Mutations affecting retina development in Medaka

In a large scale mutagenesis screen of Medaka we identified 60 recessive zygotic mutations that affect retina development. Based on the onset and type of phenotypic abnormalities, the mutants were grouped into five categories: the first includes 11 mutants that are affected in neural plate and optic vesicle formation. The second group comprises 15 mutants that are impaired in optic vesicle growth. The third group includes 18 mutants that are affected in optic cup development. The fourth group contains 13 mutants with defects in retinal differentiation. 12 of these have smaller eyes, whereas one mutation results in enlarged eyes. The fifth group consists of three mutants with defects in retinal pigmentation. The collection of mutants will be used to address the molecular genetic mechanisms underlying vertebrate eye formation.     

Release of copper from yeast copper-thionein after S-alkylation of copper-thiolate clusters.

Our knowledge on the release of copper from Cu-thionein in biological systems is limited. Other than oxidative cleavage or direct transfer, the possibility of an alkylation mechanism seemed attractive. Iodoacetamide and methyl methanesulphonate were successfully employed to alkylate the Cu-thiolate sulphur atom of homogeneous Cu(I)-thionein from yeast. The alkylation caused a weakening of the Cu-S bonding, which led to the release of copper. After equilibrium dialysis a proportion of the released copper was found in the dialysis buffer. When iodoacetamide was used carboxymethylcysteine was detected in the protein hydrolysate. A 10-fold molar excess over cysteine was sufficient for complete alkylation, which could be conveniently monitored by c.d. at 328 and 359 nm. The reaction proceeded under both aerobic and anaerobic conditions. E.p.r. measurements of Cu2+ revealed unequivocally the complete cleavage of the Cu-thiolate bonding in less than 5 h. It is possible that this mode of copper release might be of relevance to the molecular transport of this biochemically important transition metal.     

Negative Regulation of Bone Formation by the Transmembrane Wnt Antagonist Kremen-2

Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders.     

Regulation of cell behaviour by plant receptor kinases: Pattern recognition receptors as prototypical models

In this review we focus on pattern recognition receptors in plants that detect extracellular signals indicative for pathogen attack and injury. We start out with a discussion on FLS2, which binds and responds to bacterial flagellin, and then concentrate on ligand–receptor interactions as initial steps in the molecular receptor activation process. Comparison with other receptor kinases, whether involved in plant immunity or regulation of other cellular programs, might indicate common principles of receptor activation.     

Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita,western Kenya

Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4–16 years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya. Peripheral blood mononuclear cells were subjected to flow cytometric analysis and cultured to determine proliferative responses and cytokine production. The proportions of cellular subsets in children positive for P. falciparum infection at the level of microscopy were comparable to the negative children, except for a reduction in central memory-phenotype CD8⁺ T cells and natural killer cells. In functional studies, the production of cytokines by peripheral blood mononuclear cells in response to P. falciparum crude antigens exhibited strong heterogeneity among children. In addition, production of IL-2 in response to anti-CD3 and anti-CD28 monoclonal antibodies was significantly reduced in P. falciparum-positive children as compared to -negative children, suggesting a state of unresponsiveness. These data suggest that the quality of T cell immune responses is heterogeneous among asymptomatic children living in the endemic region of P. falciparum, and that the responses are generally suppressed by active infection with Plasmodium parasites.     

Tree-ring analysis and conifer growth responses to increased atmospheric CO2 levels

Summary Tree-ring data of naturally grown connifers were analyzed to evaluate the possibility of enhanced tree growth due to increased atmospheric CO₂. Tree cores were obtained from 34 sites in four different climatic regions in the northern hemisphere. In each of the four regions, the sampling sites were located along ecological gradients between the subalpine treeline and low elevations and, sometimes, the arid forest border. Growth trends after 1950, when the atmospheric CO₂ concentration increased by more than 30 l·l^-1 indicate an increase in ring-widths at eight of the 34 sites. These chronologies were from sites which moderate temperature or water stress. In four cases the growth increase in the post-1950 period coincided with favorable climatic conditions. In the remaining four cases, the growth increase exceeded the upper bound response expected from CO₂ enrichment experiments with seedling conifer species. Therefore, increased growth in any of the tree-ring chronologies examined could not be solely attributed to higher atmospheric CO₂ concentrations.Major financial supporters: Swiss National Science Foundation (application no. 1.869-0.83); Swiss Federal Institute of Forestry Research, 8903 Birmensdorf, Switzerland; other financial supporters: Carbon Dioxide Research Division, U.S. Department of Energy under subcontract no. 11X-57507V with Martin Marietta Energy Systems, IncOperated by Martin Marietta Energy Systems, Inc., under contract DE-AC05-840R21400 with U.S. Department of Energy     

Extending the scope of the controlled logical clock

Event traces are helpful in understanding the performance behavior of parallel applications since they allow the in-depth analysis of communication and synchronization patterns. However, the absence of synchronized clocks on most cluster systems may render the analysis ineffective because inaccurate relative event timings may misrepresent the logical event order and lead to errors when quantifying the impact of certain behaviors or confuse the users of time-line visualization tools by showing messages flowing backward in time. In our earlier work, we have developed a scalable algorithm called the controlled logical clock that eliminates inconsistent inter-process timings postmortem in traces of pure MPI applications, potentially running on large processor configurations. In this paper, we first demonstrate that our algorithm also proves beneficial in computational grids, where a single application is executed using the combined computational power of several geographically dispersed clusters. Second, we present an extended version of the algorithm that—in addition to message-passing event semantics—also preserves and restores shared-memory event semantics, enabling the correction of traces from hybrid applications.     

Ethnobotany of the Rama of Southeastern Nicaragua and Comparisons with Miskitu Plant Lore<Superscript>1</Superscript>

Ethnobotany of the Rama of Southeastern Nicaragua and Comparisons with Miskitu Plant Lore. The Rama are one of the three Amerindian groups of eastern Nicaragua. This is the first systematic study of Rama ethnobotany. A total of 249 plant species, in 190 genera and 78 families, were documented as useful. Included are 190 species used as medicinals, 80 as food plants, and 99 for other uses. The ethnobotanical lore of two distinct indigenous groups, the Rama and Miskitu, were compared. Out of 249 species used by the Rama, 171, or 69%, were used by both groups, and 78 unique species were used by the Rama. These results have important implications for the understanding of ethnobotany as they demonstrate how unrelated indigenous groups sharing the same ecosystem, though separated by some physical distance, can have significantly similar ethnobotanical lore.

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Resumen   Etnobotánica de los Ramas del Oriente Nicaragüense y Comparasiones con el Saber Etnobotánico de los Miskitus. Los Ramas constituyen uno de los tres grupos Amerindios del oriente Nicaragüense. Este es el primer studio sistemático de la etnobotánica Rama. Se documentó un total de 249 especies de plantas útiles en 190 géneros y 78 familias. Incluyendo 190 especies medicinales, 80 especies alimenticias y 99 especies para usos auxiliares. La erudición etnobotánica de los Ramas y los Miskitus fueron comparados. Un total de 171 de 249 especies documentadas son usados por ambos grupos y 78 especies solo por los Ramas. Estos resultados tienen implicaciones importantes para el entendimiento de la etnobotánica porque demuestran que grupos sin parentesco alguno que comparten el mismo ecosistema aunque separados por cierta distancia pueden tener una similitud significativa en la erudición etnobotánica.

     

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Introduction

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson''s disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1).

Materials and Methods

IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated.

Results

PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters.

Discussion

Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.