Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H-related 1 (CFHR1) and complement factor H-related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of approximately 84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes.     

Stimulation of the diadinoxanthin cycle by UV-B radiation in the diatom Phaeodactylum tricornutum

In this study we show that the diadinoxanthin cycle in the diatom Phaeodactylum tricornutum is stimulated by mild UV-B radiation. High steady state concentrations of diatoxanthin established during a period of strong actinic illumination with white light (300 mol photons m-2 s-1 PAR) are further increased if weak UV-B (3 mol photons m-2 s-1) is additionally applied. Short term increases in the diatoxanthin concentration caused by UV-B strongly correlate with a stoichiometric decrease in diadinoxanthin. The UV-B dependent increase in diatoxanthin is correlated with a concommitant enhancement of non-photochemical quenching of chlorophyll fluorescence and a decrease in the quantum efficiency of oxygen evolution. This indicates that UV-B induced diatoxanthin functions in thermal energy dissipation. Possible scenarios for a stimulation of the diadinoxanthin cycle by UV-B are discussed.     

Recurrent V1–V2 interaction in early visual boundary processing

A majority of cortical areas are connected via feedforward and feedback fiber projections. In feedforward pathways we mainly observe stages of feature detection and integration. The computational role of the descending pathways at different stages of processing remains mainly unknown. Based on empirical findings we suggest that the top-down feedback pathways subserve a context-dependent gain control mechanism. We propose a new computational model for recurrent contour processing in which normalized activities of orientation selective contrast cells are fed forward to the next processing stage. There, the arrangement of input activation is matched against local patterns of contour shape. The resulting activities are subsequently fed back to the previous stage to locally enhance those initial measurements that are consistent with the top-down generated responses. In all, we suggest a computational theory for recurrent processing in the visual cortex in which the significance of local measurements is evaluated on the basis of a broader visual context that is represented in terms of contour code patterns. The model serves as a framework to link physiological with perceptual data gathered in psychophysical experiments. It handles a variety of perceptual phenomena, such as the local grouping of fragmented shape outline, texture surround and density effects, and the interpolation of illusory contours. Received: 28 October 1998 / Accepted in revised form: 19 March 1999     

Diet, foraging, and use of space in wild golden-headed lion tamarins

Lion tamarins (Callitrichidae: Leontopithecus) are small frugi-faunivores that defend large home ranges. We describe results from the first long-term investigation of wild golden-headed lion tamarins (L. chrysomelas; GHLTs). We present data about activity budgets, daily activity cycles, diet, daily path length, home range size, home range overlap, and territorial encounters for three groups of GHLTs that were studied for 1.5-2.5 years in Una Biological Reserve, Bahia State, Brazil, an area characterized by aseasonal rainfall. We compare our results to those from other studies of lion tamarins to identify factors that may influence foraging and ranging patterns in this genus. Ripe fruit, nectar, insects, and small vertebrates were the primary components of the GHLT diet, and gums were rarely eaten. Fruit comprised the majority of plant feeding bouts, and the GHLTs ate at least 79 different species of plants from 32 families. The most common foraging sites for animal prey were epiphytic bromeliads. The GHLTs defended large home ranges averaging 123 ha, but showed strong affinities for core areas, spending 50% of their time in approximately 11% of their home range. Encounters with neighboring groups averaged two encounters every 9 days, and they were always aggressive. Data about time budgets and daily activity cycles reveal that the GHLTs spent most of their time foraging for resources or traveling between foraging sites distributed throughout their home ranges. The GHLTs spent much less time consuming exudates compared to lion tamarins in more seasonal environments. Additionally, the GHLTs had much larger home ranges than golden lion tamarins (L. rosalia), and did not engage in territorial encounters as frequently as L. rosalia. GHLT ranging patterns appear to be strongly influenced by resource acquisition and, to a lesser extent, by resource defense.     

Immune systems biology: immunoprofiling of cells and molecules

White blood cells and their secreted products are key elements of immune systems biology that are important indicators of patient health and disease. We have developed the SurroScan microvolume laser scanning cytometer to immunoprofile hundreds of variables, including cell populations, cell surface antigens, and intracellular molecules in antibody-based assays on small samples (about 1 mL) of whole blood, processed blood, or other fluids without cell purification or washing steps. The system enables high-throughput, robust and automated data capture and analysis. We demonstrate the utility of this immunoprofiling technology platform by surveying patient samples before and after glucocorticosteroid administration and show both the expected and novel response characteristics. This system complements recent advances in genomic and proteomic approaches to disease prediction and monitoring.