A close relative of the adrenoleukodystrophy (ALD) gene codes for a peroxisomal protein with a specific expression pattern.

Adrenoleukodystrophy (ALD), a severe demyelinating disease, is caused by mutations in a gene coding for a peroxisomal membrane protein (ALDP), which belongs to the superfamily of ATP binding cassette (ABC) transporters and has the structure of a half transporter. ALDP showed 38% sequence identity with another peroxisomal membrane protein, PMP70, up to now its closest homologue. We describe here the cloning and characterization of a mouse ALD-related gene (ALDR), which codes for a protein with 66% identity with ALDP and shares the same half transporter structure. The ALDR protein was overexpressed in COS cells and was found to be associated with the peroxisomes. The ALD and ALDR genes show overlapping but clearly distinct expression patterns in mouse and may thus play similar but nonequivalent roles. The ALDR gene, which appears highly conserved in man, is a candidate for being a modifier gene that could account for some of the extreme phenotypic variability of ALD. The ALDR gene is also a candidate for being implicated in one of the complementation groups of Zellweger syndrome, a genetically heterogeneous disorder of peroxisome biogenesis, rare cases of which were found to be associated with mutations in the PMP70 (PXMP1) gene.

Microwave Plasma Assisted ALD Development for the Deposition of Gate Oxides & ALD of High-k Dielectrics

The semiconductor industry's urge towards faster, smaller and cheaper integrated circuits has lead the industry to smaller node devices. The integrated circuits that are now under volume production belong to 22 nm and 14 nm technology nodes. In 2007 the 45 nm technology came with the revolutionary high- /metal gate structure. 22 nm technology utilizes fully depleted tri-gate transistor structure. The 14 nm technology is a continuation of the 22 nm technology. Intel is using second generation tri-gate technology in 14 nm devices. After 14 nm, the semiconductor industry is expected to continue the scaling with 10 nm devices followed by 7 nm. Recently, IBM has announced successful production of 7 nm node test chips. This is the fashion how nanoelectronics industry is proceeding with its scaling trend. For the present node of technologies selective deposition and selective removal of the materials are required. Atomic layer deposition and the atomic layer etching are the respective techniques used for selective deposition and selective removal. Atomic layer deposition still remains as a futuristic manufacturing approach that deposits materials and lms in exact places. In addition to the nano/microelectronics industry, ALD is also widening its application areas and acceptance. The usage of ALD equipments in industry exhibits a diversi cation trend. With this trend, large area, batch processing, particle ALD and plasma enhanced like ALD equipments are becoming prominent in industrial applications. In this work, the development of an atomic layer deposition tool with microwave plasma capability is described, which is a ordable even for lightly funded research labs.

Study of high-quality ALD gate dielectrics in radiation sensitive oxide field effect transistors

Radiation dosimetry is crucial in many fields, where the exposure of ionizing radiation must be precisely controlled to avoid health and environmental safety issues. Radiotherapy and radioprotection are two examples in which fast and reliable detectors are needed. Compact and large area wearable detectors are being developed to address real-life radiation dosimetry applications, their ideal properties include flexibility, lightness, and low-cost. This thesis contributed to the development of Radiation sensitive OXide Field Effect Transistors (ROXFETs), which are detectors able to provide fast and real-time radiation read out. ROXFETs are based on thin film transistors fabricated with high-mobility amorphous oxide semiconductor, making them compatible with large area, flexible, and low cost production over plastic substrates. The gate dielectric material has high dielectric constant and high atomic number, which results in high performances and high radiation sensitivity, respectively. The aim of this work was to establish a stable and reliable fabrication process for ROXFETs made with atomic layer deposited gate dielectric. A study on the effect of gate dielectric materials was performed, focusing the attention on the properties of the dielectric-semiconductor interface. Single and multi layer dielectric structures were compared during this work. Furthermore, the effect of annealing temperature was studied. The device performances were tested to understand the underlying physical processes. In this way, it was possible to determine a reliable fabrication procedure and an optimal structure for ROXFETs. An outstanding sensitivity of (65±3)V/Gy was measured in detectors with a bi-layer Ta₂O₅-Al₂O₃ gate dielectric with low temperature annealing performed at 180°C.

Phenotypic variability in a family with x-linked adrenoleukodystrophy caused by the p.Trp132Ter mutation

X-linked adrenoleukodystrophy (X-ALD) is an inherited disease with clinical heterogeneity varying from presymptomatic individuals to rapidly progressive cerebral ALD forms. This disease is characterized by increased concentration of very long chain fatty acids (VLCFAs) in plasma and in adrenal, testicular and nervous tissues. Affected individuals can be classified in different clinical settings, according to phenotypic expression and age at onset of initial symptoms. Molecular defects in X-ALD individuals usually result from ABCD1 gene mutations. In the present report we describe clinical data and the ABCD1 gene study in two boys affected with the childhood cerebral form that presented with different symptomatic manifestations at diagnosis. In addition, their maternal grandfather had been diagnosed with Addison's disease indicating phenotypic variation for X-ALD within this family. The mutation p.Trp132Ter was identified in both male patients; additionally, three females, out of eleven family members, were found to be heterozygous after screening for this mutation. In the present report, the molecular analysis was especially important since one of the heterozygous females was in first stages of pregnancy. Therefore, depending on the fetus outcome, if male and p.Trp132Ter carrier, storage of the umbilical cord blood should be recommended as hematopoietic stem cell transplantation could be considered as an option for treatment in the future.

Atividade fisica e sintomas musculo-esqueleticos : explorando relações em população de calouros de medicina

Universidade Estadual de Campinas. Faculdade de Educação Física

Molecular phylogeny of the freshwater prawn genus Macrobrachium (Decapoda, Palaemonidae), with emphasis on the relationships among selected American species

The genus Macrobrachium Bate, 1868 is one of the best examples of widespread crustacean genera distributed globally throughout tropical and subtropical waters. Previous investigators have noted the systematic complexity of the group, and have suggested rearrangements within the family Palaemonidae. Our phylogenetic analysis of new mitochondrial DNA sequences of 58 species of Macrobrachium distributed mainly in America support the hypothesis of monophyly of this genus, if Cryphiops Dana, 1852 is accepted as a generic synonym. We concluded that the independent evolution of different types of life cycle (abbreviated larval development-ALD and extended larval development-ELD) must have occurred more than once in the history of the group. Similarly, we also concluded that the current type species of the genus, Macrobrachium americanum Bate, 1868, should not be considered valid, as previously proposed. The synonymy of two members of the `olfersi` species complex (M. birai Lobao, Melo&Fernandes, 1986 and M. holthuisi Genofre&Lobao, 1978) with M. olfersi (Wiegmann, 1836) was confirmed. Similar results were found in comparing M. petronioi Melo, Lobao&Fernandes, 1986 and M. potiuna (Muller, 1880), in which the genetic divergence placed M. petronioi within the level of intraspecific variation of M. potiuna. The taxonomic status of the genus Cryphiops, as well as theories on the origin of Macrobrachium, is also called into question.

Alcoholic liver disease: A clinical series in an Australian private practice

Background and Aim: The published literature on alcoholic liver disease (ALD) in Australia lacks a large clinical series out of private practice as distinct from hospital-based hepatology referral units. This series describes the presentation and clinical features of ALD in a consecutive series out of metropolitan private practice in Australia. Methods: A retrospective descriptive study by case-note review found 297 cases of ALD at a Brisbane practice over 20 years. The main outcome measures were: clinical features and stage at presentation, reasons for referral, and the predictive value of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Results: Most patients (57.9%) had no symptoms of liver disease and 29 patients (9.8%) had neither symptoms nor signs. Cirrhosis was found in 41% of patients and hepatitis-fibrosis was found in 26% of patients. The male to female (M: F) ratio was 4.7:1. The AST/ALT ratio was not reliably predictive of ALD stage. The average reported daily alcohol intake was 131 g. Females drank less on average and presented a more vigorous clinical picture. Conclusions: This series presents the spectrum of ALD in a metropolitan Australian private practice. Many patients are asymptomatic on presentation. All heavy drinkers should be targeted for early investigation without waiting for volunteered symptoms or abnormal physical signs. The male to female ratio in ALD is higher than hitherto reported. The AST/ALT ratio is not generally applicable in the staging of ALD. The differences from hospital series data suggest the demography and epidemiology of ALD in Australia are incomplete, and further study is warranted. (C) 2001 Blackwell Science Asia Pty Ltd.

Defining quality of life for Chinese elderly stroke survivors

Purpose: This study aimed to identify the constituents and conceptual characteristics of the quality of life (QOL) of Chinese elderly stroke survivors. living in the community in Hong Kong. Method: A triangulated approach was used to identify the QOL components for this population. This process involved a comparison of QOL components gathered from three different methods, namely, focus group interviews, review of the literature and the contents of the generic Hong Kong Chinese version of the World Health Organization Quality of Life Scale (CWHOQOL-HK). Five health professionals were involved in the comparison process. A percentage of inter-judge agreement was used to determine the reliability of the comparisons made between the judges. Results: This study identified 36 components considered to contribute to the QOL of Chinese elderly stroke survivors in Hona Kong. The conceptual characteristics of their QOL generally concurred with those identified in the literature. Conclusion: Both similarities and differences were found in the QOL components identified in this study when compared to those identified in studies of Western populations who are elderly and had a stroke. The contents of the CWHOQOL-HK scale were found to lack adequacy in representing the QOL of Chinese elderly stroke survivors in Hong Kong. Recommendations are given, based on the findings of this study, to overcome this limitation for its application as a QOL measure for this population.

Mental Health and Quality of Life in Alcoholic Liver Disease Patients After Liver Transplantation: a Prospective Controlled Study

OBJECTIVE: Alcoholic liver disease (ALD) is one of the most important indications for liver transplantation. Discordant conclusions have been found concerning quality of life and mental health after transplantation in this particular group. The aim of this work was to investigate improvements in mental health and quality of life among transplanted patients for ALD. METHODS: We studied 45 consecutive transplant candidates with ALD, attending the outpatient clinics. Among these patients we transplanted 24 with the control candidates remaining in wait for transplantation. RESULTS: There was a significant improvement in all mental health and quality of life dimensions among the transplanted ALD group. We also observed a favorable evolution of coping mechanisms (CM) in this group. CONCLUSION: There is a favorable adjustment of ALD patients after transplantation as shown in CM evolution, which might explain the improved mental health and quality-of-life dimensions.

Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

Abstract Background: Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. Objective: To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Methods: Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). Results: There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). Conclusion: GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

Paper de RIP140 en la fisiopatogenia de la adrenoleucodistròfia lligada a l'X.

La adrenoleucodistrofia ligada al X (X-ALD) es un enfermedad neurometabólica fatal caracterizada por una desmielinización cerebral progresiva infantil (CCALD) o por una neurodegeneración de la médula espinal (adrenomieloneuropatía, AMN), insuficiencia adrenal y acumulación de ácidos grasos de cadena muy larga (AGCML) como el ácido hexacosanoico (C26:0) en tejidos. La enfermedad está causada por mutaciones en el gen ABCD1 el cual codifica para un transportador peroxisomoal que importa AGCML. El ratón knockout para Abcd1 (Abcd1-) desarrolla alteraciones en la médula espinal que mimetizan el modelo de enfermedad AMN con inicio de los síntomas a los 20 meses. Previamente, nuestro grupo evidenció mediante análisis de transcriptómica, una desregulación mitocondrial en el modelo murino Abcd1- . En este trabajo demostramos que tanto en el ratón Abcd1- como en la sustancia blanca afectada de pacientes X-ALD hay una depleción mitocondrial. Para poder explicar esta depleción, estudiamos los niveles de un repressor de la biogenesis mitocondrial, RIP140. En cultivo organotípico de cortes de médula espinal observamos un aumento de los niveles proteicos de RIP140 en el ratón Abcd1- y también un aumento mediado por C26:0. Estos resultados indican que la sobreexpresión de RIP140 puede ser la responsable de la depleción mitocondrial presente en el ratón Abcd1- y una posible nueva diana terapèutica para la X-ALD.

Obtenció de capes primes d'alúmina mitjançant "Atomic Layer Deposition"

En aquest projecte s'ha estudiat la posada a punt d’un equip comercial ALD per a l’obtenció de capes primes d'alúmina a escala nanomètrica utilitzant vapor d’aigua i TMA com a precursors. Per tal de comprovar a bondat de les receptes experimentals aportades pel fabricant així com comprovar alguns aspectes de la teoria ALD s’han realitzat una sèrie de mostres variant els diferents paràmetres experimentals, principalment la temperatura de deposició, el nombre de cicles, la durada del cicle i el tipus de substrat. Per a la determinació dels gruixos nanomètrics de les capes i per tant dels ritmes de creixement s’ha utilitzat la el·lipsometria, una de les poques tècniques no destructives capaç de mesurar amb gran precisió gruixos de capes o interfases de pocs àngstroms o nanòmetres. En una primera etapa s'han utilitzat els valors experimentals donats pel fabricant del sistema ALD per determinar el ritme de creixement en funció de la temperatura de dipòsit i del numero de cicles, en ambdós casos sobre diversos substrats. S'ha demostrat que el ritme de creixement augmenta lleugerament en augmentar la temperatura de dipòsit, tot i que amb una variació petita, de l'ordre del 12% en variar 70ºC la temperatura de deposició. Així mateix s'ha demostrat la linealitat del gruix amb el número de cicles, tot i que no s’observa una proporcionalitat exacta. En una segona etapa s'han optimitzat els paràmetres experimentals, bàsicament els temps de purga entre pols i pols per tal de reduir considerablement les durades dels experiments realitzats a relativament baixes temperatures. En aquest cas s’ha comprovat que es mantenien els ritmes de creixement amb una diferencia del 3,6%, 4,8% i 5,5% en optimitzar el cicles en 6,65h, 8,31h, o 8,33h, respectivament. A més, per una d'aquestes condicions s’ha demostrat que es mantenia l’alta conformitat de les capes d’alúmina. A més, s'ha realitzat un estudi de l'homogeneïtat del gruix de les capes en tota la zona de dipòsit del reactor ALD. S’ha demostrat que la variació en gruix de les capes dipositades a 120ºC és com a màxim del 6,2% en una superfície de 110 cm2. Confirmant l’excepcional control de gruixos de la tècnica ALD.

Uso do feromônio sexual sintético para captura de machos da traça-das-crucíferas

Este trabalho teve como objetivo estudar a atração dos machos da traça-das-crucíferas (Plutella xylostella L., Lepidoptera: Yponomeutidae) por diferentes formulações do feromônio sexual sintético. Os tratamentos consistiram em: 1) formulação comercial; 2) Z11,16:Ald; 3) Z11,16:Ac; 4) mistura 7:3 de 2+3; 5) mistura 5:5 de 2+3; 6) septos de borracha com hexano (testemunha); e 7) cinco fêmeas virgens. A formulação comercial do feromônio sexual sintético propiciou maior captura de machos, não diferindo significativamente de fêmeas virgens e da mistura 5:5 utilizadas como isca. Os componentes isoladamente foram pouco atrativos aos machos. Foram testados cinco modelos de armadilhas. A armadilha Pherocon 1 CP (33,2 machos/armadilha/noite) foi a mais eficiente na captura de machos, seguida pelas armadilhas Cilíndrica Aberta, Cilíndrica Fechada, Delta e Redonda Aberta. Três alturas de instalação da armadilha foram avaliadas. Ocorreu significativamente maior captura de machos na altura do ápice das plantas (30 cm do solo). As alturas de 5 e 60 cm não diferiram entre si.

Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data.

The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) in the PNPLA3 gene is associated with liver damage in chronic liver diseases. Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7) ). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15) ) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2) ). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. Conclusion: Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in HCC development.

Uso da técnica de confusão sexual no manejo populacional de Cryptoblabes gnidiella (Lepidoptera: Pyralidae) em videira

O objetivo deste trabalho foi avaliar a eficiência da técnica de confusão sexual, com o feromônio sexual sintético composto (Z)-11-hexadecenal (Z11-16: Ald) a 1,8% e (Z)-13-octadecenal (Z13-18: Ald) a 1,8%, no controle da população de traça-dos-cachos, Cryptoblabes gnidiella (Lepidoptera: Pyralidae), em cultivares de videiras (Vitis vinifera) destinadas à produção de vinhos. Os experimentos foram realizados em duas localidades na região do Vale do São Francisco, em áreas comerciais de produção de uva para processamento, com as cultivares Cabernet Sauvignon, Petit Verdot, Tempranillo e Chenin Blanc. Os tratamentos avaliados foram os seguintes: confusão sexual com uso de liberadores Splat ("specialized pheromone and lure application technology"), aplicados com pistola manual a 500 pontos por hectare (2 g por ponto); e testemunha sem aplicação. O efeito da técnica sobre os adultos de C. gnidiella foi avaliado com uso de armadilha tipo Delta, iscada em um septo com 2 g de feromônio sintético da mesma formulação. Os danos nos cachos foram avaliados à colheita. O uso da técnica de confusão sexual reduziu a captura de adultos de C. gnidiella em mais de 59% na 'Tempranillo', 68% na 'Chenin Blanc', 80% na 'Cabernet Sauvignon' e 97% na 'Petit Verdot'. À época da colheita, os danos nos frutos foram reduzidos de 65 a 100% nas áreas tratadas. O feromônio sexual sintético é eficaz para reduzir o acasalamento de C. gnidiella em vinhedos, com o uso da técnica de confusão sexual.