment of PM2.5 distributions in a contaminated atmosphere. PM2.5 concentrations recorded throughout 2014 in Shandong Province, China were used as the experimental dataset. Based on the number of STSIS procedures, we assessed various types of mapping uncertainties, including single-location uncertainties over one day and multiple days and multi-location uncertainties over one day and multiple days. A comparison of the STSIS technique with the SIS technique indicate that a better performance was obtained with the STSIS method.
Quantifying the Anthropogenic Footprint in Eastern China
Authors: Meng Chunlei , Dou Youjun
Published: April 2016

Urban heat island (UHI) is one of the most focuses in urban climate study. The parameterization of the anthropogenic heat (AH) is crucial important in UHI study, but universal method to parameterize the spatial pattern of the AH is lacking now. This paper uses the NOAA DMSP/OLS nighttime light data to parameterize the spatial pattern of the AH. Two experiments were designed and performed to quantify the influences of the AH to land surface temperature (LST) in eastern China and 24 big cities. The annual mean heating caused by AH is up to 1 K in eastern China. This paper uses the relative LST differences rather than the absolute LST differences between the control run and contrast run of common land model (CoLM) to find the drivers. The heating effect of the anthropogenic footprint has less influence on relatively warm and wet cities.
Rolling-induced Face Centered Cubic Titanium in Hexagonal Close Packed Titanium at Room Temperature
Authors: Wu H. C. , Kumar A. , Wang J. , Bi X. F. , Tomé C. N. , Zhang Z. , Mao S. X.
Published: April 2016

Combining transmission electron microscopes and density functional theory calculations, we report the nucleation and growth mechanisms of room temperature rolling induced face-centered cubic titanium (fcc-Ti) in polycrystalline hexagonal close packed titanium (hcp-Ti). Fcc-Ti and hcp-Ti take the orientation relation: 〈0001〉hcp||〈001〉fcc and "Equation missing", different from the conventional one. The nucleation of fcc-Ti is accomplished via pure-shuffle mechanism with a minimum stable thickness of three atomic layers and the growth via shear-shuffle mechanisms through gliding two-layer disconnections or pure-shuffle mechanisms through gliding four-layer disconnections. Such phase transformation offers an additional plastic deformation mode comparable to twinning.
Effects of long-term salicylate administration on synaptic ultrastructure and metabolic activity in the rat CNS
Authors: Yi Bin , Hu Shousen , Zuo Chuantao , Jiao Fangyang , Lv Jingrong , Chen Dongye , Ma Yufei , Chen Jianyong , Mei Ling , Wang Xueling , Huang Zhiwu , Wu Hao
Published: April 2016

Tinnitus is associated with neural hyperactivity in the central nervous system (CNS). Salicylate is a well-known ototoxic drug, and we induced tinnitus in rats using a model of long-term salicylate administration. The gap pre-pulse inhibition of acoustic startle test was used to infer tinnitus perception, and only rats in the chronic salicylate-treatment (14 days) group showed evidence of experiencing tinnitus. After small animal positron emission tomography scans were performed, we found that the metabolic activity of the inferior colliculus (IC), the auditory cortex (AC), and the hippocampus (HP) were significantly higher in the chronic treatment group compared with saline group (treated for 14 days), which was further supported by ultrastructural changes at the synapses. The alterations all returned to baseline 14 days after the cessation of salicylate-treatment (wash-out group), indicating that these changes were reversible. These findings indicate that long-term salicylate administration induces tinnitus, enhanced neural activity and synaptic ultrastructural changes in the IC, AC, and HP of rats due to neuroplasticity. Thus, an increased metabolic rate and synaptic transmission in specific areas of the CNS may contribute to the development of tinnitus.
In vivo markers of inflammatory response in recent-onset schizophrenia: a combined study using [11C]DPA-713 PET and analysis of CSF and plasma
Authors: Coughlin J M , Wang Y , Ambinder E B , Ward R E , Minn I , Vranesic M , Kim P K , Ford C N , Higgs C , Hayes L N , Schretlen D J , Dannals R F , Kassiou M , Sawa A , Pomper M G
Published: April 2016

Several lines of evidence suggest aberrant immune response in schizophrenia, including elevated levels of cytokines. These cytokines are thought to be produced by activated microglia, the innate immune cells of the central nervous system. However, increase in translocator protein 18 kDa (TSPO), a marker of activated glia, has not been found in patients with chronic schizophrenia using second-generation radiotracers and positron emission tomography (PET)-based neuroimaging. In this study we focused on patients with recent onset of schizophrenia (within 5 years of diagnosis). Quantified levels of TSPO in the cortical and subcortical brain regions using the PET-based radiotracer [11C]DPA-713 were compared between the patients and healthy controls. Markers of inflammation, including interleukin 6 (IL-6), were assessed in the plasma and cerebrospinal fluid (CSF) in these participants. We observed no significant change in the binding of [11C]DPA-713 to TSPO in 12 patients with recent onset of schizophrenia compared with 14 controls. Nevertheless, the patients with recent onset of schizophrenia showed a significant increase in IL-6 in both plasma (P<0.001) and CSF (P=0.02). The CSF levels of IL-6 were significantly correlated with the levels of IL-6 in plasma within the total study population (P<0.001) and in patients with recent onset of schizophrenia alone (P=0.03). Our results suggest that increased levels of IL-6 may occur in the absence of changed TSPO PET signal in the brains of medicated patients with recent onset of schizophrenia. Future development of PET-based radiotracers targeting alternative markers of glial activation and immune response may be needed to capture the inflammatory signature present in the brains of patients with early-stage disease.
Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia
Authors: Wagstyl K , Ronan L , Whitaker K J , Goodyer I M , Roberts N , Crow T J , Fletcher P C
Published: April 2016

In vivostructural neuroimaging can reliably identify changes to cortical morphology and its regional variation but cannot yet relate these changes to specific cortical layers. We propose, however, that by synthesizing principles of cortical organization, including relative contributions of different layers to sulcal and gyral thickness, regional patterns of variation in thickness of different layers across the cortical sheet and profiles of layer variation across functional hierarchies, it is possible to develop indirect morphological measures as markers of more specific cytoarchitectural changes. We developed four indirect measures sensitive to changes specifically occurring in supragranular cortical layers, and applied these to test the hypothesis that supragranular layers are disproportionately affected in schizophrenia. Our findings from the four different measures converge to indicate a predominance of supragranular thinning in schizophrenia, independent of medication and illness duration. We propose that these indirect measures offer novel ways of identifying layer-specific cortical changes, offering complementaryin vivoobservations to existing post-mortem studies.