Transparency improves concealment in cryptically coloured moths

Predation is a ubiquitous and strong selective pressure on living organisms. Transparency is a predation defence widespread in water but rare on land. Some Lepidoptera display transparent patches combined with already cryptic opaque patches. A recent study showed that transparency reduced detectability of aposematic prey with conspicuous patches. However, whether transparency has any effect at reducing detectability of already cryptic prey is still unknown. We conducted field predation experiments with free avian predators where we monitored and compared survival of a fully opaque grey artificial form (cryptic), a form including transparent windows and a wingless artificial butterfly body. Survival of the transparent forms was similar to that of wingless bodies and higher than that of fully opaque forms, suggesting a reduction of detectability conferred by transparency. This is the first evidence that transparency decreases detectability in cryptic terrestrial prey. Future studies should explore the organization of transparent and opaque patches in animals and their interplay on survival, as well as the costs and other potential benefits associated with transparency on land.     

Repair of DNA damage induced by the mycotoxin alternariol involves tyrosyl-DNA phosphodiesterase 1

Alternariol (AOH) was reported recently to act as a topoisomerase poison. To underline the relevance of topoisomerase targeting for the genotoxic properties of AOH, we addressed the question whether human tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme vital to the repair of covalent DNA-topoisomerase adducts, affects AOH-mediated genotoxicity. The relevance of TDP1 activity on AOH-induced genotoxicity was investigated by the comet assay in human cells overexpressing GFP chimera of TDP1 or the inactive mutant TDP1^H263A as well as in cells subjected to siRNA-mediated knock-down of endogenous TDP1. Cells overexpressing TDP1 exhibited significantly less DNA damage after treatment with AOH in comparison to cells expressing the inactive mutant TDP1^H263A. In accordance with these results, levels of AOH inducing DNA strand breaks were increased in TDP1-suppressed cells in comparison to cells transfected with control siRNA. The specific topoisomerase poisons camptothecin and etoposide caused comparable effects, underlining that TDP1 plays an important role in the repair of topoisomerase-mediated DNA damage. In summary, the repair enzyme TDP1 was identified as a factor for the modulation of AOH-mediated DNA damage in human cells.     

A model of erythropoiesis in adults with sufficient iron availability

In this paper we present a model for erythropoiesis under the basic assumption that sufficient iron availability is guaranteed. An extension of the model including a sub-model for the iron dynamics in the body is topic of present research efforts. The model gives excellent results for a number of important situations: recovery of the red blood cell mass after blood donation, adaptation of the number of red blood cells to changes in the altitude of residence and, most important, the reaction of the body to different administration regimens of erythropoiesis stimulating agents, as for instance in the case of pre-surgical administration of Epoetin-α. The simulation results concerning the last item show that choosing an appropriate administration regimen can reduce the total amount of the administered drug considerably. The core of the model consists of structured population equations for the different cell populations which are considered. A key feature of the model is the incorporation of neocytolysis.     

Apolipoprotein E and Low-Density Lipoprotein Binding and Internalization in Primary Cultures of Rat Astrocytes: Isoform-Specific Alterations

Abstract: Apolipoprotein (apo) E is likely involved in redistributing cholesterol and phospholipids during compensatory synaptogenesis in the injured CNS. Three common isoforms of apoE exist in human (E2, E3, and E4). The apoE4 allele frequency is markedly increased in both late-onset sporadic and familial Alzheimer's disease (AD). ApoE concentration in the brain of AD subjects follows a gradient: ApoE levels decrease as a function of E2 > E3 ? E4. It has been proposed that the poor reinnervation capacity reported in AD may be caused by impairment of the apoE/low-density lipoprotein (LDL) receptor activity. To understand further the role of this particular axis in lipid homeostasis in the CNS, we have characterized binding, internalization, and degradation of human ¹²⁵I-LDL to primary cultures of rat astrocytes. Specific binding was saturable, with a K_D of 1.8 nM and a B_max of 0.14 pmol/mg of proteins. Excess unlabeled human LDL or very LDL (VLDL) displaced 70% of total binding. Studies at 37°C confirmed that astrocytes bind, internalize, and degrade ¹²⁵I-LDL by a specific, saturable mechanism. Reconstituted apoE (E2, E3, and E4)-liposomes were labeled with ¹²⁵I and incubated with primary cultures of rat astrocytes and hippocampal neurons to examine specific binding. Human LDL and VLDL displaced binding and internalization of all apoE isoforms similarly in both astrocytes and neurons. ¹²⁵I-ApoE2 binding was significantly lower than that of the other ¹²⁵I-apoE isoforms in both cell types. ¹²⁵I-ApoE4 binding was similar to that of ¹²⁵I-apoE3 in both astrocytes and neurons. On the other hand, ¹²⁵I-apoE3 binding was significantly higher in neurons than in astrocytes. These isoform-specific alterations in apoE-lipoprotein pathway could explain some of the differences reported in the pathophysiology of AD subjects carrying different apoE alleles.     

Heterotrimeric G proteins in heart disease

Guanine nucleotide binding proteins (G proteins) are largely grouped into three classes: heterotrimeric G proteins, ras-like or small molecular weight GTP binding proteins, and others like Gh. In the heart G proteins transduce signals from a variety of membrane receptors to generate diverse effects on contractility, heart rate, and myocyte growth. This central position of G proteins forming a switchboard between extracellular signals and intracellular effectors makes them candidates possibly involved in the pathogenesis of cardiac hypertrophy, heart failure, and arrhythmia. This review focuses primarily on discoveries of heterotrimeric G protein alterations in heart diseases that help us to understand the pathogenesis and pathophysiology. We also discuss the underlying molecular mechanisms of heterotrimeric G protein signalling.     

Enzymatic resynthesis of the "reactive site" bond in the modified aprotinin derivatives [seco-15/16]aprotinin and [Di-seco-15/16,39/40]aprotinin

On incubation of [di-seco-15/16,39/40]aprotinin with human plasmin, porcine pancreatic kallikrein or bovine or porcine trypsin in neutral or slightly alkaline solutions [seco-39/40]aprotinin is slowly formed with enzymatic resynthesis of the reactive-site bond 15/16. With chymotrypsin, however, further degradation of [di-seco-15/16,39/40]aprotinin takes place without enzymatic resynthesis. The apparent rate constants for the synthesis of [seco-39/40]aprotinin with kallikrein and trypsin have been determined and indicate that the bond-forming reaction is 10-200-fold slower with [di-seco-15/16,39/40]aprotinin than with [seco-15/16]aprotinin. The newly formed [seco-39/40]aprotinin has similar kinetic constants for the complexation with its cognate enzymes as aprotinin, indicating that any distortion of the secondary binding region due to cleavage of the Arg39-Ala40 bond does not seriously influence binding and affinities.