bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Regulation of Priming Effects on Behavior
Authors: Gollwitzer Peter M. , Sheeran Paschal , Trötschel Roman , Webb Thomas L.
Published: June 2011

In three experiments, we tested whether people can protect their ongoing goal pursuits from antagonistic priming effects by using if-then plans (i.e., implementation intentions). In Experiment 1, concept priming did not influence lexical decision time for a critical stimulus when participants had formed if-then plans to make fast responses to that stimulus. In Experiment 2, participants who were primed with a prosocial goal allowed a confederate who asked for help to interrupt their work on a focal task for a longer time if they had merely formed goal intentions to perform well than if they had also formed implementation intentions for concentrating on the task. In Experiment 3, priming the goal of being fast increased driving speed and errors for participants who had formed mere goal intentions to drive only as fast as safety allowed or who had formed no goal intentions, whereas the driving of participants who had formed such goal intentions as well as implementation intentions showed no such priming effects. Our findings indicate that implementation intentions are an effective self-regulatory tool for shielding actions from disruptive concept- or goal-priming effects.
Ghent revisited: Unemployment insurance and union membership in Belgium and the Nordic countries
Authors: Van Rie Tim , Marx Ive , Horemans Jeroen
Published: June 2011

The exceptionally high union density rates in Denmark, Finland and Sweden are attributed to a particular form of voluntary unemployment insurance, known as the Ghent system. Heavily subsidized by the state and administered by union funds, it strongly motivates workers to become union members. Belgium has a partial Ghent system: while unemployment insurance is compulsory, trade unions retain an important role in the provision of benefits. Belgian union density is at an intermediate level; but as in other Ghent countries, its level is currently higher than in the 1970s. This article argues that the Belgian institutional set-up provides stronger incentives for manual workers in industry with lower educational attainment and a past unemployment record. In Denmark, Finland and Sweden, the Ghent system recruits workers across different occupations and educational levels. However, its appeal seems to have lessened over recent years, particularly among younger workers.
Institutional effects on the presence of trade unions at the workplace: Moderation in a multilevel setting
Authors: Fazekas Zoltán
Published: June 2011

Previous research has found that the presence of a union at a workplace is an important individual-level determinant of union membership. The present article, drawing on a multilevel analysis of 21 European countries, provides further evidence which nuances the conclusions of previous studies by introducing and testing institutional moderation effects. Thus, in countries with Ghent systems, having a union at workplace is less important, since probability of membership is already very high. Conversely, if there are extension mechanisms for collective agreements there is less incentive to join a trade union, and this is not compensated even when there is an active union at the workplace.
‘Norm’ of Sustainable Development
Authors: Srivastava Jayati
Published: June 2011

The article engages with the theoretical debate on norms to explicate the prescriptive power of the ‘norm’ of sustainable development. It analyses the socio-economic and political context that have been instrumental in framing of the ‘norm’ of sustainable development, in particular the approach and interventions of developing countries including India. It argues that an ostensible dichotomy between development and environment has fractured the internal cohesion of the norm. The surrounding web of normative structure that marginalises principles of justice and equity is other formidable explanation for its fragile compliance.
Issues and Challenges in ASEAN–India Relations
Authors: Amador Julio S. , Bobillo Ariane , Peñalber Amirah
Published: June 2011

Are there serious political-security conflicts between Association of Southeast Asian Nations (ASEAN) and India that could affect deepening relations? The strengthening of ASEAN and India’s cooperation has already bore fruit with the implementation of the ASEAN–India free trade area. However, political security relations have not been fully examined especially if there are possibilities of potential conflicting policy directions. This article aims to contribute to further understanding of ASEAN and India’s political and security relations through ASEAN’s non-traditional security priorities in assessing potential threats to the region. There are indeed policy areas where ASEAN and India do not see eye to eye such as on issues of nuclear proliferation and human rights. However, because of the mutuality of interest between them, potential conflicts can be resolved.
India–Nepal Economic Cooperation
Authors: Taneja Nisha , Chowdhury Subhanil , Prakash Shravani
Published: June 2011

India and Nepal signed a foreign trade agreement (FTA) in 1971 which has been renewed many times over—latest in 2009. Tariff concessions lie at the core of Indo-Nepal trade arrangements and these concessions have been administered through the ROO criteria.

The Indo–Nepal trade treaty of 1996 was a landmark as India provided duty-free access to all (except three) products manufactured in Nepal. In the period between 1996 and 2002, there was a surge in Nepal’s exports to India, mainly in vegetable ghee, copper products, acrylic yarn and zinc oxide, due to large tariff differentials between India and Nepal in the raw materials used in these items. The 2002 treaty imposed a tariff rate quota these four (the tariff rate quota (TRQ) products). Between 2001 and 2002 and 2008 and 2009, India reduced its tariffs on all products whereby Nepal lost its advantage in the TRQ products and the quota utilization has been very low.

Since the benefits of the offered by India under the trade treaties have been transitory, it is important for the two countries to devise a more comprehensive economic agreement sectors. In this direction, India can help Nepal in developing services, especially hydropower and tourism. For this, Nepal needs to develop a more effective regulatory structure and policy framework and India must invest more in the development of Nepal’s infrastructure.
Turkey’s Transition to Liberal Democracy and the Issue of its EU Membership
Authors: Mohapatra Aswini K.
Published: June 2011

Turkey has often been projected as a model by the US-based think tanks and Western media for enlargement of market democracies in its surrounding regions to contain the surge of radical Islam. The appropriateness of the Turkish democracy as a model is, however, contested by many from within the region and without. While the Arabs ridicule Turkey’s democracy as a farce and a ‘democracy of tanks’, Western critics harp on its illiberal character as reflected in the titular powers and reserved domains of military, high level of human rights abuse and denial of cultural liberties to the minority Kurds. It is in the past decade, particularly since the European Union’s (EU) decision in December 1999 to accept Turkey’s candidacy for membership that the country has experienced radical political reforms signifying a qualitative transformation of its polity to a liberal democracy. The purpose of this article is not to assess Turkey’s progression to liberal democracy or to analyse the domestic debate spurred by the reform process between the progressive Islamists and the secular establishment. Instead, it aims at examining the function of Turkey’s EU accession process in facilitating the second historic transition of Turkish polity (the first being the change-over from mono-party to multi-party system in 1946).
India’s Search for a Post-Cold War Foreign Policy
Authors: Mazumdar Arijit
Published: June 2011

During much of the Cold War, India chose to pursue a non-aligned foreign policy posture. The collapse of the Soviet Union and the end of the Cold War forced India to redefine its foreign policy and search for a new place in the emerging international order. However, almost 20 years on, India’s foreign policy still appears to lack a coherent strategic doctrine. This article identifies some of the domestic factors that hampered the development of a post-Cold War ‘grand strategy’. It argues that the emergence of coalition governments at the national level since the early 1990s, the country’s federal structure, weaknesses in India’s foreign policy institutions and the lack of a strategic culture within the country together constrain India’s search for a post-Cold War foreign policy.
Testicular gonadoblastoma in two pet domestic rabbits (Oryctolagus cuniculus domesticus)
Authors: Suzuki Manabu , Ozaki Masakazu , Ano Naoko , Nomura Koji , Ozaki Kiyokazu , Narama Isao
Published: June 2011

Testicular gonadoblastoma is an uncommon tumor in domestic animals. The current study describes a testicular gonadoblastoma in 2 pet domestic rabbits ( Oryctolagus cuniculus domesticus) based on the histomorphological, immunohistochemical, and ultrastructural characteristics of the tumor. The tumor tissue consisted of discrete tubular structures separated by a fibrous stroma. The tubular structures were composed of large round cells similar in appearance to germ cells in the seminiferous tubules, and small spindle cells with oval or elongated nuclei resembling Sertoli cells. The spindle cells showed peculiar structural patterns arranged in a coronal or follicular pattern, often forming Call–Exner bodies like those in an ovarian granulosa cell tumor. One case was concomitant with seminoma. Immunohistochemistry revealed large round cells that were positive for c-kit and placental alkaline phosphatase, while spindle cells were positive for vimentin and Wilms tumor protein. Ultrastructurally, the spherical eosinophilic material (Call–Exner body) consisted of duplicated basal lamina, and sex cord components surrounded a single degenerative cell similar to a germ cell.
Specific Sets of Intrinsic and Extrinsic Factors Drive Excitatory and Inhibitory Circuit Formation
Authors: Terauchi Akiko , Umemori Hisashi
Published: June 2011

How are excitatory (glutamatergic) and inhibitory (GABAergic) synapses established? Do distinct molecular mechanisms direct differentiation of glutamatergic and GABAergic synapses? In the brain, glutamatergic and GABAergic synaptic connections are formed with specific patterns. To establish such precise synaptic patterns, neurons pass through multiple checkpoints during development, such as cell fate determination, cell migration and localization, axonal guidance and target recognition, and synapse formation. Each stage offers key molecules for neurons/synapses to obtain glutamatergic or GABAergic specificity. Some mechanisms are based on intrinsic systems to induce gene expression, whereas others are based on extrinsic systems mediated by cell-cell or axon-target interactions. Recent studies indicate that specific formation of glutamatergic and GABAergic synapses is controlled by the expression or activation of different sets of molecules during development. In this review, the authors outline stages critical to the determination of glutamatergic or GABAergic specificity and describe molecules that act as determinants of specificities in each stage, with a particular focus on the synapse formation stage. They also discuss possible mechanisms underlying glutamatergic and GABAergic synapse formation via synapse-type specific synaptic organizers.
Real-Time fMRI
Authors: Caria Andrea , Sitaram Ranganatha , Birbaumer Niels
Published: June 2011

Real-time fMRI permits simultaneous measurement and observation of brain activity during an ongoing task. One of the most challenging applications of real-time fMRI in neuroscientific and clinical research is the possibility of acquiring volitional control of localized brain activity using real-time fMRI–based neurofeedback protocols. Real-time fMRI allows the experimenter to noninvasively manipulate brain activity as an independent variable to observe the effects on behavior. Real-time fMRI neurofeedback studies demonstrated that learned control of the local brain activity leads to specific changes in behavior. Here, the authors describe the implementation and application of real-time fMRI with particular emphasis on the self-regulation of local brain activity and the investigation of brain-function relationships. Real-time fMRI represents a promising new approach to cognitive neuroscience that could complement traditional neuroimaging techniques by providing more causal insights into the functional role of circumscribed brain regions in behavior.
Quality Evaluation of Functional Chicken Nuggets Incorporated with Ground Carrot and Mashed Sweet Potato
Authors: Bhosale S.S. , Biswas A.K. , Sahoo J. , Chatli M.K. , Sharma D.K. , Sikka S.S.
Published: June 2011

This study was envisaged to evaluate the effect of ground raw carrot (0%, 5%, 10% and 15%) and mashed sweet potato (0%, 5%, 10% and 15%) as functional ingredients on the quality of chicken meat nuggets. The products were evaluated for physicochemical quality, proximate composition, nutritive value, sensory quality as well as color and texture profile analyses. Additions of either raw carrot or mashed sweet potato represent an improvement in the nutritional value and have some beneficial effects due to the presence of dietary fibers and β-carotene. They were also found to be effective in sustaining the desired cooking yield and emulsion stability. Treated samples showed lower (p > 0.05) protein, fat and ash contents but higher (p < 0.05) moisture content than control. There were differences among the nugget samples with respect to sensory qualities, and control samples as well as samples with 10% added carrot/sweet potato had higher overall acceptability scores. Hunter color values (L*, a* and b* values) were higher (p < 0.05) for both the formulated products, while their textural parameters were nearly unchanged. In conclusion, carrot and sweet potato at 10% added level have greater potential as good source of dietary fibers and β-carotene and may find their way in meat industry.
Epidemiology of multiple sclerosis in south-western Sardinia
Authors: Cocco Eleonora , Sardu Claudia , Massa Rita , Mamusa Elena , Musu Luigina , Ferrigno Paola , Melis Maurizio , Montomoli Cristina , Ferretti Virginia , Coghe Giancarlo , Fenu Giuseppe , Frau Jessica , Lorefice Lorena , Carboni Nicola , Contu Paolo , Marrosu Maria G
Published: June 2011

Background: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south-western Sardinia (SWS) are available. SWS has a genetically homogeneous population, apart from St Peter Island, and represents a peculiar environment related to the industrial, mineralogical and military economy.

Objective: To estimate prevalence and incidence and to evaluate temporal trends and geographical distribution of MS in SWS.

Methods: MS prevalence was evaluated on 31 December 2007 and crude mean annual incidence rate was defined between 2003 and 2007. Temporal trend in MS incidence was assessed using the Armitage test. To identify MS clusters, Standard Morbidity Ratio (SMR) was calculated for each village and geographical distribution prevalence by means of a Bayesian hierarchical model.

Results: Total crude prevalence rate was 210.4 (95% CI 186.3–234.5): 280.3 (95% CI 241.4–319.3) for females, 138 (95% CI 110.1–165.8) for males. The crude mean annual incidence rate was 9.7/100,000 (95% CI 3.4–13.2): 4.7/100,000 (95% CI 2.4–17.0) and 14.6/100,000 (95% CI 11.8–34.8) for males and females respectively. MS incidence has increased over the last 50 years. Cluster analysis showed an SMR of 0.2 (95% CI 0.05–0.68, p = 0.002) on the island of San Pietro, and 2.0 (95% CI 1.35–2.95, p = 0.001) in Domusnovas. Spatial distribution of MS was confirmed by Bayesian geographical analysis.

Conclusions: Our data confirm Sardinia as a high-risk area for MS and support the relevance of genetic factors in MS, as evidenced in St Peter Island. However, we found an unexpectedly high MS prevalence in one village, in particular in males, suggesting an environmental influence on MS occurrence.
Delayed fingolimod-associated asystole
Authors: Espinosa Patricio S , Berger Joseph R
Published: June 2011

Oral fingolimod (Gilenya) is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapses and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). We report a patient with MS who developed asystole and sustained bradycardia 21 hours after the first dose of fingolimod.
Unhealthy weight control behaviors among adolescents
Authors: Vander Wal Jillon S
Published: June 2011

This article examined moderators of the association between BMI and unhealthy weight control behaviors suggested by the Dual Pathway Model among 4,529 adolescents from the Health Behavior in School-Aged Children survey. An obese classification was associated with unhealthy weight control behaviors for boys and girls. Low life satisfaction, high negative affect, and body size dissatisfaction were associated with unhealthy weight control behaviors among boys as was low life satisfaction for girls. Among girls, healthy weight classification, coupled with low negative affect or body size satisfaction, was protective against unhealthy weight control behaviors. Improved self-care may decrease obesity and unhealthy weight control behaviors.
Singing a different tune in your native language: first language attrition of prosody
Authors: de Leeuw Esther , Mennen Ineke , Scobbie James M.
Published: June 2011

First language attrition refers to the changes which a first language (L1) undergoes when a second language (L2) is acquired in a context in which L1 use is reduced (Cook, 2003; Köpke, 2004). To date, some studies have focused on complete loss of an L1, for example in the case of children whose contact with their initial language ceased after adoption (Pallier et al., 2003; Ventureyra, Pallier, & Yoo, 2004). Others have investigated more subtle cases in which changes to the L1 occur, although intelligibility remains largely, or completely, unaffected (de Leeuw, Schmid, & Mennen, 2007; Flege, 1987; Flege & Eefting, 1987; Major, 1992; Mennen, 2004). The study at hand belongs to the latter category, comprising a fine phonetic analysis of prosody in 10 late consecutive German–English bilinguals. In general, the results indicate L1 attrition in the intonational alignment of the prenuclear rise. However, interpersonal variation was also evidenced: two bilinguals performed clearly within the English monolingual norm in their German while one bilingual evidenced no L1 attrition. Intrapersonal variation occurred in the form of the start of the prenuclear rise appearing to undergo more L1 attrition than the end. The results are discussed in relation to previous studies suggesting that L1 attrition is less likely to occur in late consecutive bilinguals than in early consecutive bilinguals and, more generally, with regard to transfer and interference.
‘Tanks, terrain and black horses’: The Intra-German border, Mitteldeutschland and Third World War cultural texts
Authors: Jachimiak Peter Hughes
Published: June 2011

This article offers an insight into wargames of the Cold War as an escalation of lived experience. Utilizing the work of Bakhtin, Baudrillard and Williams, it insists that everyday life merges with simulations in order to produce chronotopic cultural texts that can be understood as dangerous illusions of virtual war. Adopting a case study approach, this article discusses the spatial aspects of Fulda Gap: The First Battle of the Next War, and how this wargame’s hexagonal spaces map onto the terrain that the gameboard represents — the so-called Fulda Gap — an area of weakness in NATO’s defence of the Intra-German border. As such, this article asserts that Fulda Gap acts as a trace of the border which is now deemed lost, and promotes an understanding of the border’s landscapes as a version of Mitteldeutschland (Middle Germany).
Liquid racism and the ambiguity of Ali G
Authors: Weaver Simon
Published: June 2011

This article analyses Ali G through the concept of ‘liquid racism’. As a polysemic and elusive form, liquid racism requires reflexivity in order to critique it fully, and is a racism that, in media representation, often polarizes debate of its meaning. The article explains how academics have struggled to explain Ali G’s relationship to racism, how his ambiguity is complicated by some social actors seeing him as a real person, before it explains how Ali G expresses three strands of liquid racism. These are ‘postmodern minstrelsy’ — Ali G as a black man, ‘ethnocultural hybrid racism’ — Ali G as a white man pretending to be black, and ‘anti-Asian racism’ — Ali G as an Asian man pretending to be black. It is the combination of the three and the erasure they inflict on one another that creates liquidity. Finally, some non-racist themes in Baron Cohen’s comedy are outlined that encourage analytic confusion.
The association between angiotensin-converting enzyme insertion/deletion gene variant and risk of focal segmental glomerulosclerosis: a systematic review and meta-analysis
Authors: Zhou Tian-Biao , Qin Yuan-Han , Su Li-Na , Lei Feng-Ying , Huang Wei-Fang , Zhao Yan-Jun , Pang Yu-Sheng , Yang Kun-Peng
Published: June 2011

Background and objective: The association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism with the risk of focal segmental glomerulosclerosis (FSGS) is still controversial. A meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and FSGS susceptibility.

Method: We performed a predefined literature search and selection of eligible relevant studies to collect data from electronic databases.

Results: In total, 12 articles were identified for the analysis of the association between ACE I/D gene polymorphism and FSGS risk. One report included an investigation in Arab and Jewish populations separately. Thus, there were seven reports in Asians, two in Caucasians, one in Africans, two in Arabs and one in Jews. In Asians, there was a markedly positive association between the D allele or DD genotype and FSGS susceptibility ( p = 0.008; p = 0.002), and the II genotype may play a protective role against FSGS onset ( p = 0.002). However, a link between ACE I/D gene polymorphism and FSGS risk was not found in Caucasians, Africans, Arabs or Jews (Caucasians: D: p = 0.11, DD: p = 0.19, II: p = 0.70; Africans: D: p = 0.40, DD: p = 0.49, II: p = 0.61; Arabs: D: p = 0.34, DD: p = 0.10, II: p = 0.42; Jews: D: p = 0.90, DD: p = 0.97, II: p = 0.83).

Conclusion: The D allele or DD homozygosity may become a significant genetic molecular marker for the onset of FSGS in Asians, but not for Caucasians, Africans, Arabs or Jews.
Media systems and political systems: Dimensions of comparison
Authors: Engesser Sven , Franzetti Annika
Published: June 2011

In social sciences, the interdependence between media systems and political systems is generally not in doubt. However, empirical knowledge about the relation between the two types of systems is rare. A deeper understanding can be gained by an international comparison of media and political systems from a macro perspective using aggregated data. The pilot study presented in this article offers an approach to international comparison based on four dimensions: freedom, diversity, centrality and tradition. These concepts serve as dimensions of comparison for both media- and political systems. The instrument is tested by using an intentionally heterogeneous sample of seven countries from around the world: China, Germany, Japan, Mexico, the Netherlands, Russia and the US. In combination with a pragmatic use of systems theory as a theoretical framework, the dimensions allow more profound insights into the relation between media- and political systems. In sum, the research project prepares the ground for future international large-N comparisons.
The role of media in the process of socialization to American politics among international students
Authors: Kononova Anastasia , Alhabash Saleem , Cropp Fritz
Published: June 2011

Mass media have been considered a powerful agent of political socialization, affecting political attitudes and behaviors of voters and non-voters. This study employed a survey of international students in the US to investigate the effects of print, television and online news on political socialization during the 2008 US presidential race. Results indicated that newspaper and television news use significantly predicted internal political efficacy and intentions to participate in American politics. Media ‘nationality’, motivation to apply for permanent residence and duration of stay in the US were explored for possible moderation of media effects on political socialization. The findings are discussed within the framework of media effects on political socialization in host and home countries.
Voice of America in the post-Cold War era: Opportunities and challenges to external media services via new information and communication technology
Authors: Sharon Wang Shaojung , Junhao Hong
Published: June 2011

This study examines Voice of America’s (VOA) services in the post-Cold War era within the framework of the information revolution and globalization. The use of new information venues has caused VOA to evolve from a pure propaganda machine to a notion of informational soft power. However, this study finds that not only is there a gap between VOA’s target audiences and its actual website visitors but its website attracts more American and western users than users in the societies it intends to influence the most. The role of informational soft power in articulating appealing ideas, values, norms and ethics through all manners of media and new information and communication technology to create the perception that US hegemony is benign poses challenges for the US’s information strategy.
Managing Pediatric Food Allergies
Authors: Crain Maria
Published: June 2011

Food allergies are increasing in the pediatric population. A review of the literature suggests that clinicians may lack knowledge about food allergy. Avoidance is currently the standard of care. As a result, managing these children and families is difficult. Clinicians must be knowledgeable in order to educate their patients. This article provides information for the pediatric provider concerning prevalence in children, pathophysiology, comorbidities, history and physical examination, diagnostic testing and referral, and educational and preventative strategies.
Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells
Authors: Schaniel Christoph , Sirabella Dario , Qiu Jiajing , Niu Xiaohong , Lemischka Ihor R. , Moore Kateri A.
Published: June 2011

The role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow and spleen, manifesting an impaired ability to maintain a self-renewing stem cell pool. Exhaustion of the stem cell pool was apparent only in the context of systemic stress by chemotherapy or transplantation of wild-type stem cells into irradiated Wif1 hosts. Paradoxically this is mediated, at least in part, by an autocrine induction of canonical Wnt signaling in stem cells on sequestration of Wnts in the environment. Additional signaling pathways are dysregulated in this model, primarily activated Sonic Hedgehog signaling in stem cells as a result of Wif1-induced osteoblastic expression of Sonic Hedgehog. We find that dysregulation of the stem cell niche by overexpression of an individual component impacts other unanticipated regulatory pathways in a combinatorial manner, ultimately disrupting niche mediated stem cell fate decisions.
Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemia
Authors: Slupianek Artur , Dasgupta Yashodhara , Ren Shu-yue , Gurdek Ewa , Donlin Milene , Nieborowska-Skorska Margaret , Fleury Fabrice , Skorski Tomasz
Published: June 2011

Chronic myeloid leukemia chronic phase (CML-CP) CD34+ cells contain numerous DNA double-strand breaks whose unfaithful repair may contribute to chromosomal instability and disease progression to blast phase (CML-BP). These phenomena are often associated with the appearance of imatinib-resistant BCR-ABL1 kinase mutants (eg, T315I) and overexpression of BCR-ABL1. Here we show that BCR-ABL1 (nonmutated and T315I mutant) promoted RAD51 recombinase-mediated unfaithful homeologous recombination repair (HomeoRR) in a dosage-dependent manner. BCR-ABL1 SH3 domain interacts with RAD51 proline-rich regions, resulting in direct phosphorylation of RAD51 on Y315 (pY315). RAD51(pY315) facilitates dissociation from the complex with BCR-ABL1 kinase, migrates to the nucleus, and enhances formation of the nuclear foci indicative of recombination sites. HomeoRR and RAD51 nuclear foci were strongly reduced by RAD51(Y315F) phosphorylation-less mutant. In addition, peptide aptamer mimicking RAD51(pY315) fragment, but not that with Y315F phosphorylation-less substitution, diminished RAD51 foci formation and inhibited HomeoRR in leukemia cells. In conclusion, we postulate that BCR-ABL1 kinase-mediated RAD51(pY315) promotes unfaithful HomeoRR in leukemia cells, which may contribute to accumulation of secondary chromosomal aberrations responsible for CML relapse and progression.
Responsiveness of HIV-specific CD4 T cells to PD-1 blockade
Authors: Porichis Filippos , Kwon Douglas S. , Zupkosky Jennifer , Tighe Daniel P. , McMullen Ashley , Brockman Mark A. , Pavlik David F. , Rodriguez-Garcia Marta , Pereyra Florencia , Freeman Gordon J. , Kavanagh Daniel G. , Kaufmann Daniel E.
Published: June 2011

Defining the T helper functions impaired by programmed death–1 (PD-1) is crucial for understanding its role in defective HIV control and determining the therapeutic potential of targeting this inhibitory pathway. We describe here the relationships among disease stage, levels of PD-1 expression, and reversibility of CD4 T-cell impairment. PD-L1 blockade in vitro enhanced HIV-specific production of Th0 (IL-2), Th1 (IFN-γ), Th2 (IL-13), and TFH (IL-21) cytokines by CD4 T cells. PD-L1 blockade caused an early increase in cytokine transcription and translation that preceded cell proliferation. Although the impact of PD-L1 blockade on cytokine expression and, to a lesser extent, cell proliferation was associated with markers of disease progression, restoration of cytokine secretion was also observed in most subjects with undetectable viremia. PD-L1 blockade restored cytokine secretion in both PD-1intermediate and PD-1high sorted CD4 T-cell subsets. Compared with PD-1high HIV-specific CD8 T cells, PD-1high HIV-specific CD4 T cells showed lower expression of the inhibitory molecules CD160 and 2B4, demonstrating marked differences in expression of inhibitory receptors between T-cell subsets. These data show that PD-1 impairs HIV-specific T helper responses both by limiting expansion of these cells and by inhibiting effector functions of multiple differentiated CD4 T-cell subsets.
Lack of TIR8/SIGIRR triggers progression of chronic lymphocytic leukemia in mouse models
Authors: Bertilaccio Maria Teresa Sabrina , Simonetti Giorgia , Dagklis Antonis , Rocchi Martina , Rodriguez Tania Veliz , Apollonio Benedetta , Mantovani Alberto , Ponzoni Maurilio , Ghia Paolo , Garlanda Cecilia , Caligaris-Cappio Federico , Muzio Marta
Published: June 2011

Inflammation is involved in the initiation and progression of several chronic lymphoid malignancies of B-cell type. Toll-like receptors (TLR) are transmembrane inflammatory receptors that on recognition of pathogen-associated molecular patterns trigger an innate immune response and bridge the innate and adaptive immune response by acting as costimulatory signals for B cells. Fine tuning of TLR and IL-1R–like (ILR) activity is regulated by TIR8 (SIGIRR), a transmembrane receptor of the TLR/ILR family which inhibits other family members. To test the hypothesis that TLR and/or ILR may play a role in the natural history of chronic B-cell tumors, we crossed Eμ-TCL1 transgenic mice, a well established model of chronic lymphocytic leukemia (CLL), with mice lacking the inhibitory receptor TIR8 that allow an unabated TLR-mediated stimulation. We here report that in the absence of TIR8 the appearance of monoclonal B-cell expansions is accelerated and mouse life span is shortened. The morphology and phenotype of the mouse leukemic expansions reproduce the progression of human CLL into an aggressive and frequently terminal phase characterized by the appearance of prolymphocytes. This study reveals an important pathogenetic implication of TLR in CLL development and progression.
Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation
Authors: Morgan Gareth J. , Davies Faith E. , Gregory Walter M. , Russell Nigel H. , Bell Sue E. , Szubert Alexander J. , Coy Nuria Navarro , Cook Gordon , Feyler Sylvia , Byrne Jenny L. , Roddie Huw , Rudin Claudius , Drayson Mark T. , Owen Roger G. , Ross Fiona M. , Jackson Graham H. , Child J. Anthony ,   for the NCRI Haematological Oncology Study Group
Published: June 2011

As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.
Decay-accelerating factor regulates T-cell immunity in the context of inflammation by influencing costimulatory molecule expression on antigen-presenting cells
Authors: Fang Chongyun , Miwa Takashi , Song Wen-Chao
Published: June 2011

Recent studies have indicated a role of complement in regulating T-cell immunity but the mechanism of action of complement in this process remains to be clarified. Here we studied mice deficient in decay-accelerating factor (DAF), a key membrane complement regulator whose deficiency led to increased complement-dependent T-cell immune responses in vivo. By crossing OT-II and OT-I T-cell receptor transgenic mice with DAF-knockout mice, we found that lack of DAF on T cells did not affect their responses to antigen stimulation. Similarly, lack of DAF on antigen-presenting cells (APCs) of naive mice did not alter their T-cell stimulating activity. In contrast, APCs from DAF-knockout mice treated with inflammatory stimuli were found to be more potent T-cell stimulators than cells from similarly treated wild-type mice. Acquisition of higher T-cell stimulating activity by APCs in challenged DAF-knockout mice required C3 and C5aR and was correlated with decreased surface PD-L1 and/or increased CD40 expression. These findings implied that DAF suppressed T-cell immunity as a complement regulator in the context of inflammation but did not play an intrinsic role on T cells or APCs. Collectively, our data suggest a systemic and indirect role of complement in T-cell immunity.
Ear diseases among secondary school students in Xi'an, China: The role of portable audio device use, insomnia and academic stress
Authors: Chen Yang , Li Xu , Xu Zhan , Li Zonghua , Zhang Pengzhi , He Ya , Wang Fangyuan , Qiu Jianhua
Published: June 2011

Background

Hearing impairment negatively impacts students' development of academic, language and social skills. Even minimal unilateral hearing loss can hinder educational performance. We investigated the prevalence of ear diseases among secondary school students in the city of Xi'an, China in order to provide a foundation for evidence-based hearing healthcare.

Methods

A stratified random sampling survey was conducted in 29 secondary schools. Demographics and medical histories were collected, and otologic examinations were performed. Questionnaires were administered to assess insomnia, academic stress and use of portable audio devices. Logistic regression analysis was used to identify factors associated with hearing impairment, and the association of sensorineural hearing loss with insomnia, academic stress and the use of portable audio devices was analyzed with the chi-square test.

Results

The percentage of students with some form of ear disease was 3.32%. External ear disease, middle ear disease and sensorineural hearing loss occurred in 1.21%, 0.64% and 1.47% of the students, respectively. Boys had a relatively higher prevalence of ear disease than girls. According to our survey, the prevalence of sensorineural hearing loss increased significantly among the students with insomnia and extended use of portable audio devices, but not among those with elevated levels of academic stress. Hearing aids and surgical treatment were needed in 1.47% and 0.89% of the students, respectively.

Conclusions

There is a high prevalence of ear disease among secondary school students, and this should be given more attention. Insomnia and the excessive use of portable audio devices may be related to adolescent sensorineural hearing loss. It is important to establish and comply with an evidence-based preventive strategy.
Fatty acids intake in the Mexican population. Results of the National Nutrition Survey 2006
Authors: Ramírez-Silva Ivonne , Villalpando Salvador , Moreno-Saracho Jessica E , Bernal-Medina Daniel
Published: June 2011

Background

There is growing evidence that quality, rather that quantity of fat is the determinant of cardiovascular risk. The objective of the study is to describe quantitatively the intake and adequacy of fatty acid classes among the Mexican population aged 5-90 years from a probabilistic survey.

Methods

Dietary intake of individual and classes of fatty acids was computed from the dataset of the 2006 Mexican National Health and Nutrition Survey (ENSANUT2006), collected by a food frequency questionnaire. Adequacy was calculated in reference to authoritative recommendations.

Results

The mean intake of total fatty acids (TFA ≈ 25%E) fell within WHO recommendations; the intakes of saturated fatty acids (SFA) among all age-groups (45-60%) and of trans fatty acids (TrFA) in 30% of school-age children and adolescents and 20% of adults exceeded international recommendations. The mean intake of polyunsaturated fatty acids (PUFA) and particularly of n6 and n3 PUFAS, was inadequately insufficient in 50% of the sample.

Conclusions

The main public health concerns are the high intake of SFA and the suboptimal intake of PUFA in Mexican population. The TrFA intake represents a low public health risk.
Molecular interplay between leptin, insulin-like growth factor-1, and β-amyloid in organotypic slices from rabbit hippocampus
Authors: Marwarha Gurdeep , Prasanthi Jaya RP , Schommer Jared , Dasari Bhanu , Ghribi Othman
Published: June 2011

Background

Evidence shows that the insulin-like growth factor-1 (IGF-1) and leptin reduce β-amyloid (Aβ) production and tau phosphorylation, two major hallmarks of Alzheimer's disease (AD). IGF-1 expression involves the JAK/STAT pathway and the expression of leptin is regulated by the mammalian target of rapamycin complex 1 (mTORC1). We have previously shown that Aβ reduces leptin by inhibiting the mTORC1 pathway and Aβ was also suggested to inhibit the JAK/STAT pathway, potentially attenuating IGF-1 expression. As IGF-1 can activate mTORC1 and leptin can modulate JAK/STAT pathway, we determined the extent to which IGF-1 and leptin can upregulate the expression of one another and protect against Aβ-induced downregulation.

Results

We demonstrate that incubation of organotypic slices from adult rabbit hippocampus with Aβ42 downregulates IGF-1 expression by inhibiting JAK2/STAT5 pathway. Leptin treatment reverses these Aβ42 effects on IGF-1 and treatment with the STAT5 inhibitor completely abrogated the leptin-induced increase in IGF-1. Furthermore, EMSA and ChIP analyses revealed that leptin increases the STAT5 binding to the IGF-1 promoter. We also show that IGF-1 increases the expression of leptin and reverses the Aβ42-induced attenuation in leptin expression via the activation of mTORC1 signaling as the mTORC1 inhibitor rapamycin completely precluded the IGF-1-induced increase in leptin expression.

Conclusion

Our results demonstrate for the first time that Aβ42 downregulates IGF-1 expression and that leptin and IGF-1 rescue one another from downregulation by Aβ42. Our study provides a valuable insight into the leptin/IGF-1/Aβ interplay that may be relevant to the pathophysiology of AD.
17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and liveE. coli
Authors: Palmer Christine D , Mancuso Christy J , Weiss Jerrold P , Serhan Charles N , Guinan Eva C , Levy Ofer
Published: June 2011

Detection and clearance of bacterial infection require balanced effector and resolution signals to avoid chronic inflammation. Detection of GNB LPS by TLR4 on mϕ induces inflammatory responses, contributing to chronic inflammation and tissue injury. LXs and Rvs are endogenous lipid mediators that enhance resolution of inflammation, and their actions on primary human mϕ responses toward GNB are largely uncharacterized. Here, we report that LXA4, LXB4, and RvD1, tested at 0.1–1 μM, inhibited LPS-induced TNF production from primary human mϕ, with ATL and 17(R)-RvD1, demonstrating potent inhibition at 0.1 μM. In addition, 17(R)-RvD1 inhibited LPS-induced primary human mϕ production of IL-7, IL-12p70, GM-CSF, IL-8, CCL2, and MIP-1α without reducing that of IL-6 or IL-10. Remarkably, when stimulated with live Escherichia coli, mϕ treated with 17(R)-RvD1 demonstrated increased TNF production and enhanced internalization and killing of the bacteria. 17(R)-RvD1-enhanced TNF, internalization, and killing were not evident for an lpxM mutant of E. coli expressing hypoacylated LPS with reduced inflammatory activity. Furthermore, 17(R)-RvD1-enhanced, E. coli-induced TNF production was evident in WT but not TLR4-deficient murine mϕ. Thus, Rvs differentially modulate primary human mϕ responses to E. coli in an LPS- and TLR4-dependent manner, such that this Rv could promote resolution of GNB/LPS-driven inflammation by reducing mϕ proinflammatory responses to isolated LPS and increasing mϕ responses important for clearance of infection.
Protein kinase Cδ is a critical component of Dectin-1 signaling in primary human monocytes
Authors: Elsori Deena H , Yakubenko Valentin P , Roome Talat , Thiagarajan Praveena S , Bhattacharjee Ashish , Yadav Satya P , Cathcart Martha K
Published: June 2011

Zymosan, a mimic of fungal pathogens, and its opsonized form (ZOP) are potent stimulators of monocyte NADPH oxidase, resulting in the production of O2.–, which is critical for host defense against fungal and bacterial pathogens and efficient immune responses; however, uncontrolled O2.– production may contribute to chronic inflammation and tissue injury. Our laboratory has focused on characterizing the signal transduction pathways that regulate NADPH oxidase activity in primary human monocytes. In this study, we examined the involvement of various pattern recognition receptors and found that Dectin-1 is the primary receptor for zymosan stimulation of O2.– via NADPH oxidase in human monocytes, whereas Dectin-1 and CR3 mediate the activation by ZOP. Further studies identified Syk and Src as important signaling components downstream of Dectin-1 and additionally identified PKCδ as a novel downstream signaling component for zymosan-induced O2.– as well as phagocytosis. Our results show that Syk and Src association with Dectin-1 is dependent on PKCδ activity and expression and demonstrate direct binding between Dectin-1 and PKCδ. Finally, our data show that PKCδ and Syk but not Src are required for Dectin-1-mediated phagocytosis. Taken together, our data identify Dectin-1 as the major PRR for zymosan in primary human monocytes and identify PKCδ as a novel downstream signaling kinase for Dectin-1-mediated regulation of monocyte NADPH oxidase and zymosan phagocytosis.
Glia maturation factor-γ mediates neutrophil chemotaxis
Authors: Aerbajinai Wulin , Liu Lunhua , Chin Kyung , Zhu Jianqiong , Parent Carole A , Rodgers Griffin P
Published: June 2011

Chemotaxis is fundamental to the directional migration of neutrophils toward endogenous and exogenous chemoattractants. Recent studies have demonstrated that ADF/cofilin superfamily members play important roles in reorganizing the actin cytoskeleton by disassembling actin filaments. GMFG, a novel ADF/cofilin superfamily protein that is expressed in inflammatory cells, has been implicated in regulating actin reorganization in microendothelial cells, but its function in neutrophils remains unclear. Here, we show that GMFG is an important regulator for cell migration and polarity in neutrophils. Knockdown of endogenous GMFG impaired fMLF- and IL-8 (CXCL8)-induced chemotaxis in dHL-60 cells. GMFG knockdown attenuated the formation of lamellipodia at the leading edge of cells exposed to fMLF or CXCL8, as well as the phosphorylation of p38 and PAK1/2 in response to fMLF or CXCL8. Live cell imaging revealed that GMFG was recruited to the leading edge of cells in response to fMLF, as well as CXCL8. Overexpression of GMFG enhanced phosphorylation of p38 but not of PAK1/2 in dHL-60 cells. In addition, we found that GMFG is associated with WAVE2. Taken together, our findings suggest that GMFG is a novel factor in regulating neutrophil chemotaxis by modulating actin cytoskeleton reorganization.
Modulation of regulatory T cell-Th17 balance by plasmacytoid dendritic cells
Authors: Gautreau Laetitia , Chabannes Dominique , Heslan Michèle , Josien Régis
Published: June 2011

Tregs represent an interesting therapeutic tool to modulate immune responses that could be deleterious in autoimmune diseases and in transplantation. However, phenotype and functions of Tregs do not seem to be stable, and recent data suggest that FoxP3-expressing Tregs can be driven to produce IL-17. In this study, we have analyzed the role of pDCs versus cDCs on Treg responses and underlined that pDCs have an intrinsic, unique capacity to induce IL-17 secretion from T cells. We showed in rats that FoxP3+ Tregs were able to secrete IL-17 only when stimulated by allogeneic, mature pDCs but not cDCs. In addition, in rats and mice, mature pDCs but not cDCs inhibited in vitro Treg-suppressive functions and in the presence of Tregs, supported Th17 differentiation from naive T cells through secretion of high amounts of IL-6. These data suggest an important role for pDCs in modulating or switching Treg function and allowing Th17 differentiation.