A New Presenilin 1 (Psen1) Mutation (p.Cys263Trp) as a Cause of Both Early and Late-Onset Alzheimer’s Disease in a Large Italian Family

Mutations in the PSEN1 gene are the most common cause of autosomal dominant Alzheimer’s disease, and are characterized by a high phenotype variability. This study describes a five-generation family, with a prevalent late-onset of the disease and a high frequency of depression, in which a new missense mutation (c.789T > G, p.Cys263Trp) in exon 8 of the PSEN1 gene was found. Only the proband presented an early onset at the age of 45 with attention deficit, followed by spatial disorientation, psychiatric symptoms and parkinsonian signs. The other two cases had a late onset of the disease and a typical presentation with memory loss. Both were characterized by a high level of anxiety and depression. The disease course was different with signs of Lewy body dementia for the proband’s mother, and pyramidal involvement and a shorter disease duration for the proband’s maternal aunt. The other eight cases with late-onset dementia and three cases with a long history of depression have been reported in the family pedigree, underlying the high phenotype variability of PSEN1 mutations.     

The dihydroxyacetonephosphate pathway for biosynthesis of ether lipids in Leishmania mexicana promastigotes

Microsatellites can be highly unstable and show a high level of polymorphism between individuals. Here we present the analysis of the CAG trinucleotide repeat polymorphism at the SBMA locus in 57 phenotypically normal individuals rigorously assigned to the Spanish Basque population. Results are compared with 100 Spanish non-Basque individuals who were already analyzed by us (175 alleles). This is the first study undertaken in these populations for this marker. In addition, we compared our results with those published for other populations. Relative allele frequencies showed differences between the samples and no unimodal distribution. The expected heterozygosity in the Basque sample was slightly lower than in the non-Basque sample. Conformity with Hardy-Weinberg equilibrium was verified by three tests. When compared with published data, the predominant alleles appear to be the same in the various populations. There are more differences between Basques and other Caucasoid samples than between non-Basques and Caucasoid samples. Population relationships were also examined by dendrograms based on genetic distances. The results obtained showed some peculiarities in the Basque population. The high degree of similarity with other dendrograms based on different markers and the efficiency of this STR marker in differentiating closely related populations, support the potential usefulness of microsatellites as tools for human population studies.     

Programming robots by example

This article presents a prototypical machine learning system (ETAR) that acquir programs for robot tasks. the long-term goal of this project is to discover how to make computer technology, in particular robots, more useful to (and controllable by) people in general. Rather than require programming expertise, the idea is to build a system that learns robot programs from users' examples. Thus the ETAR learning algorithm begins by sampling the robot path while a user physically leads it through the task. A general procedure, possibly containing loops, branches, and variables, is induced from these examples. the ETAR algorithm is novel because an implicit focus mechaism is used to control the entire generalization process. the focus forces ETAR to concentrate on the important domain objects, thus eliminating useless steps and translat the sampled sequence into a series of robot primitive motions. Loops and branches are introduced as the focus objects repeat or differ. Finally, robot positional variables are introduced as functions of the common characteristics of the objects in the focus. the programs that ETAR generates for three tasks-block stacking, obtaining an object with a certain characteristic, and sorting-are shown to provide an intuitive feel for the types of tasks that ETAR can learn. the article concludes with a general discussion of the current issues in programming by example and describes how this new learner is related to previous systems in this area. ETAR has been implemented on an Excalibur robot © 1993 John Wiley & Sons, Inc.     

Close relationships and adjustments to a life crisis: The case of breast cancer.

When life crises occur significant others are thought to help alleviate distress and resolve practical problems. Yet life crises may overwhelm significant others, eroding their ability to provide effective support. The accuracy of these contrasting accounts of relationship functioning was evaluated in a study of 102 breast cancer patients and their significant others, interviewed at 4 and 10 months after diagnosis. Results largely confirmed the negative account of relationship functioning. Although significant others provided support in response to patients' physical impairment, they withdrew support in response to patients' emotional distress. Moreover, support from significant others did not alleviate patients' distress or promote physical recovery. These results reveal limits to the effectiveness of close relationships in times of severe stress. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multivariate calibration for assays in clinical chemistry using attenuated total reflection infrared spectra of human blood plasma

A spectral analysis of human blood plasma was undertaken by use of a Fourier-transform infrared spectrometer with a circular attenuated total reflection cell. The concentrations of total protein, glucose, triglycerides, total cholesterol, urea, and uric acid were measured by chemical or enzymatic methods. For these constituents the partial least-squares (PLS) algorithm was used for a multivariate calibration including the infrared fingerprint region of the plasma spectra. Best results were achieved for total protein with an average prediction error (PRESS based on cross validation) of 2.1 g/L; other PRESS results were for glucose 22 mg/dL, triglycerides 33 mg/dL, cholesterol 31 mg/dL, urea 4.4 mg/dL, and uric acid 1.6 mg/dL.     

Characterization and mutual ligand-induced modulation of epidermal growth factor and interferon-alpha receptors on renal carcinoma cells in vitro

We have determined the binding of epidermal growth factor (EGF) and interferon (IFN)-alpha to their specific receptors on four renal carcinoma cell lines. CaKi-2, a-498 and ACHN cell lines express high numbers, and CaKi-1 expresses low number of EGF receptors (EGFRs). On all four renal carcinoma cell lines, we have also detected specific IFN-alpha binding sites. EGF and IFN-alpha binding to their receptors caused modulation of the other ligand's receptor binding. Scatchard analyses of binding data showed that IFN-alpha treatment leads to an increase of EGFR number in three out of four cell lines and to a decrease of EGFR number in one out of four (CaKi-1). No significant changes in EGF binding affinities were detected. EGF induced a reduction in IFN-alpha receptor number in all four cell lines without significant changes in IFN-alpha binding affinities. We hypothesize that presence of EGF in the microenvironment of renal cancer cells may modulate the biological effects of IFN and consequently decrease its antiproliferative activity.     

Purification of a RNA-binding protein from rat liver. Identification as ferritin L chain and determination of the RNA/protein binding characteristics

In cultured rat hepatocytes the degradation of phosphoenolpyruvate carboxykinase mRNA might be regulated by protein(s), which by binding to the mRNA alter its stability. The 3'-untranslated region of phosphoenolpyruvate carboxykinase mRNA as a potential target was used to select RNA-binding protein(s) from rat liver by the use of gel retardation assays. A cytosolic protein was isolated, which bound to the phosphoenolpyruvate carboxykinase mRNA 3'-untranslated region and other in vitro synthesized RNAs. The protein was purified to homogeneity; it had an apparent molecular mass of 400 kDa and consisted of identical subunits with an apparent size of 24.5 kDa. Sequence analysis of a tryptic peptide from the 24.5-kDa protein revealed its identity with rat ferritin light chain. Binding of ferritin to RNA was abolished after phosphorylation with cAMP-dependent protein kinase and was augmented after dephosphorylation with alkaline phosphatase. Weak binding was observed in extracts from okadaic acid-treated cultured hepatocytes compared with untreated cells. Preincubation of ferritin with an anti-phosphoserine or an anti-phosphothreonine antibody attenuated binding to RNA, while an anti-phosphotyrosine antibody generated a supershift indicating that phosphoserine and phosphothreonine but not phosphotyrosine residues were in close proximity to the RNA-binding region. Ferritin is the iron storage protein in the liver. Binding of ferritin to RNA was diminished in the presence of increasing iron concentrations, whereas the iron chelator desferal was without effect. It is concluded that ferritin might function as RNA-binding protein and that it may have important functions in the general regulation of cellular RNA metabolism.     

Asymptotic expansions of results of the boundary integral equation method for plane elastostatic problems

The accuracy of numerical results can be improved by extrapolation if the asymptotic expansion of the error for step sizes (or element lengths) h tending to zero is well-known. In this paper expansions are determined for results of an integral equation for the plane elastostatic problem with prescribed boundary tractions. Special care is paid to discontinuous derivatives of the boundary values and of the boundary itself. Furthermore, the influence of the degree of interpolation of the sought function of the integral equation and the influence of non-equidistant division of the boundary on the structure of the expansion is investigated.The paper represents a continuation and partly a completion of [1].An extensive survey of the paper is given at the end of Section 1.     

Fundamental solutions of Laplace's potential operator and Navier's elasticity operator defined on Riemann spaces with two parallel, straight branch lines

The solutions of the potential operator are established with the aid of Sommerfeld's method. Their insertion into the Neuber Papkowitsch formula yields the solutions of Navier's operator for the elasticity problem. Fundamental solutions defined on Riemann spaces can be used advantageously as the kernels of boundary integral equations for the treatment of three-dimensional problems where the domains have slits or cracks of a certain shape (e.g. where the tip line is a straight line, a circular arc or a circle). The equations established in the paper at hand supplement the fund of this type of fundamental solutions. They are suitable for example if the tip line consists of two parallel straight parts.