Phylogenetic biogeography and classification of the Drosophila montium species group (Diptera: Drosophilidae)

The Drosophila montium group is the largest clade of the subgenus Sophophora consisting of 94 palaeotropical species, whose phylogenetic relationships remain unclear. Here, I used a recent tree inferred from three nuclear genes and one mitochondrial gene for almost half of the species to reconstruct the historical biogeography of the group and propose a comprehensive classification for the totality of its species. The group originated in South-East Asia nearly 20 million years ago (mya), and dispersed to Africa in the Late Miocene. A second northward expansion into East Asia took place in the Pliocene. Based on morphological (male abdominal pigmentation and genitalia) and chorological traits congruent with the molecular tree, I divide the montium group into seven subgroups: parvula, montium, punjabiensis, serrata, kikkawai, seguyi and orosa. The polyphyletic status of some of the previously defined complexes (auraria, jambulina, serrata, kikkawai and nikananu) is also resolved.     

Karyological studies in Sonchus section Muritimi (Asteraceae) from the Iberian Peninsula

MEJÍAS, J. A. & VALDÉS, B., 1988. Karyologiepl studies in Sonchus section Madtimi (Asteraceae) from the Iberian Peninmula. Karyological data support the distinction of S. aquatilis Pourret and S. maritimus L. at the specific level. Karyological data and hybridization experiments support the idea that S. × novocaslcllanus Cirujano has been produced by the hybridization of S. crassifolius Pourret ex Willd. and S. maritimus L.     

Characterization of the iron-containing superoxide dismutase and its response to stress in cyanobacterium Spirulina (Arthrospira) platensis

Superoxide dismutase (SOD) is considered a primary antioxidant which defends against reactive oxygen species that are induced by environmental stress. In this study, we examined changes in SOD activity and expression in the cyanobacterium Spirulina (Arthrospira) platensis under iron and salinity stress; we characterized its induction under these stress conditions and we overexpressed the enzyme in a bacterial host for preliminary characterization. Analysis of SOD isoforms concludes that S. platensis was found to regulate only the iron-containing SOD isoform (FeSOD) in response to two types of stress that were tested. The FeSOD expression (on the level of both mRNA and enzyme activity) was induced by the stress conditions of salinity and iron levels. The FeSOD from S. platensis was overexpressed in Escherichia coli BL21. The recombinant FeSOD protein (about 23 kDa) was purified for characterization. It showed high specific activity and pH stability at 6.0–9.0, and it is relatively thermostable, retaining 45 % of its activity after 30 min at 90 °C. Phylogenetic analysis reveals that S. platensis FeSOD is grouped with the FeSODs from other cyanobacterial species and separated from those of the eukaryotic Chlorophyta, suggesting that the FeSOD gene may be used as a molecular marker in physiological, phylogenetic, and taxonomic studies. This study also suggests that the increased activity and expression of SOD may play a role in algal survival under stress conditions.     

Targeting HER2: A report on the in vitro and in vivo pre-clinical data supporting trastuzumab as a radioimmunoconjugate for clinical trials

The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A″-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of ¹¹¹In-trastuzumab by melanoma (A375) s.c. xenografts and ¹¹¹In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected ¹¹¹In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of ¹¹¹In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by γ-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected ¹¹¹In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.Key words: monoclonal antibody, HER2, trastuzumab, radioimmunodiagnosis, radioimmunotherapy     

A high level interface to SCOP and ASTRAL implemented in Python

Background  

Benchmarking algorithms in structural bioinformatics often involves the construction of datasets of proteins with given sequence and structural properties. The SCOP database is a manually curated structural classification which groups together proteins on the basis of structural similarity. The ASTRAL compendium provides non redundant subsets of SCOP domains on the basis of sequence similarity such that no two domains in a given subset share more than a defined degree of sequence similarity. Taken together these two resources provide a 'ground truth' for assessing structural bioinformatics algorithms. We present a small and easy to use API written in python to enable construction of datasets from these resources.     

In Vitro Transformation of Primary Human CD34+ Cells by AML Fusion Oncogenes: Early Gene Expression Profiling Reveals Possible Drug Target in AML

Different fusion oncogenes in acute myeloid leukemia (AML) have distinct clinical and laboratory features suggesting different modes of malignant transformation. Here we compare the in vitro effects of representatives of 4 major groups of AML fusion oncogenes on primary human CD34+ cells. As expected from their clinical similarities, MLL-AF9 and NUP98-HOXA9 had very similar effects in vitro. They both caused erythroid hyperplasia and a clear block in erythroid and myeloid maturation. On the other hand, AML1-ETO and PML-RARA had only modest effects on myeloid and erythroid differentiation. All oncogenes except PML-RARA caused a dramatic increase in long-term proliferation and self-renewal. Gene expression profiling revealed two distinct temporal patterns of gene deregulation. Gene deregulation by MLL-AF9 and NUP98-HOXA9 peaked 3 days after transduction. In contrast, the vast majority of gene deregulation by AML1-ETO and PML-RARA occurred within 6 hours, followed by a dramatic drop in the numbers of deregulated genes. Interestingly, the p53 inhibitor MDM2 was upregulated by AML1-ETO at 6 hours. Nutlin-3, an inhibitor of the interaction between MDM2 and p53, specifically inhibited the proliferation and self-renewal of primary human CD34+ cells transduced with AML1-ETO, suggesting that MDM2 upregulation plays a role in cell transformation by AML1-ETO. These data show that differences among AML fusion oncogenes can be recapitulated in vitro using primary human CD34+ cells and that early gene expression profiling in these cells can reveal potential drug targets in AML.