bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annexin A2 tetramer activates human and murine macrophages through TLR4
Authors: Swisher Jennifer F. A. , Burton Nicholas , Bacot Silvia M. , Vogel Stefanie N. , Feldman Gerald M. 
Published: November 2009

AbstractAnnexins are a large family of intracellular phospholipid-binding proteins, yet several extracellular roles have been identified. Specifically, annexin A2, found in a heterotetrameric complex with S100A10, not only serves as a key extracellular binding partner for pathogens and host proteins alike, but also can be shed or secreted. We reported previously that soluble annexin A2 tetramer (A2t) activates human monocyte-derived macrophages (MDM), resulting in secretion of inflammatory mediators and enhanced phagocytosis. Although a receptor for A2t has been cloned from bone marrow stromal cells, data contained in this study demonstrate that it is dispensable for A2t-dependent activation of MDM. Furthermore, A2t activates wild-type murine bone marrow–derived macrophages, whereas macrophages from myeloid differentiation factor 88–deficient mice display a blunted response, suggesting a role for Toll-like receptor (TLR) signaling. Small interfering RNA knockdown of TLR4 in human MDM reduced the response to A2t, blocking antibodies against TLR4 (but not TLR2) blocked activation altogether, and bone marrow–derived macrophages from TLR4−/− mice were refractory to A2t. These data demonstrate that the modulation of macrophage function by A2t is mediated through TLR4, suggesting a previously unknown, but important role for this stress-sensitive protein in the detection of danger to the host, whether from injury or invasion.
Regulating human Th17 cells via differential expression of IL-1 receptor
Authors: Lee Won-Woo , Kang Seong Wook , Choi Jihoon , Lee Seung-Hyun , Shah Kamini , Eynon Elizabeth E. , Flavell Richard A. , Kang Insoo 
Published: November 2009

AbstractIn humans, interleukin-1β (IL-1β) has been suggested as an essential cytokine for developing IL-17– or IL-17A–producing CD4+ T helper 17 (Th17) cells. However, little is known about the relationship of IL-1 receptor expression and Th17 cell differentiation. We report here the presence of 2 distinct CD4+ T-cell populations with and without expression of IL-1RI that correlates with the capacity to produce IL-17 in naive and memory CD4+ T cells of human peripheral blood. IL-1RI+ memory CD4+ T cells had increased gene expression of IL17, RORC, and IRF4 even before T-cell receptor triggering, indicating that the effect of IL-1β is programmed in these cells via IL-1RI. Although CD4+ T cells from umbilical cord blood did not express IL-1RI, the cytokines IL-7, IL-15, and transforming growth factor-β (TGF-β) up-regulated IL-1RI expression on naive CD4+ T cells, suggesting that IL-1RI+ naive CD4+ T cells develop in periphery. Furthermore, IL-17 production from the cytokine-treated naive CD4+ T cells was induced by IL-1β and this induction was blocked by IL-1R antagonist. These results indicate that human Th17 cell differentiation is regulated via differential expression of IL-1RI, which is controlled by IL-7 and IL-15.
The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA
Authors: Burnett Alan K. , Hills Robert K. , Green Claire , Jenkinson Sarah , Koo Kenneth , Patel Yashma , Guy Carol , Gilkes Amanda , Milligan Donald W. , Goldstone Anthony H. , Prentice Archibald G. , Wheatley Keith , Linch David C. , Gale Rosemary E. 
Published: November 2009

AbstractWe investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/internal tandem duplications, NPM1, or CEBPA mutation. There was a suggestion that ATRA reduced relapse in patients with lower MN1 levels, but no significant effect on overall survival. Results were consistent when restricted to patients with normal karyotype. ATRA has no overall effect on treatment outcomes in this group of patients. The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy. This study is registered at http://www.controlled-trials.com under ISRCTN17833622.
DG-AMMOS: A New tool to generate 3D conformation of small molecules using D istance G eometry and A utomated M olecular M echanics O ptimization for in silico S creening
Authors: Lagorce David , Pencheva Tania , Villoutreix Bruno O , Miteva Maria A 
Published: November 2009

Abstract

Background
Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats.

Results
Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine.

Conclusion
DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.
Cloning, expression in Pichia pastoris, and characterization of a thermostable GH5 mannan endo-1,4-β-mannosidase from Aspergillus niger BK01
Authors: Bien-Cuong Do , Thi-Thu Dang , Berrin Jean-Guy , Haltrich Dietmar , Kim-Anh To , Sigoillot Jean-Claude , Yamabhai Montarop 
Published: November 2009

Abstract

Background
Mannans are key components of lignocellulose present in the hemicellulosic fraction of plant primary cell walls. Mannan endo-1,4-β-mannosidases (1,4-β-D-mannanases) catalyze the random hydrolysis of β-1,4-mannosidic linkages in the main chain of β-mannans. Biodegradation of β-mannans by the action of thermostable mannan endo-1,4-β-mannosidase offers significant technical advantages in biotechnological industrial applications, i.e. delignification of kraft pulps or the pretreatment of lignocellulosic biomass rich in mannan for the production of second generation biofuels, as well as for applications in oil and gas well stimulation, extraction of vegetable oils and coffee beans, and the production of value-added products such as prebiotic manno-oligosaccharides (MOS).

Results
A gene encoding mannan endo-1,4-β-mannosidase or 1,4-β-D-mannan mannanohydrolase (E.C. 3.2.1.78), commonly termed β-mannanase, from Aspergillus niger BK01, which belongs to glycosyl hydrolase family 5 (GH5), was cloned and successfully expressed heterologously (up to 243 μg of active recombinant protein per mL) in Pichia pastoris. The enzyme was secreted by P. pastoris and could be collected from the culture supernatant. The purified enzyme appeared glycosylated as a single band on SDS-PAGE with a molecular mass of approximately 53 kDa. The recombinant β-mannanase is highly thermostable with a half-life time of approximately 56 h at 70°C and pH 4.0. The optimal temperature (10-min assay) and pH value for activity are 80°C and pH 4.5, respectively. The enzyme is not only active towards structurally different mannans but also exhibits low activity towards birchwood xylan. Apparent Km values of the enzyme for konjac glucomannan (low viscosity), locust bean gum galactomannan, carob galactomannan (low viscosity), and 1,4-β-D-mannan (from carob) are 0.6 mg mL-1, 2.0 mg mL-1, 2.2 mg mL-1 and 1.5 mg mL-1, respectively, while the kcat values for these substrates are 215 s-1, 330 s-1, 292 s-1 and 148 s-1, respectively. Judged from the specificity constants kcat/Km, glucomannan is the preferred substrate of the A. niger β -mannanase. Analysis by thin layer chromatography showed that the main product from enzymatic hydrolysis of locust bean gum is mannobiose, with only low amounts of mannotriose and higher manno-oligosaccharides formed.

Conclusion
This study is the first report on the cloning and expression of a thermostable mannan endo-1,4-β-mannosidase from A. niger in Pichia pastoris. The efficient expression and ease of purification will significantly decrease the production costs of this enzyme. Taking advantage of its acidic pH optimum and high thermostability, this recombinant β-mannanase will be valuable in various biotechnological applications.
A combination of indole-3-carbinol and genistein synergistically induces apoptosis in human colon cancer HT-29 cells by inhibiting Akt phosphorylation and progression of autophagy
Authors: Nakamura Yoshitaka , Yogosawa Shingo , Izutani Yasuyuki , Watanabe Hirotsuna , Otsuji Eigo , Sakai Tosiyuki 
Published: November 2009

Abstract

Background
The chemopreventive effects of dietary phytochemicals on malignant tumors have been studied extensively because of a relative lack of toxicity. To achieve desirable effects, however, treatment with a single agent mostly requires high doses. Therefore, studies on effective combinations of phytochemicals at relatively low concentrations might contribute to chemopreventive strategies.

Results
Here we found for the first time that co-treatment with I3C and genistein, derived from cruciferous vegetables and soy, respectively, synergistically suppressed the viability of human colon cancer HT-29 cells at concentrations at which each agent alone was ineffective. The suppression of cell viability was due to the induction of a caspase-dependent apoptosis. Moreover, the combination effectively inhibited phosphorylation of Akt followed by dephosphorylation of caspase-9 or down-regulation of XIAP and survivin, which contribute to the induction of apoptosis. In addition, the co-treatment also enhanced the induction of autophagy mediated by the dephosphorylation of mTOR, one of the downstream targets of Akt, whereas the maturation of autophagosomes was inhibited. These results give rise to the possibility that co-treatment with I3C and genistein induces apoptosis through the simultaneous inhibition of Akt activity and progression of the autophagic process. This possibility was examined using inhibitors of Akt combined with inhibitors of autophagy. The combination effectively induced apoptosis, whereas the Akt inhibitor alone did not.

Conclusion
Although in vivo study is further required to evaluate physiological efficacies and toxicity of the combination treatment, our findings might provide a new insight into the development of novel combination therapies/chemoprevention against malignant tumors using dietary phytochemicals.
Serum estradiol should be monitored not only during the peri-menopausal period but also the post-menopausal period at the time of aromatase inhibitor administration
Authors: Nagao Taeko , Kira Misako , Takahashi Masako , Honda Junko , Hirose Toshiyuki , Tangoku Akira , Zembutsu Hitoshi , Nakamura Yusuke , Sasa Mitsunori 
Published: November 2009

Abstract

Background
Aromatase inhibitor (AI) therapy is being extensively used as postoperative adjuvant therapy in patients with hormone receptor-positive postmenopausal breast cancer. On the other hand, it has been reported that ovarian function was restored when AI was administered to patients who had undergone chemical menopause with chemotherapy or tamoxifen. However, there have been no reports of comprehensive monitoring of estradiol (E2) in breast cancer patients with ordinary menopause who were being administered AI.

Patients and Methods
Beginning in March 2008, regular monitoring of the serum levels of E2, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was performed for 66 postmenopausal breast cancer patients who had been started on AI therapy. For this study, we chose anastrozole as the AI. The assays of those hormones were outsourced to a commercial clinical laboratory.

Results
In 4 of the 66 patients the serum E2 level was decreased at 3 months but had then increased at 6 months, while in 2 other patients E2 was decreased at both 3 and 6 months but had increased at 9 months.

Conclusion
The results indicate that, in some breast cancer patients with ordinary menopause, E2 rebounds following AI therapy. In the future, E2 monitoring should be performed for a larger number of patients being administered AI therapy.

Trial registration
Our trial registration number is 19-11-1211.
Modulation of experimental autoimmune encephalomyelitis by endogenous Annexin A1
Authors: Paschalidis Nikolaos , Iqbal Asif J , Maione Francesco , Wood Elisabeth G , Perretti Mauro , Flower Rod J , D'Acquisto Fulvio 
Published: November 2009

AbstractBackgroundAutoimmune diseases, like multiple sclerosis, are triggered by uncontrolled activation of cells of the immune system against self-antigen present, for instance, in the central nervous system. We have reported novel biological functions for Annexin A1, an effector of endogenous anti-inflammation, to produce positive actions on the adaptive immune system by reducing the threshold of T cell activation. In this study, we investigated the potential modulatory role of Annexin A1 in the development of experimental autoimmune encephalomyelitis, a model of multiple sclerosis.MethodsMale control C57/BL6 and AnxA1 null mice were immunized subcutaneously with an emulsion consisting of 300 μg of MOG35-55in PBS combined with an equal volume of CFA. Lymph node cells obtained from mice immunized with MOG33-55for 14 days were re-stimulatedin vitrowith MOG33-55(100 μg/ml) for 4 days and the Th1/Th17 cytokine profile measured by ELISA. Spinal cords were processed either to isolate the infiltrated T cells or fixed and stained with haematoxylin and eosin. Statistical analyses were performed using two-tailed, unpaired Student's t tests or ANOVA.ResultsOur results show a direct correlation between Annexin A1 expression and severity of EAE. Analysis of MOG35-55-induced EAE development in Annexin A1 null mice showed decreased signs of the disease compared to wild type mice. This defect was significant at the peak of the disease and accompanied by reduced infiltration of T cells in the spinal cord. Finally, analysis of the T cell recall responsein vitrofollowing stimulation with MOG35-55showed a decrease proliferation of Annexin A1 null T cells, with a significantly reduced Th1/Th17 phenotype, compared to wild type cells.ConclusionTogether these findings suggest that Annexin A1 null mice have an impaired capacity to develop EAE. Furthermore strategies aiming at reducing Annexin A1 functions or expression in T cells might represent a novel therapeutic approach for multiple sclerosis.
Multiple Myeloma Involving Skin and Pulmonary Parenchyma after Autologous Stem Cell Transplantation
Authors: Yuan Yuan , Wieczorek Rosemary , Green David L , Cook Perry , Ballard Harold , Araten David J 
Published: November 2009

Abstract
Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation.
HLA-E gene polymorphism associates with ankylosing spondylitis in Sardinia
Authors: Paladini Fabiana , Belfiore Francesca , Cocco Elisa , Carcassi Carlo , Cauli Alberto , Vacca Alessandra , Fiorillo Maria Teresa , Mathieu Alessandro , Cascino Isabella , Sorrentino Rosa 
Published: November 2009

Abstract
Introduction
Ankylosing spondylitis (AS) is a severe, chronic inflammatory disease strongly associated with HLA-B27. The presence of additional HLA risk factors has been suggested by several studies. The aim of the current study is to assess the occurrence of an additional HLA susceptibility locus in the region between HLA-E and HLA-C in the Sardinian population.

Methods
200 random controls, 120 patients with AS and 175 HLA-B27 positive controls were genotyped for six single nucleotide polymorphisms (SNPs) spanning the HLA region between HLA-E and HLA-C loci previously shown to harbour an additional susceptibility locus for AS. Allele, genotype and haplotype frequencies were compared.

Results
The data confirm our previous finding of a significant increase in patients with AS of allele A at SNP rs1264457 encoding for an Arg at the functional HLA-E polymorphism (Arg128/Gly128). This was due to a remarkable increase in the frequency of genotype A/A in patients vs HLA-B27-matched controls (51% vs 29%; P for trend: 5 × 10-5). Genotype distribution of three other SNPs mapping in genes (GNL1, PRR3 and ABCF-1) close to HLA-E and showing high LD with it, was also significantly skewed. Accordingly, haplotype distribution was also remarkably different. The frequency of the haplotype AAGA, is 42% in random controls, increases to 53% in the HLA-B27-positive controls, and reaches 68% in patients with AS (P values: 2 × 10-11 vs random and 3 × 10-4 vs HLA-B27 controls).

Conclusions
There is a strong association between the presence of a haplotype in genes mapping between HLA-E and HLA-C and AS due to an increase of homozygous markers in patients. The strongest association however, is with the HLA-E functional polymorphism rs1264457. Since HLA-E is the ligand for the NKG2A receptor, these data point to the natural killer (NK) activity as possible player in the pathogenesis of AS.
Minireview: Osteoprotective Action of Estrogens Is Mediated by Osteoclastic Estrogen Receptor-α
Authors: Imai Yuuki , Kondoh Shino , Kouzmenko Alexander , Kato Shigeaki 
Published: November 2009

AbstractThe osteoprotective action of estrogen in women has drawn considerable attention because estrogen deficiency-induced osteoporosis became one of the most widely spread diseases in developed countries. In men, the significance of estrogen action for bone health maintenance is also apparent from the osteoporotic phenotype seen in male patients with genetically impaired estrogen signaling. Severe bone loss and high bone turnover, including typical osteofeatures seen in postmenopausal women, can also be recapitulated in rodents after ovariectomy. However, the expected osteoporotic phenotype is not observed in female mice deficient in estrogen receptor (ER)-α or -β or both, even though the degenerative defects are clearly seen in other estrogen target tissues together with up-regulated levels of circulating testosterone. It has also been reported that estrogens may attenuate bone remodeling by cell autonomous suppressive effects on osteoblastogenesis and osteoclastogenesis. Hence, the effects of estrogens in bone appear to be complex, and the molecular role of bone estrogen receptors in osteoprotective estrogen action remains unclear. Instead, it has been proposed that estrogens indirectly control bone remodeling. For example, the enhanced production of cytokines under estrogen deficiency induces bone resorption through stimulation of osteoclastogenesis. However, the osteoporotic phenotype without systemic defects has been recapitulated in female (but not in male) mice by osteoclast-specific ablation of the ERα, proving that bone cells represent direct targets for estrogen action. An aberrant accumulation of mature osteoclasts in these female mutants indicates that in females, the inhibitory action of estrogens on bone resorption is mediated by the osteoclastic ERα through the shortened lifespan of osteoclasts.
Interspecific and intersexual learning rate differences in four butterfly species
Authors: Kandori Ikuo , Yamaki Takafumi , Okuyama Sei-ichi , Sakamoto Noboru , Yokoi Tomoyuki 
Published: November 2009

SUMMARY
Learning plays an important role in food acquisition for a wide range of insects and has been demonstrated to be essential during flower foraging in taxa such as bees, parasitoid wasps, butterflies and moths. However, little attention has been focused on differences in floral cue learning abilities among species and sexes. We examined the associative learning of flower colour with nectar in four butterfly species: Idea leuconoe, Argyreus hyperbius, Pieris rapae and Lycaena phlaeas. All butterflies that were trained learned the flower colours associated with food. The flower colour learning rates were significantly higher in I. leuconoe and A. hyperbius than in P. rapae and L. phlaeas. Among the four species examined, the larger and longer-lived species exhibited higher learning rates. Furthermore, female butterflies showed a significantly higher learning rate than males. This study provides the first evidence that learning abilities related to floral cues differ among butterfly species. The adaptive significance of superior learning abilities in the larger and longer-lived butterfly species and in females is discussed.
Photosensitivity to different light intensities in blind and sighted rodents
Authors: Zubidat A. E. , Nelson R. J. , Haim A. 
Published: November 2009

SUMMARY
Photoperiod is an important cue regulating biological rhythms in mammals, including ‘blind’ subterranean and sighted fossorial rodent species. These species may respond differentially to changes in light quality according to their retinal complexity. The effects of increasing light intensity on daily rhythms of urine excretion and urinary output of 6-sulfatoxymelatonin levels were compared in ‘blind’ mole rats Spalax ehrenbergi and sighted social voles, Microtus socialis. Our results show that the threshold irradiance required to entrain rhythms of voles is three magnitudes greater than that for mole rats. The results suggest that mole rats have an operational photoreceptive pathway with a lower threshold irradiance than voles. Such a low threshold reflects the remarkable capability of this ‘blind’ species to utilize light signals even under challenging light conditions.