bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human receptor tyrosine kinase Axl gene – promoter characterization and regulation of constitutive expression by Sp1, Sp3 and CpG methylation
Authors: Mudduluru Giridhar , Allgayer Heike 
Published: June 2008

Axl is a receptor tyrosine kinase which promotes anti-apoptosis, mitogenesis, invasion, angiogenesis and metastasis, and is highly expressed in cancers. However, the transcriptional regulation of this important gene has never been characterized. The present study was initiated to characterize the promoter, cis-acting elements and promoter methylation driving expression of Axl. The 2.4 kb sequence upstream of the translational start site, and sequential 5′-deletions were cloned and revealed a minimal GC-rich region (−556 to +7) to be sufficient for basal Axl promoter activity in Rko, HCT116 and HeLa cells. Within this minimal region, five Sp (specificity protein)-binding sites were identified. Two sites (Sp a and Sp b) proximal to the translation start site were indispensable for Axl promoter activity, whereas mutation of three additional upstream motifs (Sp c, Sp d and Sp e) was of additional relevance. Gel-shift assays and chromatin immunoprecipitation identified that Sp1 and Sp3 bound to all five motifs, and mutation of all motifs abolished binding. Mithramycin, which inhibits binding of Sp factors to GC-rich sites, dramatically reduced Axl promoter activity and Axl, Sp1 and Sp3 expression. In Drosophila Schneider SL2-cells, exogenous expression of Sp1/Sp3 increased Axl promoter activity. Use of Sp1/Sp3 siRNAs (small interfering RNAs) significantly reduced Axl promoter activity and protein levels in Rko and HeLa cells. Methylation-bisulfite sequencing detected methylated CpG sites within three Sp motifs (Sp a, Sp b and Sp c) and GC-rich flanking sequences, and demethylation by 5-aza-2′-deoxycytidine up-regulated Axl and Sp3 expression in low-Axl-expressing Colo206f/WiDr cells, but not in high-Axl-expressing Rko cells. The results of the present study suggest that Axl gene expression in cancer cells is (1) constitutively driven by Sp1/Sp3 bound to five core promoter motifs, and (2) restricted by methylation within/around Sp-binding sites. This might enhance the understanding and treatment of essential mechanisms associated with cancer and other diseases.
CD8+ T-cells and their interaction with other cells in damage to islet β-cells
Authors: Wong F. Susan , Siew L. Khai , Wen Li 
Published: June 2008

The autoimmune attack on pancreatic β-cells is orchestrated by a variety of cells that produce cytokines and other toxic mediators. CD8+ T-cells work together with other lymphocytes and antigen-presenting cells to mediate this damage and have been shown in animal models to be important both in the early stages of diabetes development and in the final effector stages. Recently, there has also been much interest in studying CD8+ T-cells that may play a role in human Type 1 diabetes and identifying their antigenic targets. The present paper will focus on the activation of CD8+ T-cells and their interaction with other cells of the immune system and discuss the target antigens and mechanisms of damage that the CD8+ T-cells use in the attack on the islet β-cell.
Macrophages, cytokines and β-cell death in Type 2 diabetes
Authors: Ehses Jan A. , Böni-Schnetzler Marianne , Faulenbach Mirjam , Donath Marc Y. 
Published: June 2008

The pathology of islets from patients with Type 2 diabetes displays an inflammatory process characterized by the presence of immune cell infiltration, cytokines, apoptotic cells, amyloid deposits and, eventually, fibrosis. Indeed, analysis of β-cells from patients with Type 2 diabetes displays increased IL-1β (interleukin 1β) expression. Furthermore, increased islet-associated macrophages are observed in human Type 2 diabetic patients and in most animal models of diabetes. Importantly, increased numbers of macrophages are detectable very early in high-fat-fed mice islets, before the onset of diabetes. These immune cells are probably attracted by islet-derived chemokines, produced in response to metabolic stress, and under the control of IL-1β. It follows that modulation of intra-islet inflammatory mediators, particularly interleukin-1β, may prevent islet inflammation in Type 2 diabetes and therefore presents itself as a promising therapeutic approach.
Stem cells and metabolic diseases
Authors: Bernardo Andreia S. , Docherty Kevin 
Published: June 2008

Obesity is a metabolic disorder, which has been recognized as a global epidemic. It contributes to insulin resistance, the major cause of Type 2 diabetes, as well as to the development of other related diseases. Our basic premise is that a better understanding of how adult stem cells of the pancreas contribute to the maintenance of the pancreatic β-cell pool against the increased metabolic demands associated with obesity may provide new therapeutic targets for treating diabetes. At the same time, if we knew more about the biology of adipocyte formation, maintenance and deposition in obese individuals, perhaps some control over the adipocyte tissue mass of these individuals would be facilitated and treatment of obesity would become available. Many investigations in the field are therefore aimed at describing how adipocyte stem cells function in the various sites of fat deposition and the extent to which these stem cells contribute to both brown and white adipocytes. Studies on the differentiation of human embryonic stem cells along the pancreatic and adipocyte lineages may therefore better inform approaches to these studies.
Targeting IRFs by ubiquitination: regulating antiviral responses
Authors: Higgs Rowan , Jefferies Caroline A. 
Published: June 2008

The IRF [IFN (interferon) regulatory factor] family of transcription factors control many cellular processes, including induction of key antiviral cytokines, type I IFNs, following viral infection. Recent studies have revealed several endogenous and viral proteins involved in ubiquitin-mediated regulation of IRF activity and thus having an impact on type I IFN signalling. Through the ubiquitin pathway, these proteins can manipulate the antiviral response either by initiating proteasomal degradation of the IRFs or, in contrast, by promoting activation of the IRFs.
Regulation of gene expression by the RNA-binding protein Sam68 in cancer
Authors: Rajan Prabhakar , Gaughan Luke , Dalgliesh Caroline , El-Sherif Amira , Robson Craig N. , Leung Hing Y. , Elliott David J. 
Published: June 2008

Sam68 (Src-associated in mitosis 68 kDa) is the prototypical member of the STAR (signal transducer and activator of RNA) family of RNA-binding proteins. Sam68 is implicated in a number of cellular processes including signal transduction, transcription, RNA metabolism, cell cycle regulation and apoptosis. In the present review, we summarize the functions of Sam68 as a transcriptional and post-transcriptional regulator of gene expression, with particular relevance to cancer.
Fructose modifies the hormonal response and modulates lipid metabolism during aerobic exercise after glucose supplementation
Authors: Fernández Juan M. , da Silva-Grigoletto Marzo E. , Ruano-Ruíz Juan A. , Caballero-Villarraso Javier , Moreno-Luna Rafael , Túnez-Fiñana Isaac , Tasset-Cuevas Inmaculada , Pérez-Martínez Pablo , López-Miranda José , Pérez-Jiménez Francisco 
Published: June 2008

The metabolic response when aerobic exercise is performed after the ingestion of glucose plus fructose is unclear. In the present study, we administered two beverages containing GluF (glucose+fructose) or Glu (glucose alone) in a randomized cross-over design to 20 healthy aerobically trained volunteers to compare the hormonal and lipid responses provoked during aerobic exercise and the recovery phase. After ingesting the beverages and a 15-min resting period, volunteers performed 30 min of moderate aerobic exercise. Urinary and blood samples were taken at baseline (t−15), during the exercise (t0, t15 and t30) and during the recovery phase (t45, t75 and t105). Plasma insulin concentrations were higher halfway through the exercise period and during acute recuperation (t15 and t75; P&lt;0.05) following ingestion of GluF than after Glu alone, without any differences between the effects of either intervention on plasma glucose concentrations. Towards the end of the exercise period, urinary catecholamine concentrations were lower following GluF (t45; P&lt;0.05). Plasma triacylglycerol (triglyceride) concentrations were higher after the ingestion of GluF compared with Glu (t15, t30, t45 and t105; P&lt;0.05). Furthermore, with GluF, we observed higher levels of lipoperoxides (t15, t30, t45 and t105; P&lt;0.05) and oxidized LDL (low-density lipoprotein; t30; P&lt;0.05) compared with after the ingestion of Glu alone. In conclusion, hormonal and lipid alterations are provoked during aerobic exercise and recovery by the addition of a dose of fructose to the pre-exercise ingestion of glucose.
Enriched transcription factor binding sites in hypermethylated gene promoters in drug resistant cancer cells
Authors: Li Meng , Paik Hyun-il Henry , Balch Curt , Kim Yoosung , Li Lang , Huang Tim H-M. , Nephew Kenneth P. , Kim Sun 
Published: June 2008

AbstractMotivation: In the human genome, ‘CpG islands’, CG-rich regions located in or near gene promoters, are normally unmethylated. However, in cancer cells, CpG islands frequently gain methylation, resulting in silencing of growth-limiting tumor suppressor genes. To our knowledge, the potential relationship between CpG island hypermethylation, transcription factor (TF) binding in local promoter regions and transcriptional control has not been previously explored in a genome-wide context.Results: In this study, we utilized bioinformatics tools and TF binding site(TFBs) databases to globally analyze sequences methylated in a laboratory model for the development of drug-resistant cancer. Our results demonstrated that four TFBS were enriched in hypermethylated sequences. More interestingly, overrepresentation of these TFBS was observed in hyper-/hypo-methylated sequences where significant changes in methylation levels were observed in drug-resistant cancer cells. In summary, we believe that these findings offer a means to further explore the relationship between DNA methylation and gene expression in drug resistance and tumorigenesis.Contact: sunkim2@indiana.edu; knephew@indiana.edu
Sequence-specific reconstruction from fragmentary databases using seed sequences: implementation and validation on SAGE, proteome and generic sequencing data
Authors: Sobreira Tiago J. P. , Gruber Arthur 
Published: June 2008

Abstract
Motivation: DNA assembly programs classically perform an all-against-all comparison of reads to identify overlaps, followed by a multiple sequence alignment and generation of a consensus sequence. If the aim is to assemble a particular segment, instead of a whole genome or transcriptome, a target-specific assembly is a more sensible approach. GenSeed is a Perl program that implements a seed-driven recursive assembly consisting of cycles comprising a similarity search, read selection and assembly. The iterative process results in a progressive extension of the original seed sequence. GenSeed was tested and validated on many applications, including the reconstruction of nuclear genes or segments, full-length transcripts, and extrachromosomal genomes. The robustness of the method was confirmed through the use of a variety of DNA and protein seeds, including short sequences derived from SAGE and proteome projects.
Availability: GenSeed is available under the GNU General Public License at http://www.coccidia.icb.usp.br/genseed/
Contact: argruber@usp.br
Supplementary information: Supplementary data are available at http://www.coccidia.icb.usp.br/genseed/
Bacterial Stem Rot of Poinsettia Caused by a Dickeya sp. (Pectobacterium chrysanthemi) in China
Authors: Rungnapha K. , Yu S. H. , Xie G. L. 
Published: June 2008

In December 2006, a rot symptom of unknown etiology was observed on stems of plants (Euphorbia pulcherrima cv. Fu-xing) at a flower nursery in the Zhejiang Province of China where we had previously reported leaf spot of poinsettia caused by Xanthomonas campestris (2). Chlorotic spots anywhere along the stem and purplish black petioles were the first noticeable symptoms. The spots rapidly coalesced, forming large irregular chlorotic areas. Petioles turned black and shriveled and affected leaves wilted. Infected tissues were soft and water soaked. Ten bacterial strains were isolated from the diseased samples and five were selected for identification. They were similar to those of the standard reference strains of Pectobacterium chrysanthemi (Dickeya sp.), LMG 2804 from Belgium and ZUPB20056 from China, in phenotypic tests based on the Biolog Microbial Identification System, version 4.2 (Biolog Inc., Hayward, CA), pathogenicity tests, gas chromatography of fatty acid methyl esters (FAME) using the Microbial Identification System (MIDI Inc, Newark, DE) with aerobic bacterial library (TABA50), and transmission electron microscopy (TEM,KYKY-1000B, Japan). All strains tested were gram-negative facultative anaerobic rods measuring 1.5 to 3.6 × 0.6 to 1.1 μm, with peritrichous flagella. Colonies were gray-white and slightly raised with smooth margins on nutrient agar. They were negative for trehalose and positive for phosphatase production and reducing substances from sucrose. A hypersensitive reaction was observed on tobacco cv. Benshi, 24 h after inoculation. All five isolates, LMG 2804, and ZUPB20056 were identified as P. chrysanthemi (Dickeya sp.) with a Biolog similarity index of 0.58 to 0.83, 0.68, and 0.72 and a FAME similarity index of 0.52 to 0.80, 0.59, and 0.70, respectively. Identification as P. chrysanthemi (Dickeya sp.) was confirmed by PCR with specific primers used by Nassar et al (3). Koch's postulates were completed with the inoculation of 12 4-month-old intact poinsettia plants of cv. Fu-xing with cell suspensions containing 108 CFU/ml by a pinprick at the base of the stem. All five strains induced stem infection similar to those observed in natural infections. No symptoms were noted on the two control plants inoculated with sterilized distilled water by the same method. The bacterium was reisolated from symptomatic stems of poinsettia plants. P. chrysanthemi (Dickeya sp.) was first reported in United States as the cause of bacterial stem rot of poinsettia in 1972 (1). To our knowledge, this is the first report of poinsettia stem rot caused by P. chrysanthemi (Dickeya sp.) in China. The disease cycle and the control strategies of the bacterial stem rot of poinsettia in the regions are being further studied. References: (1) H. A. J. Hoitink et al. Plant Dis. Rep. 56:480, 1972. (2) B. Li et al. Plant Pathol. 55:293, 2006. (3) A. A. Nassar et al. Appl. Environ. Microbiol. 62:2228, 1996.
Occurrence of Ourmia melon virus in the Guilan Province of Northern Iran
Authors: Gholamalizadeh R. , Vahdat A. , Hossein-Nia S. V. , Elahinia A. , Bananej K. 
Published: June 2008

A survey was conducted in 2005 and 2006 in the major cucurbit-growing areas in Guilan Province (northern Iran). Leaf samples were collected from plants of melon (Cucumis melo L.) (n = 119) and squash (Cucurbita sp.) (n = 150) showing various virus-like symptoms (mosaic, yellowing, chlorotic spot, and irregular ring spot) on leaves. All samples collected from 16 different regions were screened for the presence of 10 cucurbit viruses by double-antibody sandwich (DAS)-ELISA using polyclonal antibodies provided by H. Lecoq (INRA, Avignon, France) and V. Lisa (CNR, Torino, Italy). Virus-free cucurbits (melon, squash, and cucumber) grown in insect-proof cages were used as negative controls. Positive and negative controls were included in all tests. Ourmia melon virus (OuMV, genus Ourmiavirus) was the most prevalent virus in melon and was detected in 59% of the samples. OuMV was also detected in 20 of 150 (13%) squash samples. OuMV was detected in 4 of the 16 areas surveyed (Rasht, Somehsara, Masal, and Rood-Bar). The identification of OuMV was confirmed through differential host range reaction. Crude sap from symptomatic leaves was used to inoculate Chenopodium quinoa and Gomphrena globosa as local lesion hosts. Squash, melon, and cucumber were subsequently inoculated by using a single local lesion. Typical yellowing and chlorotic spot symptoms were observed after 40 to 45 days on melon and squash and leaf curling was observed on Nicotiana rustica. The OuMV presence in these symptomatic test plants was confirmed by DAS-ELISA and the tests were negative with Cucurbit aphid-borne yellows virus (CABYV) and Zucchini yellow mosaic virus (ZYMV) antisera. No symptoms were observed on Datura stramonium, Capsicum annum, Phaseolus vulgaris, Pisum sativum, Raphanus sativus, and Beta vulgaris, and OuMV was not detected by DAS-ELISA in these plants. Although showing no symptoms, OuMV-inoculated Vicia faba plants reacted positively in DAS-ELISA. The number of multiple infections of OuMV with other common cucurbit viruses was relatively high (46%), most frequently with ZYMV and CABYV. Since the first report of OuMV from melon in Azerbaijan-E-Gharbi Province, western Iran (1), there has been no report of OuMV occurrence in any other region of Iran or any other country in the world, and the sequence of OuMV remains to be determined. Our results show that OuMV is naturally spreading into other regions of Iran. Reference: (1) V. Lisa et al. Ann. Appl. Biol. 112:291, 1988.
First Report of Crown and Root Rot Caused by Phytophthora capsici on Hydroponically Grown Cucumbers in Norway
Authors: Herrero M. L. , Brurberg M. B. , Hermansen A. 
Published: June 2008

In December 2004, symptoms of root and crown rot were observed on cucumbers (Cucumis sativus L.) in a greenhouse in Norway. Cucumbers were the only crop of the greenhouse that used rockwool as a growing substrate in a hydroponical system. The first symptoms were detected in propagation material. One week after planting, symptoms of root and crown rot were observed and approximately 10% of the plants died. Later, losses of 50% in some greenhouses were observed. A yield reduction as much as 65% was estimated in the winter period (January and February). The two main cucumber cultivars planted were Armada and Lopez. In February 2005, Phytophthora capsici (Leonian) (1) was isolated on potato dextrose agar from a sample of cv. Lopez. The isolate produced deciduous, papillate sporangia (occasionally with two or three papilla) and pedicels that were sometimes longer than the sporangia. Sequencing of amplicons of the internal transcribed spacer region (ITS) rDNA and of the mitochondrial cytochrome c oxidase subunit 1 (Cox1) gene (2) confirmed the identification. Three isolates collected through 2005 from the same greenhouse were crossed with tester strains of P. cryptogea. Formation of oogonia and amphigynous antheridia was always observed in crosses with mating type A2; thus, all isolates were the A1 mating type. All three isolates grew well at 35°C and did not produce chlamydospores. A pathogenicity test was performed with one isolate of P. capsici. Four plants of cucumber cvs. Indira and Jessica were grown in a growth chamber at 24°C. Plants at the two-leaf stage were drenched with 20 ml of a zoospore suspension of 106 zoospores per ml per plant. After 18 days, all plants of both cultivars developed symptoms of crown rot or wilted and died. P. capsici was reisolated from inoculated plants of both cultivars. The pathogenicity test was repeated in the same way, but in a greenhouse with temperatures that ranged between 18 and 29°C. In addition, four plants of both cultivars at the four-leaf stage were inoculated with a suspension of 105 zoospores per ml. After 1 week, all plants developed crown rot or were irreversibly wilted, independently of the plant age or the zoospore concentration. To our knowledge, this is the first report of P. capsici in Norway. References: (1) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society St. Paul MN, 1996. (2) L. P. N. M. Kroon et al. Phytopathology 94:613, 2004.
Disrupting TwoArabidopsis thalianaXylosyltransferase Genes Results in Plants Deficient in Xyloglucan, a Major Primary Cell Wall Component
Authors: Cavalier David M. , Lerouxel Olivier , Neumetzler Lutz , Yamauchi Kazuchika , Reinecke Antje , Freshour Glenn , Zabotina Olga A. , Hahn Michael G. , Burgert Ingo , Pauly Markus , Raikhel Natasha V. , Keegstra Kenneth 
Published: June 2008

AbstractXyloglucans are the main hemicellulosic polysaccharides found in the primary cell walls of dicots and nongraminaceous monocots, where they are thought to interact with cellulose to form a three-dimensional network that functions as the principal load-bearing structure of the primary cell wall. To determine whether two Arabidopsis thaliana genes that encode xylosyltransferases, XXT1 and XXT2, are involved in xyloglucan biosynthesis in vivo and to determine how the plant cell wall is affected by the lack of expression of XXT1, XXT2, or both, we isolated and characterized xxt1 and xxt2 single and xxt1 xxt2 double T-DNA insertion mutants. Although the xxt1 and xxt2 mutants did not have a gross morphological phenotype, they did have a slight decrease in xyloglucan content and showed slightly altered distribution patterns for xyloglucan epitopes. More interestingly, the xxt1 xxt2 double mutant had aberrant root hairs and lacked detectable xyloglucan. The reduction of xyloglucan in the xxt2 mutant and the lack of detectable xyloglucan in the xxt1 xxt2 double mutant resulted in significant changes in the mechanical properties of these plants. We conclude that XXT1 and XXT2 encode xylosyltransferases that are required for xyloglucan biosynthesis. Moreover, the lack of detectable xyloglucan in the xxt1 xxt2 double mutant challenges conventional models of the plant primary cell wall.
Prevalence and relevance of the positivity of skin prick testing in patients with chronic urticaria
Authors: KULTHANAN Kanokvalai , JIAMTON Sukhum , RUTNIN Ni‐on , INSAWANG Metavee , PINKAEW Sumrauy 
Published: June 2008

ABSTRACTMany patients with chronic urticaria (CU) worry that foods or other allergens are responsible for their urticaria. Skin prick testing (SPT) may be one of the investigations used to provide a clear illustration. The purpose of our study was to assess the prevalence of positivity of SPT to food allergens and aeroallergens and their relevance in patients with CU, in order to demonstrate the diagnostic value of SPT in CU. We retrospectively reviewed case record forms of patients with chronic ordinary urticaria who underwent SPT in the Urticaria Clinic, Siriraj Hospital, during the period 2000–2004. The studied allergens included 16 food allergens and 12 aeroallergens. Eighty‐eight patients were enrolled. The prevalence of positive SPT among patients with CU was 47.7%. Patients who had personal histories of atopy had statistically significant positive SPT results compared with patients who had negative SPT. Of 88 patients, 26 patients (30%) gave positive results to food allergens, 36 patients (41%) gave positive results to aeroallergens and 20 patients (22.7%) gave positive results to both food and aeroallergens. One‐third of the subjects (34.6%) who had positive SPT results to food allergens had clinical relevance of food allergy in some systems but only one patient had clinical relevance of food‐induced urticaria. Half of the patients who had a history of aeroallergen sensitivity gave a positive SPT response for aeroallergens; however, there was no clinical relevance to their CU. Our study showed that the prevalence of positive SPT to food allergens and aeroallergens in patients with CU was common but had little clinical relevance to CU.