Different amino acid substitutions at the same position in rhodopsin lead to distinct phenotypes

PURPOSE: Identification of a novel rhodopsin mutation in a family with retinitis pigmentosa and comparison of the clinical phenotype to a known mutation at the same amino acid position. METHODS: Screening for mutations in rhodopsin was performed in 78 patients with retinitis pigmentosa. All exons and flanking intronic regions were amplified by PCR, sequenced, and compared to the reference sequence derived from the National Center for Biotechnology Information (NCBI, Bethesda, MD) database. Patients were characterized clinically according to the results of best corrected visual acuity testing (BCVA), slit lamp examination (SLE), funduscopy, Goldmann perimetry (GP), dark adaptometry (DA), and electroretinography (ERG). Structural analyses of the rhodopsin protein were performed with the Swiss-Pdb Viewer program available on-line (http://www.expasy.org.spdvbv/ provided in the public domain by Swiss Institute of Bioinformatics, Geneva, Switzerland). RESULTS: A novel rhodopsin mutation (Gly90Val) was identified in a Swiss family of three generations. The pedigree indicated autosomal dominant inheritance. No additional mutation was found in this family in other autosomal dominant genes. The BCVA of affected family members ranged from 20/25 to 20/20. Fundus examination showed fine pigment mottling in patients of the third generation and well-defined bone spicules in patients of the second generation. GP showed concentric constriction. DA demonstrated monophasic cone adaptation only. ERG revealed severely reduced rod and cone signals. The clinical picture is compatible with retinitis pigmentosa. A previously reported amino acid substitution at the same position in rhodopsin leads to a phenotype resembling night blindness in mutation carriers, whereas patients reported in the current study showed the classic retinitis pigmentosa phenotype. The effect of different amino acid substitutions on the three-dimensional structure of rhodopsin was analyzed by homology modeling. Distinct distortions of position 90 (shifts in amino acids 112 and 113) and additional hydrogen bonds were found. CONCLUSIONS: Different amino acid substitutions at position 90 of rhodopsin can lead to night blindness or retinitis pigmentosa. The data suggest that the property of the substituted amino acid distinguishes between the phenotypes.

Abnormalities of pancreatic islets by targeted expression of a dominant-negative KATP channel

ATP-sensitive K+ (KATP) channels are known to play important roles in various cellular functions, but the direct consequences of disruption of KATP channel function are largely unknown. We have generated transgenic mice expressing a dominant-negative form of the KATP channel subunit Kir6.2 (Kir6.2G132S, substitution of glycine with serine at position 132) in pancreatic beta cells. Kir6.2G132S transgenic mice develop hypoglycemia with hyperinsulinemia in neonates and hyperglycemia with hypoinsulinemia and decreased beta cell population in adults. KATP channel function is found to be impaired in the beta cells of transgenic mice with hyperglycemia. In addition, both resting membrane potential and basal calcium concentrations are shown to be significantly elevated in the beta cells of transgenic mice. We also found a high frequency of apoptotic beta cells before the appearance of hyperglycemia in the transgenic mice, suggesting that the KATP channel might play a significant role in beta cell survival in addition to its role in the regulation of insulin secretion.

Position-dependent activity of α-fetoprotein enhancer element III in the adult liver is due to negative regulation

α-Fetoprotein (AFP) transcription is activated early in hepatogenesis, but is dramatically repressed within several weeks after birth. AFP regulation is governed by multiple elements including three enhancers termed EI, EII, and EIII. All three AFP enhancers continue to be active in the adult liver, where EI and EII exhibit high levels of activity in pericentral hepatocytes with a gradual reduction in activity in a pericentral-periportal direction. In contrast to these two enhancers, EIII activity is highly restricted to a layer of cells surrounding the central veins. To test models that could account for position-dependent EIII activity in the adult liver, we have analyzed transgenes in which AFP enhancers EII and EIII were linked together. Our results indicate that the activity of EIII is dominant over that of EII, indicating that EIII is a potent negative regulatory element in all hepatocytes except those encircling the central veins. We have localized this negative activity to a 340-bp fragment. This suggests that enhancer III may be involved in postnatal AFP repression.

Regulation of meiotic chromatin loop size by chromosomal position.

At meiotic prophase, chromatin loops around a proteinaceous core, with the sizes of these loops varying between species. Comparison of the morphology of sequence-related inserts at different sites in transgenic mice demonstrates that loop size also varies with chromosomal geography. Similarly, chromatin loop lengths differ dramatically for interstitially and terminally located hamster telomeric sequences. Sequences, telomeric or otherwise, located at chromosome termini, closely associate with the meiotic proteinaceous core, forming shorter loops than identical interstitial sequences. Thus, we present evidence that different chromatin packaging mechanisms exist for interstitial versus terminal chromosomal regions, which act separately from those operating at the level of the DNA sequence. Chromosomal position plays the dominant role in chromatin packaging.

ISSP Position Stand: Career Development and Transitions of Athletes

The ISSP Position Stand on Career Development and Transitions of Athletes draws attention to viewing athletes from the perspective of their career development and their broader historical and socio‐cultural contexts. The particular focus of this paper is on career transitions as turning phases in career development. Successfully coping with transitions both within and outside of sport allows greater opportunity for an athlete to live a long and successful life in sport as well as being able to adjust effectively to the post‐career. Alternatively, failure in coping with a transition is often followed by negative consequences (e.g., premature dropout from sport, neuroses, alcohol/drug abuse, etc.). Therefore, helping athletes prepare for and/or cope with career transitions should be of primary concern for coaches, managers, athletes’ parents, and sport psychology consultants. In this paper we emphasize the role of contextual factors in career development/transition research and practice. Based on the literature review, we propose six statements and related recommendations for athletes and their significant others, as well as for researchers and consultants

Az ellátási láncban elfoglalt pozíció és a szolgálatosodás – üzleti modellek Európában (Supply chain position and servitization – business models in Europe)

A szerzők célja, hogy megvizsgálják, milyen kölcsönhatásban áll az ellátási láncban elfoglalt pozíció, valamint a szolgálatosodás szintje az európai termelővállalatoknál. Vizsgálatuk azt mutatja, hogy a globalizáció és a termelés nemzetközivé válása mindkét tényezőt jelentős mértékben befolyásolja. A termelés globalizációs trendjeinek megfelelően így a kelet-európai (fejlődő), illetve a nyugat-európai (fejlett) országokban eltérő üzleti modellek válnak dominánssá, amelyek különböző ellátásilánc-pozícióval és más-más szintű szolgáltatásnyújtással jellemezhetőek. A domináns üzleti modellek mellett természetesen más üzleti modellek is működőképesnek bizonyulhatnak a két vizsgált régióban. A létesítmények elhelyezésére, valamint az üzleti eredményességre vonatkozó mutatók elemzésbe történő bevonásával cikkük az Európában működő üzleti modellek kialakításának okára, valamint jövőbeli fenntarthatóságára is megpróbál választ adni. __________ The objective of this paper is to examine the relationship between supply chain position and level of servitization in European manufacturing companies. The analysis shows that globalization and internationalization of production has dramatic impact on both phenomena. Due to the globalization trends different business models became dominant in the less developed Eastern-European and the more developed Western European countries, which can be characterized by different supply chain position and servitization level. Certainly other business models can also be successful in the two regions. Involving facility location motivations and business performance indicators the article shed light on the reasons of why these business models came alive and how sustainable they can be.

Supply chain position and servitization efforts of companies in Eastern and Western Europe

Our paper investigates the supply chain position of manufacturing companies in Europe, and the relation of this position to the extent and kind of services these companies provide. Our research builds on analyzing differences between Western and Eastern European companies. For the empirical research the database from the fifth round of the International Manufacturing Strategy Survey is used which covers 445 manufacturing companies from 13 European countries. Based on the connection between supply chain position and the extent and type of services offered dominant business models are identified both in Eastern and Western Europe.

Domináns vállalat versenyképességének hatása az ellátási láncban (Effects of competitiveness of the dominant company in the supply chain)

Beszállító, gyártó és vevő vállalatok alkotnak egy ellátási láncot. Optimális esetben a vállalatok integrált rendszerben működnek, az együttműködés bizal mi alapon nyugszik, így a közös stratégiai döntések révén versenyképes lesz a lánc. Az ellátási láncban lehet egy kulcsfontosságú vállalat, amelyik domináns hatalmi pozícióval rendelkezik. A kutatás célja, hogy feltárja a hatalommal rendelkező vállalat szerepét a partnercégek és az ellátási lánc versenyképességének alakulásában. A szakirodalom alapján a hipotézis feltételezi, hogy van kapcsolat a versenyképesség és a domináns vállalat szerepvállalása között. A szerzők elemzése primer kutatáson alapul, a kérdőív válaszait SPSS statisztikai kiértékeléssel végezték. Az eredmények azt mutatták, hogy a domináns vállalat versenyképességétől valóban függ a partnercégek versenyképessége. Szignifikáns kapcsolat megléte bizonyítja a hipotézist. A vizsgálatok kiemelik, hogy a verseny már egy szinttel feljebb, az ellátási lánc szintjén értelmezhető: globális ellátási láncok versenyeznek egymással. _____ Supplier, producer and buyer companies make up a supply chain. In an optimal case the companies are integrated, partnership rests on trust which results in common strategic decisions leading to competitiveness. Each supply chain has a key company with dominant power position. The objective of the research is to analyse how the company with power affects competitiveness of partner firms and the supply chain as a whole. Based on theories hypothesis assumes a link between competitiveness and power position and its influence. Methodology of the analysis is based on primary research; the authors used SPSS statistical analysis to evaluate the answers of questionnaire. Findings include that partner firms’ competitiveness rely on competitiveness of the company with dominant power position. Significant connections prove that the hypothesis is true. Results show that competitiveness is being moved up to supply chain level. Global supply chains compete with each other.

Factors Associated With Reporting Of Abuse Against Children And Adolescents By Nurses Within Primary Health Care.

to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents. cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used. female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting. the study's results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents.

A dança na formação docente em educação física

Universidade Estadual de Campinas . Faculdade de Educação Física

Protocolo de avaliação da força muscular em ombros de sedentarios e atletas utilizando dinamometro isocinetico

Universidade Estadual de Campinas . Faculdade de Educação Física

PENCALC: a program for penetrance estimation in autosomal dominant diseases

We present a computer program developed for estimating penetrance rates in autosomal dominant diseases by means of family kinship and phenotype information contained within the pedigrees. The program also determines the exact 95% credibility interval for the penetrance estimate. Both executable (PenCalc for Windows) and web versions (PenCalcWeb) of the software are available. The web version enables further calculations, such as heterozygosity probabilities and assessment of offspring risks for all individuals in the pedigrees. Both programs can be accessed and down-loaded freely at the home-page address http://www.ib.usp.br/~otto/software.htm.

Effects of prone and supine position on oxygenation and inflammatory mediator in a hydrochloric acid-induced lung dysfunction in rats

PURPOSE: To compare the effectiveness of mechanical ventilation of supine versus prone position in hydrochloric acid (HCl)-induced lung dysfunction. METHODS: Twenty, adult, male, Wistar-EPM-1 rats were anesthetized and randomly grouped (n=5 animals per group) as follows: CS-MV (mechanical ventilation in supine position); CP-MV (mechanical ventilation in prone position); bilateral instillation of HCl and mechanical ventilation in supine position (HCl+S); and bilateral instillation of HCl and mechanical ventilation in prone position (HCl+P). All groups were ventilated for 180 minutes. The blood partial pressures of oxygen and carbon dioxide were measured in the time points 0 (zero; 10 minutes before lung injury for stabilization), and at the end of times acid injury, 60, 120 and 180 minutes of mechanical ventilation. At the end of experiment the animals were euthanized, and bronchoalveolar lavages (BALs) were taken to determine the contents of total proteins, inflammatory mediators, and lungs wet-to-dry ratios. RESULTS: In the HCl+P group the partial pressure of oxygen increased when compared with HCl+S (128.0±2.9 mmHg and 111.0±6.7 mmHg, respectively) within 60 minutes. TNF-α levels in BAL do not differ significantly in the HCl+P group (516.0±5.9 pg/mL), and the HCl+S (513.0±10.6 pg/mL). CONCLUSION: The use of prone position improved oxygenation, but did not reduce TNF-α in BAL upon lung dysfunction induced by HCl.

Pharmacist professionals in the prevention of drug abuse: updating roles, and opportunities

The objective of this paper was to prepare and provide resources to pharmacists and other healthcare professionals, enabling them to carry out a critical analysis on drug abuse, acquiring knowledge in several areas that effectively contribute to their personal development in this professional field. Professionals play a crucial role in the reduction and prevention of substances abuse, since they are able to advise patient about illicit drugs, psychotropic medicines and alcohol abuse. There is an urgent need to specialize pharmacists to act in the national public health service and contribute to actions aimed at the surrounding community.