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71.
Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.  相似文献   
72.
Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Non-motor symptoms and signs such as psychiatric disturbances, sleep problems and metabolic dysfunction are part of the disease manifestation. These aspects may relate to changes in the hypothalamus, an area of the brain involved in the regulation of emotion, sleep and metabolism. Neuropathological and imaging studies using both voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) as well as positron emission tomography (PET) have demonstrated pathological changes in the hypothalamic region during early stages in symptomatic HD. In this investigation, we aimed to establish a robust method for measurements of the hypothalamic volume in MRI in order to determine whether the hypothalamic dysfunction in HD is associated with the volume of this region. Using T1-weighted imaging, we describe a reproducible delineation procedure to estimate the hypothalamic volume which was based on the same landmarks used in histologically processed postmortem hypothalamic tissue. Participants included 36 prodromal HD (pre-HD), 33 symptomatic HD (symp-HD) and 33 control participants who underwent MRI scanning at baseline and 18 months follow-up as part of the IMAGE-HD study. We found no evidence of cross-sectional or longitudinal changes between groups in hypothalamic volume. Our results suggest that hypothalamic pathology in HD is not associated with volume changes.  相似文献   
73.

Background

The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett’s oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.

Methods

This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS).

Results

Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.

Conclusion

Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.  相似文献   
74.
Müller cells are the principal glial cells of the retina. Their end-feet form the limits of the retina at the outer and inner limiting membranes (ILM), and in conjunction with astrocytes, pericytes and endothelial cells they establish the blood-retinal barrier (BRB). BRB limits material transport between the bloodstream and the retina while the ILM acts as a basement membrane that defines histologically the border between the retina and the vitreous cavity. Labeling Müller cells is particularly relevant to study the physical state of the retinal barriers, as these cells are an integral part of the BRB and ILM. Both BRB and ILM are frequently altered in retinal disease and are responsible for disease symptoms.There are several well-established methods to study the integrity of the BRB, such as the Evans blue assay or fluorescein angiography. However these methods do not provide information on the extent of BRB permeability to larger molecules, in nanometer range. Furthermore, they do not provide information on the state of other retinal barriers such as the ILM. To study BRB permeability alongside retinal ILM, we used an AAV based method that provides information on permeability of BRB to larger molecules while indicating the state of the ILM and extracellular matrix proteins in disease states. Two AAV variants are useful for such study: AAV5 and ShH10. AAV5 has a natural tropism for photoreceptors but it cannot get across to the outer retina when administered into the vitreous when the ILM is intact (i.e., in wild-type retinas). ShH10 has a strong tropism towards glial cells and will selectively label Müller glia in both healthy and diseased retinas. ShH10 provides more efficient gene delivery in retinas where ILM is compromised. These viral tools coupled with immunohistochemistry and blood-DNA analysis shed light onto the state of retinal barriers in disease.  相似文献   
75.
Intense and chronic disturbance may arrest natural succession, reduce environmental quality and lead to ecological interaction losses. Where natural succession does not occur, ecological restoration aims to accelerate this process. While plant establishment and diversity is promoted by restoration, few studies have evaluated the effect of restoration activities on ecological processes and animal diversity. This study assessed herbivory and lepidopteran diversity associated with two pioneer tree species growing in 4-year-old experimental restoration plots in a tropical dry forest at Sierra de Huautla, in Morelos, Mexico. The study was carried out during the rainy season of 2010 (July-October) in eleven 50 x 50 m plots in three different habitats: cattle-excluded, cattle-excluded with restoration plantings, and cattle grazing plots. At the beginning of the rainy season, 10 juveniles of Heliocarpus pallidus (Malvaceae) and Ipomoea pauciflora (Convolvulaceae) were selected in each plot (N = 110 trees). Herbivory was measured in 10 leaves per plant at the end of the rainy season. To evaluate richness and abundance of lepidopteran larvae, all plants were surveyed monthly. Herbivory was similar among habitats and I. pauciflora showed a higher percentage of herbivory. A total of 868 lepidopteran larvae from 65 morphospecies were recorded. The family with the highest number of morphospecies (9 sp.) was Geometridae, while the most abundant family was Saturnidae, with 427 individuals. Lepidopteran richness and abundance were significantly higher in H. pallidus than in I. pauciflora. Lepidopteran richness was significantly higher in the cattle-excluded plots, while abundance was significantly higher in the non-excluded plots. After four years of cattle exclusion and the establishment of plantings, lepidopteran richness increased 20 –fold in the excluded plots compared to the disturbed areas, whereas herbivory levels were equally high in both restored and disturbed sites. Restoration with plantings and exclusion of cattle and plantings was shown to be a successful strategy for attracting lepidopterans and cattle exclusion was the main factor explaining lepidopteran diversity.  相似文献   
76.
In this study, two different semen cryopreservation protocols were compared to freeze goat semen. The ejaculates (n = 12) were collected by using electro-ejaculator from six mature bucks (two ejaculates per each buck). Each ejaculate was divided into two groups as Protocol 1 (P1) and Protocol 2 (P2). In P1, semen was diluted directly in an extender containing 15% egg yolk, 300 mM Tris, 28 mM glucose, 95 mM citric acid 5% glycerol to a concentration of 200 × 106 sperm/mL. In P2, after the removal of seminal plasma by centrifugation, the semen sample was diluted with the first portion of milk extender consist of 100 mg/mL skimmed milk powder and 27.75 mM glucose (without glycerol) to a concentration of 400 × 106 sperm/mL. The second portion of the milk extender containing 14% glycerol was added to semen gradually in order to achieve sperm concentration 200 × 106 sperm/mL and 7% glycerol level in the final volume. Extended semen was loaded in 0.25 mL straws, held for 2 h at 4 °C, frozen in nitrogen vapor and stored in liquid nitrogen. Post-thaw motility and live sperm rate (mean ± SEM) were significantly lower (P < 0.05) in P1 as compared to P2 (47.50 ± 1.23% vs. 55.63 ± 1.72%; 80.04 ± 1.29% vs. 84.04 ± 1.08%, respectively). However, live intact, total intact, abnormal, reacted acrosome and DNA damaged sperm rates were similar (P > 0.05) in both protocols. It was concluded that both protocols used in this study provided reasonable post-thaw parameters; however, P2 yielded better motility and live sperm rate compared to P1.  相似文献   
77.
Age, growth, spawning period and maturity of the solenette (Buglossidium luteum Risso, 1810) were studied in the central Aegean Sea to provide fisheries managers with essential data for science‐based management. A total of 1220 samples were collected by trawl hauls from July 2004 to June 2007 in ?zmir Bay (Turkey). Sample sizes ranging from 5.3 to 11.6 cm total length were composed of 46% females, 32% males and 22% immature individuals, with a female to male ratio of 1 : 0.7. Age composition stages of the females were from I to IV, and males between I and III. The length–weight relationship was calculated as W = 0.0101L3.008 for all samples. Estimated von Bertalanffy growth parameters were L = 13.30 cm, to = ?0.440 year and k = 0.481 year?1, with a growth performance index of 1.93 (?’). The spawning period began in April and continued until July. Lengths at first maturity of females and males were 8.1 and 7.9 cm total length, respectively. Both sexes matured at the age of 2 years.  相似文献   
78.
Lake Okaro is a small, warm monomictic lake in central North Island, New Zealand, which progressed from oligotrophic to eutrophic through the 1960s. Trends in phosphorus (P) concentrations in the lake are linked to multiple restoration efforts over a 5-year period (2003–2008). The restoration procedures include a 2.3 ha constructed wetland established in February 2006 and riparian margin protection to reduce external loading, as well as an Alum application in December 2003 and sediment capping using modified zeolite in September 2008 to reduce internal loading. The annual average total phosphorus (TP) concentration in the lake decreased by 41% from 2004–2005 to 2007–2008. Two predictive models based on external P loading data generally underestimated the measured TP concentrations in the water column due to internal P loading. The relatively rapid response of TP concentrations after reduction of the internal loading using modified zeolite suggests that this technique can effect a rapid decrease in lake water TP concentrations though the trophic state of Lake Okaro showed high resilience to the reduced P loading. It is concluded that the combined effect of all restoration procedures resulted in a relatively rapid decrease in TP concentrations in Lake Okaro, which may be prolonged by continued external load reduction.  相似文献   
79.
80.
Six cycloartane-type triterpene glycosides were isolated from Astragalus icmadophilus along with two known cycloartane-type glycosides, five known oleanane-type triterpene glycosides and one known flavonol glycoside. The structures of the six compounds were established as 3-O-[α-L-arabinopyranosyl-(1  2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1  2)-O-α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxy cycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-3,4-diacetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24(S),25-pentahydroxycycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-3-acetoxy-α-L-arabinopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,25-tetrahydroxy-20(R),24(S)-epoxycycloartane, 3-O-[α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane, 3-O-[α-L-rhamnopyranosyl-(1  2)-O-α-L-arabinopyranosyl-(1  2)-O-β-D-xylopyranosyl]-6-O-β-D-glucopyranosyl-3β,6α,16β,24α-tetrahydroxy-20(R),25-epoxycycloartane by the extensive use of 1D- and 2D-NMR experiments along with ESIMS and HRMS analysis.The first four compounds are cyclocanthogenin and cycloastragenol glycosides, whereas the last two are based on cyclocephalogenin as aglycone, more unusual in the plant kingdom, so far reported only from Astragalus spp.  相似文献   
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