A human IL10 BAC transgene reveals tissue-specific control of IL-10 expression and alters disease outcome.

Interleukin (IL)-10 is an immunoregulatory cytokine that is produced by diverse cell populations. Studies in mice suggest that the cellular source of IL-10 is a key determinant in various disease pathologies, yet little is known regarding the control of tissue-specific human IL-10 expression. To assess cell type-specific human IL-10 regulation, we created a human IL-10 transgenic mouse with a bacterial artificial chromosome (hIL10BAC) in which the IL10 gene is positioned centrally.

Large-scale analysis of putative soybean regulatory gene expression identifies a Myb gene involved in soybean nodule development.

Nodulation is the result of a symbiosis between legumes and rhizobial bacteria in soil. This symbiosis is mutually beneficial, with the bacteria providing a source of nitrogen to the host while the plant supplies carbon to the symbiont. Nodule development is a complex process that is tightly regulated in the host plant cell through networks of gene expression.

EPHA2 is associated with age-related cortical cataract in mice and humans.

Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract.

B7-H1 blockade increases survival of dysfunctional CD8(+) T cells and confers protection against Leishmania donovani infections.

Experimental visceral leishmaniasis (VL) represents an exquisite model to study CD8(+) T cell responses in a context of chronic inflammation and antigen persistence, since it is characterized by chronic infection in the spleen and CD8(+) T cells are required for the development of protective immunity. However, antigen-specific CD8(+) T cell responses in VL have so far not been studied, due to the absence of any defined Leishmania-specific CD8(+) T cell epitopes. In this study, transgenic Leishmania donovani parasites expressing ovalbumin were used to characterize the development, function, and fate of Leishmania-specific CD8(+) T cell responses.

Generation of Phaseolus vulgaris ESTs and investigation of their regulation upon Uromyces appendiculatus infection.

Background: Phaseolus vulgaris (common bean) is the second most important legume crop in the world after soybean. Consequently, yield losses due to fungal infection, like Uromyces appendiculatus (bean rust), have strong consequences. Several resistant genes were identified that confer resistance to bean rust infection.

System analysis of an Arabidopsis mutant altered in de novo fatty acid synthesis reveals diverse changes in seed composition and metabolism.

Embryo-specific overexpression of biotin carboxyl carrier protein 2 (BCCP2) inhibited plastid acetyl-coenzyme A carboxylase (ACCase), resulting in altered oil, protein, and carbohydrate composition in mature Arabidopsis (Arabidopsis thaliana) seed. To characterize gene and protein regulatory consequences of this mutation, global microarray, two-dimensional difference gel electrophoresis, iTRAQ, and quantitative immunoblotting were performed in parallel. These analyses revealed that (1) transgenic overexpression of BCCP2 did not affect the expression of three other ACCase subunits; (2) four subunits to plastid pyruvate dehydrogenase complex were 25% to 70% down-regulated at protein but not transcript levels; (3) key glycolysis and de novo fatty acid/lipid synthesis enzymes were induced; (4) multiple storage proteins, but not cognate transcripts, were up-regulated; and (5) the biotin synthesis pathway was up-regulated at both transcript and protein levels.

The humanized CD40 antibody SGN-40 demonstrates pre-clinical activity that is enhanced by lenalidomide in chronic lymphocytic leukaemia.

Antibody-based therapies, such as rituximab and alemtuzumab, have contributed significantly to the treatment of Chronic Lymphocytic leukaemia (CLL). The CD40 antigen is expressed predominantly on B-cells and represents a potential target for immune-based therapies. SGN-40 is a humanized IgG1 monoclonal antibody currently in Phase I/II clinical trials for indolent lymphomas, diffuse large B cell lymphomas and Multiple Myeloma.

The PtdIns 3-kinase/Akt pathway regulates macrophage-mediated ADCC against B cell lymphoma.

Macrophages are important effectors in the clearance of antibody-coated tumor cells. However, the signaling pathways that regulate macrophage-induced ADCC are poorly defined. To understand the regulation of macrophage-mediated ADCC, we used human B cell lymphoma coated with Rituximab as the tumor target and murine macrophages primed with IFNgamma as the effectors.

Combined effects of complement factor H genotypes, fish consumption, and inflammatory markers on long-term risk for age-related macular degeneration in a cohort.

At baseline in 1992-1994, the authors assessed the combined effects of complement factor H (CFH) genotypes with smoking, fish consumption, and inflammatory markers on the risk of age-related macular degeneration (AMD) in 3,654 persons aged > or =49 years. They reexamined 75% of the survivors after 5 and 10 years, confirming incident AMD by side-by-side photographic grading. Of the 2,452 persons followed in the Blue Mountains Eye Study, 1,881 were genotyped (rs1061170), with CC, CT, and TT identified in 13.

Establishment of a protein reference map for soybean root hair cells.

Root hairs are single tubular cells formed from the differentiation of epidermal cells on roots. They are involved in water and nutrient uptake and represent the infection site on leguminous roots by rhizobia, soil bacteria that establish a nitrogen-fixing symbiosis. Root hairs develop by polar cell expansion or tip growth, a unique mode of plant growth shared only with pollen tubes.

A critical assessment of Mus musculus gene function prediction using integrated genomic evidence.

Background: Several years after sequencing the human genome and the mouse genome, much remains to be discovered about the functions of most human and mouse genes. Computational prediction of gene function promises to help focus limited experimental resources on the most likely hypotheses. Several algorithms using diverse genomic data have been applied to this task in model organisms; however, the performance of such approaches in mammals has not yet been evaluated.

Transcription profiling of soybean nodulation by Bradyrhizobium japonicum.

Legumes interact with nodulating bacteria that convert atmospheric nitrogen into ammonia for plant use. This nitrogen fixation takes place within root nodules that form after infection of root hairs by compatible rhizobia. Using cDNA microarrays, we monitored gene expression in soybean (Glycine max) inoculated with the nodulating bacterium Bradyrhizobium japonicum 4, 8, and 16 days after inoculation, timepoints that coincide with nodule development and the onset of nitrogen fixation.

GeneFAS: A tool for prediction of gene function using multiple sources of data.

Characterizing gene function is one of the major challenging tasks in the postgenomic era. To address this challenge, we developed GeneFAS (gene function annotation system), a computer system with a graphical user interface for cellular function prediction by integrating information from protein-protein interactions, protein complexes, microarray gene expression profiles, and annotations of known proteins. GeneFAS can provide biologists a workspace for their organism of interest, to integrate different types of experimental data and annotation information, and facilitate biological discovery and hypothesis generation using all the information.

Complement factor H polymorphisms, renal phenotypes and age-related macular degeneration: the Blue Mountains Eye Study.

Complement factor H (CFH) is a key regulator of the alternative pathway of complement and its mutations have been associated with membranoproliferative glomerulonephritis type II, atypical hemolytic uremic syndrome and age-related macular degeneration (AMD), suggesting that alternative pathway dysregulation is a common pathogenetic feature of these ocular and renal conditions. In this study we tested the hypothesis that common CFH variants have a global role in renal function in the Australian population-based Blue Mountains Eye Study (BMES). We replicated the association of I62V with estimated glomerular filtration rate (GFR; P=0.

Isolation, identification and application of novel bacterial consortium TJ-1 for the decolourization of structurally different azo dyes.

A novel bacterial consortium (TJ-1), which could decolorize Acid Orange 7 (AO7) and manyother azo dyes, was developed. In TJ-1 three bacterial strains were identified as Aeromonas caviae, Proteus mirabilis and Rhodococcus globerulus by 16S rRNA gene sequence analysis. AO7 decolorization was significantly higher with the use of consortium as compared to the use of individual strains, indicating complementary interactions among these strains.

IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro.

Interleukin-21 (IL-21) is a recently identified gamma-chain receptor cytokine family member that promotes B-cell apoptosis as well as activation of innate immune system. Based on this, we hypothesized that IL-21 might enhance the apoptosis induced by fludarabine and rituximab and also play a role in augmenting immune-mediated clearance of the chronic lymphocytic leukemia (CLL) cells. Our studies demonstrate that the majority of CLL patients have surface IL-21 receptor-alpha, and its expression correlates with apoptosis, tyrosine phosphorylation of STAT1, and up-regulation of the proapoptotic BH3 domain protein BIM.

An integrated probabilistic approach for gene function prediction using multiple sources of high-throughput data.

Characterising gene function is one of the major challenging tasks in the post-genomic era. Various approaches have been developed to integrate multiple sources of high-throughput data to predict gene function. Most of those approaches are just used for research purpose and have not been implemented as publicly available tools.

Cellular function prediction and biological pathway discovery in Arabidopsis thaliana using microarray data.

Determination of protein function and biological pathway is one of the most challenging problems in the post-genomic era. To address this challenge, we have developed a new integrated probabilistic method for cellular function prediction using microarray gene expression profiles, in conjunction with predicted protein-protein interactions and annotations of known proteins. Our approach is based on a novel assessment for the relationship between correlation of two genes' expression profiles and their functional relationship in terms of the Gene Ontology (GO) hierarchy.

The activation of natural killer cell effector functions by cetuximab-coated, epidermal growth factor receptor positive tumor cells is enhanced by cytokines.

Purpose: Natural killer (NK) cells express an activating Fc receptor (FcgammaRIIIa) that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab is a therapeutic monoclonal antibody directed against the HER1 antigen. We hypothesized that the NK cell response to cetuximab-coated tumor cells could be enhanced by the administration of NK cell-stimulatory cytokines.

An oligonucleotide microarray resource for transcriptional profiling of Bradyrhizobium japonicum.

A DNA microarray, comprising 70-mer oligonucleotides, representing 8,453 open reading frames (ORFs), was constructed based on the Bradyrhizobium japonicum strain USDA110 genomic sequence. New annotation predicted 199 additional genes, which were added to the microarray and were shown to be transcribed. These arrays were used to profile transcription in cells under a variety of conditions, including growth in minimal versus rich medium, osmotic stress, and free-living cells versus bacteroids.

Transcriptional and physiological responses of Bradyrhizobium japonicum to desiccation-induced stress.

The growth and persistence of rhizobia and bradyrhizobia in soils are negatively impacted by drought conditions. In this study, we used genome-wide transcriptional analyses to obtain a comprehensive understanding of the response of Bradyrhizobium japonicum to drought. Desiccation of cells resulted in the differential expression of 15 to 20% of the 8,453 [corrected] B.