Letteratura scientifica selezionata sul tema "Tissue specificity"

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Articoli di riviste sul tema "Tissue specificity"

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Vinogradov, A. E. "Isochores and tissue-specificity". Nucleic Acids Research 31, n. 17 (1 settembre 2003): 5212–20. http://dx.doi.org/10.1093/nar/gkg699.

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Pei, Guangsheng, Yulin Dai, Zhongming Zhao e Peilin Jia. "deTS: tissue-specific enrichment analysis to decode tissue specificity". Bioinformatics 35, n. 19 (1 marzo 2019): 3842–45. http://dx.doi.org/10.1093/bioinformatics/btz138.

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Abstract Motivation Diseases and traits are under dynamic tissue-specific regulation. However, heterogeneous tissues are often collected in biomedical studies, which reduce the power in the identification of disease-associated variants and gene expression profiles. Results We present deTS, an R package, to conduct tissue-specific enrichment analysis with two built-in reference panels. Statistical methods are developed and implemented for detecting tissue-specific genes and for enrichment test of different forms of query data. Our applications using multi-trait genome-wide association studies data and cancer expression data showed that deTS could effectively identify the most relevant tissues for each query trait or sample, providing insights for future studies. Availability and implementation https://github.com/bsml320/deTS and CRAN https://cran.r-project.org/web/packages/deTS/ Supplementary information Supplementary data are available at Bioinformatics online.
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Lundborg, Göran, Lars B. Dahlin, Nils Danielsen e Ann K. Nachemson. "Tissue Specificity in Nerve Regeneration". Scandinavian Journal of Plastic and Reconstructive Surgery 20, n. 3 (gennaio 1986): 279–83. http://dx.doi.org/10.3109/02844318609004486.

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Milgrom, Felix. "Tissue Specificity and Autoimmune Responses". Immunological Investigations 18, n. 1-4 (gennaio 1989): xxxi—xliv. http://dx.doi.org/10.3109/08820138909112222.

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Rossignol, Rodrigue, Monique Malgat, Jean-Pierre Mazat e Thierry Letellier. "Threshold Effect and Tissue Specificity". Journal of Biological Chemistry 274, n. 47 (19 novembre 1999): 33426–32. http://dx.doi.org/10.1074/jbc.274.47.33426.

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Alderton, Gemma. "Tissue specificity in cancer drivers". Science 363, n. 6432 (14 marzo 2019): 1187.14–1189. http://dx.doi.org/10.1126/science.363.6432.1187-n.

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Aguet, François, e Kristin G. Ardlie. "Tissue Specificity of Gene Expression". Current Genetic Medicine Reports 4, n. 4 (29 settembre 2016): 163–69. http://dx.doi.org/10.1007/s40142-016-0105-2.

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Funder, John W. "Target tissue specificity of mineralocorticoids". Trends in Endocrinology & Metabolism 1, n. 3 (gennaio 1990): 145–48. http://dx.doi.org/10.1016/1043-2760(90)90026-y.

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de Graaf, D. C., e F. J. Jacobs. "Tissue specificity of Nosema apis". Journal of Invertebrate Pathology 58, n. 2 (settembre 1991): 277–78. http://dx.doi.org/10.1016/0022-2011(91)90073-y.

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Miyazaki, Jun-Ichi, Toshiki Makioka, Yoshihiro Fujiwara e Tamio Hirabayashi. "Tissue specificity of crustacean tropomyosin". Journal of Experimental Zoology 263, n. 3 (1 settembre 1992): 235–44. http://dx.doi.org/10.1002/jez.1402630303.

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Tesi sul tema "Tissue specificity"

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Mistry, Nitesh. "Human papillomavirus tropism : determinants of viral tissue specificity". Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1149.

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Bartsakoulia, Marina. "Investigating the reversibility and tissue specificity of mitochondrial disorders". Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3832.

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Mitochondrial disorders comprise a large group of heterogeneous disorders which are characterized by impairments in the cellular energy production. One of the great challenges of mitochondrial disease is the variety of clinical features present in patients. Mitochondrial disorders affect more than one organ leading to complex multisystem dysfunctions. Tissues, in which the metabolic demand is higher, such as skeletal muscle, neurons, liver or heart are typically affected. Mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) often lead to mitochondrial disorders. Although mtDNA encodes key proteins for the normal function of the mitochondrial respiratory chain enzymes, the vast majority of the essential components and proteins needed for the maintenance and replication of the mitochondrial DNA are encoded by the nDNA. Exome sequencing in combination with bioinformatics tools has proven really effective in determining novel alterations in the genomic sequence. One aim of this thesis was to evaluate novel mutations from affected patients with combined respiratory deficiencies. As a result, mutations in C12orf65 and in the novel disease gene MiD49, associated with mitochondrial disorders, are thoroughly presented. Vitamin supplements, pharmacological agents and exercise therapy are common strategies used in patients suffering from mitochondrial disorders. It has been shown that in cell lines of patients suffering from two rare reversible infantile mitochondrial diseases (reversible infantile respiratory chain deficiency and reversible infantile hepatopathy due to TRMU deficiency) supplementation of L-cysteine resulted in an improvement in most respiratory chain complexes activities. During my PhD I studied and proved that L-cysteine supplementation was also beneficial in cells from patients suffering from common forms of mitochondrial disorders such as MELAS and MERRF as the supplementation resulted in improved mitochondrial respiratory chain function. Finally, direct conversion of fibroblasts to neuronal progenitor cells was used to model mitochondrial disorders and study the tissue specificity. This project was very challenging due to the complex characteristics of mitochondrial biology. In summary, this thesis reveals the description of novel genes and mutations associated with combined mitochondrial deficiencies. Furthermore, we detected a positive effect of L-cysteine on a subset of mitochondrial disorders, which can be the base of further therapy development.
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Dos, Santos Brilha Sara Sofia. "Tissue specificity of MMP gene expression and secretion in tuberculosis". Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/51148.

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In tuberculosis (TB), matrix metalloproteinases (MMPs) have a major role in tissue destruction and cavitation. The composition of each extracellular matrix (ECM) gives specificity to tissues and is important in control of local immune responses by acting as a “molecular postcode”. Hence, it is likely to have important implications in TB. During central nervous system (CNS) infection, the effect of TB on blood-brain barrier (BBB) function is unknown. I hypothesised that the ECM environment may determine the MMP response during innate immune activation in pulmonary and CNS TB. I aimed to investigate the effect of adhesion to the lung’s ECM in regulation of MMP expression and activity. I also aimed to develop a BBB cellular model and investigate the role of Mycobacterium tuberculosis (Mtb)-driven MMP secretion on BBB function. In a model of pulmonary TB, human bronchial epithelial cells (NHBEs) and monocytes were exposed to ECM components and stimulated with conditioned medium from Mtb-infected monocytes (CoMtb) or infected with Mtb. Type I collagen (Coll-I) matrix was shown to decrease MMP-1 mRNA accumulation by 48% and collagenolytic activity compared to NHBEs in the absence of matrix. MMP-1 co-localised with integrin α2β1 resulting in enhanced cell migration in wound healing assays. In contrast, soluble Coll-I led to integrin α2β1 occupancy without clustering and caused a 7-fold increase in collagenolytic activity but decreased migration. In Mtb-infected monocytes, adhesion to ECM components increased MMP-1 secretion by over 60%. Fibronectin and Coll-I also increased MMP-10 by 55% and 90% respectively. Surface expression of integrin αVβ3 was upregulated by Mtb-infection and adhesion to Coll-I. Activation of integrin αVβ3 mimicked the effect of Coll-I MMP secretion, while its inhibition impaired monocyte migration. CoMtb-stimulation of the BBB model decreased trans-endothelial electrical resistance from 154±1.2ohm.cm2 to 111.6±4.7ohm.cm2, while Papp increased 3-fold. Coll-IV and tight junction proteins (TJPs) degradation was also detected. MMP concentrations increased 125-fold for MMP-1 (0.35±2 to 43.8±5.1ng/mL) and 619-fold for MMP-9 (0.072±0.014 to 44.6±8.9ng/ml). Treatment with the MMP inhibitor Ro32-3555 prevented BBB disruption. Neutrophil and monocyte transmigration increased 60% and 80% respectively and returned to control levels with MMP blockade. MMP-9 was shown to be responsible for BBB disruption and its inhibition by antibodies prevented BBB disruption. The Hedgehog pathway was downregulated during infection, resulting in decrease TJPs gene expression, which contributes to BBB dysfunction. In summary, the ECM regulates both epithelial and monocyte expression of MMP-1 via integrins signalling. In the CNS, MMP-9 drives tissue destruction and BBB disruption which may be a potential reversible event in CNS TB immunopathology.
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Ayala, Fierro Felix. "Tissue specificity for metabolism and toxicity of arsine and arsenite". Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284050.

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Accidental exposure to arsine (AsH₃) is possible in the semiconductor industry, metal mining, painting and herbicide preparation. First symptoms include intravascular hemolysis and dark red urine (hematuria), followed by abdominal pain, jaundice, and anemia. Exposure to AsH₃ is fatal in up to 25% of the reported human cases, usually caused by acute oliguric renal failure. The mechanism of AsH₃ toxicity in the kidney is unknown and was studied in vitro using established cell lines, primary cells, and isolated kidney. The hypothesis was that AsH₃ cause renal toxicity by its conversion to arsenite (AsIII). Renal cells were more susceptible to As(III) cytotoxic effects on ion homeostasis and cell integrity, but AsH₃ showed oxidative stress-like toxicity. Red blood cells were only susceptible to direct AsH₃ cytotoxicity. Hepatocytes, chosen because liver is also affected by AsH₃, were susceptible to both arsenicals. It was established that AsH₃ produce tissue specific toxicity. The toxicity of the AsH₃-produced hemolysate was also investigated. The complete hemolysate was toxic and this toxicity was associated with the soluble hemolytic products. AsH₃-induced nephrotoxicity was also studied in the isolated rat kidney. Unmetabolized AsH₃ was more toxic than hemolytic products in this system. Damage was found in the glomeruli, tubular epithelial cells, and vascular peritubular capillaries. Finally, the total amount of arsenicals produced by AsH₃ oxidation in the rat kidney and liver homogenates was determined. As(III) was formed four times as much compared to As(V) in the kidney. By comparison, the liver metabolized less than half of the arsenite formed by the kidney. In summary, in vitro systems were used to model tissue selectivity for AsH₃ toxicity and to investigate AsH₃ renal cytotoxicity. Red blood cells and hepatocytes were susceptible to unmetabolized AsH₃. AsH₃ was required to form As(III) to produce renal toxicity. The soluble hemolytic products produced by AsH₃ also contributed to the in vitro renal toxicity. Renal dysfunction produced by AsH₃ exposure (the cause for mortality), is caused by a combination of AsH₃-produced oxidative-stress toxicity and by cell integrity damage produced by As(III) formed from AsH₃ oxidation, and delivered to the kidney as soluble toxicants in the hemolysate.
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Yang, Rick L. "Tissue specificity of signal transmission and differential growth during maize root gravitropism". Connect to resource, 1992. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1244222463.

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Jia, Yizhen, e 贾亦真. "Bioinformatics study of the lineage and tissue specificity of genes and gene expression". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45540652.

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Freeman, Alistair Iain. "5' variants of glucocorticoid receptor mRNA : further studies of tissue-specificity and regulation". Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/24590.

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Glucocorticoids have diverse physiological functions: they affect central nervous system function, intermediary metabolism and restore homeostasis after stress. Secretion of glucocorticoids is regulated by the hypothalamic-pituitary-adrenal (HPA) axis; negative feedback at the hypothalamus and pituitary suppresses glucocorticoid secretion while the hippocampus exerts additional control over HPA axis activity. Glucocorticoids exert most of their actions, including negative feedback, via the glucocorticoid receptor (GR). The glucocorticoid sensitivity of a given cell/tissue is dependent on the level of GR expression. The regulation of the GR gene is complex; GR levels in adult animals are subject to glucocorticoid regulation and can be permanently "programmed" by early life events, with hippocampal GR permanently increased by neonatal handling (via alterations in serotonin turnover) and decreased by prenatal dexamethasone exposure. Evidence suggests that these effects may be mediated through differential regulation of variant exon-1 containing GR mRNAs; in rats the GR gene contains 8 protein-coding exons (exons 2-9) and at least 11 alternate untranslated exons 1 (exons li-ln) which may reflect transcription regulated by alternate promoters. The aim of this thesis was to further investigate the distribution of these variant GR transcripts and examine whether glucocorticoids themselves differentially regulate GR mRNA and its alternate exons 1 in a tissue and region-specific manner. Tissue and region-specific differences in the expression of variant GR mRNA transcripts were found in rat and mouse. Most GR mRNA variants were ubiquitously expressed, but those containing exon 11 were restricted to rat thymus, liver and hippocampus and mouse spleen, while those containing exon 14 were absent from rat cerebral cortex and mouse lung, heart and abdominal fat. In situ mRNA hybridisation on rat brain showed that all the exons 1 studied showed differences in their regional expression when compared to distribution of the total population of GR mRNAs. In contrast, in rat liver and thymus GR mRNA variants showed the same regional distribution as total GR mRNA with highest expression in periportal region of the liver and the thymic cortex. To investigate whether glucocorticoids differentially regulate variant GR mRNAs, in situ mRNA hybridisation was used to investigate the expression variant exons 1 in the hippocampus of adult rats subjected to 72h (ST) or 3-week (LT) adrenalectomy with glucocorticoid replacement. Variant GR mRNAs containing exons 1₅, 1₇, 1₁₀ and 1₁₁ were not affected by adrenalectomy or supraphysiological glucocorticoid replacement in ST or LT animals. However, both adrenalectomy and supraphysiological glucocorticoid replacement significantly upregulated total GR mRNA in the hippocampus of ST animals while adrenalectomy significantly upregulated total GR mRNA in the hippocampus of LT animals. In situ mRNA hybridisation and RNase protection analysis were used to investigate expression of variant GR mRNAs in the liver. Glucocorticoid manipulations did not significantly affect expression of variant GR mRNAs containing exons 1₅, 1₆, 1₁₀ and 1₁₁. However, in ST adrenalectomised animals glucocorticoid replacement significantly downregulated GR mRNA levels compared to adrenalectomised animals given vehicle alone. Adrenalectomy had no effect on total GR mRNA expression in the LT animals, although in these animals the periportal :perivenous ratio of GR expression was significantly increased by adrenalectomy compared to sham. Preliminary data from DNase I hypersensitive site mapping in control animals showed an area of DNase I sensitive chromatin around the position of exon 1₁₀, present in the majority of GR mRNA in the liver. In the thymus, although adrenalectomy with either high and low dose glucocorticoid replacement in ST animals caused a significant downregulation of GR mRNA in the cortex and medulla compared to sham, the expression of exons 1₁, 1₆ and 1₁₀ of the GR gene was not significantly affected by glucocorticoid manipulations. There was no effect of glucocorticoid manipulation on GR or its variants in the LT animals. These results demonstrate tissue-specific differences in the distribution of GR mRNA variants, suggesting that variations in promoter usage may have a role in determining the "set-point" of GR expression in different tissues. The observed tissue-specific effects of glucocorticoids on GR mRNA expression could not be accounted for by changes in expression of any of the variant GR mRNA transcripts studied. This suggests that either the expression of another variant mRNA (known or novel) is regulated by glucocorticoids or that expression of all or a subset of the variant GR mRNAs changed with a magnitude too small to be detected in this study.
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Wieser, Daniela. "Exploiting gene expression and protein data for predicting remote homology and tissue specificity". Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/159177/.

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In this thesis I describe my investigations of applying machine learning methods to high throughput experimental and predicted biological data. The importance of such analysis as a means of making inferences about biological functions is widely acknowledged in the bioinformatics community. Specifically, this work makes three novel contributions based on the systematic analysis of publicly archived data of protein sequences, three dimensional structures, gene expression and functional annotations: (a) remote homology detection based on amino acid sequences and secondary structures; (b) the analysis of tissue-specific gene expression for predictive signals in the sequence and secondary structure of the resulting protein product; and (c) a study of ageing in the fruit fly, a commonly used model organism, in which tissue specific and whole-organism gene expression changes are contrasted. In the problem of remote homology detection, a kernel-based method that combines pairwise alignment scores of amino acid sequences and secondary structures is shown to improve the prediction accuracies in a benchmark task defined using the Structural Classification of Proteins (SCOP) database. While the task of predicting SCOP superfamilies should be regarded as an easy one, with not much room for performance improvement, it is still widely accepted as the gold standard due to careful manual annotation by experts in the subject of protein evolution. A similar method is introduced to investigate whether tissue specificity of gene expression is correlated with the sequence and secondary structure of the resulting protein product. An information theoretic approach is adopted for sorting fruit fly and mouse genes according to their tissue specificity based on gene expression data. A classifier is then trained to predict the degree of specificity for these genes. The study concludes that the tissue specificity of gene expression is correlated with the sequence, and to a certain extent, with the secondary structure of the gene’s protein product. The sorted list of genes introduced in the previous chapter is used to investigate the tissue specificity of transcript profiles obtained from a study of ageing in the fruit fly. The same list is utilised to investigate how filtering tissue-restricted genes affects gene set enrichment analysis in the ageing study, and to examine the specificity of age-associated genes identified in the literature. The conclusion drawn in this chapter is that categorisation of genes according to their tissue specificity using Shannon’s information theory is useful for the interpretation of whole-fly gene expression data.
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Youngman, Kenneth R. "Mechanisms of regulation of polymeric immunoglobulin receptor expression: Cytokine induction and tissue specificity". Case Western Reserve University School of Graduate Studies / OhioLINK, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=case1057587491.

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Roulis, Eileen V. "The genetic diversity of Chlamydia pneumoniae and its implications for host and tissue specificity". Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/96034/1/Eileen_Roulis_Thesis.pdf.

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Chlamydia pneumoniae is a wide spread human and animal pathogen, associated with a number of acute and chronic disease states. In this thesis, next-generation sequencing technologies were used to identify genetic markers involved in the diverse presentation of Chlamydia pneumoniae infections. The findings presented in this study describe a phylogenetically distinct human Chlamydia pneumoniae line, as well as a number of minor DNA sequence changes that may account for the biological fitness of particular strains to different diseases and animal hosts. The outcomes of this thesis have considerably expanded our knowledge of the genetic and evolutionary diversity of this common pathogen.
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Libri sul tema "Tissue specificity"

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service), ScienceDirect (Online, a cura di. Tissue-specific vascular endothelial signals and vector targeting. Amsterdam: Elsevier, 2009.

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Shulman, S. Tissue Specificity and Autoimmunity. Springer, 2011.

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The tissue-specificity of lymphocyte migration into inflamed tissues: A comparative study of synovium, skin and bowel. Ottawa: National Library of Canada = Bibliothèque nationale du Canada, 1991.

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Petzold, Axel. Tissue Biomarkers and Neuroprotection. A cura di David L. Reich, Stephan Mayer e Suzan Uysal. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190280253.003.0004.

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This chapter reviews the evidence for using biomarkers to measure damage to the central nervous system (CNS) in neurocritical care and perioperative medicine. A conceptual framework is provided to guide the optimal timing of blood, cerebrospinal fluid, and structural imaging biomarker assessment in relation to the onset of injury. A selection of well-validated, cell type–specific biomarkers of CNS tissue damage are reviewed, including their composition, biokinetics, and specificity for neurons, axons, astrocytes, and microglia. Each of these biomarkers will be reviewed in the pertinent clinical settings of stroke, traumatic brain injury, cardiac arrest, Guillain-Barré syndrome, and neurological complications of critical illness and surgery.
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Sprouse, Adrienne. Toxins (DRAFT). A cura di Madeleine M. Castellanos. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190225889.003.0010.

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This chapter describes the categories of 300+ environmental chemicals measured in the blood and urine of Americans by the US Centers for Disease Control and Prevention. Some are endocrine-disrupting chemicals (EDCs) and substitute for endogenous hormones in a variety of metabolic processes affecting sexual health, obesity, diabetes, and behavior. The Monotonic Dose-Response (linear dose-response) is inappropriate when evaluating the health consequences of EDCs. Nonmonotonic Dose-Response Curves are better for considering the affinity of the ligand for the receptor, receptor saturation, ligand specificity, and tissue specificity of the receptor distribution. These factors combine to explain why ambient levels of many environmental chemicals cause damage to tissues or development and why low-level exposures can create disease different from higher level exposures. Exposure during critical stages of fetal development may cause permanent changes not apparent until adulthood. Environmental chemicals that are not EDCs may harm by altering genetic material and causing apoptosis.
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Kasprzak, Jaroslaw D., Anita Sadeghpour e Ruxandra Jurcut. Doppler echocardiography. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198726012.003.0003.

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Doppler examination is an integral part of the echocardiogram. Current systems are equipped with spectral Doppler in continuous wave mode (offering measurements of high velocities with limited spatial specificity due to integration of signal along the scan line), pulsed wave mode (high spatial specificity with maximal recordable velocity reduced by the Nyquist limit), and colour Doppler flow mapping (allowing rapid identification of flow pattern within a cross-sectional B-mode sector). Tissue Doppler echocardiography emerged as a basic tool for sampling regional myocardial velocities, in pulsed wave or colour velocity mapping mode. Finally, three-dimensional systems improve spatial presentation of flow phenomena by integrating Doppler-derived flow patterns in three-dimensional datasets.
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Freifeld, Alison G. An Introduction. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199938568.003.0100.

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This chapter focuses on solid tumors and how they can be treated. Solid tumors, lymphomas, and leukemias represent a widely diverse array of cancers. Until recently, the general approach to treating all of them was to administer cytotoxic anticancer drugs that damage proliferating cells by interfering with mitosis and other essential steps in cellular replication. Localized solid tumors are largely treated by surgical resection and radiotherapy, with cytotoxic chemotherapy being commonly used adjunctively or in cases of metastatic disease. A major drawback of this approach has been the lack of specificity in that cytotoxic drugs will destroy actively dividing normal cells as well as malignant cells. The “shotgun approach” of using intensive cytotoxic chemotherapies has been the mainstay of cancer treatment for at least 6 decades. The chapter concludes that in addition to the tissue damage and immunomodulating effects of anticancer drugs, it should be remembered that cancers themselves may increase the chances for infection.
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Yilmaz, Ali, e Anca Florian. Myocarditis: imaging techniques. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0367.

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The clinical presentation of myocarditis is multifaceted and electrocardiogram (ECG) changes as well as biomarkers tend to be non-specific. Therefore, the diagnosis of myocarditis can be challenging and should be based on an integrated approach including patient history, physical examination, non-invasive tests such as ECG and serum biomarkers, and non-invasive cardiac imaging. As myocarditis may lead to global ventricular dysfunction, regional wall motion abnormalities, and/or diastolic dysfunction, echocardiography should be routinely performed. However, hallmarks of acute myocarditis comprise structural changes such as cardiomyocyte swelling, an increase in extracellular space and water content, accumulation of inflammatory cells, potential necrosis or apoptosis of cardiomyocytes, and myocardial remodelling with fibrotic tissue replacement that can be depicted by cardiovascular magnetic resonance. Nuclear techniques are still not routinely recommended for the work-up of myocarditis—with the possible exception of suspected sarcoidosis—due to limited data, limited diagnostic specificity, limited availability, and risk from radiation exposure. This chapter focuses on those non-invasive cardiac imaging techniques that are used in daily clinical practice for work-up of suspected myocarditis. However, as research continues and novel imaging techniques become available, it is hoped that even more accurate and timely diagnosis of myocarditis will be possible in the near future.
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Hayashi, Daichi, Ali Guermazi e Frank W. Roemer. Radiography and computed tomography imaging of osteoarthritis. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0016.

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Osteoarthritis (OA) is the most prevalent joint disorder in the elderly worldwide and there is still no effective treatment, other than joint arthroplasty for end-stage OA, despite ongoing research efforts. Imaging is essential for assessing structural joint damage and disease progression. Radiography is the most widely used first-line imaging modality for structural OA evaluation. Its inherent limitations should be noted including lack of ability to directly visualize most OA-related pathological features in and around the joint, lack of sensitivity to longitudinal change and missing specificity of joint space narrowing, and technical difficulties regarding reproducibility of positioning of the joints in longitudinal studies. Magnetic resonance imaging (MRI) is widely applied in epidemiological studies and clinical trials. Computed tomography (CT) is an important additional tool that offers insight into high-resolution bony anatomical details and allows three-dimensional post-processing of imaging data, which is of particular importance for orthopaedic surgery planning. However, its major disadvantage is limitations in the assessment of soft tissue structures compared to MRI. CT arthrography can be useful in evaluation of focal cartilage defects or meniscal tears; however, its applicability may be limited due to its invasive nature. This chapter describes the roles and limitations of both conventional radiography and CT, including CT arthrography, in clinical practice and OA research. The emphasis is on OA of the knee, but other joints are also mentioned where appropriate.
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Schwitter, Juerg, e Jens Bremerich. Cardiac magnetic resonance in the intensive and cardiac care unit. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0023.

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Current applications of cardiac magnetic resonance offer a wide spectrum of indications in the setting of acute cardiac care. In particular, cardiac magnetic resonance is helpful for the differential diagnosis of chest pain by the detection of ischaemia, myocardial stunning, myocarditis, and pericarditis. Also, Takotsubo cardiomyopathy and acute aortic diseases can be evaluated by cardiac magnetic resonance and are important differential diagnoses in patients with acute chest pain. In patients with restricted windows for echocardiography, according to guidelines, cardiac magnetic resonance is the method of choice to evaluate complications of an acute myocardial infarction. In an acute myocardial infarction, cardiac magnetic resonance allows for a unique characterization of myocardial damage by quantifying necrosis, microvascular obstruction, oedema (i.e. area at risk), and haemorrhage. These features will help us to understand better the pathophysiological events during infarction and will also allow us to assess new treatment strategies in acute myocardial infarction. To which extent the information on tissue damage will guide patient management is not yet clear, and further research, e.g. in the setting of the European Cardiovascular MR registry, is ongoing to address this issue. Recent studies also demonstrated the possiblity to reduce costs in the management of acute coronary syndromes when cardiac magnetic resonance is integrated into the routine work-up. In the near future, applications of cardiac magnetic resonance will continue to expand in the acute cardiac care units, as manufacturers are now strongly focusing on this aspect of user-friendliness. Finally, in the next decade or so, magnetic resonance imaging of other nuclei, such as fluorine and carbon, might become a reality in clinics, which would allow for metabolic and targeted molecular imaging with excellent sensitivity and specificity.
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Capitoli di libri sul tema "Tissue specificity"

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Fameli, Nicola, A. Mark Evans e Cornelis van Breemen. "Tissue Specificity". In Store-operated Ca2+ entry (SOCE) pathways, 231–47. Vienna: Springer Vienna, 2011. http://dx.doi.org/10.1007/978-3-7091-0962-5_16.

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Blatter, Lothar A. "Tissue Specificity". In Store-operated Ca2+ entry (SOCE) pathways, 249–63. Vienna: Springer Vienna, 2011. http://dx.doi.org/10.1007/978-3-7091-0962-5_17.

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Stone, T. W., e H. A. Simmonds. "Tissue specificity of purine metabolism". In Purines: Basic and Clinical Aspects, 23–50. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3911-3_3.

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Orfanos, Stylianos E., Linhua Zou e John D. Catravas. "Pharmacodynamics, tissue-specificity of ACE inhibitors". In ACE Inhibitors, 163–70. Basel: Birkhäuser Basel, 2001. http://dx.doi.org/10.1007/978-3-0348-7579-0_12.

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Zipori, Dov. "Stem Cells with No Tissue Specificity". In Biology of Stem Cells and the Molecular Basis of the Stem State, 57–108. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60761-130-1_3.

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Phinney, B. O., C. R. Spray, Y. Suzuki e P. Gaskin. "Gibberellin Metabolism in Maize: Tissue Specificity". In Gibberellins, 22–31. New York, NY: Springer New York, 1991. http://dx.doi.org/10.1007/978-1-4612-3002-1_3.

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Freitas, Maria João, Daniela Patrício e Margarida Fardilha. "Sperm Signaling Specificity: From Sperm Maturation to Oocyte Recognition". In Tissue-Specific Cell Signaling, 257–77. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-44436-5_9.

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Madison, Edwin L. "Substrate Specificity of Tissue Type Plasminogen Activator". In Advances in Experimental Medicine and Biology, 109–21. Boston, MA: Springer US, 1997. http://dx.doi.org/10.1007/978-1-4615-5391-5_11.

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Botelho, Lynne H. Parker, Christina Cade, Penny E. Phillips e Gabor M. Rubanyi. "Tissue Specificity of Endothelin Synthesis and Binding". In Endothelin, 72–102. New York, NY: Springer New York, 1992. http://dx.doi.org/10.1007/978-1-4614-7514-9_6.

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Ryan, Clarence A. "Proteinase Inhibitor Gene Families: Tissue Specificity and Regulation". In Plant Gene Research, 223–33. Vienna: Springer Vienna, 1988. http://dx.doi.org/10.1007/978-3-7091-6950-6_12.

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Atti di convegni sul tema "Tissue specificity"

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Majumder, S. K., A. Uppal e P. K. Gupta. "Nitrogen Laser Excited Autofluorescence Spectroscopy for Discrimination of Human Breast Malignancy". In Biomedical Optical Spectroscopy and Diagnostics. Washington, D.C.: Optica Publishing Group, 2006. http://dx.doi.org/10.1364/bosd.1996.ft3.

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The results of our in-vitro studies on N2 laser excited autofluorescence from pathologically characterized cancerous and adjoining normal human breast tissues obtained after resection from 15 patients with breast cancer are presented. A 6-variable multivariate linear regression (MVLR) analysis used for maximizing discrimination between tissue types resulted in a sensitivity of 85.5% and a specificity of 87.07% towards cancer for unpaired comparison and a sensitivity of 93.1% and specificity of 87.1% for paired comparison of the tissue spectra.
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Wang, Yan. "Tissue and Drug Specificity of Drug Sensitivities in Different Cancer Cell Lines". In ICCBB '21: 2021 5th International Conference on Computational Biology and Bioinformatics. New York, NY, USA: ACM, 2021. http://dx.doi.org/10.1145/3512452.3512462.

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Stepp, Herbert, e Alexander Hohla. "Clinical results with UV-excited autofluorescence spectroscopy in different organs". In European Conference on Biomedical Optics. Washington, D.C.: Optica Publishing Group, 2001. http://dx.doi.org/10.1364/ecbo.2001.4432_221.

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UV-excitation with 308 nm was applied clinically to normal and diseased tissues from the urinary bladder, the brain and the lungs. With a multifiber catheter, fluorescence spectra were recorded and evaluated using the most significant wavelength ratios. Correlation with histology showed the following sensitivities / specificities for the detection of malignant tissue: bladder 90% / 81%, brain 62% / 100%, lungs 80% / 76%. Compared to 5-ALA induced PPIX-fluorescence (bladder), a higher specificity was observed. The results obtained intraoperatively were compared with UV-imaging and spectroscopy on frozen tissue sections.
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Moore, Amanda R., Jason Liang, Robert Piskol, Lisa McGinnis, Donald S. Kirkpatrick e Shiva Malek. "Abstract 2923:RAS-mutant mouse models confirm tissue-specificity and reveal unique oncogenic activity of KrasQ61R". In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-2923.

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Fanous, Michael J., Gabriel Popescu, Chuqiao Shi, Megan Caputo, Laurie Rund, Rodney Johnson, Tapas Das, Matthew Kuchan e Nahil Sobh. "Label-free screening of myelin distribution in brain tissue using phase imaging with computational specificity (PICS)". In Quantitative Phase Imaging VII, a cura di Gabriel Popescu, YongKeun Park e Yang Liu. SPIE, 2021. http://dx.doi.org/10.1117/12.2584463.

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Sakakura, Masayoshi, Sohelia Borhani, Virgilia Macias, Andre Kajdacsy-Balla e Gabriel Popescu. "Label-free imaging of collagen fibers in tissue slices using phase imaging with computational specificity (PICS)". In Quantitative Phase Imaging VIII, a cura di Gabriel Popescu, YongKeun Park e Yang Liu. SPIE, 2022. http://dx.doi.org/10.1117/12.2616616.

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Dattamajumdar, A. K., D. Wells, J. Parnell, D. Ganguly e T. C. Wright. "Preliminary results from multi-center clinical trials for detection of cervical squamous intraepithelial lesions using a novel full-field evoked tissue fluorescence based imaging instrument". In European Conference on Biomedical Optics. Washington, D.C.: Optica Publishing Group, 2001. http://dx.doi.org/10.1364/ecbo.2001.4432_312.

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We report preliminary results from a multi-center trial of evaluating the performance of a novel, full-field multispectral tissue fluorescence imaging system (Cerviscan™) designed to detect cervical squamous intraepithelial lesions. Spectral data from multiple regions of 48 patients enrolled from clinical performance sites in the US and Canada are included in this preliminary analysis. This includes 30 women used for the training set and 18 use for the testing set. In the testing set, 37/43 SIL and 70/80 NonSIL regions were correctly identified for a sensitivity of 86% and specificity of 87.5%. Cerviscan™ locates cervical precancerous lesions with high sensitivity and specificity and has the potential to permit ‘see and treat’ patient management.
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Prassas, Ioannis, Shalini Makawita e Eleftherios Diamandis. "Abstract 5075: An integratedin silicoand proteomic approach towards the identification of novel cancer biomarkers based on tissue specificity". In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-5075.

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Fanous, Michael J., Gabriel Popescu e masayoshi sakakuru. "Digital histopathology of tumor associated collagen signatures (TACS) in breast cancer tissue using phase imaging with computation specificity (PICS)". In Quantitative Phase Imaging VIII, a cura di Gabriel Popescu, YongKeun Park e Yang Liu. SPIE, 2022. http://dx.doi.org/10.1117/12.2615275.

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Pickard, David C. O., Irving J. Bigio, Stephen G. Bown, Gavin M. Briggs, Andrew C. Lee, Paul M. Ripley e Sunil Lakhani. "Optical Biopsy for the Diagnosis of Breast Tumours". In European Conference on Biomedical Optics. Washington, D.C.: Optica Publishing Group, 2001. http://dx.doi.org/10.1364/ecbo.2001.4432_143.

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Elastic scattering or spectroscopy offers the possibility of distinguishing between cancerous and noncancerous tissue in suspicious breast lumps with a relatively simple optical measurement. The measurement of the relative reflection of light has previously been shown to be sensitive to both the size and distribution of intra and intercellular structures as well as absorption from chromophores present in the tissue. Coupling a white tight source and spectrometer to optic fibres makes it possible to construct probes that can be inserted through the skin or used during the operation or on excised tissue such as the sentinel node. This ‘optical biopsy' is correlated with a conventional histopathological specimen obtained at the same point. Spectra have been obtained from a large number of patients with benign and malignant lesions. Some of the differences that appear in these spectra have been identified and these are discussed. To a relatively high degree of sensitivity and specificity it is shown to be possible to distinguish between malignant tumours, benign lesions and normal tissue.
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Rapporti di organizzazioni sul tema "Tissue specificity"

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Shani, Moshe, e C. P. Emerson. Genetic Manipulation of the Adipose Tissue via Transgenesis. United States Department of Agriculture, aprile 1995. http://dx.doi.org/10.32747/1995.7604929.bard.

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The long term goal of this study was to reduce caloric and fat content of beef and other red meats by means of genetic modification of the animal such that fat would not be accumulated. This was attempted by introducing into the germ line myogenic regulatory genes that would convert fat tissue to skeletal muscle. We first determined the consequences of ectopic expression of the myogenic regulatory gene MyoD1. It was found that deregulation of MyoD1 did not result in ectopic skeletal muscle formation but rather led to embryonic lethalities, probably due to its role in the control of the cell cycle. This indicated that MyoD1 should be placed under stringent control to allow survival. Embryonic lethalities were also observed when the regulatory elements of the adipose-specific gene adipsin directed the expression of MyoD1 or myogenin cDNAs, suggesting that these sequences are probably not strong enough to confer tissue specificity. To determine the specificity of the control elements of another fat specific gene (adipocyte protein 2-aP2), we fused them to the bacterial b-galactosidase reporter gene and established stable transgenic strains. The expression of the reporter gene in none of the strains was adipose specific. Each strain displayed a unique pattern of expression in various cell lineages. Most exciting results were obtained in a transgenic strain in which cells migrating from the ventro-lateral edge of the dermomyotome of developing somites to populate the limb buds with myoblasts were specifically stained for lacZ. Since the control sequences of the adipsin or aP2 genes did not confer fat specificity in transgenic mice we have taken both molecular and genetic approaches as an initial effort to identify genes important in the conversion of a multipotential cell such as C3H10T1/2 cell to adipoblast. Several novel adipocyte cell lines have been established that differ in the expression of transcription factors of the C/EBP family known to be markers for adipocyte differentiation. These studies revealed that one of the genetic programming changes which occur during 10T1/2 conversion from multipotential cell to a committed adipoblast is the ability to linduce C/EBPa gene expression. It is expected that further analysis of this gene would identify elements which regulate this lineage-specific expression. Such elements might be good candidates in future attempts to convert adipoblasts to skeletal muscle cells in vivo.
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Levy, Avraham A., e Virginia Walbot. Regulation of Transposable Element Activities during Plant Development. United States Department of Agriculture, agosto 1992. http://dx.doi.org/10.32747/1992.7568091.bard.

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We have studied the regulation of the maize Ac and MuDR transposable elements activities during plant development. Ac was studied in an heterologous system (transgenic tobacco plants and cell suspensions) while MuDR was studied in the native maize background. The focus of this study was on the transcriptional regulation of Ac and MuDR. For Ac, the major achievements were to show that 1-It is autoregulated in a way that the Ac-encoded transposase can repress the activity of its own promoter; 2-It is expressed at low basal level in all the plant organs that were studied, and its activity is stronger in dividing tissues -- a behaviour reminiscent of housekeeping genes; 3- the activity of Ac promoter is cell cycle regulated -- induced at early S-phase and increasing until mitosis; 4- host factor binding sites were identified at both extremities of Ac and may be important for transposition. For MuDR, It was shown that it encodes two genes, mudrA and mudrB, convergently transcribed from near-identical promoters in the terminal inverted repeats. Distinct 5' start sites, alternative splicing, production of antisense RNA and tissue specificity were all shown to be involved in the regulation of MuDR.
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Rafaeli, Ada, Russell Jurenka e Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, gennaio 2008. http://dx.doi.org/10.32747/2008.7695862.bard.

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The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.
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Elizur, Abigail, Amir Sagi, Gideon Hulata, Clive Jones e Wayne Knibb. Improving Crustacean Aquaculture Production Efficiencies through Development of Monosex Populations Using Endocrine and Molecular Manipulations. United States Department of Agriculture, giugno 2010. http://dx.doi.org/10.32747/2010.7613890.bard.

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Background Most of Australian prawn aquaculture production is based on P. monodon. However, the Australian industry is under intense competition from lower priced overseas imports. The availability of all-female monosex populations, by virtue of their large size and associated premium prize, will offer competitive advantage to the industry which desperately needs to counteract competitors within this market. As for the redclaw production in Israel, although it is at its infancy, the growers realized that the production of males is extremely advantageous and that such management strategy will change the economic assumptions and performances of this aquaculture to attract many more growers. Original objectives (as in original proposal) Investigating the sex inheritance mechanism in the tiger prawn. Identification of genes expressed uniquely in the androgenic gland (AG) of prawns and crayfish. The above genes and/or their products will be used to localize the AG in the prawn and manipulate the AG activity in both species. Production of monosex populations through AG manipulation. In the prawn, production of all-female populations and in the crayfish, all-male populations. Achievements In the crayfish, the AG cDNA library was further screened and a third AG specific transcript, designated Cq-AG3, had been identified. Simultaneously the two AG specific genes, which were previously identified, were further characterized. Tissue specificity of one of those genes, termed Cq-AG2, was demonstrated by northern blot hybridization and RNA in-situ hybridization. Bioinformatics prediction, which suggested a 42 amino acid long signal anchor at the N-terminus of the deduced Cq-AG2, was confirmed by immunolocalization of a recombinant protein. Cq-IAG's functionality was demonstrated by dsRNA in-vivo injections to intersex crayfish. Cq-IAGsilencing induced dramatic sex-related alterations, including male feature feminization, reduced sperm production, extensive testicular apoptosis, induction of the vitellogeningene expression and accumulation of yolk proteins in the ovaries. In the prawn, the AG was identified and a cDNA library was created. The putative P. monodonAG hormone encoding gene (Pm-IAG) was identified, isolated and characterized for time of expression and histological localization. Implantation of the AG into prawn post larvae (PL) and juveniles resulted in phenotypic transformation which included the appearance of appendix masculina and enlarged petasma. The transformation however did not result in sex change or the creation of neo males thus the population genetics stage to be executed with Prof. Hulata did not materialized. Repeated AG implantation is currently being trialed. Major conclusions and Implications, both scientific and agricultural Cq-IAG's involvement in male sexual differentiation had been demonstrated and it is strongly suggested that this gene encodes an AG hormone in this crayfish. A thorough screening of the AG cDNA library shows Cq-IAG is the prominent transcript within the library. However, the identification of two additional transcripts hints that Cq-IAG is not the only gene mediating the AG effects. The successful gene silencing of Cq-IAG, if performed at earlier developmental stages, might accomplish full and functional sex reversal which will enable the production of all-male crayfish populations. Pm-IAG is likely to play a similar role in prawns. It is possible that repeated administration of the AG into prawn will lead to the desired full sex reversal, so that WZ neo males, crossed with WZ females can result in WW females, which will form the basis for monosex all-female population.
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Freeman, Stanley, e Daniel Legard. Epidemiology and Etiology of Colletotrichum Species Causing Strawberry Diseases. United States Department of Agriculture, settembre 2001. http://dx.doi.org/10.32747/2001.7695845.bard.

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Abstract (sommario):
Diseases caused by Colletotrichum spp. are one of the most important limitations on international strawberry production, affecting all vegetative and fruiting parts of the plant. From 1995 to 1997, C. acutatum infections reached epidemic levels in Israeli strawberry nurseries, causing extensive loss of transplants in fruit-bearing fields and additional reductions in yield. Although C. acutatum also occurs on strawberry in Florida, recent crown rot epidemics have been primarily caused by C. gloeosporioides. Little is known about the basic epidemiology of these important diseases on strawberry. The source of initial inoculum for epidemics in Israel, Florida (other US states including California) and the rest of the world is not well understood. Subspecies relationships between Colletotrichum isolates that cause the different diseases on strawberry (i.e. attack different tissues) are also not well understood. Objectives of this proposal were to detennine the potential of infested soil, strawberry debris and other hosts as sources of primary inoculum for strawberry diseases caused by Colletotrichum spp. in Israel and Florida. In addition, traditional (ie. morphological characteristics, benomyl sensitivity, vegetative compatibility grouping) and DNA based methods were used to investigate the etiology of these diseases in order to resolve epidemiologically important subspecies variation. In Israel it was found that C. gloeosporioides and C. acutatum infecting strawberry could remain viable in sterilized soil for up to one year and in methyl-bromide fumigated soil for up to 4 months; inoculum in mummified fruit remained viable for at least 5 months under field conditions whereas that in infected crowns was not recovered. Therefore, the contribution of these inocula to disease epidemics should be considered. The host range and specificity of C. acutatum from strawberry was examined on pepper, eggplant, tomato, bean and strawberry under greenhouse conditions. The fungus was recovered from all plant species over a three-month period but caused disease symptoms only on strawberry. C. acutatum was also isolated from healthy looking, asymptomatic plants of the weed species, Vicia and Conyza, growing in infected strawberry fruiting fields. Isolates of C. acutatum originating from strawberry and anemone infected both plant species in artificial inoculations. The habitation of a large number of plant species including weeds by C. acutatum suggests that although it causes disease only on strawberry and anemone in Israel, these plants may serve as a potential inoculum source for strawberry infection and pennit survival of the pathogen between seasons. In Florida, isolates of Colletotrichum spp. from diseased strawberry fruit and crowns were evaluated to detennine their etiology and the genetic diversity of the pathogens. Only C. acutatum was recovered from fruit and C. gloeosporioides were the main species recovered from crowns. These isolates were evaluated at 40 putative genetic loci using random amplified polymorphic DNA (RAPD). Genetic analysis of RAPD markers revealed that the level of linkage disequilibrium among polymorphic loci in C. gloeosporioides suggested that they were a sexually reproducing population. Under field conditions in Florida, it was detennined that C. gloeosporioides in buried crowns survived
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Savaldi-Goldstein, Sigal, e Todd C. Mockler. Precise Mapping of Growth Hormone Effects by Cell-Specific Gene Activation Response. United States Department of Agriculture, dicembre 2012. http://dx.doi.org/10.32747/2012.7699849.bard.

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Abstract (sommario):
Plant yield largely depends on a complex interplay and feedback mechanisms of distinct hormonal pathways. Over the past decade great progress has been made in elucidating the global molecular mechanisms by which each hormone is produced and perceived. However, our knowledge of how interactions between hormonal pathways are spatially and temporally regulated remains rudimentary. For example, we have demonstrated that although the BR receptor BRI1 is widely expressed, the perception of BRs in epidermal cells is sufficient to control whole-organ growth. Supported by additional recent works, it is apparent that hormones are acting in selected cells of the plant body to regulate organ growth, and furthermore, that local cell-cell communication is an important mechanism. In this proposal our goals were to identify the global profile of translated genes in response to BR stimulation and depletion in specific tissues in Arabidopsis; determine the spatio-temporal dependency of BR response on auxin transport and signaling and construct an interactive public website that will provide an integrated analysis of the data set. Our technology incorporated cell-specific polysome isolation and sequencing using the Solexa technology. In the first aim, we generated and confirmed the specificity of novel transgenic lines expressing tagged ribosomal protein in various cell types in the Arabidopsis primary root. We next crossed these lines to lines with targeted expression of BRI1 in the bri1 background. All lines were treated with BRs for two time points. The RNA-seq of their corresponding immunopurified polysomal RNA is nearly completed and the bioinformatic analysis of the data set will be completed this year. Followed, we will construct an interactive public website (our third aim). In the second aim we started revealing how spatio-temporalBR activity impinges on auxin transport in the Arabidopsis primary root. We discovered the unexpected role of BRs in controlling the expression of specific auxin efflux carriers, post-transcriptionally (Hacham et al, 2012). We also showed that this regulation depends on the specific expression of BRI1 in the epidermis. This complex and long term effect of BRs on auxin transport led us to focus on high resolution analysis of the BR signaling per se. Taking together, our ongoing collaboration and synergistic expertise (hormone action and plant development (IL) and whole-genome scale data analysis (US)) enabled the establishment of a powerful system that will tell us how distinct cell types respond to local and systemic BR signal. BR research is of special agriculture importance since BR application and BR genetic modification have been shown to significantly increase crop yield and to play an important role in plant thermotolerance. Hence, our integrated dataset is valuable for improving crop traits without unwanted impairment of unrelated pathways, for example, establishing semi-dwarf stature to allow increased yield in high planting density, inducing erect leaves for better light capture and consequent biomass increase and plant resistance to abiotic stresses.
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Friedmann, Michael, Charles J. Arntzen e Hugh S. Mason. Expression of ETEC Enterotoxin in Tomato Fruit and Development of a Prototype Transgenic Tomato for Dissemination as an Oral Vaccine in Developing Countries. United States Department of Agriculture, marzo 2003. http://dx.doi.org/10.32747/2003.7585203.bard.

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Abstract (sommario):
The broad objective of the project was to develop a feasible approach to combat diarrheal disease caused by ETEC through the development of a low-cost oral immunogen in tomato fruit, expressed in the context of a prototype tomato that would answer the shortcomings of plant oral vaccines, especially in terms of produce handling and control of gene escape. Specifically, the goals for Boyce Thompson Institute (BTI) on this project were to develop transgenic tomato lines that express the enterotoxigenic E. coli (ETEC) heat-labile enterotoxin (LT) subunits A and/or B for use in oral edible vaccines, and to optimize expression and assembly of these antigens in tomato fruits.LT-B is a useful vaccine antigen against ETEC disease, since antibodies against LT-B can prevent binding and delivery of the holotoxinLT. Mutant forms of the toxic LT-A subunit that have reduced toxicity can be co-expressed and assembled with LT-Bpentamers to form mutant LT (mLT) complexes that could be used as mucosaladjuvants for other oral vaccines. Work on the project is continuing at Arizona State University, after Dr. Mason moved there in August 2002. A number of approaches were taken to ensure the expression of both subunits and bring about their assembly inside the transgenic fruits. Initially, expression was driven by the fruit-specific E-8 promoter for LT-B and the constitutive CaMV 35S promoter for LT-A(K63). While LT-B accumulated up to 7 µg per gram ripe fruit, assembled LT-K63 was only 1 µg per gram. Since promoter activities for the two genes likely differed in cell type and developmental stage specificity, the ratios of A and B subunits was not optimal for efficient assembly in all cells. In order to maximize the chance of assembly of mLT in fruit, we focused on constructs in which both genes are driven by the same promoter. These included co-expression plasmids using the 35S promoter for both, while switching to attenuated mLTs (LT-R72 and LT-G192) that have shown greater potential for oral adjuvanticity than the initial LT-K63, and thus are better candidates for a plant-derived adjuvant. Other, more novel approaches were then attempted, including several new vectors using the tomato fruit-specific E8 promoter driving expression of both LT-B and mutant LT-A, as well as a dicistronic construct for co-expression of both LT-B and mutant LT-A genes from a single promoter, and a geminivirusreplicon construct. We describe in the Appendix the results obtained in transgenic tomato lines transformed with these constructs. Overall, each contributed to enhanced expression levels, but the assembly itself of the holotoxin to high levels was not observed in the fruit tissues. The Israeli lab’s specific objective was to develop transgenic tomato lines expressing the LTholotoxin antigen bearing attributes to prevent gene escape (male sterility and orange fruit color) and to improve the dissemination of the oral vaccine (long shelf-life tomato cherry fruit or tomato processing background). Breeding lines bearing a number of attributes to prevent gene escape were developed by combining material and backcrossing either to a tomato cherry background, or two different processing backgrounds. Concomitantly, (these lines can be utilized for the creation of any future oral vaccine or other therapeutic-expressing tomato, either by crosses or transformation), the lines were crossed to the holotoxin-expressing tomatoes received from the United States, and this transgenic material was also incorporated into the backcrossing programs. To date, we have finalized the preparation of the cherry tomato material, both non-transgenic (bearing all the desired attributes), and transgenic, expressing the holotoxin. The level of expression of LT-B in the cherry fruits was comparable to the original transgenic tomatoes. Since it was not higher, this would necessitate the consumption of more fruits to reach a desired dose. A final backcross has been made for both the non-transgenic and the transgenic material in the processing lines. Auxin sprays resulted in high percentages of fruit set, but the processing genotypes gave many puffed fruits.
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