Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: Involvement of src family protein kinases

The increased production of amyloid beta -peptide (A beta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to A beta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to A beta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar A beta (25-35) and A beta (1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-( 4-chlorophenyl)- 7(t-butyl) pyrazol(3,4-D) pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from A beta (25-35)-treated neurons showed an increased association of Fyn with FAK. A beta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in A beta -treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to A beta exposure and may be critical for subsequent neurodegenerative changes

Immunological characterization of chromogranins A and B and secretogranin II in the bovine pancreatic islet

Antisera against chromogranin A and B and secretogranin II were used for analysing the bovine pancreas by immunoblotting and immunohistochemistry. All three antigens were found in extracts of fetal pancreas by one dimensional immunoblotting. A comparison with the soluble proteins of chromaffin granules revealed that in adrenal medulla and in pancreas antigens which migrated identically in electrophoresis were present. In immunohistochemistry, chromogranin A was found in all pancreatic endocrine cell types with the exception of most pancreatic polypeptide-(PP-) producing cells. For chromogranin B, only a faint immunostaining was obtained. For secretorgranin II, A-and B-cells were faintly positive, whereas the majority of PP-cells exhibited a strong immunostaining for this antigen. These results establish that chromogranins A and B and secretogranin II are present in the endocrine pancreas, but that they exhibit a distinct cellular localization

Glucagon-like peptide-1(7–36) amide is a new incretin/enterogastrone candidate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72032/1/j.1365-2362.1991.tb01802.x.pd

Temporal variation in sex allocation in the mealybug <em>Planococcus citri</em>:Adaptation, constraint, or both?

Sex ratio theory has been very successful in predicting under which circumstances parents should bias their investment towards a particular offspring sex. However, most examples of adaptive sex ratio bias come from species with well-defined mating systems and sex determining mechanisms, while in many other groups there is still an on-going debate about the adaptive nature of sex allocation. Here we study the sex allocation in the mealybug Planococcus citri, a species in which it is currently unclear how females adjust their sex ratio, even though experiments have shown support for facultative sex ratio adjustment. Previous work has shown that the sex ratio females produce changes over the oviposition period, with males being overproduced early and late in the laying sequence. Here we investigate this complex pattern further, examining both the robustness of the pattern and possible explanations for it. We first show that this sex allocation behaviour is indeed consistent across lines from three geographical regions. Second, we test whether females produce sons first in order to synchronize reproductive maturation of her offspring, although our data provide little evidence for this adaptive explanation. Finally we test the age at which females are able to mate successfully and show that females are able to mate and store sperm before adult eclosion. Whilst early-male production may still function in promoting protandry in mealybugs, we discuss whether mechanistic constraints limit how female allocate sex across their lifetime

Visualization and Movement as Configurations of Human-Nonhuman Engagements : Precolonial Geometric Earthwork Landscapes of the Upper Purus, Brazil

Producing geometric designs and images on materials, such as pottery, basketry, and bead artwork, as well as the human body, is elemental and widespread among Amazonian Indigenous peoples. In this article, we examine the different geometric forms identified in the precolonial geoglyph architecture of southwestern Amazonia in the context of geometric design making and relational ontologies. Our aim is to explore earthwork iconography through the lens of Amerindian visual arts and movement. Combining ethnographic and archaeological data from the Upper Purus, Brazil, the article shows how ancient history and socio-cosmology are deeply "written" onto the landscape in the form of geometric earthworks carved out of the soil, which materialize interactions between nonhuman and human actors. We underline skills in visualization, imaginative practices, and movement as ways to promote well-balanced engagements with animated life forms. Here, iconography inserted in the landscape is both a form of writing and also emerges as an agent, affecting people through visual and corporal practices.Peer reviewe

Plasma gut hormone levels in 37 patients with pheochromocytomas

Pheochromocytomas are usually recognized by the effects of overproduction of catecholamines, but there are clinical features that cannot be ascribed to catecholamine excess that may be due to vasoactive peptides. We, therefore, measured blood levels of vasoactive intestinal peptides (VIP), substance P, somatostatin (SS), and motilin in 50 instances in 37 patients with pheochromocytomas-21 malignant, 10 benign intra-adrenal, and 6 ectopic (5 paracardial and 1 perirenal). Hormone levels were considered raised if the level was more than 3 S.D. above the mean value found in 52 healthy subjects. Of the 37 patients, 20 (54%) had an abnormality in 1 or more gut hormone levels. The most common abnormality was a raised SS in 9/37 (24%). In addition to these, however, 3 (8%) others had raised VIP, 5 (13.5%) raised motilin, and 3 (8%) raised substance P. Patients with benign adrenal adenomas had raised levels of SS and substance P. Ectopic pheochromocytomas produced only SS in addition to catecholamines, but malignant pheochromocytomas could secrete all 4 peptides, and more than 1 in the same patient. We conclude that pheochromocytomas may secrete multiple vasoactive peptides, and they are more likely to do so if malignant. Somatostatin is the most commonly secreted peptide and is found with benign adrenal and ectopic (paracardiac) tumors. If the level of more than 1 peptide is elevated, the likelihood of malignancy is significantly increased . Les phéochromocytomes sont généralement déceléspar les effets dûs à la surproduction de catécholamines, mais certains troubles ne peuvent être attribués à ce phénomène et relèvent peut être de l'action de peptides vasoactifs. Les auteurs se sont donc attachés à doser dans le sang le VIP, la substance P, la somatostatine (SS), et la motiline. Ces dosages furent pratiqués 50 fois chez 37 malades porteurs de phéochromocytomes: 21 malins, 10 bénins et 6 ectopiques (5 paracardiaque et 1 péri-rénal). Les taux des hormones furent considérés comme élevés lorsque leur niveau fut supérieur à plus de 3 fois le taux de 52 sujets sains. Sur les 37 malades 20 (54%) présentaient un excès d'une ou de plusieurs hormones digestives. L'anomalie constatée la plus fréquente fut l'élévation de la SS (9 fois sur 37 soit 24%). Ajoutée à ce fait fut l'élévation de la VIP chez 3 sujets (8%), de la motiline chez 5 (13.5%) et de la substance P chez 3 (8%). Les phéochromocytomes bénins surrénaliens présentaient à la fois une élévation du taux de la SS et de la substance P. Les phéochromocytomes ectopiques en revanche présentaient seulement une élévation de la SS. Les phéochromocytomes malins pouvaient sécréter les 4 peptides ou plus d'un chez le même malade. En conclusion les phéochromocytomes peuvent secréter de multiples peptides vasoactifs et plus particulièrement lorsqu'ils sont malins. La SS est la substance qui est la plus souvent secrétée et elle est trouvée dans les tumeurs bénignes surrénaliennes ou ectopiques. Si plus d'une de ces substances est produite en excès les risques de malignité de la tumeur sont significativement plus importants. Los feocromocitomas generalmente son diagnosticados por los efectos del exceso de producción de catecolaminas pero hay características clínicas que no pueden ser atribuidas al exceso de catecolaminas y que pueden ser más bien manifestación de péptidos vasoactivos. Hemos establecido los niveles sanguíneos del péptido intestinal vasoactivo (VIP), de la sustancia P, de la somatostatina (SS), y de la motilina en 50 determinaciones en 37 pacientes con feocromocitomas; 21 malignos, 10 benignos intra-adrenales, y 6 ectópicos (5 paracardiales y 1 perirrenal). Se consideró que los niveles hormonales estaban elevados cuando el nivel era de más de 3 de desviación estandar sobre el valor promedio en 52 individuos normales. De 37 pacientes, 20 (54%) presentaron un valor anormal en 1 o más determinaciones del nivel de hormonas intestinales. La anormalidad más común fue la elevación de la SS en 9/37 (24%). Además de esto, sinembargo, otros 3 (8%) presentaban elevación de VIP, 5 (13.5%) elevación de sustancia P. Los adenomas suprarrenales benignos exhibieron niveles elevados de SS y de sustancia P. Los feocromocitomas ectópicos demostraron producción sólo de SS además de catecolaminas, pero los feocromocitomas malignos demostraron ser capaces de secretar todos los 4 péptidos, y más de 1 en el mismo paciente. Hemos llegado a la conclusión de que los feocromocitomas pueden secretar múltiples peptidos vasoactivos y que ésto tiende a ocurrir cuando son malignos. La SS es el péptido más frecuentemente secretado y se lo encuentra en los tumores suprarrenales benigno y ectópico (paracardiacos). Si se encuentran niveles elevados de más de 1 péptido, la posibilidad de malignidad aparece significativamente aumentada.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41274/1/268_2005_Article_BF01655534.pd

UNPLANNED REPRESENTATION TO HOSPITAL BY PATIENTS WITH DIABETES: DEVELOPMENT AND PILOT FEASIBILITY TESTING OF A SCREENING TOOL.

BackgroundUnplanned representation of patients with diabetes recently discharged from emergency department or in-patient hospitals is a common but complex problem worldwide. This study set out to examine the feasibility of a risk screening interview and whether component characteristics may be associated with unplanned representation of patients with diabetes to a tertiary metropolitan hospital.MethodsA screening interview comprised of demographic, social and clinical characteristics was developed and piloted using prospective cross-sectional survey design. A convenience sample of 55 patients was recruited and screened. Outcomes were the occurrence of unplanned representation to hospital within 28 or 90 days of hospital discharge from the index presentation.ResultsThe screening interview was shown to be broadly feasible and acceptable for use by staff and patients, with identified areas for modification. Seventeen participants (30.9%) experienced unplanned representation within 90 days of hospital discharge; for 13 participants (23.6%) this occurred within 28 days. Characteristics linked with unplanned representation to hospital were identified.ConclusionsPreliminary data indicated the feasibility of tool use and informed refinement for future testing of the ability of the screening interview to predict those patients with diabetes at high risk of unplanned representation to hospital to enhance effective care planning

Excavations at Grimes Graves Norfolk 1972-1976 fascicule 3 shaft X Bronze Age flint, chalk and metalworking

55.00SIGLEAvailable from British Library Document Supply Centre- DSC:GPC/01932 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours.

The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells