Involvement of RD20, a member of caleosin family,in ABA-mediated regulation of germination in Arabidopsis thaliana

The RD20 gene encodes a member of the caleosin family, which is primarily known to function in the mobilization of seed storage lipids during germination. In contrast to other caleosins, RD20 expression is early-induced by water deficit conditions and we recently provided genetic evidence for its positive role in drought tolerance in Arabidopsis. RD20 is also responsive to pathogen infection and is constitutively expressed in diverse tissues and organs during development suggesting additional roles for this caleosin. This addendum describes further exploration of phenotypic alterations in T-DNA insertional rd20 mutant and knock-out complemented transgenic plants in the context of early development and susceptibility to a phytopathogenic bacteria. We show that the RD20 gene is involved in ABA-mediated inhibition of germination and does not play a significant role in plant defense against Pseudomonas syringae.Key words: ABA, Arabidopsis thaliana, biotic stress, caleosin, germination, RD20     

miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response

Although there is evidence that redox regulation has an essential role in malignancies, its impact on tumor prognosis remains unclear. Here we show crosstalk between oxidative stress and the miR-200 family of microRNAs that affects tumorigenesis and chemosensitivity. miR-141 and miR-200a target p38α and modulate the oxidative stress response. Enhanced expression of these microRNAs mimics p38α deficiency and increases tumor growth in mouse models, but it also improves the response to chemotherapeutic agents. High-grade human ovarian adenocarcinomas that accumulate miR-200a have low concentrations of p38α and an associated oxidative stress signature. The miR200a-dependent stress signature correlates with improved survival of patients in response to treatment. Therefore, the role of miR-200a in stress could be a predictive marker for clinical outcome in ovarian cancer. In addition, although oxidative stress promotes tumor growth, it also sensitizes tumors to treatment, which could account for the limited success of antioxidants in clinical trials.     

Antifouling Bastadin Congeners Target Mussel Phenoloxidase and Complex Copper(II) Ions

Synthetically prepared congeners of sponge-derived bastadin derivatives such as 5,5′-dibromohemibastadin-1 (DBHB) that suppress the settling of barnacle larvae were identified in this study as strong inhibitors of blue mussel phenoloxidase that is involved in the firm attachment of mussels to a given substrate. The IC₅₀ value of DBHB as the most active enzyme inhibitor encountered in this study amounts to 0.84 μM. Inhibition of phenoloxidase by DBHB is likely due to complexation of copper(II) ions from the catalytic centre of the enzyme by the α-oxo-oxime moiety of the compound as shown here for the first time by structure activity studies and by X-ray structure determination of a copper(II) complex of DBHB.     

Rain forest expansion mediated by successional processes in vegetation thickets in the Western Ghats of India

Aim The objective of this study was to document succession from grassland thickets to rain forest, and to provide evidence for their potential as restoration tools. Location The Linganamakki region (State of Karnataka) of the Central Western Ghats of India. Method We selected thirty vegetation thickets ranging from 4 to 439 m² in area in the vicinity of rain forest. The area of each small thicket was estimated as an oval using its maximum length and its maximum width. When the shape was irregular (mostly in large thickets) the limits of the thicket were mapped and the area calculated from the map. Plant species were identified, the number of individuals was estimated and their heights measured. Results There was a progression in the thickets from early to late successional species. Small thickets were characterized by ecotone species and savanna trees such as Catunaregam dumetorum. Savanna trees served as a nucleus for thicket formation. Colonizing species were mostly bird‐dispersed. As succession proceeded in larger thickets, the proportion of evergreen, late‐successional rain forest trees increased. The species composition of the large thickets differed depending on the species composition of reproductive adults in the nearby forested areas. The species within small thickets were also found in the large thickets. The nestedness in species composition suggested that species turnover was deterministic based on thicket size. Human disturbance (leaf and wood collection by the local populations) affected the species composition and the species–area relationship of thickets. Main conclusions Vegetation thickets are nodal centres for rain forest colonization within grasslands. They expand and replace savanna. Early successional bird‐dispersed species established around savanna trees followed by late‐successional rain forest trees dispersed from the nearby forest by birds. Restoration programmes that reproduce natural successional processes such as those observed in thickets will be more successful and less expensive than the methods currently being employed, where trees are individually planted in grassland. Wood harvesting is the only factor that prevents thicket growth and coalescence and hampers forest expansion.     

Cutaneous Phaeohyphomycosis due to Alternaria Infectoria

Here we report a case of cutaneous alternariosis in a 74-year-old man treated by corticotherapy for myasthenia, and presenting with papular, crusted lesions on the left elbow and the right knee. Histological examination of the biopsy specimens showed fungal hyphae associated with round-shaped cells which were highly suggestive of alternariosis. Mycological culture allowed the isolation of a dematiaceous fungus which was identified as a member of the Alternaria infectoria species-group. This was confirmed by PCR amplification and sequencing of the internal transcribed spacer domain of the gene encoding nuclear ribosomal DNA and of the mitochondrial small subunit ribosomal DNA domain. The fungus was therefore referred to the Scientific Institute of Public Health where it was identified as Alternaria infectoria, on the basis of its very small 1 or 2-celled conidia often arranged in long chains and presenting with very long secondary conidiophores. Corticotherapy was stopped and a local antifungal treatment with ketoconazole was initiated, allowing the stabilisation of the cutaneous lesions within 2 months.     

Modelling Human Granulopoiesis under Poly-chemotherapy with G-CSF Support

Cytotoxic drugs administered in polychemotherapy cause a characteristic neutropenic period depending on the schedule of the drugs, which can partly be prevented by G-CSF growth factor support. To quantify these effects and to gain a deeper insight into the dynamics of bone marrow recovery after such suppressing and stimulating disturbances, we construct a biomathematical compartment model of human granulopoiesis under polychemotherapy with G-CSF support. The underlying assumptions and mathematical techniques used to obtain the model are explained in detail. A large variety of biological and clinical data as well as knowledge from a model of murine haematopoiesis are evaluated to construct a physiological model for humans.Particular emphasis is placed on estimating the influence of chemotherapeutic drugs on the granulopoietic system. As a result, we present an innovative method to estimate the bone marrow damage caused by cytotoxic drugs with respect to single identifiable cell stages only on the basis of measured peripheral blood leukocyte dynamics. Conversely, our model can be used in a planning phase of a clinical trial to estimate the haematotoxicity of regimens based on new combinations of drugs already considered and with or without growth factor support.Acknowledgement This paper was supported by the DFG (Deutsche Forschungsgemeinschaft) in the framework of the project Aufbau von Simulationsmodellen der h{\a}matopoetischen Dynamik nach konventioneller und hochdosierter Chemotherapie und Zytokingabe beim Menschen (Nr. LO 342/8-2). We would like to thank the German High Grade Non-Hodgkins-Lymphoma Study Group and the German Hodgkins Lymphoma Study Group for the kind provision of data.     

Development of an efficient strategy for the synthesis of the ETB receptor antagonist BQ-788 and some related analogues

BQ-788 [N-cis-2,6-dimethylpiperidine-1-carbonyl-L-gamma-methylleucyl-D-1-methoxycarbonyltryptophanyl-D-norleucine sodium salt] is a very potent and selective ETB receptor antagonist. The formation of the highly hindered trisubstituted urea functionality in the peptide chain and the carbamination on the indole nitrogen of the tryptophan side chain are major challenges in the synthesis of this particular antagonist. Furthermore, the high cost of the unnatural amino acids in the sequence of BQ-788 and its reported synthesis render this pseudopeptide very expensive to produce. In order to improve the yield and to reduce the number of steps compared to previous reported syntheses, we developed an efficient strategy involving a novel one-pot procedure for the synthesis of a highly hindered trisubstituted urea. Under very mild conditions, the urea was obtained by using triphosgene and sodium iodide. This strategy allowed us to synthesize BQ-788 in seven steps with an overall yield of 53%. We also generalized the use of this powerful methodology by creating some new structural analogues of the cis-2,6-dimethylpiperidine moiety by replacing it with other bulky secondary amines. We evaluated the antagonist properties of those three new analogues of BQ-788 in two bioassays in vitro. These new antagonists were less potent than BQ-788 in an ETB rich preparation and inactive in an ETA rich preparation.     

Relationship between allelic state of T-DNA and DNA methylation of chromosomal integration region in transformed <Emphasis Type="Italic">Arabidopsis thaliana</Emphasis> plants

T-DNA insertions are currently used as a tool to introduce, or knock out, specific genes. The expression of the inserted gene is frequently haphazard and up to now, it was proposed that transgene expression depends on the site of insertion within the genome, as well as the number of copies of the transgene. In this paper, we show that the allelic state of a T-DNA insertion can be at the origin of epigenetic silencing. A T-DNA insertional mutant was characterized to explore the function of AtBP80a′, a vacuolar sorting receptor previously associated with germination. Seeds homozygous for the T-DNA do not germinate, but this can be overcome by a cold treatment and maintained by the following generations. The non-germinating phenotype is only observed in homozygous seed produced by heterozygous plants indicating that it is correlated with the allelic state of the T-DNA in parental lines. Analysis of the region between the T-DNA insertion and the ATG codon of atbp80a′ showed that cytosine methylation is highly enhanced in chromatin containing the T-DNA. Data presented here show that an unpaired DNA region during meiosis could be at the origin of a de novo cytosine methylation mechanism.