272. Poziom białka S-100 u chorych na czerniaka złośliwego w III i IV stopniu zaawansowania klinicznego

Cel pracyBiałko S-100 występuje fizjologicznie w komórkach układu nerwowego, mięśniach prążkowanych, makrofagach i melanocytach. Obecność tego białka stwierdzono również w komórkach czerniaka złośliwego. S-100 jest rutynowo stosowane do identyfikacji komórek czerniaka w diagnostyce histopatologicznej. W ostatnich latach stwierdzono podwyższony poziom białka S-100 we krwi obwodowej u chorych na czerniaka złośliwego. Celem pracy było porównanie poziomu białka S-100 w surowicy chorych na czerniaka w III i IV stopniu zaawansowania klinicznego.Materiał i metodyBadania przeprowadzono w grupie pacjentów, leczonych z powodu czerniaka w Wielkopolskim Centrum Onkologii. Diagnoza i stopień zaawansowania choroby były potwierdzone badaniami histopatologicznymi, klinicznymi i technikami obrazowymi (RTG, USG, TK). Oznaczenie poziomu białka S-100 wykonano w surowicy krwi chorych (44 pacjentów w III stopniu i 41 pacjentów w IV stopniu zaawansowania klinicznego) metodą immunoluminometryczną przy użyciu zestawu Liaison Sangtec S100. Równocześnie przeprowadzono badania kontrolne w surowicy krwi osób zdrowych (n=16). Jako punkt odcięcia (cut-off) przyjęto wartość zalecaną przez producenta 0.15 μg/1.WynikiPodwyższony poziom białka S-100 powyżej wartości cut-off (0,15 μg/l) stwierdzono u 15 z 44 (34%) pacjentów w III stopniu i u 32 z 41 (78%) pacjentów w IV stopniu zaawansowania klinicznego. Analiza statystyczna potwierdziła znamienną statystycznie różnicę między stężeniem białka S-100 w surowicach pochodzących od pacjentów w III i IV stopniu. Czułość stosowanej metody wyniosła 55%, swoistość 100%, dodatnia wartość predykcyjna 100%, ujemna wartość predykcyjna 30%.WnioskiWyniki badań wskazują, że oznaczanie poziomu białka S-100 w surowicy może być dodatkowym wskaźnikiem laboratoryjnym w ocenie stopnia zaawansowania klinicznego chorych na czerniaka złośliwego

Phase Transition in Sexual Reproduction and Biological Evolution

Using Monte Carlo model of biological evolution we have discovered that populations can switch between two different strategies of their genomes' evolution; Darwinian purifying selection and complementing the haplotypes. The first one is exploited in the large panmictic populations while the second one in the small highly inbred populations. The choice depends on the crossover frequency. There is a power law relation between the critical value of crossover frequency and the size of panmictic population. Under the constant inbreeding this critical value of crossover does not depend on the population size and has a character of phase transition. Close to this value sympatric speciation is observed.Comment: 13 pages, 8 figure

Chromatic Illumination Discrimination Ability Reveals that Human Colour Constancy Is Optimised for Blue Daylight Illuminations

The phenomenon of colour constancy in human visual perception keeps surface colours constant, despite changes in their reflected light due to changing illumination. Although colour constancy has evolved under a constrained subset of illuminations, it is unknown whether its underlying mechanisms, thought to involve multiple components from retina to cortex, are optimised for particular environmental variations. Here we demonstrate a new method for investigating colour constancy using illumination matching in real scenes which, unlike previous methods using surface matching and simulated scenes, allows testing of multiple, real illuminations. We use real scenes consisting of solid familiar or unfamiliar objects against uniform or variegated backgrounds and compare discrimination performance for typical illuminations from the daylight chromaticity locus (approximately blue-yellow) and atypical spectra from an orthogonal locus (approximately red-green, at correlated colour temperature 6700 K), all produced in real time by a 10-channel LED illuminator. We find that discrimination of illumination changes is poorer along the daylight locus than the atypical locus, and is poorest particularly for bluer illumination changes, demonstrating conversely that surface colour constancy is best for blue daylight illuminations. Illumination discrimination is also enhanced, and therefore colour constancy diminished, for uniform backgrounds, irrespective of the object type. These results are not explained by statistical properties of the scene signal changes at the retinal level. We conclude that high-level mechanisms of colour constancy are biased for the blue daylight illuminations and variegated backgrounds to which the human visual system has typically been exposed

Role of Homer Proteins in the Maintenance of Sleep-Wake States

Sleep is an evolutionarily conserved process that is linked to diurnal cycles and normal daytime wakefulness. Healthy sleep and wakefulness are integral to a healthy lifestyle; this occurs when an organism is able to maintain long bouts of both sleep and wake. Homer proteins, which function as adaptors for group 1 metabotropic glutamate receptors, have been implicated in genetic studies of sleep in both Drosophila and mouse. Drosophila express a single Homer gene product that is upregulated during sleep. By contrast, vertebrates express Homer as both constitutive and immediate early gene (H1a) forms, and H1a is up-regulated during wakefulness. Genetic deletion of Homer in Drosophila results in fragmented sleep and in failure to sustain long bouts of sleep, even under increased sleep drive. However, deletion of Homer1a in mouse results in failure to sustain long bouts of wakefulness. Further evidence for the role of Homer1a in the maintenance of wake comes from the CREB alpha delta mutant mouse, which displays a reduced wake phenotype similar to the Homer1a knockout and fails to up-regulate Homer1a upon sleep loss. Homer1a is a gene whose expression is induced by CREB. Sustained behaviors of the sleep/wake cycle are created by molecular pathways that are distinct from those for arousal or short bouts, and implicate an evolutionarily-conserved role for Homer in sustaining these behaviors

Limits of Calcium Clearance by Plasma Membrane Calcium ATPase in Olfactory Cilia

BACKGROUND: In any fine sensory organelle, a small influx of Ca(2+) can quickly elevate cytoplasmic Ca(2+). Mechanisms must exist to clear the ciliary Ca(2+) before it reaches toxic levels. One such organelle has been well studied: the vertebrate olfactory cilium. Recent studies have suggested that clearance from the olfactory cilium is mediated in part by plasma membrane Ca(2+)-ATPase (PMCA). PRINCIPAL FINDINGS: In the present study, electrophysiological assays were devised to monitor cytoplasmic free Ca(2+) in single frog olfactory cilia. Ca(2+) was allowed to enter isolated cilia, either through the detached end or through membrane channels. Intraciliary Ca(2+) was monitored via the activity of ciliary Ca(2+)-gated Cl(-) channels, which are sensitive to free Ca(2+) from about 2 to 10 microM. No significant effect of MgATP on intraciliary free Ca(2+) could be found. Carboxyeosin, which has been used to inhibit PMCA, was found to substantially increase a ciliary transduction current activated by cyclic AMP. This increase was ATP-independent. CONCLUSIONS: Alternative explanations are suggested for two previous experiments taken to support a role for PMCA in ciliary Ca(2+) clearance. It is concluded that PMCA in the cilium plays a very limited role in clearing the micromolar levels of intraciliary Ca(2+) produced during the odor response

Atypical AT Skew in Firmicute Genomes Results from Selection and Not from Mutation

The second parity rule states that, if there is no bias in mutation or selection, then within each strand of DNA complementary bases are present at approximately equal frequencies. In bacteria, however, there is commonly an excess of G (over C) and, to a lesser extent, T (over A) in the replicatory leading strand. The low G+C Firmicutes, such as Staphylococcus aureus, are unusual in displaying an excess of A over T on the leading strand. As mutation has been established as a major force in the generation of such skews across various bacterial taxa, this anomaly has been assumed to reflect unusual mutation biases in Firmicute genomes. Here we show that this is not the case and that mutation bias does not explain the atypical AT skew seen in S. aureus. First, recently arisen intergenic SNPs predict the classical replication-derived equilibrium enrichment of T relative to A, contrary to what is observed. Second, sites predicted to be under weak purifying selection display only weak AT skew. Third, AT skew is primarily associated with largely non-synonymous first and second codon sites and is seen with respect to their sense direction, not which replicating strand they lie on. The atypical AT skew we show to be a consequence of the strong bias for genes to be co-oriented with the replicating fork, coupled with the selective avoidance of both stop codons and costly amino acids, which tend to have T-rich codons. That intergenic sequence has more A than T, while at mutational equilibrium a preponderance of T is expected, points to a possible further unresolved selective source of skew