Evolutionary contingency and SETI revisited

The well-known argument against the Search for ExtraTerrestrial Intelligence (SETI) due to George Gaylord Simpson is re-analyzed almost half a century later, in the light of our improved understanding of preconditions for the emergence of life and intelligence brought about by the ongoing “astrobiological revolution”. Simpson’s argument has been enormously influential, in particular in biological circles, and it arguably fueled the most serious opposition to SETI programmes and their funding. I argue that both proponents and opponents of Simpson’s argument have occasionally mispresented its core content. Proponents often oversimplify it as just another consequence of biological contingency, thus leaving their position open to general arguments limiting the scope of contingency in evolution (such as the recent argument of Geerat Vermeij based on selection effects in the fossil record). They also tend to neglect that the argument has been presented as essentially atemporal, while referring to entities and processes that are likely to change over time; this has become even less justifiable as our astrobiological knowledge increased in recent years. Opponents have failed to see that the weaknesses in Simpson’s position could be removed by restructuring of the argument; I suggest one way of such restructuring, envisioned long ago in the fictional context by Stanislaw Lem. While no firm consensus has emerged on the validity of Simpson’s argument so far, I suggest that, contrary to the original motivation, today it is less an anti-SETI argument, and more an astrobiological research programme. In this research programme, SETI could be generalized into a platform for testing some of the deepest assumptions about evolutionary continuity and the relative role of contingency versus convergence on unprecedented spatial and temporal scales.     

Orthosteric Binding of ρ-Da1a,a Natural Peptide of Snake Venom Interacting Selectively with the α1A-Adrenoceptor

ρ-Da1a is a three-finger fold toxin from green mamba venom that is highly selective for the α_1A-adrenoceptor. This toxin has atypical pharmacological properties, including incomplete inhibition of ³H-prazosin or ¹²⁵I-HEAT binding and insurmountable antagonist action. We aimed to clarify its mode of action at the α_1A-adrenoceptor. The affinity (pKi 9.26) and selectivity of ρ-Da1a for the α_1A-adrenoceptor were confirmed by comparing binding to human adrenoceptors expressed in eukaryotic cells. Equilibrium and kinetic binding experiments were used to demonstrate that ρ-Da1a, prazosin and HEAT compete at the α_1A-adrenoceptor. ρ-Da1a did not affect the dissociation kinetics of ³H-prazosin or ¹²⁵I-HEAT, and the IC₅₀ of ρ-Da1a, determined by competition experiments, increased linearly with the concentration of radioligands used, while the residual binding by ρ-Da1a remained stable. The effect of ρ-Da1a on agonist-stimulated Ca²⁺ release was insurmountable in the presence of phenethylamine- or imidazoline-type agonists. Ten mutations in the orthosteric binding pocket of the α_1A-adrenoceptor were evaluated for alterations in ρ-Da1a affinity. The D106^3.32A and the S188^5.42A/S192^5.46A receptor mutations reduced toxin affinity moderately (6 and 7.6 times, respectively), while the F86^2.64A, F288^6.51A and F312^7.39A mutations diminished it dramatically by 18- to 93-fold. In addition, residue F86^2.64 was identified as a key interaction point for ¹²⁵I-HEAT, as the variant F86^2.64A induced a 23-fold reduction in HEAT affinity. Unlike the M1 muscarinic acetylcholine receptor toxin MT7, ρ-Da1a interacts with the human α_1A-adrenoceptor orthosteric pocket and shares receptor interaction points with antagonist (F86^2.64, F288^6.51 and F312^7.39) and agonist (F288^6.51 and F312^7.39) ligands. Its selectivity for the α_1A-adrenoceptor may result, at least partly, from its interaction with the residue F86^2.64, which appears to be important also for HEAT binding.     

Vergleichend-anatomische Untersuchung einer interglazialen Konifere

Ohne Zusammenfassung     

Antibacterial effect of borreverine, an alkaloid isolated from Borreria verticillata (Rubiaceae)

Borreria verticillata, a very common tropical plant, is used in traditional pharmacopeia to recover cutaneous infections. The Borreverine alkaloid extracted from this plant had an antimicrobial action in vitro. The minimal inhibitory concentration is lower than 50 micrograms/ml for Gram positive cocci, (specially Staphylococcus aureus) and than 6 micrograms/ml for Vibrio cholerae and upper than 200 micrograms/ml for several Gram negative rod-bacteria (Enterobacteria and Pseudomonas). These preliminary results underline the interest in the research about the antimicrobial agents from plant origin, in particular concerning naturally or chemically modified alkaloids.     

Adenosine A2A Receptor Signaling and Golf Assembly Show a Specific Requirement for the γ7 Subtype in the Striatum

The adenosine A_2A receptor (A_2AR) is increasingly recognized as a novel therapeutic target in Parkinson disease. In striatopallidal neurons, the G-protein α_olf subtype is required to couple this receptor to adenylyl cyclase activation. It is now well established that the βγ dimer also performs an active role in this signal transduction process. In principal, sixty distinct βγ dimers could arise from combinatorial association of the five known β and 12 γ subunit genes. However, key questions regarding which βγ subunit combinations exist and whether they perform specific signaling roles in the context of the organism remain to be answered. To explore these questions, we used a gene targeting approach to specifically ablate the G-protein γ₇ subtype. Revealing a potentially new signaling paradigm, we show that the level of the γ₇ protein controls the hierarchial assembly of a specific G-protein α_olfβ₂γ₇ heterotrimer in the striatum. Providing a probable basis for the selectivity of receptor signaling, we further demonstrate that loss of this specific G-protein heterotrimer leads to reduced A_2AR activation of adenylyl cyclase. Finally, substantiating an important role for this signaling pathway in pyschostimulant responsiveness, we show that mice lacking the G-protein γ₇ subtype exhibit an attenuated behavioral response to caffeine. Collectively, these results further support the A_2AR G-protein α_olfβ₂γ₇ interface as a possible therapeutic target for Parkinson disease.