Aggregation Properties of the Small Nuclear Ribonucleoprotein U1-70K in Alzheimer Disease

Recent evidence indicates that U1-70K and other U1 small nuclear ribonucleoproteins are Sarkosyl-insoluble and associate with Tau neurofibrillary tangles selectively in Alzheimer disease (AD). Currently, the mechanisms underlying the conversion of soluble nuclear U1 small nuclear ribonucleoproteins into insoluble cytoplasmic aggregates remain elusive. Based on the biochemical and subcellular distribution properties of U1-70K in AD, we hypothesized that aggregated U1-70K itself or other biopolymers (e.g. proteins or nucleic acids) interact with and sequester natively folded soluble U1-70K into insoluble aggregates. Here, we demonstrate that total homogenates from AD brain induce soluble U1-70K from control brain or recombinant U1-70K to become Sarkosyl-insoluble. This effect was not dependent on RNA and did not correlate with detergent-insoluble Tau levels as AD homogenates with reduced levels of these components were still capable of inducing U1-70K aggregation. In contrast, proteinase K-treated AD homogenates and Sarkosyl-soluble AD fractions were unable to induce U1-70K aggregation, indicating that aggregated proteins in AD brain are responsible for inducing soluble U1-70K aggregation. It was determined that the C terminus of U1-70K, which harbors two disordered low complexity (LC) domains, is necessary for U1-70K aggregation. Moreover, both LC1 and LC2 domains were sufficient for aggregation. Finally, protein cross-linking and mass spectrometry studies demonstrated that a U1-70K fragment harboring the LC1 domain directly interacts with aggregated U1-70K in AD brain. Our results support a hypothesis that aberrant forms of U1-70K in AD can directly sequester soluble forms of U1-70K into insoluble aggregates.     

Ecology and systematics of a new species of Uromunna (Crustacea: Isopoda) from Spanish eelgrass beds

Uromunna naherba sp. nov. is described from eelgrass beds (Zostera marina and Z. noltii) of the NW Iberian Peninsula. This is the second species of the genus reported from the NE Atlantic, after U. petiti. The new species was more abundant on rhizomes than on the leaves of the plants. Seasonal samples show that ovigerous females are present throughout the year, but become more abundant in late spring and summer, when adult males decrease in frequency. Ovigerous females appear in only one size class. Owing to the yearly productivity cycle of the eelgrasses, these data suggest that the species is semelparous and completes its lifecycle within 1 year. The taxonomic characters of the genus are discussed.     

Caveolin-1 upregulation contributes to c-Myc-induced high-grade prostatic intraepithelial neoplasia and prostate cancer

Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer cells and showed that it promotes prostate cancer progression. Here, we report that Cav-1 was overexpressed in 41.7% (15 of 36) of human high-grade prostatic intraepithelial neoplasia (HGPIN) specimens obtained during radical prostatectomies. Positive correlations exist between Cav-1-positive (Cav-1(+)) HGPIN and Cav-1(+) primary prostate cancer (rho = 0.655, P < 0.0001) and between Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether Cav-1 cooperates with c-Myc in development of premalignant lesions and prostate cancer in vivo, we generated transgenic mice with c-Myc overexpression driven by the ARR(2)PB promoter. In this ARR(2)PB-c-myc model, Cav-1 overexpression was found in mouse PIN (mPIN) lesions and prostate cancer cells and was associated with a significantly higher ratio of proliferative to apoptotic labeling in mPIN lesions than in the Cav-1-negative epithelia adjacent to those lesions (10.02 vs. 4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels of P-Akt and VEGF-A, which were previously associated with Cav-1-induced prostate cancer cell survival and positive feedback regulation of cellular Cav-1 levels, respectively. In multiple prostate cancer cell lines, Cav-1 protein (but not mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection abrogated c-Myc-induced Cav-1 overexpression, suggesting a c-Myc-VEGF-Cav-1 signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc in the development of HGPIN and prostate cancer. Furthermore, Cav-1 overexpression in HGPIN is potentially a biomarker for early identification of patients who tend to develop Cav-1(+) primary prostate cancer.     

Simple and sensitive method for quantification of low tobramycin concentrations in human plasma using HPLC-MS/MS

After oral administration of tobramycin, as part of selective decontamination of the digestive tract (SDD) in critically ill patients, absorption of tobramycin from the gut into the blood may take place. To quantify low concentrations of tobramycin in human plasma, we developed and validated a simple (sample pre-treatment consisting of protein precipitation with acetonitrile using 200microl plasma), rapid (runtime 3min using a Pathfinder MR reversed-phase column) and sensitive (concentration range of 0.05-1.0mg/l using MS/MS detection) method.     

Anatomical and taxonomical studies of the Antarctic nudibranchsAustrodoris kerguelenensis (Bergh, 1884) andA. georgiensis n. sp. from the Scotia Sea

During the expedition ANTARTIDA 8611 to the Scotia Sea, organized by the Spanish Oceanographic Institute, several specimens ofAustrodoris were collected. Although nearly all have been identified asAustrodoris kerguelenensis (Bergh, 1884), one of them shows some anatomical features, mainly related to the reproductive system, that allows us to identify this specimen as a new species, which we have namedA. georgiensis. Therefore, with the aim of clarifying the taxonomical value of this species, a comparative study of the anatomy ofA. kerguelenensis andA. georgiensis is presented. Some new data on the diet ofA. kerguelenensis are also presented.     

Terminal deletion of (1)(q42) and its phenotypical manifestations

Summary A 5-year-old male with multiple malformations (dwarfism, microcephalia with brachycephalic shape of skull, mongoloid lid axis, epicanthus, convergent strabismus, flat root of the nose, micrognathia, missing uvula, deformed low-set ears, hypoplastic genitals, and general hypotonia), severe mental retardation, and cerebral paroxysms caused by a partial monosomy (1)(q42qter) is described. This case is compared with other cases with a partial monosomy or ring-1 chromosomes.To whom offprint requests should be sent     

Description of the antarctic notaspideanPolictenidia tomasi gen.nov. and sp.nov. (Gastropoda,Opisthobranchia) from the Scotia Sea proposing also a new notaspidean tribe

During the expedition “ANTARTIDA 9101”, organized by the Spanish Oceanographic Institute, two specimens of an unknown notaspidean species were collected. These differed considerably from other notaspidean species, mainly by the presence of three gills and a prebranchial sac with large external expansions. Since these specimens have three gills, while members of the order Notaspidea have been described as having only one, this feature is doubly interesting: firstly, from the systematic point of view, the definition of the order has to be modified, and secondly, it generates a phylogenetic discussion of the possible affinity between the notaspideans with one gill and doridaceans, which possess several gills.