bluuebunny/crossref_metadata_2025 huggingface dataset:
The Hand Pronation Phenomenon: A Franco-German Tale
Authors: Tremolizzo L. , Galbusera R. , Riva M.A. , Cesana G.C. , Appollonio I. , Ferrarese C.
Published: September 2011

The hand pronation phenomenon due to a pyramidal tract lesion is a sign commonly used for identifying a mild paresis, but the first descriptions of this maneuver seem to have been only partially investigated by the historians of neuroscience. Here we illustrate that this sign was most probably originally described by Adolf Strümpell (1853–1925) in 1901 and subsequently re-proposed by the illustrious French neurologist Joseph Babinski (1857–1932) in 1907, although with a slightly different focus of application. Finally, the Pronationsphaenomen was analyzed in detail in the subsequent work of Nikolaus Gierlich (1865–1944), a less-known German neurologist who tried one of the first detailed reports of the phylogenetic significance of this sign, publishing a paper in 1925. These works are reported here, detailing the existing discrepancies, along with notes on the relevant surrounding historical context. In particular, the undervalued contribution of Gierlich to the history of neuroscience and to the phylogenetic approach to semeiotics is analyzed in more detail and acknowledged.
What Can We Learn about Autism from Studying Fragile X Syndrome?
Authors: Budimirovic Dejan B. , Kaufmann Walter E.
Published: September 2011

Despite early controversy, it is now accepted that a substantial proportion of children with fragile X syndrome (FXS) meets diagnostic criteria for autism spectrum disorder (ASD). This change has led to an increased interest in studying the association of FXS and ASD because of the clinical consequences of their co-occurrence and the implications for a better understanding of ASD in the general population. Here, we review the current knowledge on the behavioral, neurobiological (i.e., neuroimaging), and molecular features of ASD in FXS, as well as the insight into ASD gained from mouse models of FXS. This review covers critical issues such as the selectivity of ASD in disorders associated with intellectual disability, differences between autistic features and ASD diagnosis, and the relationship between ASD and anxiety in FXS patients and animal models. While solid evidence supporting ASD in FXS as a distinctive entity is emerging, neurobiological and molecular data are still scarce. Animal model studies have not been particularly revealing about ASD in FXS either. Nevertheless, recent studies provide intriguing new leads and suggest that a better understanding of the bases of ASD will require the integration of multidisciplinary data from FXS and other genetic disorders.
Chronic Serous Otitis Media as a Manifestation of Temporal Meningioma
Authors: Keereweer S. , Metselaar R.M. , Dammers R. , Hardillo J.A.U.
Published: September 2011

Chronic serous otitis media is a common problem in the daily routine of the otorhinolaryngologist. In the majority of cases, the cause is related to dysfunction of the eustachian tube due to viral or bacterial rhinitis and occasionally to nasopharyngeal tumors. We report a case of a patient presenting with chronic serous otitis media that was resistant to conventional therapy. MRI with gadolinium finally revealed that the middle ear fluid was caused by leakage of cerebrospinal fluid (CSF) due to bone destruction by a temporal meningioma. The CSF leakage was closed by surgery. Histopathology confirmed meningioma in the temporal bone.
Venous Thromboembolism Does Not Share Strong Familial Susceptibility With Ischemic Stroke
Authors: Zöller Bengt , Li Xinjun , Ohlsson Henrik , Sundquist Jan , Sundquist Kristina
Published: September 2011

Background—

Coagulation allelic variants associated with venous thromboembolism (VTE) have been suggested to be involved in the pathogenesis of ischemic stroke. This nationwide study aimed at determining whether VTE shares familial susceptibility with ischemic stroke.

Method and Results—

The Swedish Multigeneration Register of 0- to 75-year-old subjects was linked to the Swedish Hospital Discharge Register and the Cause of Death Register for the period 1987 to 2007. Odds ratios (ORs) for VTE and ischemic stroke were determined in 2 ways: odds of ischemic stroke in offspring whose parents had been diagnosed with VTE, and odds of VTE in offspring whose parents had been diagnosed with ischemic stroke. The analyses were repeated for siblings and spouses. Offspring of parents with VTE (n=25 929) were at increased risk for ischemic stroke (n=5595): OR, 1.10 (95% confidence interval [CI], 1.06–1.14). Siblings of probands with VTE (n=45 132) had no increased risk of ischemic stroke (n=1716): OR, 1.05 (95% CI, 1.00–1.11). Spouses of probands with VTE (n=24 106) were at increased risk for ischemic stroke (n=940): OR, 1.18 (95% CI, 1.10–1.27). The risks for VTE in relatives of probands with ischemic stroke were OR, 1.15; 95% CI, 1.10–1.21 (offspring); OR, 1.07; 95% CI, 1.02–1.12 (siblings); and OR, 1.21; 95% CI, 1.11–1.32 (spouses).

Conclusions—

VTE does not share strong familial susceptibility with ischemic stroke in the Swedish population. Moreover, familial nongenetic factors contribute to the observed weak familial associations. The present study suggests that it is unlikely that strong shared disease-causing mutations exist to a large extent in the Swedish population.
Regional Patterns of Tropical Indo-Pacific Climate Change: Evidence of the Walker Circulation Weakening
Authors: Tokinaga Hiroki , Xie Shang-Ping , Timmermann Axel , McGregor Shayne , Ogata Tomomichi , Kubota Hisayuki , Okumura Yuko M.
Published: September 2011

Regional patterns of tropical Indo-Pacific climate change are investigated over the last six decades based on a synthesis of in situ observations and ocean model simulations, with a focus on physical consistency among sea surface temperature (SST), cloud, sea level pressure (SLP), surface wind, and subsurface ocean temperature. A newly developed bias-corrected surface wind dataset displays westerly trends over the western tropical Pacific and easterly trends over the tropical Indian Ocean, indicative of a slowdown of the Walker circulation. This pattern of wind change is consistent with that of observed SLP change showing positive trends over the Maritime Continent and negative trends over the central equatorial Pacific. Suppressed moisture convergence over the Maritime Continent is largely due to surface wind changes, contributing to observed decreases in marine cloudiness and land precipitation there.

Furthermore, observed ocean mixed layer temperatures indicate a reduction in zonal contrast in the tropical Indo-Pacific characterized by larger warming in the tropical eastern Pacific and western Indian Ocean than in the tropical western Pacific and eastern Indian Ocean. Similar changes are successfully simulated by an ocean general circulation model forced with the bias-corrected wind stress. Whereas results from major SST reconstructions show no significant change in zonal gradient in the tropical Indo-Pacific, both bucket-sampled SSTs and nighttime marine air temperatures (NMAT) show a weakening of the zonal gradient consistent with the subsurface temperature changes. All these findings from independent observations provide robust evidence for ocean–atmosphere coupling associated with the reduction in the Walker circulation over the last six decades.
The Creation of a High Equivalent Potential Temperature Reservoir in Tropical Storm Humberto (2001) and Its Possible Role in Storm Deepening
Authors: Dolling Klaus P. , Barnes Gary M.
Published: September 2011

Thirty global positioning system dropwindsondes (GPS sondes) were used to identify and examine the creation of a reservoir of high equivalent potential temperature (θe) in the nascent eye of Tropical Storm Humberto (2001). The θe did not increase in the high surface wind portion of the storm as it does in mature hurricanes; instead air spiraled into the light-wind center of the developing storm where it was trapped by subsidence under a mesoscale convectively generated vortex (MCV). An energy budget revealed that the inflow column took 7 h to reach the storm center during which a combined average surface enthalpy flux of ~230 W m−2 was diagnosed via the bulk aerodynamic equations. This estimate is close to the 250 W m−2 required for balance based on the energy acquired by the column. The high θe in the lowest kilometer, overlain by a near dry-adiabatic layer under the anvil base, resulted in convective available potential energy (CAPE) exceeding 2500 m2 s−2. This conditionally unstable air later served as fuel for the convection within the nascent eyewall. The authors speculate that CAPE of such a large magnitude could accelerate the updraft and stretch the vorticity field, essentially turning garden-variety cumulonimbi into the vortical hot towers argued by several researchers to play a role in tropical cyclone formation and intensification.
A Development-Friendly Reform of the International Financial Architecture
Authors: Ocampo José Antonio
Published: September 2011

The current financial crisis demonstrated, once again, the need for deep reforms of the international monetary and financial architecture. This article argues that reforms under way are insufficient, as they are partial in scope and rely excessively on an ad hoc body, the G20. It thus calls for an international architecture that meets two basic criteria. First, it should be comprehensive. This means that a broad range of reforms should be undertaken: better macroeconomic policy coordination; regulatory reform, including cross-border capital flows; ample countercyclical IMF and development financing with limited conditionality; global monetary reform; and the creation of an international debt court. Second, inclusive institutions should stand at the center of the new architecture, structured as a multilayered network of global, regional, and national financial institutions.
Waves of Change Within Civil Society in Latin America
Authors: Lavalle Adrian Gurza , Bueno Natália S.
Published: September 2011

For the past half a century, Latin American scholars have been pointing toward the emergence of new social actors as agents of social and political democratization. The first wave of actors was characterized by the emergence of novel agents—mainly, new popular movements—of social transformation. At first, the second wave, epitomized by nongovernmental organizations (NGOs), was celebrated as the upsurge of a new civil society, but later on, it was the target of harsh criticism. The literature often portrays this development in Latin American civil society as a displacement trend of actors of the first wave by the second wave—“NGOization”—and even denounces new civil society as rootless, depoliticized, and functional to retrenchment. Thus, supposedly, NGOization encumbers social change. The authors argue that NGOization diagnosis is a flawed depiction of change within civil society. Rather than NGOization related to the depoliticization and neoliberalization of civil society, in Mexico City and São Paulo, there has been modernization of organizational ecologies, changes in the functional status of civil society, and interestingly, specialization aimed at shaping public agenda. The authors argue that such specialization, instead of encumbering social change, brings about different repertoires of strategies and skills purposively developed for influencing policy and politics. Their argument relies on comparative systematic evidence. Through network analysis, they examine the organizational ecology of civil society in Mexico City and São Paulo.
Confiance et reconnaissance
Authors: Quéré Louis
Published: September 2011

This paper investigates the links between trust and recognition, first in terms of value judgments about social categories, then in terms of mutual commitments under inequality conditions, finally in terms of mutual recognition as competent members of a collectivity. It criticizes purely cognitive approaches of trust, which, because they reduce trust to propositional attitudes, fail to account for the dynamics and the rationality of its process.
Cognition et communication: Un paradigme de recherche et d’application
Authors: Nosulenko Valery , Samoylenko Elena
Published: September 2011

The paradigm ‘Cognition and Communication’ has served as a methodological basis for interdisciplinary studies carried out within the framework of Franco-Russian research projects in the field of psychology. The importance of investigating human cognition and activity in relationship with communication processes has been taken as a starting-point for these studies. This 25-year collaboration has made possible the development of new perspectives (e.g. the perceived quality approach) and research methods (e.g. techniques of free verbalization analysis) as well as their application in field studies. This collaboration has also resulted in a fruitful exchange of theoretical approaches among French and Russian researchers. The studies carried out in the field of cognition and communication have involved a number of disciplines: general, experimental and social psychology, ergonomics and education. This article presents a synthesis of a number of results obtained within the framework of Franco-Russian projects as well as various perspectives for future collaboration.
When Being Right Is Not Enough
Authors: Einav Shiri , Robinson Elizabeth J.
Published: September 2011

Recent evidence demonstrates that children are selective in their social learning, preferring to learn from a previously accurate speaker than from a previously inaccurate one. We examined whether children assessing speakers’ reliability take into account how speakers achieved their prior accuracy. In Study 1, when faced with two accurate informants, 4- and 5-year-olds (but not 3-year-olds) were more likely to seek novel information from an informant who had previously given the answers unaided than from an informant who had always relied on help from a third party. Similarly, in Study 2, 4-year-olds were more likely to trust the testimony of an unaided informant over the testimony provided by an assisted informant. Our results indicate that when children reach around 4 years of age, their selective trust extends beyond simple generalizations based on informants’ past accuracy to a more sophisticated selectivity that distinguishes between truly knowledgeable informants and merely accurate informants who may not be reliable in the long term.
Fast Automatic Translation and Morphological Decomposition in Chinese-English Bilinguals
Authors: Zhang Taoli , van Heuven Walter J. B. , Conklin Kathy
Published: September 2011

In this study, we investigated automatic translation from English to Chinese and subsequent morphological decomposition of translated Chinese compounds. In two lexical decision tasks, Chinese-English bilinguals responded to English target words that were preceded by masked unrelated primes presented for 59 ms. Unbeknownst to participants, the Chinese translations of the words in each critical pair consisted of a fully opaque compound word (i.e., a compound with two constituent morphemes that were semantically unrelated to the compound) and a monomorphemic word that was either the first or the second morpheme of the compound. The data revealed that bilinguals responded faster to English word pairs whose Chinese translations repeated the first morpheme than to English word pairs whose Chinese translations did not repeat the first morpheme, but no effect of hidden second-morpheme repetition was found. This effect of hidden first-morpheme repetition suggests that participants translated English words to Chinese and decomposed the translated compounds into their constituent morphemes. Because the primes were presented for only 59 ms, translation and morphological decomposition must be fast and automatic.
The reversal effect of prohibition signs
Authors: Keizer Kees , Lindenberg Siegwart , Steg Linda
Published: September 2011

In public places one encounters many prohibition signs, as well as traces of the norm-violating behavior these signs are trying to reduce, like graffiti or litter. Based on goal framing theory and previous research, we argue that signs of (dis)respect of others for norms serve as norm-support cues which can weaken or strengthen the influence of norms. This norm-support mechanism implies that (traces of) norm violating behavior by others (i.e. negative norm-support cues) inhibit the influence of norms in general. We also hypothesize that making a known norm salient by means of a prohibition sign will not only focus people on this norm, but also on the corresponding (negative) norm-support cues in that particular situation, thereby enhancing the influence of these norm-support cues. Therefore, we expected that a prohibition sign placed in a setting with corresponding negative norm-support cues induces rather than reduces violations of the very same norm (i.e. same-norm reversal effect) and other norms (cross-norm reversal effect). We report results of two (quasi) field experiments that support the negative norm-support mechanism as well as the reversal effect of prohibition signs when cues show noncompliance. These findings are not only intriguing but they have important and clear practical implications.
Introduction
Authors: Smith Joanne R. , Louis Winnifred R. , Schultz P.Wesley
Published: September 2011

The study of social influence is central to social psychology and to understanding group processes and intergroup relations. Social influence research covers a broad range of topics, from persuasion and attitude change, to compliance and conformity, to collective action and social change. This Special Issue presents eleven empirical articles that represent the diversity of current basic and applied research on social influence.
Nerds, Geeks, and the Hip/Square Dialectic in Contemporary Television
Authors: Quail Christine
Published: September 2011

Despite the easily identifiable concept of a “nerd,” only a few significant articles on nerds and popular culture, and specifically television, exist. This article contributes to television studies by addressing this overlooked, yet popularly significant, representation and lived reality in terms of race, gender, and sexuality. The article introduces the hip/square dialectic and explores the sociocultural construction of nerds vis-à-vis the hip/square dialectic as commodity. The article historicizes the hip/square construct of the nerd or geek on television, assesses claims about the emergence of geek chic, and introduces three reality television case studies: Tranji and reality TV nerd dancing; William Hung, American Idol loser; and the Beauty and the Geek program. At issue is the political-economic factors in the production and circulation of the nerd commodity and the racial and gendered or sexualized politics of the televisual nerd discourses and performances.
Diffusion in Direct Democracy: The Effect of Political Information on Proposals for Tax and Expenditure Limits in the U.S. States
Authors: Seljan Ellen C. , Weller Nicholas
Published: September 2011

Many theories of policy diffusion contend that the flow of information is the driving force in the diffusion process. Prior scholarship has identified at least two types of information: information about policy and information about political viability. Few empirical approaches have been able to distinguish between these separate mechanisms. The authors argue that an analysis of policy proposals can untangle political information from policy-based information. They employ their strategy with data on the proposal of tax and expenditure limits (TELs) in the U.S. states since 1970 through direct democracy. The authors find that states in close geographic proximity to states that have rejected TELs are significantly less likely to propose TELs themselves. Since this event does not reveal information about policy effectiveness, the authors conclude that information about political viability systematically diffuses from state to state at the proposal stage of policy making.
Students’ production of curricular knowledge: perspectives on empowerment in financial capability education
Authors: Farnsworth Valerie , Davis Pauline , Kalambouka Afroditi , Ralph Susan , Shi Xin , Farrell Peter
Published: September 2011

The aim of this article is to extend our understanding of the relationship between knowledge of personal finance and empowerment. The analysis is based on interview data obtained as part of a longitudinal study of students, aged 16–19, who completed a financial capability course in the UK. The analysis presents a set of cultural models or storylines implied in student discourse about what it means to be financially capable. Possibilities for empowerment are interpreted from these cultural models with implications for how we define the boundaries of financial capability education. References to empowerment in terms of having a voice and feeling confident to make consumer decisions and to advise others in matters of finance were common across the interview data. However, a form of knowledge and empowerment that positioned students not as aware consumers but as individuals with a critical awareness of financial and economic systems was less evident.
The Impact of Sexual Harassment on Depressive Symptoms during the Early Occupational Career
Authors: Houle Jason N. , Staff Jeremy , Mortimer Jeylan T. , Uggen Christopher , Blackstone Amy
Published: September 2011

Sexual harassment has been theorized as a stressor with consequences for the physical and mental health of its targets. Although social scientists have documented a negative association between sexual harassment and mental health, few longitudinal studies have investigated the association between sexual harassment and depressive symptoms. Using longitudinal survey data from the Youth Development Study, combined with in-depth interviews, this article draws on Louise Fitzgerald’s theoretical framework, stress theory, and the life course perspective to assess the impact of sexual harassment on depressive affect during the early occupational career. In support of Fitzgerald’s model, the authors’ findings confirm that sexual harassment is a stressor that is associated with increased depressive symptoms. Quantitative results show that women and men who experience more frequent sexual harassment at work have significantly higher levels of depressed mood than nonharassed workers, even after controlling for prior harassment and depressive symptoms. Moreover, the authors find evidence that sexual harassment early in the career has long-term effects on depressive symptoms in adulthood. Interviews with a subset of survey respondents point to a variety of coping strategies and reveal further links between harassment and other aspects of mental health, such as anger and self-doubt.
Latent KSHV infection increases the vascular permeability of human endothelial cells
Authors: Guilluy Christophe , Zhang Zhigang , Bhende Prasanna M. , Sharek Lisa , Wang Ling , Burridge Keith , Damania Blossom
Published: September 2011

Kaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.
Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation?
Authors: Ustun Celalettin , Miller Jeffrey S. , Munn David H. , Weisdorf Daniel J. , Blazar Bruce R.
Published: September 2011

The microenviroment of acute myelogenous leukemia (AML) is suppressive for immune effector cells. Regulatory T cells (Tregs) have been recognized as a contributor factor and may be recruited and exploited by leukemic cells to evade immunesurveillance. Studies have shown that the frequencies of marrow and blood Tregs are greater in patients with AML than in control patients. Although increased Tregs have been associated with a decreased risk of GVHD after allogeneic HCT and hence may impede the graft-versus-tumor effect, recent findings indicate that that this may not be the case. Because there is a need to improve outcomes of standard treatment (chemotherapy with or without allogeneic HCT) in AML, targeting Tregs present an outstanding opportunity in AML because discoveries may apply throughout its treatment. Here, we review data on the roles of Tregs in mediating immune system-AML interactions. We focused on in vitro, animal, and observational human studies of Tregs in AML biology, development, prognosis, and therapy in different settings (eg, vaccination and HCT). Manipulation of Tregs or other types of immunomodulation may become a part of AML treatment in the future.
Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies
Authors: Hwang Pei-Ing , Wu Huan-Bin , Wang Chin-Di , Lin Bai-Ling , Chen Cheng-Tao , Yuan Shinsheng , Wu Guani , Li Ker-Chau
Published: September 2011

Background

To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue.

Results

By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific G ene E xpression T emplates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.

Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity.

Conclusions

These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.
Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection
Authors: Paul Vivek Daniel , Sundarrajan Sudarson , Rajagopalan Sanjeev Saravanan , Hariharan Sukumar , Kempashanaiah Nanjundappa , Padmanabhan Sriram , Sriram Bharathi , Ramachandran Janakiraman
Published: September 2011

Background

Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy.

Results

We developed a recombinant lysis-deficientStaphylococcus aureusphage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized inS. aureusstrain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat) gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test thein vivoefficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenicS. aureusat a dose that results in 80% mortality (LD80). Treatment with the endolysin-deficient phage rescued mice from the fatalS. aureusinfection.

Conclusions

A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistantS. aureuswithout causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host. The recombinant phage effectively rescued mice from fatalS. aureusinfection. To our knowledge this is the first report of a lysis-deficient staphylococcal phage.
Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza
Authors: Almansa Raquel , Anton Andres , Ramirez Paula , Martin-Loeches Ignacio , Banner David , Pumarola Tomás , Xu Luoling , Blanco Jesús , Ran Longsi , Lopez-Campos Guillermo , Martin-Sanchez Fernando , Socias Lorenzo , Loza Ana , Andaluz David , Maravi Enrique , Gordón Mónica , Gallegos Maria C , Fernandez Victoria , León Cristobal , Merino Pedro , Marcos Maria Ángeles , Gandía Francisco , Bobillo Felipe , Resino Salvador , Eiros Jose Mª , Castro Carmen , Mateo Paula , Gonzalez-Rivera Milagros , Rello Jordi , de Lejarazu Raul Ortiz , Kelvin David J , Bermejo-Martin Jesus F
Published: September 2011

Background

Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients.

Methods

Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient.

Results

Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence of a significant positive association between the levels of these mediators, evidencing that they are simultaneously regulated in response to the virus.

Conclusions

Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.
Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults
Authors: Schreiner Felix , El-Maarri Osman , Gohlke Bettina , Stutte Sonja , Nuesgen Nicole , Mattheisen Manuel , Fimmers Rolf , Bartmann Peter , Oldenburg Johannes , Woelfle Joachim
Published: September 2011

Background

Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial.

Methods

We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay.

Results

Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability.

Conclusion

The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.
Alcohol consumption in tertiary education students
Authors: Reavley Nicola J , Jorm Anthony F , McCann Terence V , Lubman Dan I
Published: September 2011

Background

Heavy alcohol consumption among adolescents and young adults is an issue of significant public concern. With approximately 50% of young people aged 18-24 attending tertiary education, there is an opportunity within these settings to implement programs that target risky drinking. The aim of the current study was to survey students and staff within a tertiary education institution to investigate patterns of alcohol use, alcohol-related problems, knowledge of current National Health and Medical Research Council (NHMRC) guidelines for alcohol consumption and intentions to seek help for alcohol problems.

Methods

Students of an Australian metropolitan university (with staff as a comparison group) participated in a telephone interview. Questions related to knowledge of NHMRC guidelines, drinking behaviour, alcohol-related problems and help-seeking intentions for alcohol problems. Level of psychological distress was also assessed.

Results

Of the completed interviews, 774 (65%) were students and 422 (35%) were staff. While staff were more likely to drink regularly, students were more likely to drink heavily. Alcohol consumption was significantly higher in students, in males and in those with a history of earlier onset drinking. In most cases, alcohol-related problems were more likely to occur in students. The majority of students and staff had accurate knowledge of the current NHMRC guidelines, but this was not associated with lower levels of risky drinking. Psychological distress was associated with patterns of risky drinking in students.

Conclusions

Our findings are consistent with previous studies of tertiary student populations, and highlight the disconnect between knowledge of relevant guidelines and actual behaviour. There is a clear need for interventions within tertiary education institutions that promote more effective means of coping with psychological distress and improve help-seeking for alcohol problems, particularly among young men.
Solid-state dye-sensitized solar cells based on ZnO nanoparticle and nanorod array hybrid photoanodes
Authors: Lee Tao-Hua , Sue Hung-Jue , Cheng Xing
Published: September 2011

The effect of ZnO photoanode morphology on the performance of solid-state dye-sensitized solar cells (DSSCs) is reported. Four different structures of dye-loaded ZnO layers have been fabricated in conjunction with poly(3-hexylthiophene). A significant improvement in device efficiency with ZnO nanorod arrays as photoanodes has been achieved by filling the interstitial voids of the nanorod arrays with ZnO nanoparticles. The overall power conversion efficiency increases from 0.13% for a nanorod-only device to 0.34% for a device with combined nanoparticles and nanorod arrays. The higher device efficiency in solid-state DSSCs with hybrid nanorod/nanoparticle photoanodes is originated from both large surface area provided by nanoparticles for dye adsorption and efficient charge transport provided by the nanorod arrays to reduce the recombinations of photogenerated carriers.
A scalable multi-sink gradient-based routing protocol for traffic load balancing
Authors: Yoo Hongseok , Shim Moonjoo , Kim Dongkyun
Published: September 2011

Wireless sensor networks have been assumed to consist of a single sink and multiple sensor nodes which do not have mobility. In these networks, sensor nodes near the sink dissipate their energy so fast due to their many-to-one traffic pattern, and finally they die early. This uneven energy depletion phenomenon known as the hot spot problem becomes more serious as the number of sensor nodes (i.e., their scale) increases. Recently, multi-sink wireless sensor networks have been envisioned to solve the hot spot problem. Gradient routing protocols are known to be appropriate for the networks in that network traffic is evenly distributed to multiple sinks to prolong network lifetime and they are scalable. Each node maintains its gradient representing the direction toward a neighbor node to reach one of the sinks. In particular, existing protocols allow a sensor node to construct its gradient using the cumulative traffic load of a path for load balancing. However, they have a critical drawback that a sensor node cannot efficiently avoid using the path with the most overloaded node. Hence, this paper introduces a new Gradient routing protocol for LOad-BALancing (GLOBAL) with a new gradient model to maximize network lifetime.

The proposed gradient model considers both of the cumulative path load and the traffic load of the most overloaded node over the path in calculating each node's gradient value. Therefore, packets are forwarded over the least-loaded path, which avoids the most overloaded node. In addition, it is known that assigning a unique address to each sensor node causes much communication overhead. Since the overhead increases as the network scales, routing protocols using an address to indicate the receiver in forwarding a packet are not scalable. Thus, GLOBAL also includes an addressing-free data forwarding strategy. Through ns-2 simulation, we verify that GLOBAL achieves better performance than the shortest path routing and load-aware gradient routing ones.
Epithelial-Mesenchymal Transition in tumor microenvironment
Authors: Jing Yingying , Han Zhipeng , Zhang Shanshan , Liu Yan , Wei Lixin
Published: September 2011

The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and also in the tumor invasion process. In addition, EMT also causes disruption of cell-cell adherence, loss of apico-basal polarity, matrix remodeling, increased motility and invasiveness in promoting tumor metastasis. The tumor microenvironment plays an important role in facilitating cancer metastasis and may induce the occurrence of EMT in tumor cells. A large number of inflammatory cells infiltrating the tumor site, as well as hypoxia existing in a large area of tumor, in addition many stem cells present in tumor microenvironment, such as cancer stem cells (CSCs), mesenchymal stem cells (MSCs), all of these may be the inducers of EMT in tumor cells. The signaling pathways involved in EMT are various, including TGF-β, NF-κB, Wnt, Notch, and others. In this review, we discuss the current knowledge about the role of the tumor microenvironment in EMT and the related signaling pathways as well as the interaction between them.
Syndecan-1 antigen, a promising new target for triple-negative breast cancer immuno-PET and radioimmunotherapy. A preclinical study on MDA-MB-468 xenograft tumors
Authors: Rousseau Caroline , Ruellan Anne Lise , Bernardeau Karine , Kraeber-Bodéré Françoise , Gouard Sebastien , Loussouarn Delphine , Saï-Maurel Catherine , Faivre-Chauvet Alain , Wijdenes John , Barbet Jacques , Gaschet Joëlle , Chérel Michel , Davodeau François
Published: September 2011

Background

Overexpression of syndecan-1 (CD138) in breast carcinoma correlates with a poor prognosis and an aggressive phenotype. The objective of this study was to evaluate the potential of targeting CD138 by immuno-PET imaging and radioimmunotherapy (RIT) using the antihuman syndecan-1 B-B4 mAb radiolabeled with either 124I or 131I in nude mice engrafted with the triple-negative MDA-MB-468 breast cancer cell line.

Method

The immunoreactivity of 125I-B-B4 (80%) was determined, and the affinity of 125I-B-B4 and the expression of CD138 on MDA-MB-468 was measured in vitro by Scatchard analysis. CD138 expression on established tumors was confirmed by immunohistochemistry. A biodistribution study was performed in mice with subcutaneous MDA-MB-468 and 125I-B-B4 at 4, 24, 48, 72, and 96 h after injection and compared with an isotype-matched control. Tumor uptake of B-B4 was evaluated in vivo by immuno-PET imaging using the 124I-B-B4 mAb. The maximum tolerated dose (MTD) was determined from mice treated with 131I-B-B4 and the RIT efficacy evaluated.

Results

125I-B-B4 affinity was in the nanomolar range (Kd = 4.39 ± 1.10 nM). CD138 expression on MDA-MB-468 cells was quite low (Bmax = 1.19 × 104 ± 9.27 × 102 epitopes/cell) but all expressed CD138 in vivo as determined by immunohistochemistry. The tumor uptake of 125I-B-B4 peaked at 14% injected dose (ID) per gram at 24 h and was higher than that of the isotype-matched control mAb (5% ID per gram at 24 h). Immuno-PET performed with 124I-B-B4 on tumor-bearing mice confirmed the specificity of B-B4 uptake and its retention within the tumor. The MTD was reached at 22.2 MBq. All mice treated with RIT (n = 8) as a single treatment at the MTD experienced a partial (n = 3) or complete (n = 5) response, with three of them remaining tumor-free 95 days after treatment.

Conclusion

These results demonstrate that RIT with 131I-B-B4 could be considered for the treatment of metastatic triple-negative breast cancer that cannot benefit from hormone therapy or anti-Her2/neu immunotherapy. Immuno-PET for visualizing CD138-expressing tumors with 124I-B-B4 reinforces the interest of this mAb for diagnosis and quantitative imaging.
Identification of improved IL28B SNPs and haplotypes for prediction of drug response in treatment of hepatitis C using massively parallel sequencing in a cross-sectional European cohort
Authors: Smith Katherine R , Suppiah Vijayaprakash , O'Connor Kate , Berg Thomas , Weltman Martin , Abate Maria Lorena , Spengler Ulrich , Bassendine Margaret , Matthews Gail , Irving William L , Powell Elizabeth , Riordan Stephen , Ahlenstiel Golo , Stewart Graeme J , Bahlo Melanie , George Jacob , Booth David R ,   the International Hepatitis C Genetics Consortium (IHCGC)
Published: September 2011

Background

The hepatitis C virus (HCV) infects nearly 3% of the World's population, causing severe liver disease in many. Standard of care therapy is currently pegylated interferon alpha and ribavirin (PegIFN/R), which is effective in less than half of those infected with the most common viral genotype. Two IL28B single nucleotide polymorphisms (SNPs), rs8099917 and rs12979860, predict response to (PegIFN/R) therapy in treatment of HCV infection. These SNPs were identified in genome wide analyses using Illumina genotyping chips. In people of European ancestry, there are 6 common (more than 1%) haplotypes for IL28B, one tagged by the rs8099917 minor allele, four tagged by rs12979860.

Methods

We used massively parallel sequencing of the IL28B and IL28A gene regions generated by polymerase chain reaction (PCR) from pooled DNA samples from 100 responders and 99 non-responders to therapy, to identify common variants. Variants that had high odds ratios and were validated were then genotyped in a cohort of 905 responders and non-responders. Their predictive power was assessed, alone and in combination with HLA-C.

Results

Only SNPs in the IL28B linkage disequilibrium block predicted drug response. Eighteen SNPs were identified with evidence for association with drug response, and with a high degree of confidence in the sequence call. We found that two SNPs, rs4803221 (homozygote minor allele positive predictive value (PPV) of 77%) and rs7248668 (PPV 78%), predicted failure to respond better than the current best, rs8099917 (PPV 73%) and rs12979860 (PPV 68%) in this cross-sectional cohort. The best SNPs tagged a single common haplotype, haplotype 2. Genotypes predicted lack of response better than alleles. However, combination of IL28B haplotype 2 carrier status with the HLA-C C2C2 genotype, which has previously been reported to improve prediction in combination with IL28B, provides the highest PPV (80%). The haplotypes present alternative putative transcription factor binding and methylation sites.

Conclusions

Massively parallel sequencing allowed identification and comparison of the best common SNPs for identifying treatment failure in therapy for HCV. SNPs tagging a single haplotype have the highest PPV, especially in combination with HLA-C. The functional basis for the association may be due to altered regulation of the gene. These approaches have utility in improving diagnostic testing and identifying causal haplotypes or SNPs.