肺癌患者PTEN基因启动子高甲基化的检测

目的 探讨肺癌患者组织、外周血浆及支气管肺泡灌洗液(BALF)中张力蛋白同源的磷酸酶基因(PTEN)启动子异常基因化状况及其在肺癌诊断中的价值.方法 用甲基化特异性PCR方法检测组织、血浆及BALF中的PTEN基因启动子区CpG岛甲基化.结果 45例肺癌患者中,PTEN基因启动子异常甲基化率组织为26.67%(12/45)、血浆为15.56%(7/45),BALF为22.22%(10/45);而非肺癌组织、正常对照血浆、非肺癌患者BALF中未检出甲基化;血浆、BALF中甲基化改变与肿瘤组织甲基化状况显著相关(P<0.01).结论 血浆、BALF中PTEN基因异常甲基化改变的检测在肺癌的早期特异诊断等方面有一定的价值.     

Burkholderia thailandensis Isolated from the Environment,United States

Burkholderia thailandensis, an opportunistic pathogen found in the environment, is a bacterium closely related to B. pseudomallei, the cause of melioidosis. Human B. thailandensis infections are uncommon. We isolated B. thailandensis from water in Texas and Puerto Rico and soil in Mississippi in the United States, demonstrating a potential public health risk.     

Symtoms and Social Adjustment of Schizophrenic Patients as Evaluated by Their Family Members: A Cross-Cultural Psychiatric Study between Offshore Islands and an Urban City

Abstract: We conducted a comparative study of symptoms and social adjustment of schizophrenic patients on offshore islands and one urban region in Japan. In the evaluation of symptoms and social behavior by family members, no differences were observed between the two regions. Looking at social adjustment in the two regions, no differences were observed by family members either in the performance level or in the expectation level of socially expected activities. However, on the offshore islands, the expectation level of socially expected activities by family members was significantly higher than the level of self-accomplishment set by schizophrenic patients themselves. As for leisure activities, both family members and patients on the islands evaluated the level of performance to be significantly higher than in the urban region, and the level of satisfaction of the patients themselves was also higher on the islands. Considering both these findings and Japanese traditional views of work and leisure, it is believed that on the islands patients are required to engage in more productive activities and less leisure activities than in the urban region. Further it seems that patients on the islands compared to patients in the urban region may have greater difficulty in social adjustment.     

Health and welfare in St Helena: the contribution of W.J.J. Arnold, Colonial Surgeon, 1903–1925

St Helena is a remote south Atlantic island subject to insular problems of isolation and economic weakness which impact on health and welfare. It has long been British and in 1900 was used as a prison camp for Boers. One of the medical team looking after them was W.J.J. Arnold who remained on the island, as Colonial Surgeon and Acting Governor until his death in 1925. This paper considers the then health and welfare problems of this underdeveloped, isolated population and investigates their amelioration with reference to the work of Dr Arnold.     

Selection Pressure and Altered Hepatocellular Islands after a Single Injection of Aflatoxin B1

Development of glutathione S-transferase placental form (GST-P)-positive focal populations was investigated subsequent to single injections of the hepatocarcinogens aflatoxin B1 (AfB1), dimethylnitrosamine (DMN) and diethylnitrosamine (DEN). While DEN proved far more potent at inducing putative initiated hepatocytes, the AfB1 treatment was associated with a very rapid (3 weeks) development of lesions approaching nodular proportions. Autoradiographic investigation revealed selective incorporation of label into GST-P-positive hepatocytes and oval cells at the day 7 time point following AfB1 treatment. Administration of butylated hydroxyanisole (BHA) subsequent to carcinogen injection was associated with a decrease in the final yield of lesions and increased tritiated thymidine incorporation in perivenular zone 3 background hepatocytes. The results suggest that 'selection pressure', resulting in rapid growth and development of putative preneoplastic lesions, is inherent in a single injection of the mycotoxin and indicate that variations of the present short-term model may be useful for elucidating the mechanisms underlying AfB1-induced hepatocarcinogenesis.     

5-氮杂胞苷与雌二醇对SLE患者CpG基序甲基化状态与DNMT1表达的影响

目的 探讨5-氮杂胞苷与雌二醇对SLE患者与正常人CpG基序甲基化状态与DNA 甲基转移酶1（DNMT1）表达的影响。方法 分离12例SLE患者与11例正常人外周血淋巴细胞,经植物血凝素刺激1天后,分为未处理组、5-氮杂胞苷组、雌二醇组,继续培养3 d后分别用5-甲基胞嘧啶抗体与流式细胞仪检测CpG基序甲基化水平和实时定量逆转录－聚合酶链反应（RT-PCR）分析DNMT1的mRNA表达水平。结果 与非处理组相比,5-氮杂胞苷组SLE患者（t = 18.60,P < 0.01）与正常人（t = 5.63,P < 0.01）的CpG基序甲基化水平均下降。DNMT1表达水平（正常人t = 2.17,P > 0.05,SLE患者t = 1.56,P > 0.05）的下降无统计学意义。雌二醇组SLE患者与正常人的CpG基序甲基化水平（正常人t = 1.93,P > 0.05;SLE患者t = 1.53,P > 0.05）与DNMT1的mRNA（正常人t = 0.11,P > 0.05;SLE患者t = 0.93,P > 0.05）表达水平的差异均无统计学意义。结论 5-氮杂胞苷可抑制CpG基序甲基化状态,其抑制作用的产生与DNMT1表达水平的下降无明显相关性。雌二醇对CpG基序甲基化状态与DNMT1的表达水平的影响无统计学意义。     

Aspects of genome plasticity in pathogenic Escherichia coli

The species Escherichia coli comprises not only non-pathogenic or commensal variants that belong to the normal intestinal flora of most mammals, but also various pathogenic strains causing diverse intestinal and extraintestinal infections in man and animals. Virulence factors and mechanisms involved in pathogenesis have been successfully analyzed for many years resulting in a wealth of knowledge about many E. coli pathotypes. However, our knowledge on the genome content, diversity and variability between pathogenic and also non-pathogenic subtypes is only slowly accumulating. Pathotypes have been largely defined by the presence or absence of particular DNA segments that in most cases appear to have been acquired via horizontal gene transfer events. As these regions are frequently subjected to excisions, rearrangements, and transfers they contribute to the previously unexpected and underestimated rapid evolution of E. coli variants resulting in the development of novel strains and even pathotypes. In these studies various novel aspects of genome diversity and plasticity in extraintestinal and intestinal pathogenic E. coli pathotypes have been addressed and the results have been directly applied for the improvement of diagnostic methods.     

Anthropogenic transitions from forested to human-dominated landscapes in southern Macaronesia

The extinction of iconic species such as the dodo and the deforestation of Easter Island are emblematic of the transformative impact of human colonization of many oceanic islands, especially those in the tropics and subtropics. Yet, the interaction of prehistoric and colonial-era colonists with the forests and forest resources they encountered can be complex, varies between islands, and remains poorly understood. Long-term ecological records (e.g., fossil pollen) provide the means to understand these human impacts in relation to natural change and variability pre- and postcolonization. Here we analyze paleoecological archives in forested landscapes of the Canary Islands and Cabo Verde, first colonized approximately 2,400 to 2,000 and 490 y ago, respectively. We demonstrate sensitivity to regional climate change prior to human colonization, followed by divergent but gradual impacts of early human settlement. These contrast with more rapid transformation in the colonial era, associated with significant increases in anthropogenic pressures. In the Canary Islands, at least two native tree taxa became extinct and lowland thermophilous woodlands were largely converted to agricultural land, yet relictual subtropical laurel forests persisted with limited incursion of nonnative species. In Cabo Verde, in contrast, thermophilous woodlands were depleted and substituted by open landscapes and introduced woodlands. Differences between these two archipelagos reflect the changing cultural practices and societal interactions with forests and illustrate the importance of long-term data series in understanding the human footprint on island ecosystems, information that will be critically important for current and future forest restoration and conservation management practices in these two biodiversity hotspots.

Human colonization of virtually the entirety of the tropics and subtropics was accomplished by the start of the Holocene (1, 2). However, remote oceanic islands provide the exceptions to this generalization, many having been first colonized in late prehistoric times (approximately in the last 3,000 y) or in the colonial era (post-1400 CE) (2). Humans have since transformed these systems, via habitat conversion, resource exploitation, hunting, and the introduction of nonnative species. Cases such as Easter Island exemplify a complete loss of preexisting forest cover (3), but often ecological cascades have had profound impacts within persisting forest communities. The loss of the dodo on Mauritius (4) and most of the land birds of Guam (5) (following the introduction of the brown tree snake) are emblematic. Moreover, the response of island forests to anthropogenic drivers varies greatly among islands: whereas forested areas on Hawaii contain many nonnative species (6), Canarian laurel forests are composed almost entirely of native species of trees and shrubs (7). Understanding the legacy of human impacts on these remote oceanic islands, and particularly on their forests, requires a combination of paleoecological and archaeological studies over timelines that incorporate both pre- and posthuman dynamics (8).For prehistoric settlers, island forests provided vital ecosystem services such as food (fruits, animal prey), medicines, shelter, tools, timber, wood for hearths, and regulatory services, including water flow regulation and soil erosion protection. The forested landscapes also provided growing conditions suitable for agricultural conversion. While prehistoric island societies typically interacted and traded with other islands or regions, most land-use decisions were made locally (8, 9). Island forests were subjected to clearance by fire (9), increasing agricultural activities, accelerated soil erosion (10), and the introduction of species such as goats, pigs, and rats (11), which are often implicated in extinctions of native vertebrates (11, 12). Colonial-era first colonists, in contrast, frequently made land-use decisions focused on colonial trading networks, leading to aggressive, rapid acts of deforestation and land-use change, and generally involving accelerated rates of nonnative species introduction (13).Here we present comparative paleoecological analyses of two oceanic archipelagos from the biogeographical region of Macaronesia (which comprises Cabo Verde, Canaries, Selvagens, Madeira, and Azores), namely 1) Cabo Verde, settled by the Portuguese in 1462 CE and the first tropical European colony, and 2) the subtropical Canary Islands, first settled by people from North Africa around 2,400 to 2,000 cal BP (14) and subsequently conquered by the Castilians over the course of the 15th century. In the early colonial period, both archipelagos were inextricably connected to the development and spread of agricultural, economic, and societal practices in the colonialization of the New World tropics (13) (SI Appendix). They thus provide ideal model systems (15, 16) through which to understand how humans have impacted forested landscapes through diverse stages of technological and cultural development (8, 17–19).Our analyses are based on five sequences from natural sediment deposits (volcanic calderas), representing two major ecosystem types (Fig. 1): first, thermophilous woodlands, thought to have originally spanned ∼100 to 600 meters above sea level (masl) in the Canaries and found from 500 to 1,500 masl in Cabo Verde, and second, laurel forest, which occurs from 500 to 600 m to 1,000 to 1,200 m in the Canary Islands but is absent from Cabo Verde (Fig. 2). To provide a comparative synthesis of the natural dynamics of these forested landscapes over time and how humans have changed them, we use multivariate analyses (ordination) to integrate paleoecological datasets of forest composition (fossil pollen), fire regimes (charcoal), erosion (sediment elemental composition and median grain size), soil organic content (loss on ignition), and herbivore introductions (spores of coprophilous fungi). Prior to human colonization, forest variability within the last 10 ka showed evidence of the ecosystems responding to regional climate change, whereas after human colonization there is evidence for increased incidence of fire, soil erosion, and the arrival of domesticated animals (goats, pigs). These latter changes are associated with a reduction in the forest cover in both archipelagos and compositional convergence within the thermophilous woodland zone of the Cabo Verde islands.Open in a separate windowFig. 1.Maps of the Cabo Verde and the Canary Islands and photographs and elevation of the studied volcanic calderas. We use Anthropocene in an informal sense to indicate the period since human colonization, which differs island to island. (Lower) Chronological axes showing geological, climatic, and human milestones of the last 20 My in southern Macaronesia. See SI Appendix, Supplementary Text for references.Open in a separate windowFig. 2.Distribution of woodland vegetation types in southern Macaronesia. (Left) Schematic elevational zonation. (Right) Remaining distribution of laurel forest and thermophilous woodlands in the Canary Islands based on ref. 43 and of introduced woodland in Cabo Verde based on ref. 44.     

The stinging Apidae and Vespidae (Hymenoptera: Apocrita) in Iranian islands,Qeshm, Abu–Musa,Great Tunb and Lesser Tunb on the Persian Gulf

ObjectiveTo study the stinging flying Hymenoptera (Apidae and Vespidae) fauna in four Iranian Islands, Qeshm, Greater Tunb, Lesser Tunb and Abu-Musa on the Persian Gulf.MethodsThe flies were captured by used of Malaise trap, fly trap, bottle trap and insect net-hashing from March 2011 to July 2012.ResultsIn this study, 11 species of stinging Hymenoptera were reported for the first time in Persian Gulf region.ConclusionsSome of this species such as Vespa orientalis and Polistes olivaceus are more common in the Persian Gulf islands and can cause clinical problem to islands resident and travelers.     

Alterations in postnatal neurogenesis and dopamine dysregulation in schizophrenia: a hypothesis

An increasing number of studies demonstrate the important role of several susceptibility genes for schizophrenia, such as neuregulin-1 and DISC1, in early postnatal and adult neurogenesis. Its significance for the pathophysiology of the disease, including its relation to neurotransmitter systems implicated in schizophrenia (like the dopamine system), remains, however, unknown. Here, we review molecular and cellular components of the dopamine system associated with postnatal neurogenesis and plasticity, both in rodents and in primates, and discuss their possible implication in schizophrenia. We focus mainly on the islands of Calleja, complex aggregations of granule cells in the ventral striatum, generated early postnatally in the subventricular zone. In contrast to the involution of the primate olfactory bulb, the islands of Calleja attain their maximal development in humans, an evolution paralleled by a larger ventral subventricular zone and more connections with other structures, including temporal cortical areas. The islands of Calleja express high levels of neuronal nitric oxide (NO) synthase and D3 dopamine receptors and are densely interconnected by dopaminergic projections with the ventral tegmental area. D3 receptors modulate subventricular zone neurogenesis and dopamine release. Their genetic deletion induces striatal hyperdopaminergia. We review data indicating a high plasticity of postnatal islands of Calleja, potentially facilitating susceptibility to schizophrenia-related risk factors. In this context, we propose a new pathophysiological model, where altered neurogenesis of the islands of Calleja may contribute to dysfunction of the dopamine and NO systems and psychosis through convergence of genetic and environmental disease-associated factors.