bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploiting the Annexin A1 pathway for the development of novel anti‐inflammatory therapeutics
Authors: Perretti Mauro , Dalli Jesmond 
Published: October 2009

The appreciation that the inflammatory reaction does not ‘spontaneously’ finish, but rather that inflammatory resolution is an active phenomenon brought about by endogenous anti‐inflammatory agonists opens multiple opportunities for a reassessment of the complexity of inflammation and its main mediators. This review dwells on one of these pathways, the one centred around the glucocorticoid‐regulated protein Annexin A1 and its G protein‐coupled receptor. In recent years, much of the knowledge detailing the processes by which Annexin A1 expresses its anti‐inflammatory role on innate immunity has been produced. Moreover, the generation of the Annexin A1 null mouse colony has provided important proof‐of‐concept experiments demonstrating the inhibitory properties of this mediator in the context of inflammatory and/or tissue‐injury models. Therefore, Annexin A1 acts as a pivotal homeostatic mediator, where if absent, inflammation would overshoot and be prolonged. This new understanding scientific information could guide us onto the exploitation of the biological properties of Annexin A1 and its receptor to instigate novel drug discovery programmes for anti‐inflammatory therapeutics. This line of research relies on the assumption that anti‐inflammatory drugs designed upon endogenous anti‐inflammatory mediators would be burdened by a lower degree of secondary effects as these agonists would be mimicking specific pathways activated in our body for safe disposal of inflammation. We believe that the next few years will produce examples of such new drugs and the validity of this speculation could then be assessed.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Numerical Comparative Study on the Hemodynamic Performance of a New Helical Graft With Noncircular Cross Section and SwirlGraft
Authors: Sun Anqiang , Fan Yubo , Deng Xiaoyan 
Published: October 2009

AbstractThe helically distributed ribbons of thrombus, formed in the commercially available SwirlGraft (Veryan Medical, London, UK), are the result of its wall shear stress distribution, which has zonary areas of low wall shear stress. In order to overcome the inherent deficiency of the SwirlGraft, a new helical graft with a noncircular cross section was proposed and compared numerically with the SwirlGraft in terms of wall shear stress distribution, helicity of the swirling flow created, and pressure drop over the grafts. The numerical results showed that due to the modification to the geometrical configuration of the SwirlGraft, wall shear stress in the new helical graft model was enhanced, and the zones of low wall shear stress existing in the SwirlGraft were completely eliminated. The present numerical study also predicted a slightly steeper pressure drop and reduction in helicity in the new helical graft model in comparison with the SwirlGraft model. Based on the study, we believe that the new helical graft with a noncircular cross section may reduce the possibility of acute thrombus formation in the graft because the enhanced wall shear stress can impede the stay and adherence of platelets and leukocytes to the surface of the graft.
FHL1 interacts with oestrogen receptors and regulates breast cancer cell growth
Authors: Ding Lihua , Niu Chang , Zheng Yiqiong , Xiong Zhihong , Liu Yufei , Lin Jing , Sun Huiwei , Huang Ke , Yang Wen , Li Xiru , Ye Qinong 
Published: October 2009

AbstractFour and a half LIM protein 1 (FHL1) belongs to the Lin‐1, Isl‐1 and Mec‐3 (LIM)‐only protein family and plays important roles in muscle growth and carcinogenesis. However, the biological function of FHL1 remains largely unknown. Here, we show that FHL1 physically and functionally interacted with oestrogen receptors (ERs), which are involved in breast cancer development and progression. FHL1 bound specifically to the activation function‐1 domain of ER. Physical interaction of FHL1 and ER is required for FHL1 repression of oestrogen‐responsive gene transcription. FHL1 affected recruitment of ER to an oestrogen‐responsive promoter and ER binding to an oestrogen‐responsive element. Overexpression of FHL1 in breast cancer cells decreased expression of oestrogen‐responsive proteins, whereas knockdown of endogenous FHL1 with FHL1 small interfering RNA increased the expression of these proteins. Further analysis of 46 breast cancer samples showed that FHL1 expression negatively associated with oestrogen‐responsive gene expression in breast cancer cells. FHL1 inhibited anchorage‐dependent and ‐independent breast cancer cell growth. These results suggest that FHL1 may play an important role in ER signalling as well as breast cancer cell growth regulation.
Plasma gelsolin facilitates interaction between β2 glycoprotein I and α5β1 integrin
Authors: Bohgaki Miyuki , Matsumoto Masaki , Atsumi Tatsuya , Kondo Takeshi , Yasuda Shinsuke , Horita Tetsuya , Nakayama Keiichi I. , Okumura Fumihiko , Hatakeyama Shigetsugu , Koike Takao 
Published: October 2009

AbstractAntiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL) that directly recognizes plasma β2‐glycoprotein I (β2GPI). Tissue factor (TF), the major initiator of the extrinsic coagulation system, is induced on monocytes by aPL in vitro, explaining in part the pathophysiology in APS. We previously reported that the mitogen‐activated protein kinase (MAPK) pathway plays an important role in aPL‐induced TF expression on monocytes. In this study, we identified plasma gelsolin as a protein associated with β2GPI by using immunoaffinity chromatography and mass spectrometric analysis. An in vivo binding assay showed that endogenous β2GPI interacts with plasma gelsolin, which binds to integrin a5β1 through fibronectin. The tethering of β2GPI to monoclonal anti‐β2GPI autoantibody on the cell surface was enhanced in the presence of plasma gelsolin. Immunoblot analysis demonstrated that p38 MAPK protein was phosphorylated by monoclonal anti‐β2GPI antibody treatment, and its phosphorylation was attenuated in the presence of anti‐integrin a5β1 antibody. Furthermore, focal adhesion kinase, a downstream molecule of the fibronectin‐integrin signalling pathway, was phosphorylated by anti‐β2GPI antibody treatment. These results indicate that molecules including gelsolin and integrin are involved in the anti‐β2GPI antibody‐induced MAPK pathway on monocytes and that integrin is a possible therapeutic target to modify a prothrombotic state in patients with APS.
A systems biology perspective on sVEGFR1: its biological function, pathogenic role and therapeutic use
Authors: Wu Florence T. H. , Stefanini Marianne O. , Gabhann Feilim Mac , Kontos Christopher D. , Annex Brian H. , Popel Aleksander S. 
Published: October 2009

Abstract

Introduction
Molecular biology of sVEGFR1
Physiological and pathophysiological roles of sVEGFR1
Molecular mechanism of sVEGFR1’s anti‐angiogenic potential
sVEGFR1 as a clinical marker for disease
Plasma VEGF and sVEGFR1: non‐uniform predictors of angiogenic status across all diseases
Systems biology perspective: unifying interpretation of plasma angiogenic markers
Concluding remarks

Angiogenesis is the growth of new capillaries from pre‐existent microvasculature. A wide range of pathological conditions, from atherosclerosis to cancer, can be attributed to either excessive or deficient angiogenesis. Central to the physiological regulation of angiogenesis is the vascular endothelial growth factor (VEGF) system – its ligands and receptors (VEGFRs) are thus prime molecular targets of pro‐angiogenic and anti‐angiogenic therapies. Of growing interest as a prognostic marker and therapeutic target in angiogenesis‐dependent diseases is soluble VEGF receptor‐1 (sVEGFR1, also known as sFlt‐1) – a truncated version of the cell membrane‐spanning VEGFR1. For instance, it is known that sVEGFR1 is involved in the endothelial dysfunction characterizing the pregnancy disorder of pre‐eclampsia, and sVEGFR1’s therapeutic potential as an anti‐angiogenic agent is being evaluated in pre‐clinical models of cancer. This mini review begins with an examination of the protein domain structure and biomolecular interactions of sVEGFR1 in relation to the full‐length VEGFR1. A synopsis of known and inferred physiological and pathological roles of sVEGFR1 is then given, with emphasis on the utility of computational systems biology models in deciphering the molecular mechanisms by which sVEGFR1’s purported biological functions occur. Finally, we present the need for a systems biology perspective in interpreting circulating VEGF and sVEGFR1 concentrations as surrogate markers of angiogenic status in angiogenesis‐dependent diseases.
Ankyrin protein networks in membrane formation and stabilization
Authors: Cunha Shane R. , Mohler Peter J. 
Published: October 2009

Abstract

Introduction
Mechanisms that target and stabilize ankyrin
Ankyrins and disease
Conclusion

In eukaryotic cells, ankyrins serve as adaptor proteins that link membrane proteins to the underlying cytoskeleton. These adaptor proteins form protein complexes consisting of integral membrane proteins, signalling molecules and cytoskeletal components. With their modular architecture and ability to interact with many proteins, ankyrins organize and stabilize these protein networks, thereby establishing the infrastructure of membrane domains with specialized functions. To this end, ankyrin collaborates with a number of proteins including cytoskeletal proteins, cell adhesion molecules and large structural proteins. This review addresses the targeting and stabilization of protein networks related to ankyrin interactions with the cytoskeletal protein β‐spectrin, L1‐cell adhesion molecules and the large myofibrillar protein obscurin. The significance of these interactions for differential targeting of cardiac proteins and neuronal membrane formation is also presented. Finally, this review concludes with a discussion about ankyrin dysfunction in human diseases such as haemolytic anaemia, cardiac arrhythmia and neurological disorders.
Vaccination with SIVmac239Δnef activates CD4+ T cells in the absence of CD4+ T‐cell loss
Authors: Reeves R.K. , Gillis J. , Wong F.E. , Johnson R.P. 
Published: October 2009

AbstractBackground  Pathogenic HIV and SIV infections characteristically deplete central memory CD4+ T cells and induce chronic immune activation, but it is controversial whether this also occurs after vaccination with attenuated SIVs and whether depletion or activation of CD4+ T‐cell play roles in protection against wild‐type virus challenge.Methods  Rhesus macaques were vaccinated with SIVmac239Δnef and quantitative and phenotypic polychromatic flow cytometry analyses were performed on mononuclear cells from blood, lymph nodes and rectal biopsies.Results  Animals vaccinated with SIVmac239Δnef demonstrated no loss of CD4+ T cells in any tissue, and in fact CCR5+ and CD28+CD95+ central memory CD4+ T cells were significantly increased. In contrast, CD4+ T‐cell numbers and CCR5 expression significantly declined in unvaccinated controls challenged with SIVmac239. Also, intracellular Ki67 increased acutely as much as 3‐fold over baseline in all tissues after SIVmac239Δnef vaccination then declined following primary infection.Conclusion  We demonstrated in this study that SIVmac239Δnef vaccination did not deplete CD4+ T cells but transiently activated and expanded the memory cell population. However, increases in numbers and activation of memory CD4+ T cells did not appear to influence protective immunity.
CD4 T cell subsets in the mucosa are CD28+Ki‐67−HLA‐DR−CD69+ but show differential infection based on α4β7 receptor expression during acute SIV infection
Authors: Kader M. , Bixler S. , Roederer M. , Veazey R. , Mattapallil J.J. 
Published: October 2009

AbstractBackground  CD4 T cell depletion in the mucosa has been well documented during acute HIV and SIV infections. The demonstration the HIV/SIVcan use the α4β7 receptor for viral entry suggests that these viruses selectively target CD4 T cells in the mucosa that express high levels of α4β7 receptor.Methods  Mucosal samples obtained from SIV infected rhesus macaques during the early phase of infection were used for immunophenotypic analysis. CD4 T cell subsets were sorted based on the expression of β7 and CD95 to quantify the level of SIV infection in different subsets of CD4 T cells. Changes in IL‐17, IL‐21, IL‐23 and TGFβ mRNA expression was determined using Taqman PCR.Results  CD4 T cells in the mucosa were found to harbor two major population of cells; ‐25% of CD4 T cells expressed the α4+β7hi phenotype, whereas the rest of the 75% expressed an α4+β7int phenotype. Both the subsets were predominantly CD28+Ki‐67‐HLA‐DR‐ but CD69+, and expressed detectable levels of CCR5 on their surface. Interestingly, however, α4+β7hiCD4 T cells were found to harbor more SIV than the α4+β7int subsets at day 10 pi. Early infection was associated with a dramatic increase in the expression of IL‐17, and IL‐17 promoting cytokines IL‐21, IL‐23, and TGFβ that stayed high even after the loss of mucosal CD4 T cells.Conclusions  Our results suggest that the differential expression of the α4β7 receptor contributes to the differences in the extent of infection in CD4 T cell subsets in the mucosa. Early infection is associated dysregulation of the IL‐17 network in mucosal tissues involves other non‐Th‐17 cells that likely contributes to the pro‐inflammatory environment in the mucosa during acute stages of SIV infection.
Anti‐retroviral therapy fails to restore the severe Th‐17: Tc‐17 imbalance observed in peripheral blood during simian immunodeficiency virus infection
Authors: Kader M. , Bixler S. , Piatak M. , Lifson J. , Mattapallil J.J. 
Published: October 2009

AbstractBackground  Human immuno deficiency virus and simian immunodeficiency virus infections are characterized by a severe loss of Th‐17 cells (IL‐17+CD4+ T cells) that has been associated with disease progression and systemic dissemination of bacterial infections. Anti‐retroviral therapy (ART) has led to repopulation of CD4+ T cells in peripheral tissues with little sustainable repopulation in mucosal tissues. Given the central importance of Th‐17 cells in mucosal homeostasis, it is not known if the failure of ART to permanently repopulate mucosal tissues is associated with a failure to restore Th‐17 cells that are lost during infection.Methods  Dynamics of α4+β7hi CD4+ T cells in peripheral blood of SIV infected rhesus macaques were evaluated and compared to animals that were treated with ART. The frequency of Th‐17 and Tc‐17 cells was determined following infection and after therapy. Relative expression of IL‐21, IL‐23, and TGFβ was determined using Taqman PCR.Results  Treatment of SIV infected rhesus macaques with anti‐retroviral therapy was associated with a substantial repopulation of mucosal homing α4+β7hiCD4+ T cells in peripheral blood. This repopulation, however, was not accompanied by a restoration of Th‐17 responses. Interestingly, SIV infection was associated with an increase in Tc‐17 responses (IL‐17+CD8+ T cells) suggesting to a skewing in the ratio of Th‐17: Tc‐17 cells from a predominantly Th‐17 phenotype to a predominantly Tc‐17 phenotype. Surprisingly, Tc‐17 responses remained high during the course of therapy suggesting that ART failed to correct the imbalance in Th‐17 : Tc‐17 responses induced following SIV infection.Conclusions  ART was associated with substantial repopulation of α4+β7hi CD4+ T cells in peripheral blood with little or no rebound of Th‐17 cells. On the other hand, repopulation of α4+β7hi CD4+ T cells was accompanied by persistence of high levels of Tc‐17 cells in peripheral blood. The dysregulation of Th‐17 and Tc‐17 responses likely plays a role in disease progression.
Macaca fascicularis are highly susceptible to an RT‐SHIV following intravaginal inoculation: a new model for microbicide evaluation
Authors: Jiang Y. , Tian B. , Agy M.B. , Saifuddin M. , Tsai C.‐C. 
Published: October 2009

AbstractBackground  Human immunodeficiency virus type 1 (HIV‐1) reverse transcriptase (RT) is a major target for antiretroviral strategy to block or curtail HIV infection. A suitable RT‐SHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and microbicides specifically targeting HIV‐1 RT.Methods  Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID50 of RT‐SHIVtc. Systemic infections of RT‐SHIVtc exposed macaques were determined by both virological and immunologic parameters during 24 weeks post‐challenge.Results  Within 2 weeks post‐inoculation, 13 of 15 macaques became infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4+T cell counts in peripheral blood and seroconversion.Conclusions  Results serve to validate the infectivity and pathogenicity of RT‐SHIVtc following vaginal exposure in M. fascicularis. This RT‐SHIVtc/macaque model could be suitable for the pre‐clinical evaluation of non‐nucleoside RT inhibitor‐based anti‐HIV microbicides.
Spatial distributions of multiple plant species affect herbivore foraging selectivity
Authors: Wang Ling , Wang Deli , Bai Yuguang , Jiang Guitong , Liu Jushan , Huang Yue , Li Yexing 
Published: October 2009

Spatial distribution of food resources is an important factor determining herbivore foraging. Previous studies have demonstrated that clumped distribution of preferred species increases its consumption by herbivores in single‐ or two‐species systems. However, the potential impact of distribution pattern of less preferred species on foraging was ignored. In natural grasslands with high species diversity and complexity, the spatial distribution of preferred species impacts on herbivore foraging may be strongly correlated with the distribution of less preferred species.Our aims were to determine the effect of distribution of both preferred and other plant species on herbivore foraging under conditions close to a native, multi‐species foraging environment, and conceptualize the relationships between spatial distribution of food resources and herbivore consumption. We hypothesized that random distribution of non‐preferred species reduces herbivore consumption of preferred species because the dispersion of less preferred species likely disturbs herbivore foraging. We conducted an experiment using three species with five combinations of clumped and random distribution patterns. Three species Lathyrus quinquenervius, Phragmites australis and Leymus chinensis, were of high, intermediate and low preferences by sheep, respectively. Results showed that distribution of low preferred species, but not that of high preferred one, affected the consumption of preferred species. Sheep obtained higher consumption of high preferred species when low preferred species followed a clumped distribution than a random distribution. Distance between aggregations of high and low preferred species did not affect sheep foraging. It was concluded that the effects of spatial distribution of preferred species on its consumption are dependent on herbivore foraging strategy, and sheep can consume more preferred species when there is a consistent spatial pattern between preferred species and the entire food resource, and that the random dispersion of low preferred species in grassland may reduce herbivore consumption of high preferred species, thus minimizing selective grazing.
Long‐Term Results of Endosteal Implants Following Radical Oral Cancer Surgery with and without Adjuvant Radiation Therapy
Authors: Linsen Sabine S. , Martini Markus , Stark Helmut 
Published: October 2009

ABSTRACTPurpose: The aim of this study was to analyze the long‐term survival of implants and implant‐retained prostheses in patients after ablative surgery of oral cancer with or without adjunctive radiation therapy.Materials and Methods: Between 1997 and 2008, 66 patients who had undergone ablative tumor surgery in the oral cavity were treated with dental implants (n = 262). Thirty‐four patients received radiation therapy in daily fractions of 2 Gy administered on 18 to 30 days. Implants were inserted in the maxilla (49; 18.7%) or mandible (213; 81.3%), in non‐irradiated residual (65; 24.8%) or grafted bone (44; 16.8%) and in irradiated residual (15.6%) or grafted bone (39; 14.9%). Seventeen fixed protheses and 53 removable dentures (34 bar attachments, 9 telescopic and 10 ball retained dentures) were inserted.Results: Mean follow‐up after implant insertion was 47.99 (±34.31) months (range 12–140 months). The overall 1‐, 5‐, and 10‐year survival rates of all implants were 96.6%, 96.6%, and 86.9%, respectively. Fourteen implants were lost in nine patients (5.3% of all implants); eight implants were primary losses, and five secondary losses because of an operation of tumor recurrence. There was no significantly lower implant survival for implants inserted into irradiated bone (p = .302), bone and/or soft‐tissue grafts (p = .436), and maxilla or mandible (p = .563). All prosthetic restorations in patients without tumor recurrence could be maintained during the observation period.Conclusions: Implant survival is not significantly influenced by radiation therapy, grafts (bone and/or soft tissue), or location (maxilla or mandible). However, implants placed in irradiated bone exhibit a higher failure rate during the healing period than those placed in non‐irradiated bone. No superstructure was particularly favorable. Osseointegrated implants can be used successfully in patients with prior history of ablative surgery with and without additional radiation therapy.
A Clinical and Histological Case Series Study on Calcium Sulfate for Maxillary Sinus Floor Augmentation and Delayed Placement of Dental Implants
Authors: Dasmah Amir , Hallman Mats , Sennerby Lars , Rasmusson Lars 
Published: October 2009

ABSTRACTBackground: Maxillary sinus floor augmentation is a procedure that is indicated in cases when the volume of the posterior maxillary bone is inadequate. The goal of this treatment is to obtain sufficient amount of bone tissue in order to gain osseointegration of endosseous implants.Purpose: The purpose of this study was to conduct a clinical and histological analysis of calcium sulfate (CaS) as bone graft substitute in sinus floor augmentation.Material and Methods: Ten patients with edentulous maxillas were included in this study. They had moderate to severe atrophy of the posterior maxilla. Surgiplaster (Classimplant®, Rome, Italy) was used as graft material in the maxillary sinus and was covered by BioGide® (Geistlish Pharmaceutical, Wolhusen, Switzerland). After 4 months of graft healing, 40 dental implants were placed and a biopsy for histomorphometry was taken at these occasions. The specimens were viewed by light microscope, and the extent of bone regeneration and remaining graft material was evaluated. Radiographs were taken at the time of sinus augmentation and after 4 months of graft healing.Results: At the time of abutment surgery, one implant was considered as a failure and was consequently removed, giving a survival rate of 97.5% after 1 year of loading. Radiographs showed a mean of 26.5% shrinkage of the augmented area. A significant resorption of CaS was noted with a mean value of 8.8% of remaining graft material after 4 months of healing. The biopsies also revealed new bone formation with a mean value of 21.2% of the total biopsy area. Histology showed signs of an acellular substitution of CaS with bone‐like tissue.Conclusion: The results of this study show that new bone regeneration occurs in the maxillary sinus after augmentation with CaS. This enabled successful placement, integration, and loading of dental implants in the posterior maxilla, as only 1 of 40 implants was lost during 1 year of follow‐up.