Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

Abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

Noonan syndrome: a clinical and genetic study of 31 patients

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

Cerebral vasculopathy in children with sickle cell disease A study of genetic modulators of the disease

Sickle cell disease (SCD) is a genetic disorder with recessive transmission, caused by the mutation HBB:c.20A>T. It originates hemoglobin S that forms polymers inside the erythrocyte, upon deoxygenation, deforming it and ultimately leading to premature hemolysis. The disease presents with high heterogeneity of clinical manifestations, the most devastating of which, ischemic stroke, occurs in 11% of patients until 20 years of age. In this study, we tried to identify genetic modifiers of risk and episodes of stroke by studying 66 children with SCD, grouped according to the degree of cerebral vasculopathy (Stroke, Risk and Control). Association studies were performed between the three phenotypic groups and hematological and biochemical parameters of patients, as well as with 23 polymorphic regions in genes related to vascular cell adhesion (VCAM-1, THBS-1 and CD36), vascular tonus (NOS3 and ET-1) and inflammation (TNF-α and HMOX-1). Relevant data was collected from patient’s medical records. Known genetic modulators of SCD (beta-globin cluster haplotype and HBA and BCL11A genotypes) and putative genetic modifiers of cerebral vasculopathy were characterized. Differences in their distribution among groups were assessed. VCAM-1 rs1409419 allele C and NOS3 rs207044 allele C were associated to stroke events, while VCAM-1 rs1409419 allele T was found to be protective. Alleles 4a and 4b of NOS3 27 bp VNTR appeared to be respectively associated to stroke risk and protection. HMOX-1 longer STRs seemed to predispose to stroke. Higher hemoglobin F levels were found in Control group, as a result of Senegal haplotype or of BCL11A rs11886868 allele T, and higher lactate dehydrogenase levels, marker of hemolysis, were found in Risk group. Molecular mechanisms underlying the modifier functions of the relevant genetic variants are discussed.

Appraisal of surgical treatment of 47 cases of patellofemoral instability

INTRODUCTION: Patellofemoral instability is a common knee disease. Its etiology is complex and variable, with many components making different contributions in each individual, resulting in several distinct clinical presentations. Our goal was to analyze the results of surgical treatment in our hospital over a period of 10 years. PATIENTS AND METHODS: We analyzed 55 knees of 47 patients who underwent surgery for patellofemoral instability and were classified into 2 main groups: proximal realignment and combined proximal and distal realignment. Three other groups were analyzed according to the duration of preoperative symptoms: less than 1 year (group I); 1 to 10 years (group II); and more than 10 years (group III). RESULTS: There were 62% good results overall, with 78% good results in groups I and II. Group III had 81% bad results, showing that a late diagnosis of advanced disease results in a poor prognosis. In addition to late diagnosis, bad results were usually associated with incorrect diagnosis or choice of surgical technique. There was no significant difference between isolated proximal realignment and combined proximal and distal realignment in groups I or II, but in group III, the combined technique yielded better results. DISCUSSION: Our results indicate that patellofemoral instability should be addressed in its early stages. Patients with long-lasting symptoms or more severe disease seem to achieve better results with combined techniques. CONCLUSION: Proximal and distal realignments produce better results than isolated proximal realignment in patients with joint degeneration or with greater duration of disease. The realignment surgery does not produce good results in patients with advanced disease.

Leverage instability and persistence: Evidence from the United States and Europe

We find that leverage behavior both in level and time-series variation is very similar between the United States and Europe throughout the 1990-2013 period. Leverage regimes are simultaneously unstable and persistent for both regions. We define instability as the extent to which firms largely deviate from their long-term leverage mean, while persistence as the extent to which today’s leverage influences its future levels. We then show that this simultaneous evidence imply a mean-reversion behavior of leverage and discuss some of its implications for future research on this field.

Genetic algorithm for shipping route estimation with long-range tracking data : automatic reconstruction of shipping routes based on the historical ship positions for maritime safety applications

Ship tracking systems allow Maritime Organizations that are concerned with the Safety at Sea to obtain information on the current location and route of merchant vessels. Thanks to Space technology in recent years the geographical coverage of the ship tracking platforms has increased significantly, from radar based near-shore traffic monitoring towards a worldwide picture of the maritime traffic situation. The long-range tracking systems currently in operations allow the storage of ship position data over many years: a valuable source of knowledge about the shipping routes between different ocean regions. The outcome of this Master project is a software prototype for the estimation of the most operated shipping route between any two geographical locations. The analysis is based on the historical ship positions acquired with long-range tracking systems. The proposed approach makes use of a Genetic Algorithm applied on a training set of relevant ship positions extracted from the long-term storage tracking database of the European Maritime Safety Agency (EMSA). The analysis of some representative shipping routes is presented and the quality of the results and their operational applications are assessed by a Maritime Safety expert.

Implementação de um modelo de geometric semantic genetic programming para aplicação naval

Recaí sob a responsabilidade da Marinha Portuguesa a gestão da Zona Económica Exclusiva de Portugal, assegurando a sua segurança da mesma face a atividades criminosas. Para auxiliar a tarefa, é utilizado o sistema Oversee, utilizado para monitorizar a posição de todas as embarcações presentes na área afeta, permitindo a rápida intervenção da Marinha Portuguesa quando e onde necessário. No entanto, o sistema necessita de transmissões periódicas constantes originadas nas embarcações para operar corretamente – casos as transmissões sejam interrompidas, deliberada ou acidentalmente, o sistema deixa de conseguir localizar embarcações, dificultando a intervenção da Marinha. A fim de colmatar esta falha, é proposto adicionar ao sistema Oversee a capacidade de prever as posições futuras de uma embarcação com base no seu trajeto até à cessação das transmissões. Tendo em conta os grandes volumes de dados gerados pelo sistema (históricos de posições), a área de Inteligência Artificial apresenta uma possível solução para este problema. Atendendo às necessidades de resposta rápida do problema abordado, o algoritmo de Geometric Semantic Genetic Programming baseado em referências de Vanneschi et al. apresenta-se como uma possível solução, tendo já produzido bons resultados em problemas semelhantes. O presente trabalho de tese pretende integrar o algoritmo de Geometric Semantic Genetic Programming desenvolvido com o sistema Oversee, a fim de lhe conceder capacidades preditivas. Adicionalmente, será realizado um processo de análise de desempenho a fim de determinar qual a ideal parametrização do algoritmo. Pretende-se com esta tese fornecer à Marinha Portuguesa uma ferramenta capaz de auxiliar o controlo da Zona Económica Exclusiva Portuguesa, permitindo a correta intervenção da Marinha em casos onde o atual sistema não conseguiria determinar a correta posição da embarcação em questão.

Genetic algorithms for the non emergency patients transport service

The authors would like to thank the anonymous reviewers for their valuable comments and suggestions to improve the paper. The authors would like to thank Dr. Elaine DeBock for reviewing the manuscript.

Genetic breeding on the bee Melipona scutellaris (Apidae, Meliponinae)

A selection of queens of Melipona scutellaris through the most productive colonies were carried out during eight months in an orange honeyflow. Each of the colonies was evaluated by its production, that is, the gross weight production ( pollen, brood, geopropolis and wax of each hive). With this data a coefficient of repeatability was estimated by the intraclass correlation method, obtained r = 0.835 ± 0.071. The repeatibility is very high showing that the analysed data (production) is repeatable. Selection was then carried out using the regression coefficient of each colony and the respective production gain. Using these data the colonies were divided into three groups according to the method Vencovsky and Kerr (1982): a with the colonies of highest productivity, b of least productivity, and c of intermediary productivity. Colonies with the highest production (Group a) gave their queens to those of the lowest production (Group b) after their queens were taken out and killed; while those of intermediate (Group c) stayed with the same queens during the entire experiment both before and after the selection. The modifications in weight, that is, the genetic response was (R)= 7.98 gr per day which indicated a selection gain. The estimate of the realized herdability is twice the rate of the response to selection (R) by the selection differential (S2). That is then h²R=2(R/S2) then h²R= 0.166

Geographic pattern of genetic diversity in natural populations of Rosewood (Aniba rosaeodora), in the Central Amazonia

Rosewood (Aniba rosaeodora Ducke, Lauraceae) is an Amazonian evergreen tree and a source of the purest linalool, the main component of its essential oil, which is very valuable in the international perfumery market. After decades of over-exploitation it is currently considered as threatened. We evaluated the genetic diversity and its distribution in four populations in Central Amazonia. Thirty-five reliable RAPD markers were generated, of which 32 were polymorphic (91.4%). Variation was higher within the populations (76.5%; p < 0.0001) and geographic distribution contributed to population differentiation (23.4%; p < 0.0001). The Amazon River had a small influence on gene flow (3.3%; p < 0.0001), but we identified evidence of gene flow across the river. There were significant differences in marker frequencies (p < 0.05), in agreement with the low gene flow (Nm = 2.02). The correlation between genetic distance and gene flow was - 0.95 (p = 0.06) and between geographic distance and gene flow was -0.78 (p = 0.12). There was a geographic cline of variability across an East-West axis, influenced as well by the Amazon River, suggesting the river could be a barrier to gene flow. Although threatened, these Rosewood populations retain high diversity, with the highest levels in the Manaus population, which has been protected for over 42 years in a Reserve.

Genetic diversity in rosewood saplings (Aniba rosaeodora ducke, Lauraceae): an ecological approach

This article takes an ecological approach to the genetic diversity of Rosewood (Aniba rosaeodora Ducke) in a central Amazonian terra firme forest north of Manaus. Planted Rosewood setting, under partial shaded canopy, were assessed in terms of fruiting production, frugivory, and seed dispersal. Using RAPD molecular analysis procedures, the influence of the spatial distribution of adult trees on the genetic diversity (polymorphism) of saplings was assessed with genetic samples from 34 reproductive trees and 60 saplings. The density and distribution patterns the reproductive trees did not modify the sapling"s diversity (1.86%, AMOVA). Two types of adult tree dispersion were identified; i) clumped and ii) more widely dispersed. Polymorphism (77.5%) and gene flow were high between these. Although more sapling genetic variability in areas with a higher density of mature plants was not as high as expected, density did not affect the genetic diversity of samplings, indicating a high incidence of gene flow amongst trees. In planted Rosewood population (surrounded by low disturbed forest), fruiting trees experienced a high level of removal of seeds by toucans (Rhamphastidae), about of 50%. The high gene flow found among native trees suggested that toucans, promoting seed rain at short and long distances from maternal trees, actively contribute to the maintenance of genetic diversity within wild rosewood populations.

PTX3-based genetic testing for risk of aspergillosis after lung transplant

PTX3-based genetic testing for risk of aspergillosis after lung transplant

A genetic perspective on African prehistory

The various genetic systems (mitochondrial DNA, the Y-chromosome and the genome-wide autosomes) indicate that Africa is the most genetically diverse continent in the world and the most likely place of origin for anatomically modern humans. However, where in Africa modern humans arose and how the current genetic makeup within the continent was shaped is still open to debate. Here, we summarize the debate and focus especially on the maternally inherited mitochondrial DNA (mtDNA) and a recently revised chronology for the African mtDNA tree. We discuss the possible origin of modern humans in southern, eastern or Central Africa; the possibility of a migration from southern to eastern Africa more than 100 ka, carrying lineages within mtDNA haplogroup L0; the evidence for a climate-change-mediated population expansion in eastern Africa involving mtDNA haplogroup L3, leading to the “out-of-Africa” migration around 70–60 ka; the re-population of North Africa from the Near East around 40–30 ka suggested by mtDNA haplogroups U6 and M1; the evidence for population expansions and dispersals across the continent at the onset of the Holocene ; and the impact of the Bantu dispersals in Central, eastern and southern Africa within the last few millennia.