Can transposable element copy number distribution parameters be estimated from natural populations of Drosophila melanogaster?

The copy frequency distribution of a transposable element family in a Drosophila melanogaster natural population is generally characterised by the values of the Charlesworths' model parameters α and β (Charlesworth & Charlesworth, 1983). The estimation of these parameters is made using the observed distribution of the occupied sites in a population sample. Several results have been interpreted as due either to the influence of stochastic factors or to deterministic factors (transposition, excision, selection…). The accuracy of this method was tested by estimations performed on samples from simulated populations. The results show that with the sample size usually used for natural population studies, the confidence intervals are too large to reasonably deduce either the element copy number distribution or the values of transposition and excision rate and selective coefficients.     

The "Alzheimer's disease signature": potential perspectives for novel biomarkers

Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis.     

A new coumarin from Ferula loscosii and the correct structure of coladonin

From the roots of Ferula loscosii the coumarins umbelliprenin, coladin and coladonin and the new natural isovaleryl derivative of the latter have been isolated. A study which confirms the structure of coladonin and its difference from farnesiferol A is also given.     

Parsing a Cognitive Task: A Characterization of the Mind's Bottleneck

Parsing a mental operation into components, characterizing the parallel or serial nature of this flow, and understanding what each process ultimately contributes to response time are fundamental questions in cognitive neuroscience. Here we show how a simple theoretical model leads to an extended set of predictions concerning the distribution of response time and its alteration by simultaneous performance of another task. The model provides a synthesis of psychological refractory period and random-walk models of response time. It merely assumes that a task consists of three consecutive stages—perception, decision based on noisy integration of evidence, and response—and that the perceptual and motor stages can operate simultaneously with stages of another task, while the central decision process constitutes a bottleneck. We designed a number-comparison task that provided a thorough test of the model by allowing independent variations in number notation, numerical distance, response complexity, and temporal asynchrony relative to an interfering probe task of tone discrimination. The results revealed a parsing of the comparison task in which each variable affects only one stage. Numerical distance affects the integration process, which is the only step that cannot proceed in parallel and has a major contribution to response time variability. The other stages, mapping the numeral to an internal quantity and executing the motor response, can be carried out in parallel with another task. Changing the duration of these processes has no significant effect on the variance.     

The mouse immune interferon receptor gene is located on chromosome 10

When mouse L cells are incubated with 32P-labeled recombinant murine immune interferon ( [32P]Mu-IFN-gamma) and subsequently cross-linked with disuccinimidyl suberate, a major complex with an apparent molecular mass of 95,000-125,000 daltons can be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The complex was not formed when the binding was performed in the presence of excess unlabeled Mu-IFN-gamma or when Chinese hamster ovary cells were used. This complex therefore represents the Mu-IFN-gamma receptor (or its interferon-binding subunit). The chromosomal location of the Mu-IFN-gamma receptor (or the binding subunit of the receptor) gene, termed Ifgr, was identified by performing the binding and cross-linking reactions on a series of mouse-hamster somatic cell hybrids with different subsets of mouse chromosomes. The presence of mouse chromosome 10 was shown to be necessary and sufficient for the formation of the cross-linked complex. Thus, the gene coding for the binding subunit of the Mu-IFN-gamma receptor was localized to mouse chromosome 10. The presence of this chromosome in the hybrid cells was not sufficient, however, to confer antiviral resistance to the hybrids when they were treated with Mu-IFN-gamma and challenged with encephalomyocarditis virus.     

Chromosome-specific subsets of human alphoid DNA identified by a chromosome 2-derived clone

We have cloned an alphoid DNA fragment, pBS4D, from the DNA of a human-hamster hybrid cell line containing chromosome 2 as its only cytologically detectable human component. Under high stringency conditions, pBS4D hybridized in situ mostly to chromosome 2 and to a lesser extent to chromosomes 18 and 20. Restriction analysis using the DNA from selected somatic hybrid cell lines revealed that the genomic organization of this alphoid DNA differs on each of these three chromosomes.     

Cobalt-substituted derivatives ofCarcinus hemocyanin

Summary Four derivatives ofCarcinus maenas hemocyanin containing Co(II) in the active site have been prepared under different experimental conditions. Two of them contain one Co(II) ion/active site and most probably represent isomeric forms containing Co(II) either in the fast-reacting or in the slow-reacting position within the active site. A third derivative contains two Co(II) ions active site, which reproduces the metal/protein stoichiometry of native hemocyanin. The fourth derivative is a metal hybrid form containing one Cu(I) ion and one Co(II) ion/active site. The derivatives have been characterized by absorption, circular dichroic and fluorescence spectroscopies. The results indicate that in all derivatives the metal is bound with a low coordination number, in agreement with the presence of three histidine residues/copper ion in the native protein. The two alternative metal-binding positions have different structures as shown by the different spectroscopic properties of the bound Co(II) ions. A marked hyperchromic effect on the optical absorption of Co(II) is observed as a result of the presence of a metal ion in the neighbouring metal-binding position in the active site.     

The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels.

We have established the human nck sequence as a new oncogene. Nck encodes one SH2 and three SH3 domains, the Src homology motifs found in nonreceptor tyrosine kinases, Ras GTPase-activating protein, phosphatidylinositol 3-kinase, and phospholipase C-gamma. Overexpression of human nck in 3Y1 rat fibroblasts results in transformation as judged by alteration of cell morphology, colony formation in soft agar, and tumor formation in nude BALB/c mice. However, overexpression of nck does not induce detectable elevation of the phosphotyrosine content of specific proteins, as is observed for v-crk, another SH2/SH3-containing oncogene. Despite this fact, we demonstrate that Nck retains the ability to bind tyrosine phosphorylated proteins in vitro, using a fusion protein of Nck with glutathione-S-transferase (GST). Moreover, when incubated with lysates prepared from v-src-transformed 3Y1 cells or the nck-overexpressing cell lines, GST-Nck binds to both p60v-src and serine/threonine kinases, respectively. Although phosphotyrosine levels are not elevated in the nck-expressing fibroblasts, vanadate treatment of these cells results in a phosphotyrosine pattern that is altered from the parental 3Y1 pattern, suggestive of a perturbation of indigenous tyrosine kinase pathways. These results suggest the possibility that human nck induces transformation in 3Y1 fibroblasts by virtue of its altered affinity or specificity for the normal substrates of its rat homolog and that Nck may play a role in linking tyrosine and serine/threonine kinase pathways within the cell.     

Effect of chemical sympathectomy on renal hydroelectrolytic handling in dogs with chronic caval constriction

The effect of renal selective chemical sympathectomy by intrarenal infusion of 6-hydroxydopamine (6-OHDA, 5 mg/kg body weight) on the renal excretion of water and electrolytes was studied in 7 dogs in whom a syndrome of sodium and water retention and ascites formation was induced by partial constriction of thoracic inferior vena cava. Propranolol (1 mg) and phentolamine (3 mg) were also injected to obviate acute systemic hemodynamic changes. Sympathectomy was performed once in 4 dogs and three times in 3 dogs. Sympathectomy induced an abrupt and transient increase in urinary flow (from 170 +/- 30 to 890 +/- 60 ml/24 h) and sodium excretion (from 4.5 +/- 1.5 to 178 +/- 21 mEq/24 h). This was accompanied by an important fall in plasma renin activity (from 2.2 +/- 0.2 to 0.5 +/- 0.1 ng angiotensin I/ml/h) and aldosterone, and disappearance of ascites. It is concluded that chemical sympathectomy, by increasing renal sodium and water excretion, mobilizes the ascites induced by chronic caval constriction, a fact that highlights the role of the renal sympathetic system in the pathogenesis of sodium and water retention by the kidney.     

Desangeloylshairidin,X-ray structure determination of a sesquiterpene lactone from Guillonea scabra

The structure and absolute configuration of desangeloylshairidin, a guaianolide isolated from Guillonea scabra, have been established by X-ray diffraction analysis. No conformational change was observed in its seven-membered ring between the crystal and deuterochloroform solution states.