bluuebunny/crossref_metadata_2025 huggingface dataset:
Authoritarianism and Public Opinion on Church and State in the United States
Authors: Castle Jeremiah J.
Published: July 2016

Despite the continued debate over the relationship between church and state in American politics, our understanding of the sources of attitudes on controversies over religious establishment and religious free exercise is limited. I argue that authoritarianism is an unrecognized but important predictor of mass-level attitudes on church and state. I argue that individuals with higher levels of authoritarianism are more likely to support religious establishment as a means of maintaining social conformity and reinforcing the existing social order. Likewise, those with higher levels of authoritarianism should exhibit reduced support for religious free exercise when minority groups are in question as a means of imposing greater costs on social out-groups. Using data from the 2008 Cooperative Campaign Analysis Project, I find strong support for my theory. Even after controlling for a variety of alternative explanations, authoritarianism remains an important factor in attitudes toward both religious establishment and religious free exercise.
Prenatal and early-life predictors of atopy and allergic disease in Canadian children: results of the Family Atherosclerosis Monitoring In earLY life (FAMILY) Study
Authors: Batool T. , Reece P. L. , Schulze K. M. , Morrison K. M. , Atkinson S. A. , Anand S. S. , Teo K. K. , Denburg J. A. , Cyr M. M. ,   the FAMILY Study Investigators
Published: July 2016

Prenatal and early-life environmental exposures play a key role in the development of atopy and allergic disease. The Family Atherosclerosis Monitoring In earLY life Study is a general, population-based Canadian birth cohort that prospectively evaluated prenatal and early-life traits and their association with atopy and/or allergic disease. The study population included 901 babies, 857 mothers and 530 fathers. Prenatal and postnatal risk factors were evaluated through questionnaires collected during the antenatal period and at 1 year. The end points of atopy and allergic diseases in infants were evaluated through questionnaires and skin prick testing. Key outcomes included atopy (24.5%), food allergy (17.5%), cow’s milk allergy (4.8%), wheezing (18.6%) and eczema (16%). The association between infant antibiotic exposure [odds ratio (OR): 2.04, 95% confidence interval (CI): 1.45–2.88] and increased atopy was noted in the multivariate analysis, whereas prenatal maternal exposure to dogs (OR: 0.60, 95% CI: 0.42–0.84) and acetaminophen (OR: 0.68, 95% CI: 0.51–0.92) was associated with decreased atopy. This population-based birth cohort in Canada demonstrated high rates of atopy, food allergy, wheezing and eczema. Several previously reported and some novel prenatal and postnatal exposures were associated with atopy and allergic diseases at 1 year of age.
Influence of gestational age on serum incretin levels in preterm infants
Authors: Shoji H. , Watanabe A. , Ikeda N. , Mori M. , Kitamura T. , Hisata K. , Shimizu T.
Published: July 2016

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from the intestine in response to enteral feeding to stimulate insulin secretion. We investigated the relationship serum GIP and GLP-1 levels with gestational age, and insulin secretion in preterm infants. Serum GIP and GLP-1 levels were measured at birth and at 1, 2 and 4 weeks after birth in 30 infants, including 12 born before 30th week of gestation (early group) and 18 born after 30th week of gestation (late group). Blood glucose and serum insulin levels were measured, and the quantitative insulin sensitivity check index (QUICKI) was also calculated. The levels of GLP-1 at 2 and 4 weeks were significantly higher in the early group than those in the late group. The levels of GIP were not significantly different between two groups. At 4 weeks, serum insulin level was significantly higher and QUICKI was significantly lower in the early group. Furthermore, GLP-1 levels were significantly correlated with QUICKI and the serum insulin levels in all infants at 4 weeks. In preterm infants, enteral feeding to premature intestine may be associated with GLP-1 secretion. GLP-1 is also related to stimulated insulin secretion in early postnatal period.
Androphobia, Demasculinization, and Professional Conflicts:The Herstories of the Physical Therapy Profession Deconstructed
Authors: Ottosson Anders
Published: July 2016

Research on the beginning of the physical therapy profession in different countries often identifies it as a traditional female occupation. Its original semiprofessional character is also pointed out. It lacked professional attributes with masculine connotations, such as a high degree of autonomy and a unique scientific body of knowledge. But on all accounts this understanding is wrong. Originally the profession was an occupation for men only, who were very professionally independent and in charge of a state-sanctioned science of their own. Yet no modern physical therapists know about this, and neither do scholars studying the profession's origin. Why is that? The aim of this article is to highlight the gender mechanisms shaping a discourse strong enough to change our historical consciousness, in this case preventing us from seeing the masculine context out of which the physical therapy profession grew. The analysis explaining the phenomenon centers on two gender-altering and conflict-laden processes, one that was homosocial (men against men) and one that was heterosocial (women against men). Common to both was that they were ultimately powered by a fear of masculinity, here conceptualized as androphobia. Simplified the physical therapy profession came to be perceived as too masculine, and due to this its excess of masculinity was actively eliminated from the profession even in physical form (read: males). The profession was demasculinized and the same happened to its old history, which made the latter unwanted and finally obscured behind new herstories.
The Discovery of Mental Hospital Patients:A Historical Epidemiology of Institutionalization in the American North, 1880–1920
Authors: Maeda Hiroshi
Published: July 2016

Historians of the American mental hospital still do not firmly grasp who mental hospital patients were. Although the field's signature debate on the nature of the mental hospital as “repressive” or “humanitarian” involves the characterization of the patients —based on their demographic traits—as victims of repression or beneficiaries of humanitarianism, there has actually not been a thorough demographic analysis of the patients. This article ascertains and examines the defining characteristics of the patient population within the context of that enduring debate. It first identifies demographic groups that were more prone to institutionalization than would have been expected from their susceptibility to insanity. They symbolized the patient population in the late nineteenth century when insanity did not necessarily result in institutionalization. This article then discovers essentially the same demographic groups ended up in mental hospitals in both the hinterland and metropolitan areas of the North from the late nineteenth to the early twentieth century. It also finds a protective effect that marriage had against institutionalization operated in a socially conservative way. Finally, it weaves together the demographic traits of the patients deemed indicative of the mental hospital's repressiveness and the ones considered reflective of its humanitarianism into a panoptic portrayal that presents the patients as both victims and beneficiaries of the mental hospital. This article's analysis of the patients as a complex, multifaceted population helps transcend the binary framework of the debate on the nature of the mental hospital and deepen our understanding of who they were.
Twinning in Norway Following the Oslo Massacre: Evidence of a ‘Bruce Effect’ in Humans
Authors: Catalano Ralph A , Saxton Katherine B , Gemmill Alison , Hartig Terry
Published: July 2016

Emerging theory and empirical work suggest that the ‘Bruce Effect’, or the increase in spontaneous abortion observed in non-human species when environments become threatening to offspring survival, may also appear in humans. We argue that, if it does, the effect would appear in the odds of twins among male and female live births. We test the hypothesis, implied by our argument, that the odds of a twin among male infants in Norway fell below, while those among females rose above, expected levels among birth cohorts in gestation in July 2011 when a deranged man murdered 77 Norwegians, including many youths. Results support the hypothesis and imply that the Bruce Effect operates in women to autonomically raise the standard of fetal fitness necessary to extend the gestation of twins. This circumstance has implications for using twins to estimate the relative contributions of genes and environment to human responses to exogenous stimuli.
Projektteams und -manager beraten und coachen
Authors: Wastian Monika , Kraus Rafaela , Rosenstiel Lutz
Published: July 2016

Worauf muss bei der Zusammenstellung neuer Projektteams geachtet werden und unter welchen Bedingungen sind Teams besonders leistungsfähig? Was müssen Projektmanager mitbringen und wie können sie die Herausforderungen der Führung von Projekten besser bewältigen? Wie kann die Kommunikation in Projekten gestaltet und der Informationsfluss verbessert werden? Worauf ist beim Management von Stakeholdern und beim Umgang mit Risiken, Krisen und Konflikten in Projekten zu achten?
Zu all diesen Fragen bietet dieses Buch für die Personalarbeit in Projekten relevantes psychologisches Know-how aus Wissenschaft und Praxis. Es zeigt übersichtlich und anschaulich auf, worauf es beim Faktor Mensch in Projekten ankommt und bietet eine Fülle wissenschaftlich fundierter Hintergrundinformationen und praktisch einsetzbarer Instrumente aus der Psychologie. Ausführliche Fallbeispiele animieren dazu, psychologisches Projektcoaching zur Unterstützung von Projektleitungen, aber auch zur Optimierung der Prozesse und der Teamarbeit in Projekten einzusetzen.
Die dargestellten Inhalte sind nicht nur für Personalmanager und Führungskräfte von Interesse, sondern auch für Trainer, Berater und andere wissenschaftlich interessierte Praktiker, die Projekte kompetent beraten und unterstützen möchten.
Improving the Sleep of Children’s Hospital Employees Through an Email-Based Sleep Wellness Program
Authors: Smith Kevin C. , Wallace Dustin P.
Published: July 2016

Health care worker sleepiness and fatigue increases the risk of adverse events, compromises patient safety, and increases risk to personal safety and well-being. Addressing sleep problems in large health care institutions through traditional face-to-face interventions can be expensive and difficult to implement to a large employee pool. Little is known about the use of more cost-effective and time-efficient sleep health programs with health care professionals, such as online or email-based sleep interventions. The purpose of this article was to describe the development, implementation, and outcomes of Sleep Smart, an email-based employee sleep wellness program. Sleep Smart was created by a clinical psychologist board certified in behavioral sleep medicine, with consultation and review by an experienced employee wellness coordinator. It consisted of 8 weekly e-mailed modules highlighting different aspects of sleep, paired with online surveys. Participants (employees of a large midwestern tertiary children’s hospital and some spouses [ n = 1,333]) completed measures including the Insomnia Severity Index (ISI) and the Pittsburgh Sleep Quality Index (PSQI) at baseline and after completing the program. Results indicate a significant improvement in sleep quality, reduction in insomnia symptoms, decreases in daytime fatigue and reported sleepiness while driving, and a reduction in sleep medication usage. Outcomes from this study support additional exploration of cost-effective technology-based sleep health initiatives aimed at health care professionals. Improving hospital employee sleep could positively affect the delivery of care and patient safety. Challenges specific to employee wellness program evaluation and data collection and information for psychologists interested in this work is discussed.
Competition's Role in Developing Psychological Strength and Outstanding Performance
Authors: Worrell Frank C. , Knotek Steven E. , Plucker Jonathan A. , Portenga Steve , Simonton Dean Keith , Olszewski-Kubilius Paula , Schultz Sheila R. , Subotnik Rena F.
Published: July 2016

Competition, a topic closely associated with outstanding performance, continues to be a contentious topic ( Bonta, 1997 ; Murayama & Elliot, 2012a , 2012b ), particularly in the realm of education and schooling ( D. W. Johnson & Johnson, 1987 , 2009 ). Is competition a useful or detrimental strategy for promoting outstanding performance? Does competition contribute positively to performance or should it be avoided? In this article, we took on the challenge of exploring the relationship between competition and high performance and making recommendations about how competition can be used in promoting adaptive youth development. We begin by defining competition and outstanding performance. We then discuss competition in the context of the positive psychology movement, followed by brief reviews of literature showcasing how competition is related to enhanced performance in sport, organizational settings, and academic domains. Next, we discuss competition's relationship to creativity. The article closes with a discussion of the implications of this work for practice and research. It is our hope that this work will result in increased attention to high performance psychology as an important focus for scholarship and application in a wide range of arenas, from schools and the workplace to athletic and artistic venues.
A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours
Authors: Mercado-Lubo Regino , Zhang Yuanwei , Zhao Liang , Rossi Kyle , Wu Xiang , Zou Yekui , Castillo Antonio , Leonard Jack , Bortell Rita , Greiner Dale L. , Shultz Leonard D. , Han Gang , McCormick Beth A.
Published: July 2016

Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.
Super-resolution spectroscopic microscopy via photon localization
Authors: Dong Biqin , Almassalha Luay , Urban Ben E. , Nguyen The-Quyen , Khuon Satya , Chew Teng-Leong , Backman Vadim , Sun Cheng , Zhang Hao F.
Published: July 2016

Traditional photon localization microscopy analyses only the spatial distributions of photons emitted by individual molecules to reconstruct super-resolution optical images. Unfortunately, however, the highly valuable spectroscopic information from these photons have been overlooked. Here we report a spectroscopic photon localization microscopy that is capable of capturing the inherent spectroscopic signatures of photons from individual stochastic radiation events. Spectroscopic photon localization microscopy achieved higher spatial resolution than traditional photon localization microscopy through spectral discrimination to identify the photons emitted from individual molecules. As a result, we resolved two fluorescent molecules, which were 15 nm apart, with the corresponding spatial resolution of 10 nm—a four-fold improvement over photon localization microscopy. Using spectroscopic photon localization microscopy, we further demonstrated simultaneous multi-colour super-resolution imaging of microtubules and mitochondria in COS-7 cells and showed that background autofluorescence can be identified through its distinct emission spectra.
The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia
Authors: Ashton Thomas M. , Fokas Emmanouil , Kunz-Schughart Leoni A. , Folkes Lisa K. , Anbalagan Selvakumar , Huether Melanie , Kelly Catherine J. , Pirovano Giacomo , Buffa Francesca M. , Hammond Ester M. , Stratford Michael , Muschel Ruth J. , Higgins Geoff S. , McKenna William Gillies
Published: July 2016

Tumour hypoxia renders cancer cells resistant to cancer therapy, resulting in markedly worse clinical outcomes. To find clinical candidate compounds that reduce hypoxia in tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify a number of drugs with this property. For this study we focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases the OCR by more than 80% in a wide range of cancer cell lines at pharmacological concentrations. In addition, atovaquone eradicates hypoxia in FaDu, HCT116 and H1299 spheroids. Similarly, it reduces hypoxia in FaDu and HCT116 xenografts in nude mice, and causes a significant tumour growth delay when combined with radiation. Atovaquone is a ubiquinone analogue, and decreases the OCR by inhibiting mitochondrial complex III. We are now undertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby increasing the efficacy of radiotherapy.
Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Authors: Steinthorsdottir Valgerdur , Thorleifsson Gudmar , Aradottir Kristrun , Feenstra Bjarke , Sigurdsson Asgeir , Stefansdottir Lilja , Kristinsdottir Anna M. , Zink Florian , Halldorsson Gisli H. , Munk Nielsen Nete , Geller Frank , Melbye Mads , Gudbjartsson Daniel F. , Geirsson Reynir T. , Thorsteinsdottir Unnur , Stefansson Kari
Published: July 2016

We conducted a genome-wide association scan (GWAS) of endometriosis using 25.5 million sequence variants detected through whole-genome sequencing (WGS) of 8,453 Icelanders and imputed into 1,840 cases and 129,016 control women, followed by testing of associated variants in Danish samples. Here we report the discovery of a new endometriosis susceptibility locus on 4q12 (rs17773813[G], OR=1.28; P=3.8 × 10−11), upstream of KDR encoding vascular endothelial growth factor receptor 2 (VEGFR2). The variant correlates with disease severity (P=0.0046) when moderate/severe endometriosis cases are tested against minimal/mild cases. We further report association of rs519664[T] in TTC39B on 9p22 with endometriosis (P=4.8 × 10−10; OR=1.29). The involvement of KDR in endometriosis risk highlights the importance of the VEGF pathway in the pathogenesis of the disease.
An exome array study of the plasma metabolome
Authors: Rhee Eugene P. , Yang Qiong , Yu Bing , Liu Xuan , Cheng Susan , Deik Amy , Pierce Kerry A. , Bullock Kevin , Ho Jennifer E. , Levy Daniel , Florez Jose C. , Kathiresan Sek , Larson Martin G. , Vasan Ramachandran S. , Clish Clary B. , Wang Thomas J. , Boerwinkle Eric , O’Donnell Christopher J. , Gerszten Robert E.
Published: July 2016

The study of rare variants may enhance our understanding of the genetic determinants of the metabolome. Here, we analyze the association between 217 plasma metabolites and exome variants on the Illumina HumanExome Beadchip in 2,076 participants in the Framingham Heart Study, with replication in 1,528 participants of the Atherosclerosis Risk in Communities Study. We identify an association between GMPS and xanthosine using single variant analysis and associations between HAL and histidine, PAH and phenylalanine, and UPB1 and ureidopropionate using gene-based tests (P<5 × 10−8 in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metabolism. Further, we show how an examination of variants across the spectrum of allele frequency highlights independent association signals at select loci and generates a more integrated view of metabolite heritability. These studies build on prior metabolomics genome wide association studies to provide a more complete picture of the genetic architecture of the plasma metabolome.
TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16INK4a protein expression
Authors: Parroche P , Roblot G , Le Calvez-Kelm F , Tout I , Marotel M , Malfroy M , Durand G , McKay J , Ainouze M , Carreira C , Allatif O , Traverse-Glehen A , Mendiola M , Pozo-Kreilinger J J , Caux C , Tommasino M , Goutagny N , Hasan U A
Published: July 2016

Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16INK4a was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16INK4a post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis.
Polaritonic Rabi and Josephson Oscillations
Authors: Rahmani Amir , Laussy Fabrice P.
Published: July 2016

The dynamics of coupled condensates is a wide-encompassing problem with relevance to superconductors, BECs in traps, superfluids, etc. Here, we provide a unified picture of this fundamental problem that includes i) detuning of the free energies, ii) different self-interaction strengths and iii) finite lifetime of the modes. At such, this is particularly relevant for the dynamics of polaritons, both for their internal dynamics between their light and matter constituents, as well as for the more conventional dynamics of two spatially separated condensates. Polaritons are short-lived, interact only through their material fraction and are easily detuned. At such, they bring several variations to their atomic counterpart. We show that the combination of these parameters results in important twists to the phenomenology of the Josephson effect, such as the behaviour of the relative phase (running or oscillating) or the occurence of self-trapping. We undertake a comprehensive stability analysis of the fixed points on a normalized Bloch sphere, that allows us to provide a generalized criterion to identify the Rabi and Josephson regimes in presence of detuning and decay.
A high-content image-based method for quantitatively studying context-dependent cell population dynamics
Authors: Garvey Colleen M. , Spiller Erin , Lindsay Danika , Chiang Chun-Te , Choi Nathan C. , Agus David B. , Mallick Parag , Foo Jasmine , Mumenthaler Shannon M.
Published: July 2016

Tumor progression results from a complex interplay between cellular heterogeneity, treatment response, microenvironment and heterocellular interactions. Existing approaches to characterize this interplay suffer from an inability to distinguish between multiple cell types, often lack environmental context and are unable to perform multiplex phenotypic profiling of cell populations. Here we present a high-throughput platform for characterizing, with single-cell resolution, the dynamic phenotypic responses (i.e. morphology changes, proliferation, apoptosis) of heterogeneous cell populations both during standard growth and in response to multiple, co-occurring selective pressures. The speed of this platform enables a thorough investigation of the impacts of diverse selective pressures including genetic alterations, therapeutic interventions, heterocellular components and microenvironmental factors. The platform has been applied to both 2D and 3D culture systems and readily distinguishes between (1) cytotoxic versus cytostatic cellular responses; and (2) changes in morphological features over time and in response to perturbation. These important features can directly influence tumor evolution and clinical outcome. Our image-based approach provides a deeper insight into the cellular dynamics and heterogeneity of tumors (or other complex systems), with reduced reagents and time, offering advantages over traditional biological assays.
Nano-Wilhelmy investigation of dynamic wetting properties of AFM tips through tip-nanobubble interaction
Authors: Wang Yuliang , Wang Huimin , Bi Shusheng , Guo Bin
Published: July 2016

The dynamic wetting properties of atomic force microscopy (AFM) tips are of much concern in many AFM-related measurement, fabrication, and manipulation applications. In this study, the wetting properties of silicon and silicon nitride AFM tips are investigated through dynamic contact angle measurement using a nano-Wilhelmy balance based method. This is done by capillary force measurement during extension and retraction motion of AFM tips relative to interfacial nanobubbles. The working principle of the proposed method and mathematic models for dynamic contact angle measurement are presented. Geometric models of AFM tips were constructed using scanning electronic microscopy (SEM) images taken from different view directions. The detailed process of tip-nanobubble interaction was investigated using force-distance curves of AFM on nanobubbles. Several parameters including nanobubble height, adhesion and capillary force between tip and nanobubbles are extracted. The variation of these parameters was studied over nanobubble surfaces. The dynamic contact angles of the AFM tips were calculated from the capillary force measurements. The proposed method provides direct measurement of dynamic contact angles for AFM tips and can also be taken as a general approach for nanoscale dynamic wetting property investigation.
Comparative analysis of plastid genomes of non-photosynthetic Ericaceae and their photosynthetic relatives
Authors: Logacheva Maria D. , Schelkunov Mikhail I. , Shtratnikova Victoria Y. , Matveeva Maria V. , Penin Aleksey A.
Published: July 2016

Although plastid genomes of flowering plants are typically highly conserved regarding their size, gene content and order, there are some exceptions. Ericaceae, a large and diverse family of flowering plants, warrants special attention within the context of plastid genome evolution because it includes both non-photosynthetic and photosynthetic species with rearranged plastomes and putative losses of “essential” genes. We characterized plastid genomes of three species of Ericaceae, non-photosynthetic Monotropa uniflora and Hypopitys monotropa and photosynthetic Pyrola rotundifolia, using high-throughput sequencing. As expected for non-photosynthetic plants, M. uniflora and H. monotropa have small plastid genomes (46 kb and 35 kb, respectively) lacking genes related to photosynthesis, whereas P. rotundifolia has a larger genome (169 kb) with a gene set similar to other photosynthetic plants. The examined genomes contain an unusually high number of repeats and translocations. Comparative analysis of the expanded set of Ericaceae plastomes suggests that the genes clpP and accD that are present in the plastid genomes of almost all plants have not been lost in this family (as was previously thought) but rather persist in these genomes in unusual forms. Also we found a new gene in P. rotundifolia that emerged as a result of duplication of rps4 gene.
Immune DNA signature of T-cell infiltration in breast tumor exomes
Authors: Levy Eric , Marty Rachel , Gárate Calderón Valentina , Woo Brian , Dow Michelle , Armisen Ricardo , Carter Hannah , Harismendy Olivier
Published: July 2016

Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes.
Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodelling of temporomandibular joint
Authors: Jiao Kai , Zeng Guang , Niu Li-Na , Yang Hong-xu , Ren Gao-tong , Xu Xin-yue , Li Fei-fei , Tay Franklin R. , Wang Mei-qing
Published: July 2016

This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and β-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities.
A New Skin Tensiometer Device: Computational Analyses To Understand Biodynamic Excisional Skin Tension Lines
Authors: Paul Sharad P. , Matulich Justin , Charlton Nick
Published: July 2016

One of the problems in planning cutaneous surgery is that human skin is anisotropic, or directionally dependent. Indeed, skin tension varies between individuals and at different body sites. Many a surgeon has tried to design different devices to measure skin tension to help plan excisional surgery, or to understand wound healing. However, many of the devices have been beset with problems due to many confounding variables - differences in technical ability, material (sutures) used and variability between different users. We describe the development of a new skin tensiometer that overcomes many historical technical issues. A new skin tension measuring device is presented here. It was designed to be less user-dependent, more reliable and usable on different bodily sites. The design and computational optimizations are discussed. Our skin tensiometer has helped understand the differences between incisional and excisional skin lines. Langer, who pioneered the concept of skin tension lines, created incisional lines that differ from lines caused by forces that need to be overcome when large wounds are closed surgically (excisional tension). The use of this innovative device has led to understanding of skin biomechanics and best excisional skin tension (BEST) lines.
Serum bile acids and GLP-1 decrease following telemetric induced weight loss: results of a randomized controlled trial
Authors: Biemann Ronald , Penner Marina , Borucki Katrin , Westphal Sabine , Luley Claus , Rönicke Raik , Biemann Kathleen , Weikert Cornelia , Lux Anke , Goncharenko Nikolai , Marschall Hanns-Ulrich , Schneider Jochen G. , Isermann Berend
Published: July 2016

Bile acids (BAs) are increasingly recognised as metabolic regulators, potentially improving insulin sensitivity following bariatric surgery. However, physiological relevance of such observations remains unknown. Hence, we analysed serum BA composition and associated gut-derived hormone levels following lifestyle-induced weight loss in individuals with metabolic syndrome (MetS). 74 non-smoking men (45–55 yr) with MetS were randomised to a lifestyle-induced weight loss program (supervision via telemonitoring) or to a control arm. Before and after a 6 months intervention period clinical and laboratory parameters, body composition, serum BA profile, FGF-19 and GLP-1 concentrations were determined in fasting blood samples. 30 participants in the control and 33 participants in the treatment arm completed the study and were included in the data analysis. In participants of the treatment arm lifestyle-induced weight loss resulted in markedly improved insulin sensitivity. Serum levels of BA species and total GLP-1 decreased, while FGF-19 remained stable. Serum BA composition changed towards an increased 12α-hydroxylated/non-12α-hydroxylated ratio. None of these parameters changed in participants of the control arm. Our results demonstrate that improved metabolic control by lifestyle modifications lowers serum levels of BAs and GLP-1 and changes serum BA composition towards an increased 12α/non-12α ratio (ICTRP Trial Number: U1111-1158-3672).
Parallel Quantum Circuit in a Tunnel Junction
Authors: Faizy Namarvar Omid , Dridi Ghassen , Joachim Christian
Published: July 2016

Spectral analysis of 1 and 2-states per line quantum bus are normally sufficient to determine the effective Vab(N) electronic coupling between the emitter and receiver states through the bus as a function of the number N of parallel lines. When Vab(N) is difficult to determine, an Heisenberg-Rabi time dependent quantum exchange process must be triggered through the bus to capture the secular oscillation frequency Ωab(N) between those states. Two different linear and "Equation missing" regimes are demonstrated for Ωab(N) as a function of N. When the initial preparation is replaced by coupling of the quantum bus to semi-infinite electrodes, the resulting quantum transduction process is not faithfully following the Ωab(N) variations. Because of the electronic transparency normalisation to unity and of the low pass filter character of this transduction, large Ωab(N) cannot be captured by the tunnel junction. The broadly used concept of electrical contact between a metallic nanopad and a molecular device must be better described as a quantum transduction process. At small coupling and when N is small enough not to compensate for this small coupling, an N2 power law is preserved for Ωab(N) and for Vab(N).
Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells
Authors: Hwang Hyundoo , Shin Changsik , Park Juhee , Kang Enoch , Choi Bongseo , Han Jae-A , Do Yoonkyung , Ryu Seongho , Cho Yoon-Kyoung
Published: July 2016

Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1β and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1β, IL-6 and IFN-γ. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.
PACSIN2 polymorphism is associated with thiopurine-induced hematological toxicity in children with acute lymphoblastic leukaemia undergoing maintenance therapy
Authors: Smid Alenka , Karas-Kuzelicki Natasa , Jazbec Janez , Mlinaric-Rascan Irena
Published: July 2016

Adequate maintenance therapy for childhood acute lymphoblastic leukemia (ALL), with 6-mercaptopurine as an essential component, is necessary for retaining durable remission. Interruptions or discontinuations of the therapy due to drug-related toxicities, which can be life threatening, may result in an increased risk of relapse. In this retrospective study including 305 paediatric ALL patients undergoing maintenance therapy, we systematically investigated the individual and combined effects of genetic variants of folate pathway enzymes, as well as of polymorphisms in PACSIN2 and ITPA, on drug-induced toxicities by applying a multi-analytical approach including logistic regression (LR), classification and regression tree (CART) and generalized multifactor dimensionality reduction (GMDR). In addition to the TPMT genotype, confirmed to be a major determinant of drug related toxicities, we identified the PACSIN2 rs2413739TT genotype as being a significant risk factor for 6-MP-induced toxicity in wild-type TPMT patients. A gene-gene interaction between MTRR (rs1801394) and MTHFR (rs1801133) was detected by GMDR and proved to have an independent effect on the risk of stomatitis, as shown by LR analysis. To our knowledge, this is the first study showing PACSIN2 genotype association with hematological toxicity in ALL patients undergoing maintenance therapy.
A novel gene OsAHL1 improves both drought avoidance and drought tolerance in rice
Authors: Zhou Liguo , Liu Zaochang , Liu Yunhua , Kong Deyan , Li Tianfei , Yu Shunwu , Mei Hanwei , Xu Xiaoyan , Liu Hongyan , Chen Liang , Luo Lijun
Published: July 2016

A novel gene, OsAHL1, containing an AT-hook motif and a PPC domain was identified through genome-wide profiling and analysis of mRNAs by comparing the microarray of drought-challenged versus normally watered rice. The results indicated OsAHL1 has both drought avoidance and drought tolerance that could greatly improve drought resistance of the rice plant. Overexpression of OsAHL1 enhanced multiple stress tolerances in rice plants during both seedling and panicle development stages. Functional studies revealed that OsAHL1 regulates root development under drought condition to enhance drought avoidance, participates in oxidative stress response and also regulates the content of chlorophyll in rice leaves. OsAHL1 specifically binds to the A/T rich sequence region of promoters or introns and hence directly regulates the expression of many stress related downstream genes.
Sestrin2 Silencing Exacerbates Cerebral Ischemia/Reperfusion Injury by Decreasing Mitochondrial Biogenesis through the AMPK/PGC-1α Pathway in Rats
Authors: Li Lingyu , Xiao Lina , Hou Yanghao , He Qi , Zhu Jin , Li Yixin , Wu Jingxian , Zhao Jing , Yu Shanshan , Zhao Yong
Published: July 2016

Sestrin2 (Sesn2) exerts neuroprotective properties in some neurodegenerative diseases. However, the role of Sesn2 in stroke is unclear. The AMP-activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α (AMPK/PGC-1α) pathway plays an important role in regulating mitochondrial biogenesis, which helps prevent cerebral ischemia/reperfusion (I/R) injury. Here, we aimed to determine whether Sesn2 alleviated I/R damage by regulating mitochondrial biogenesis through the AMPK/PGC-1α signaling pathway. To be able to test this, Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h with Sesn2 silencing. At 24 h after reperfusion, we found that neurological deficits were exacerbated, infarct volume was enlarged, and oxidative stress and neuronal damage were greater in the Sesn2 siRNA group than in the MCAO group. To explore protective mechanisms, an AMPK activator was used. Expression levels of Sesn2, p-AMPK, PGC-1α, NRF-1, TFAM, SOD2, and UCP2 were significantly increased following cerebral I/R. However, upregulation of these proteins was prevented by Sesn2 small interfering RNA (siRNA). In contrast, activation of AMPK with 5′-aminoimidazole-4-carboxamide riboside weakened the effects of Sesn2 siRNA. These results suggest that Sesn2 silencing may suppress mitochondrial biogenesis, reduce mitochondrial biological activity, and finally aggravate cerebral I/R injury through inhibiting the AMPK/PGC-1α pathway.
ClC-3 Chloride Channel Proteins Regulate the Cell Cycle by Up-regulating cyclin D1-CDK4/6 through Suppressing p21/p27 Expression in Nasopharyngeal Carcinoma Cells
Authors: Ye Dong , Luo Hai , Lai Zhouyi , Zou Lili , Zhu Linyan , Mao Jianwen , Jacob Tim , Ye Wencai , Wang Liwei , Chen Lixin
Published: July 2016

It was shown in this study that knockdown of ClC-3 expression by ClC-3 siRNA prevented the activation of hypotonicity-induced chloride currents and arrested cells at the G0/G1 phase in nasopharyngeal carcinoma CNE-2Z cells. Reconstitution of ClC-3 expression with ClC-3 expression plasmids could rescue the cells from the cell cycle arrest caused by ClC-3 siRNA treatments. Transfection of cells with ClC-3 siRNA decreased the expression of cyclin D1, cyclin dependent kinase 4 and 6 and increased the expression of cyclin dependent kinase inhibitors (CDKIs), p21 and p27. Pretreatments of cells with p21 and p27 siRNAs depleted the inhibitory effects of ClC-3 siRNA on the expression of CDK4 and CDK6, but not on that of cyclin D1, indicating the requirement of p21 and p27 for the inhibitory effects of ClC-3 siRNA on CDK4 and CDK6 expression. ClC-3 siRNA inhibited cells to progress from the G1 phase to the S phase, but pretreatments of cells with p21 and p27 siRNAs abolished the inhibitory effects of ClC-3 siRNA on the cell cycle progress. Our data suggest that ClC-3 may regulate cell cycle transition between G0/G1 and S phases by up-regulation of the expression of CDK4 and CDK6 through suppression of p21 and p27 expression.
Modulation of Dendritic-Epithelial Cell Responses against Sphingomonas Paucimobilis by Dietary Fibers
Authors: Bermudez-Brito Miriam , Faas Marijke M , de Vos Paul
Published: July 2016

Non-fermenting Gram-negative bacilli, such as Sphingomonas paucimobilis (S.paucimobilis), are among the most widespread causes of nosocomial infections. Up to now, no definitive guidelines exist for antimicrobial therapy for S. paucimobilis infections. As we have shown that some dietary fibers exhibit pronounced immune-regulatory properties, we hypothesized that specific immune active dietary fibers might modulate the responses against S. paucimobilis. We studied the immunomodulatory effects of dietary fibers against S. paucimobilis on cytokine release and maturation of human dendritic cells (DCs) in co-cultures of DCs and intestinal epithelial cells (IECs). S. paucimobilis infection resulted in increased release of pro-inflammatory cytokines and chemokines by DCs/IECs; these effects were strongly attenuated by specific dietary fibers. Chicory inulin, sugar beet pectin and both starches had the strongest regulatory effects. IL-12 and TNF-α were drastically diminished upon exposure to chicory inulin and sugar beet pectin, or both starches. High-maize 260, was more effective in the reduction of chemokine release than the others fibers tested. In summary, chicory inulin, sugar beet pectin, High-maize 260 and Novelose 330 attenuate S. paucimobilis-induced cytokines. These results demonstrate that dietary fibers with a specific chemical composition can be used to manage immune responses against pathogens such as S. paucimobilis.
Expression profiling and functional characterization of miR-192 throughout sheep skeletal muscle development
Authors: Zhao Qian , Kang Ye , Wang Hong-Yang , Guan Wei-Jun , Li Xiang-Chen , Jiang Lin , He Xiao-Hong , Pu Ya-Bin , Han Jian-Lin , Ma Yue-Hui , Zhao Qian-Jun
Published: July 2016

MicroRNAs (miRNAs) are evolutionarily conserved, small, non-coding RNAs that have emerged as key regulators of myogenesis. Here, we examined the miRNA expression profiles of developing sheep skeletal muscle using a deep sequencing approach. We detected 2,396 miRNAs in the sheep skeletal muscle tissues. Of these, miR-192 was found to be up-regulated in prenatal skeletal muscle, but was down-regulated postnatally. MiR-192 expression also decreased during the myogenic differentiation of sheep satellite cells (SCs). MiR-192 overexpression significantly attenuated SCs myogenic differentiation but promoted SCs proliferation, whereas miR-192 inhibition enhanced SCs differentiation but suppressed SCs proliferation. We found that miR-192 targeted retinoblastoma 1 (RB1), a known regulator of myogenesis. Furthermore, knockdown of RB1 in cultured cells significantly inhibited SCs myogenic differentiation but accelerated SCs proliferation, confirming the role of RB1 in myogenesis. Taken together, our findings enrich the ovine miRNA database and outline the miRNA transcriptome of sheep during skeletal muscle development. Moreover, we show that miR-192 affects SCs proliferation and myogenic differentiation via down-regulation of RB1.