bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Autonomic Nerve Function In Hypothyroids By Time Domain Method of Heart Rate Variability
Authors: Ahmed Matia , Begum Noorzahan , Ferdousi Sultana 
Published: July 2012

Background: Cardiovascular complications are common in hypothyroids .Time domain measures of HRV is useful to determine the cardiac autonomic regulation by assessing sympathovagal balance.Objective: To assess the cardiac autonomic nerve function activity by time domain measures of heart rate variability in patients with hypothyroidism.Methods: This cross sectional study was carried out in the Department of Physiology, Banghabandhu Sheikh Mujib Medical University between July 2008 to June 2009 on 60 female patients with hypothyroidism aged 30-50 years. 30 age matched apparently healthy euthyroid subjects were also studied as control. Hypothyroid patients were divided into 2 subgroups, one group includes patients on their 1st day of diagnosis, before starting of treatment and another group includes patients with medication for 12-18 months. The patients were selected from the Out Patients Department of Endocrinology Wing BSMMU. Serum TSH and FT4 levels of all subjects were measured by AxSYM system. For assessing HRV by time domain method, mean R-R interval, mean heart rate, SDNN, RMSSD and variance were measured by a Polyrite. For statistical analysis, Independent Sample t test and One Way ANOVA were used.Results: The mean serum TSH was significantly higher and FT4 was significantly lower (p<0.001) in newly diagnosed hypothyroids than those of control and treated group. In untreated hypothyroid patients the mean values of heart rate, SDNN, RMSSD,variance were found significantly (p<0.001) lower in comparison to both control and treated patients. No significant difference in these hormonal levels and all these time domain measures were found between control and treated group.Conclusion: This study concludes that decrease parasympathetic nerve activity may be a consequence of hypothyroidism, if not treated properly. DOI: http://dx.doi.org/10.3329/jbsp.v7i1.11162 J Bangladesh Soc Physiol. 2012, June; 7(1): 48-52
Mutations industrielles et dynamiques territoriales
Authors: Perrat Jacques 
Published: July 2012

L’industrie reste un secteur-clé du développement économique de notre pays, à condition pour elle de relever les défis des nouvelles exigences environnementales. C’est le principal objectif des politiques publiques d’innovation. Les acteurs régionaux et locaux manquent souvent d’un cadre méthodologique adéquat pour appréhender l’impact de ces politiques sur les potentiels productifs de leurs territoires. Ce texte tente de répondre à ce besoin. La notion de complexe territorialisé de compétences est proposée pour évaluer le degré de performances technoproductives et institutionnelles d’un territoire, mais aussi sa capacité à maintenir ou à améliorer son rang dans la « hiérarchie des places » globale, face, notamment, à la stratégie des firmes multinationales.
Coûts de transaction et adoption des MAE territorialisées à enjeu eau
Authors: Rousset Sylvain , Louis Mathilde 
Published: July 2012

Les mesures agroenvironnementales territorialisées (MAET) sont un nouvel instrument d’intervention publique pour atteindre l’objectif de bon état des milieux aquatiques prévu par la Directive cadre sur l’eau (DCE). A mi-parcours du Programme de Développement Rural Hexagonal 2007-2013, le taux de couverture des territoires à enjeu eau reste modeste. En référence au cadre de l’économie néo-institutionnelle, on formule la proposition selon laquelle les coûts de transaction jouent un rôle décisif dans les freins à l’adoption des mesures proposées par les opérateurs locaux. Une enquête auprès d’agriculteurs éligibles aux MAET en Poitou-Charentes confirme l’importance de l’accès à l’information et des préférences des producteurs en matière de flexibilité contractuelle.
Territorialisation de la politique rurale européenne en Emilie Romagne
Authors: Landel Pauline , Le Roy Anne 
Published: July 2012

Cet article propose une analyse de la traduction régionale du Règlement de Développement Rural (RDR) 2007-2013 en Emilie Romagne en Italie. Construisant une démarche interdisciplinaire, nous analysons la mise en œuvre du RDR par la Région à partir des objectifs affichés dans la programmation, des leviers socioéconomiques sollicités, complétés par l’étude des modalités institutionnelles de mise en œuvre. Cette analyse débouche sur celle des instruments de territorialisation des mesures de développement rural (mesures de l’Axe 3 du RDR). Deux types de conclusions peuvent être tirés de cette étude. D’une part, le choix des instruments de territorialisation s’explique par le jeu de contraintes spécifiques dans lequel s’élabore l’action publique de développement rural, entre objectifs de renouvellement et rapports de pouvoirs en présence. D’autre part, d’un point de vue méthodologique, l’analyse de politique publique permet de révéler ces choix de territorialisation et d’alimenter une démarche d’évaluation compréhensive des effets des politiques publiques.
Induction of Type I IFN Is a Physiological Immune Reaction to Apoptotic Cell-Derived Membrane Microparticles
Authors: Schiller Martin , Parcina Marijo , Heyder Petra , Foermer Sandra , Ostrop Jenny , Leo Albrecht , Heeg Klaus , Herrmann Martin , Lorenz Hanns-Martin , Bekeredjian-Ding Isabelle 
Published: July 2012

Abstract
Membrane microparticles (MMP) released from apoptotic cells deliver signals that secure the anti-inflammatory response beyond the nearest proximity of the apoptotic cell. Plasmacytoid dendritic cells (pDC) are sentinels prepared to detect cellular processes that endanger the organism. They play a key role in the regulation of both pro- and anti-inflammatory immune responses. Based on the assumption that pDC could participate in the initiation of the anti-inflammatory response to apoptotic cells, we investigated the effects of apoptotic cell-derived MMP on human pDC. The results obtained in our experiments confirmed that MMP released from apoptotic cells trigger IFN-α secretion from human pDC. They further suggest that pDC activation results from sensing of DNA contained in MMP. MMP-DNA displays a particularly strong stimulatory activity compared with MMP-RNA and other sources of DNA. Inhibition of MMP-induced IFN-α secretion by cytochalasin D, chloroquine, and an inhibitory G-rich oligodeoxynucleotide identify TLR9 as the receptor for MMP-DNA. In marked contrast to the pDC response in autoimmune patients, in healthy subjects MMP-mediated stimulation of pDC-derived IFN-α was found to be independent of FcγRIIA (CD32A). Based on our findings, we conclude that induction of pDC-derived IFN-α by MMP is a physiological event; future investigations are necessary to elucidate whether pDC activation promotes inflammation or propagates tolerance in the context of apoptotic cell clearance.
IL-2 Receptor Signaling Is Essential for the Development of Klrg1+ Terminally Differentiated T Regulatory Cells
Authors: Cheng Guoyan , Yuan Xiaomei , Tsai Matthew S. , Podack Eckhard R. , Yu Aixin , Malek Thomas R. 
Published: July 2012

Abstract
Thymic-derived natural T regulatory cells (Tregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs has been shown to express Klrg1, but it remains unclear as to what extent Klrg1 defines a unique Treg subset. In this study, we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1− Tregs. This subset is a recent Ag-responsive and highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving Ag-activated conventional T lymphocytes also operates for Tregs.
IL-10 Regulates Il12b Expression via Histone Deacetylation: Implications for Intestinal Macrophage Homeostasis
Authors: Kobayashi Taku , Matsuoka Katsuyoshi , Sheikh Shehzad Z. , Russo Steven M. , Mishima Yoshiyuki , Collins Colm , deZoeten Edwin F. , Karp Christopher L. , Ting Jenny P. Y. , Sartor R. Balfour , Plevy Scott E. 
Published: July 2012

Abstract
To prevent excessive inflammatory responses to commensal microbes, intestinal macrophages, unlike their systemic counterparts, do not produce inflammatory cytokines in response to enteric bacteria. Consequently, loss of macrophage tolerance to the enteric microbiota plays a central role in the pathogenesis of inflammatory bowel diseases. Therefore, we examined whether the hyporesponsive phenotype of intestinal macrophages is programmed by prior exposure to the microbiota. IL-10, but not in vivo exposure to the microbiota, programs intestinal macrophage tolerance, because wild-type (WT) colonic macrophages from germ-free and specific pathogen-free (SPF)-derived mice produce IL-10, but not IL-12 p40, when activated with enteric bacteria. Basal and activated IL-10 expression is mediated through a MyD88-dependent pathway. Conversely, colonic macrophages from germ-free and SPF-derived colitis-prone Il10−/− mice demonstrated robust production of IL-12 p40. Next, mechanisms through which IL-10 inhibits Il12b expression were investigated. Although Il12b mRNA was transiently induced in LPS-activated WT bone marrow-derived macrophages (BMDMs), expression persisted in Il10−/− BMDMs. There were no differences in nucleosome remodeling, mRNA stability, NF-κB activation, or MAPK signaling to explain prolonged transcription of Il12b in Il10−/− BMDMs. However, acetylated histone H4 transiently associated with the Il12b promoter in WT BMDMs, whereas association of these factors was prolonged in Il10−/− BMDMs. Experiments using histone deacetylase (HDAC) inhibitors and HDAC3 short hairpin RNA indicate that HDAC3 is involved in histone deacetylation of the Il12b promoter by IL-10. These results suggest that histone deacetylation on the Il12b promoter by HDAC3 mediates homeostatic effects of IL-10 in macrophages.
Atypical Hemolytic Uremic Syndrome-Associated Variants and Autoantibodies Impair Binding of Factor H and Factor H-Related Protein 1 to Pentraxin 3
Authors: Kopp Anne , Strobel Stefanie , Tortajada Agustín , Rodríguez de Córdoba Santiago , Sánchez-Corral Pilar , Prohászka Zoltán , López-Trascasa Margarita , Józsi Mihály 
Published: July 2012

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a renal disease associated with complement alternative pathway dysregulation and is characterized by endothelial injury. Pentraxin 3 (PTX3) is a soluble pattern recognition molecule expressed by endothelial cells and upregulated under inflammatory conditions. PTX3 activates complement, but it also binds the complement inhibitor factor H. In this study, we show that native factor H, factor H-like protein 1, and factor H-related protein 1 (CFHR1) bind to PTX3 and that PTX3-bound factor H and factor H-like protein 1 maintain their complement regulatory activities. PTX3, when bound to extracellular matrix, recruited functionally active factor H. Residues within short consensus repeat 20 of factor H that are relevant for PTX3 binding were identified using a peptide array. aHUS-associated factor H mutations within this binding site caused a reduced factor H binding to PTX3. Similarly, seven of nine analyzed anti-factor H autoantibodies isolated from aHUS patients inhibited the interaction between factor H and PTX3, and five autoantibodies also inhibited PTX3 binding to CFHR1. Moreover, the aHUS-associated CFHR1*B variant showed reduced binding to PTX3 in comparison with CFHR1*A. Thus, the interactions of PTX3 with complement regulators are impaired by certain mutations and autoantibodies affecting factor H and CFHR1, which could result in an enhanced local complement-mediated inflammation, endothelial cell activation, and damage in aHUS.
Identification of IL-7–Producing Cells in Primary and Secondary Lymphoid Organs Using IL-7–GFP Knock-In Mice
Authors: Hara Takahiro , Shitara Soichiro , Imai Kumiko , Miyachi Hitoshi , Kitano Satsuki , Yao Hisayuki , Tani-ichi Shizue , Ikuta Koichi 
Published: July 2012

Abstract
IL-7 is a cytokine crucial for development and maintenance of lymphocytes and other hematopoietic cells. However, how IL-7–expressing cells are distributed in lymphoid organs is not well known. To address this question, we established and analyzed IL-7–GFP knock-in mice. Thymic epithelial cells (TECs) expressed high GFP levels in the cortex and medulla, as detected with an anti-GFP Ab. Thymic mesenchymal cells also expressed GFP. Flow cytometry analysis suggested that cortical TECs expressed higher GFP levels than did medullary TECs. In bone marrow, immunohistochemistry indicated high levels of GFP in many VCAM-1+ mesenchymal stromal cells and in some VCAM-1− cells. Additionally, half of the VCAM-1+CD31− stromal cells and some platelet-derived growth factor receptor α+ stromal cells were GFP+, as detected by flow cytometry. Moreover, we detected GFP expression in fibroblastic reticular cells in the T cell zone and cortical ridge of lymph nodes. Remarkably, lymphatic endothelial cells (LECs) expressed GFP at high levels within the lymph node medulla, skin epidermis, and intestinal tissues. Additionally, we detected abundant IL-7 transcripts in isolated LECs, suggesting that LECs produce IL-7, a heretofore unknown finding. Furthermore, GFP is expressed in a subpopulation of intestinal epithelial cells, and that expression was markedly upregulated in a dextran sulfate sodium-induced acute colitis model. Overall, IL-7–GFP knock-in mice serve as a unique and powerful tool to examine the identity and distribution of IL-7–expressing cells in vivo.
Type I IFN Receptor and the B Cell Antigen Receptor Regulate TLR7 Responses via Distinct Molecular Mechanisms
Authors: Poovassery Jayakumar S. , Bishop Gail A. 
Published: July 2012

Abstract
Toll-like receptor 7 (TLR7) signals to B cells are critically involved in the innate immune response to microbes, as well as pathogenesis of autoimmune diseases, but the molecular mechanisms that normally regulate these responses are incompletely understood. We previously reported that repeated stimulation through TLR7 induces a state of hyporesponsiveness (TLR tolerance) in both human and mouse B cells, characterized by marked inhibition of particular signaling pathways. BCR signals prevent and overcome TLR7 tolerance. Because optimal responses to TLR7 in B cells require type I IFN, we investigated whether BCR-mediated effects on TLR7 tolerance are mediated by type I IFN receptor (IFNAR) signals. Surprisingly, although BCR-mediated reversal of TLR7 tolerance was IFNAR independent, IFNAR signals alone also blocked TLR7 tolerance, despite enhancing TLR7 expression. Both BCR and IFNAR signals restored the phosphorylation of the transcriptional regulator c-Jun, but only BCR signals blocked the tolerance-mediated inhibition of JNK. Both BCR and IFNAR-mediated regulation was dependent on activation of the PI3K/Akt/mammalian target of rapamycin signaling pathway, indicating a central role for this axis in integrating TLR7, BCR, and IFNAR signals in B cells. These new findings reveal distinct and overlapping signaling mechanisms used by BCR and IFNAR in the regulation of TLR7 tolerance and activation.
T Cell Responses to Known Allergen Proteins Are Differently Polarized and Account for a Variable Fraction of Total Response to Allergen Extracts
Authors: Oseroff Carla , Sidney John , Vita Randi , Tripple Victoria , McKinney Denise M. , Southwood Scott , Brodie Tess M. , Sallusto Federica , Grey Howard , Alam Rafeul , Broide David , Greenbaum Jason A. , Kolla Ravi , Peters Bjoern , Sette Alessandro 
Published: July 2012

Abstract
A panel of 133 allergens derived from 28 different sources, including fungi, trees, grasses, weeds, and indoor allergens, was surveyed utilizing prediction of HLA class II-binding peptides and ELISPOT assays with PBMC from allergic donors, resulting in the identification of 257 T cell epitopes. More than 90% of the epitopes were novel, and for 14 allergen sources were the first ever identified to our knowledge. The epitopes identified in the different allergen sources summed up to a variable fraction of the total extract response. In cases of allergens in which the identified T cell epitopes accounted for a minor fraction of the extract response, fewer known protein sequences were available, suggesting that for low epitope coverage allergen sources, additional allergen proteins remain to be identified. IL-5 and IFN-γ responses were measured as prototype Th2 and Th1 responses, respectively. Whereas in some cases (e.g., orchard grass, Alternaria, cypress, and Russian thistle) IL-5 production greatly exceeded IFN-γ, in others (e.g., Aspergillus, Penicillum, and alder) the production of IFN-γ exceeded IL-5. Thus, different allergen sources are associated with variable polarization of the responding T cells. The present study represents the most comprehensive survey to date of human allergen-derived T cell epitopes. These epitopes might be used to characterize T cell phenotype/T cell plasticity as a function of seasonality, or as a result of specific immunotherapy treatment or varying disease severity (asthma or rhinitis).
Lipocalin 2 Deficiency Dysregulates Iron Homeostasis and Exacerbates Endotoxin-Induced Sepsis
Authors: Srinivasan Gayathri , Aitken Jesse D. , Zhang Benyue , Carvalho Frederic A. , Chassaing Benoit , Shashidharamurthy Rangaiah , Borregaard Niels , Jones Dean P. , Gewirtz Andrew T. , Vijay-Kumar Matam 
Published: July 2012

Abstract
Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhibit elevated intracellular labile iron. In this study, we report that LPS induced systemic Lcn2 by 150-fold in wild-type mice at 24 h. Relative to wild-type littermates, Lcn2KO mice were markedly more sensitive to endotoxemia, exhibiting elevated indices of organ damage (transaminasemia, lactate dehydrogenase) and increased mortality. Such exacerbated endotoxemia was associated with substantially increased caspase-3 cleavage and concomitantly elevated immune cell apoptosis. Furthermore, cells from Lcn2KO mice were hyperresponsive to LPS ex vivo, exhibiting elevated cytokine secretion. Additionally, Lcn2KO mice exhibited delayed LPS-induced hypoferremia despite normal hepatic hepcidin expression and displayed decreased levels of the tissue redox state indicators cysteine and glutathione in liver and plasma. Desferroxamine, an iron chelator, significantly protects Lcn2KO mice from LPS-induced toxicity, including mortality, suggesting that Lcn2 may act as an antioxidant in vivo by regulating iron homeostasis. Thus, Lcn2-mediated regulation of labile iron protects the host against sepsis. Its small size and simple structure may make Lcn2 a deployable treatment for sepsis.
Ouverture de 'Market-Driven Management and Global Markets - 1'
Authors: Brondoni Silvio M. 
Published: July 2012

The serious financial crisis that has hit the ‘Western’ world will generate longterm effects and the emergency measures adopted by the more responsible Governments to offset the credit paralysis (support to the mortgage market, public investment in key sectors, incentives to mass consumption, etc.) will take years (at least two to four) to produce positive consequences in the real economy of domestic and international markets. Globalisation and new competition boundaries thus force companies to adopt a new ‘philosophy of market-oriented competitive management’ (‘market-driven management’), which reformulates the traditional marketing management approach, introduced in the 1950s by Alfred P. Sloan of GM. In fact, marketing management presuppose an understanding of demand (and above all of its segments). With market-driven management on the other hand, market orientation helps to identify a temporary competition space, in ther works a ‘demand vacuum’, which must be maintained highly unstable, by constant innovative proposals. In global, over-supplied markets, where consumers are increasingly voluble and disloyal, market-driven management is very attractive because it favours: 1. activities focused on the profitability of competition, rather than on mere customer satisfaction; 2. market policies based on innovation and competitive pricing; 3. and finally, even very short-term performance metrics.
Market-Driven Management: the Policy Implications
Authors: Bellini Nicola 
Published: July 2012

The first policy implication of the diffusion of a Market-Driven Management approach is the same as the spreading of globalization, i.e. the obsolescence of industrial policies as traditionally designed and managed by Nation-States with the established toolbox of protectionism and subsidies, picking ‘national champions’, etc. The growing asymmetry between the physical jurisdiction of political bodies and the global operation space of modern corporations feeds the apparent trend toward company ‘denationalization’.
Ouverture de 'Market-Driven Management and Global Markets - 2'
Authors: Brondoni Silvio M. 
Published: July 2012

Global markets endorse the principles of market-space competition, where competition space represents a factor of competition. Firms compete with one another in extensive markets, without geographical and administrative boundaries; they adopt highly flexible managerial directions, featuring the absolute predominance of intangible assets and aimed at exploiting global economies of scale, focused on dimension and relationship. Global markets redefine market-space competition and substantiate global managerial economics. The distinctive features of these are: asset management without physical or administrative limits; increasingly sophisticated products which are rapidly rendered obsolete because they are easily imitable at decreasing cost; competitive interrelations, developed between transnational networks, which go far beyond the multinational (or multidomestic). Globalisation changes corporate organisation and the role of strategic alliances, imposing collaborative network strategies on groups of firms with competitive relations; these then tend to form ‘closed’ relationships of cooperation to pursue a global vision in keeping with their huge corporate size.
Ouverture de ‘Market-Driven Management and Competitive Customer Value – 1’
Authors: Brondoni Silvio M. 
Published: July 2012

The globalisation of the market generates unprecedented over-supply well in excess of the market potential. This oversupply thus becomes a structural factor of development. In open markets, global competition has set new rules (manufacturing delocalisation, global distribution players, competitive imitation, instable and non-loyal consumption) which have significantly scaled down the model of economic development based on the isolated small and medium sized enterprise without global networking relations. Instead they emphasise the importance of a robust national development policy based on the ‘identity of the industrial system’, in other words on precise ‘intangible macro-system factors’.