Identification of Aluminum Responsive Genes in Al-Tolerant Soybean Line PI 416937

Soybean is one of the most aluminum (Al) sensitive plants. The complex inheritance of Al tolerance trait has so far undermined breeding efforts to develop Al-tolerant soybeans. Discovering the genetic factors underlying the Al tolerance mechanisms would undoubtedly accelerate the pace of such endeavor. As a first step toward this goal, we analyzed the transcriptome profile in roots of Al-tolerant soybean line PI 416937 comparing Al-treated and untreated control plants using DNA microarrays. Many genes involved in transcription activation, stress response, cell metabolism and signaling were differentially expressed. Patterns of gene expression and mechanisms of Al toxicity and tolerance suggest that Cys2His2 and ADR6 transcription activators, cell wall modifying enzymes, and phytosulfokines growth factor play role in soybean Al tolerance. Our data provide insights into the molecular mechanisms of soybean Al tolerance and will have practical value in genetic improvement of Al tolerance trait

Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc

Background Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-β superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing mouse tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-β has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-β action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing mouse IVD and to begin to understand the mechanism of TGF-β action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing mouse vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice as well as in sclerotome cultures treated with TGF-β or BMP4. Results Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We also generated lists of genes regulated by TGF-β or BMP4 in cultured sclerotome. As expected, treatment with BMP4 resulted in up-regulation of cartilage marker genes including Acan, Sox 5, Sox6, and Sox9. In contrast, treatment with TGF-β1 did not regulate expression of cartilage markers but instead resulted in up-regulation of many IVD markers including Fmod and Adamtsl2. Conclusions We propose TGF-β has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-β that warrant further investigation as regulators of IVD development

GenDrux: A biomedical literature search system to identify gene expression-based drug sensitivity in breast cancer

Background This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications. Results GenDrux, a pilot system, is developed in the domain of breast cancer and can be accessed at http://www.microarray.uab.edu/drug_gene.pl. GenDrux can be queried based on drug, gene and/or disease name. From over 8,000 relevant abstracts from the biomedical literature related to breast cancer, we have archived a corpus of more than 4,000 articles that depict gene expression-drug activity relationships for breast cancer and related cancers. The archiving process has been automated. Conclusions The successful development, implementation, and evaluation of this and similar systems when created may provide clinicians with a tool for literature management, clinical decision making, thus setting the platform for personalized therapy in the future

GenDrux: A biomedical literature search system to identify gene expression-based drug sensitivity in breast cancer

Background This paper describes the development of a web-based tool, GenDrux, which extracts and presents (over the Internet) information related to the disease-gene-drug nexus. This information is archived from the relevant biomedical literature using automated methods. GenDrux is designed to alleviate the difficulties of manually processing the vast biomedical literature to identify disease-gene-drug relationships. GenDrux will evolve with the literature without additional algorithmic modifications. Results GenDrux, a pilot system, is developed in the domain of breast cancer and can be accessed at http://www.microarray.uab.edu/drug_gene.pl. GenDrux can be queried based on drug, gene and/or disease name. From over 8,000 relevant abstracts from the biomedical literature related to breast cancer, we have archived a corpus of more than 4,000 articles that depict gene expression-drug activity relationships for breast cancer and related cancers. The archiving process has been automated. Conclusions The successful development, implementation, and evaluation of this and similar systems when created may provide clinicians with a tool for literature management, clinical decision making, thus setting the platform for personalized therapy in the future

Influence of aging and hemorrhage injury on Sirt1 expression: Possible role of myc-Sirt1 regulation in mitochondrial function

AbstractTrauma–hemorrhage (T–H) causes hypoxia and organ dysfunction. Mitochondrial dysfunction is a major factor for cellular injury due to T–H. Aging also has been known to cause progressive mitochondrial dysfunction. In order to study the effect of aging on T–H-induced mitochondrial dysfunction, we recently developed a rodent mitochondrial genechip with probesets representing mitochondrial and nuclear genes contributing to mitochondrial structure and function. Using this chip we recently identified signature mitochondrial genes altered following T–H in 6 and 22month old rats; augmented expression of the transcription factor c-myc was the most pronounced. Based on reports of c-myc-IL6 collaboration and c-myc-Sirt1 negative regulation, we further investigated the expression of these regulatory factors with respect to aging and injury. Rats of ages 6 and 22months were subjected to T–H or sham operation and left ventricular tissues were tested for cytosolic cytochrome c, mtDNA content, Sirt1 and mitochondrial biogenesis factors Foxo1, Ppara and Nrf-1. We observed increased cardiac cytosolic cytochrome c (sham vs T–H, p<0.03), decreased mitochondrial DNA content (sham vs T–H, p<0.05), and decreased Sirt1 expression (sham vs TH, p<0.05) following T–H and with progressing age. Additionally, expression of mitochondrial biogenesis regulating transcription factors Foxo1 and Nrf-1 was also decreased with T–H and aging. Based upon these observations we conclude that Sirt1 expression is negatively modulated by T–H causing downregulation of mitochondrial biogenesis. Thus, induction of Sirt1 is likely to produce salutary effects following T–H induced injury and hence, Sirt1 may be a potential molecular target for translational research in injury resolution

Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes

A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential

Wireless local area network in a prehospital environment

BACKGROUND: Wireless local area networks (WLANs) are considered the next generation of clinical data network. They open the possibility for capturing clinical data in a prehospital setting (e.g., a patient's home) using various devices, such as personal digital assistants, laptops, digital electrocardiogram (EKG) machines, and even cellular phones, and transmitting the captured data to a physician or hospital. The transmission rate is crucial to the applicability of the technology in the prehospital setting. METHODS: We created two separate WLANs to simulate a virtual local are network environment such as in a patient's home or an emergency room (ER). The effects of different methods of data transmission, number of clients, and roaming among different access points on the file transfer rate were determined. RESULTS: The present results suggest that it is feasible to transfer small files such as patient demographics and EKG data from the patient's home to the ER at a reasonable speed. Encryption, user control, and access control were implemented and results discussed. CONCLUSIONS: Implementing a WLAN in a centrally managed and multiple-layer-controlled access control server is the key to ensuring its security and accessibility. Future studies should focus on product capacity, speed, compatibility, interoperability, and security management

Aging Influences Cardiac Mitochondrial Gene Expression and Cardiovascular Function following Hemorrhage Injury

Cardiac dysfunction and mortality associated with trauma and sepsis increase with age. Mitochondria play a critical role in the energy demand of cardiac muscles, and thereby on the function of the heart. Specific molecular pathways responsible for mitochondrial functional alterations after injury in relation to aging are largely unknown. To further investigate this, 6- and 22-month-old rats were subjected to trauma-hemorrhage (T-H) or sham operation and euthanized following resuscitation. Left ventricular tissue was profiled using our custom rodent mitochondrial gene chip (RoMitochip). Our experiments demonstrated a declined left ventricular performance and decreased alteration in mitochondrial gene expression with age following T-H and we have identified c-Myc, a pleotropic transcription factor, to be the most upregulated gene in 6- and 22-month-old rats after T-H. Following T-H, while 142 probe sets were altered significantly (39 up and 103 down) in 6-month-old rats, only 66 were altered (30 up and 36 down) in 22-month-old rats; 36 probe sets (11 up and 25 down) showed the same trend in both groups. The expression of c-Myc and cardiac death promoting gene Bnip3wereincreased, and Pgc1-α and Ppar-a a decreased following T-H. Eleven †RNA transcripts on mtDNA were upregulated following T-H in the aged animals, compared with the sham group. Our observations suggest a c-myc-regulated mitochondrial dysfunction following T-H injury and marked decrease in age-dependent changes in the transcrip-tional profile of mitochondrial genes following T-H, possibly indicating cellular senescence. To our knowledge, this is the first report on mitochondrial gene expression profile following T-H in relation to aging

Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

<p>Abstract</p> <p>Background</p> <p><it>CALM1 </it>gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca²⁺-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the <it>CALM1 </it>core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.</p> <p>Methods</p> <p>A case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.</p> <p>Results</p> <p>No significant difference was detected in genotype or allele distribution between knee OA and control groups (all <it>P </it>> 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.</p> <p>Conclusion</p> <p>The present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.</p