Regulatory interplay between pap operons in uropathogenic Escherichia coli

Pathogenic bacteria have a large repertoire of surface organelles involved in adherence, motility and protein export, but how individual bacteria co-ordinate surface organelle expression to prevent interference and excessive immune stimulation is unclear. Phase variation is a mechanism by which expression of surface factors is limited to a fraction of the bacterial population; however, the presence of multiple homologous surface structures controlled by related mechanisms and regulators antagonizes the independent expression achieved by phase variation. To investigate whether other mechanisms have evolved to sort out the bacterial cell surface, we examined regulatory cross-talk between multiple phase-variable pyelonephritis-associated pili (pap) operons in Escherichia coli isolates associated with urinary tract infections. Allelic variation identified in the regulatory regions and regulators acts synergistically to limit coexpression of homologous fimbrial operons. In particular, there is evidence that papI is under positive selection and PapI variants displayed differences in their capacity to activate related pap operons. Alleles of the high-affinity binding site for PapB were shown to contain a variable number of (T/A)3 repeats occurring every 9 bp that altered the sensitivity of pap operon activation. Taken together with other examples of surface organelle cross-talk, we illustrate how this regulation could promote sequential expression.

Molecular and Clinical Characteristics of Pituitary Adenoma Predisposition (PAP)

Pituitary adenomas are common benign neoplasms. Although most of them are sporadic, a minority occurs in familial settings. Heterozygous germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were found to underlie familial pituitary adenomas, a condition designated as pituitary adenoma predisposition (PAP). PAP confers incomplete penetrance of mostly growth hormone (GH) secreting adenomas in young patients, who often lack a family history of pituitary adenomas. This thesis work aimed to clarify the molecular and clinical characteristics of PAP. Applying the multiplex ligation-dependent probe amplification assay (MLPA), we found large genomic AIP deletions to account for a subset of PAP. Therefore, MLPA could be considered in PAP suspected patients with no AIP mutations found with conventional sequencing. We generated an Aip mouse model to examine pituitary tumorigenesis in vivo. The heterozygous Aip mutation conferred complete penetrance of pituitary adenomas that were mostly GH-secreting, rendering the phenotype of the Aip mouse similar to that of PAP patients. We suggest that AIP may function as a candidate gatekeeper gene in somatotrophs. To clarify molecular mechanisms of tumorigenesis, we elucidated the expression of AIP-related molecules in human and mouse pituitary tumors. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT) was reduced in mouse Aip-deficient adenomas, and similar ARNT reduction was also evident in human AIP mutation positive adenomas. This suggests that in addition to participating in the hypoxia pathway, estrogen receptor signaling and xenobiotic response pathways, ARNT may play a role in AIP-related tumorigenesis. We also studied the characteristics and the response to therapy of PAP patients and found them to have an aggressive disease phenotype with young age at onset. Therefore, improvement in treatment outcomes of PAP patients would require their efficient identification and earlier diagnosis of the pituitary adenomas. The possible role of the RET proto-oncogene in tumorigenesis of familial AIP mutation negative pituitary adenomas was evaluated, but none of the found RET germline variants were considered pathogenic. Surprisingly, RET immunohistochemistry suggested possible underexpression of RET in AIP mutation positive pituitary adenomas an observation that merits further investigation.

Sphaerotilus natans: description of the morphology, growth and systematics of [Translation from: Schr. Ver. Zellstoff u. Pap.-Chem. u. -Ing., 26, 20-37, 1956]

The morphology, increase and systematica of Sphaerotilus natans is studied and culture methods examined.

IL15／PAP融合蛋白基因克隆及其原核与植物表达载体的构建

将IL15和PAP基因通过一甘氨酸接头（Gly4Ser）3连接在一起，构建原核和植物表达载体，以期表达具有导向杀伤活性的融合蛋白．在引物设计中，通过引物在IL15基因下游引入（Gly4Ser）3的编码序列和Bam HI位点，然后采取分步克隆及PCR、酶切、连接等一系列分子克隆方法，将IL15和PAP基因融合在一起，构建融合蛋白的原核与植物表达载体．经PCR和Nco Ⅰ／Sal Ⅰ双酶切鉴定及测序，证实原核表达载体pET32a-IL15／PAP及植物表达载体pB-ⅠP中均插入了正确的融合基因序列．

Técnicas e soluções para remoção da Smear Layer

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária

Pap Test Fact Sheet

This paper, written in English and Spanish, tells what a pap test is and what the test results mean.

Prova de Aptidão Profissional (PAP) : um universo de possibilidades de intervenção a descobrir

Trabalho de projeto de mestrado, Ciências da Educação (Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2014

Correlación entre la citología cérvico-vaginal por el método de papanicolau y el reporte de anatomía patológica en pacientes histeroctomizadas con pap anormal [por] Felizardo Eizondo Yzaguirre

Tesis (Especialidad en Ginecología y Obstetricia). U. A. N. L.

Gabriel el cerrajero. Las hijas de mi papá, por Facundo

UANL

Étude de la variation de phase des fimbriae F1651, Pap et CS31A et de l'impact des régulateurs homologues de PapI

Les Escherichia coli pathogènes extra-intestinaux (ExPEC) sont responsables d’une grande variété de maladies. Plus particulièrement, certaines souches ExPEC, du sous-groupe d’E. coli uropathogènes, sont porteuses de fimbriae de type P. Cette famille d’adhésines est soumise à une régulation transcriptionnelle appelée variation de phase; un mécanisme du tout ou rien. Il s’agit d’une compétition entre deux protéines régulatrices : la Dam méthylase et la nucléoprotéine Lrp. Ce mécanisme est aussi soumis à l’influence des régulateurs locaux PapB et PapI, deux régulateurs essentiels. Afin d’étudier PapI et ses homologues ainsi que leur impact sur la variation de phase des fimbriae F1651, Pap et CS31A. Grâce à une fusion chromosomique entre la région régulatrice de clp et les gènes lacZYA, nous avons étudié l’effet, en trans, de PapI et FooI qui ont pu restaurer la variation de phase avec une forte tendance pour la phase OFF. Pour étudier l’action de ces protéines sur foo et pap, nous avons utilisé un système utilisant gfp comme gène rapporteur de l’activité des promoteurs des opérons pap et foo. Cela a permis d’observer la variation de phase au niveau cellulaire par cytométrie en flux et en temps réel par microscopie à fluorescence. Ces expériences ont confirmé que la population de cellules F1651 positives a un phénotype d’expression de F1651 partielle alors que les cellules Pap sont en majorité en phase OFF. PapI et FooI n’ont pas la même influence sur la variation de phase, puisque FooI favorise une plus grande fréquence de variation de phase.