Striking difference in response to expanding brood parasites by birds in western and eastern Beringia

Two species of obligate brood‐parasitic Cuculus cuckoos are expanding their ranges in Beringia. Both now breed on the Asian side, close to the Bering Strait, and are found in Alaska during the breeding season. From May to July 2017, we used painted 3D‐printed model eggs of two cuckoo host‐races breeding in northeastern Siberia to test behavioral responses of native songbirds on both sides of the Bering Strait, with particular attention to species that are known cuckoo hosts in their Siberian range. Each host nest was tested after the second egg was laid and, if possible, again 4 days later with a model of a different type. Although our Siberian study site was also outside the known breeding ranges of the cuckoos, we found that Siberian birds had strong anti‐parasite responses, with 14 of 22 models rejected. In contrast, birds in Alaska had virtually no detectable anti‐parasite behaviors, with only one of 96 models rejected; the rejecters were Red‐throated Pipits (Anthus cervinus). Such differences suggest that the cuckoos might successfully parasitize naïve hosts and become established in North America whether or not their historic host species are widely available.     

Mutational analysis of the conserved basic domain of human immunodeficiency virus tat protein.

The tat trans-activators encoded by the known strains of primate immunodeficiency virus share a conserved, highly basic protein domain. Mutagenesis of this sequence in the tat gene of human immunodeficiency virus type 1 is shown here to reduce, but not eliminate, the trans-activation of human immunodeficiency virus type 1-specific gene expression. The degree of inhibition is shown to vary in a dose-dependent manner and is most marked at low levels of tat expression. Multiple mutations of the basic domain of tat were found to impair both the in vivo stability and the nuclear localization of the tat protein. It is proposed that this protein domain serves to efficiently target the tat gene product to its appropriate site or substrate within the nucleus of expressing cells.     

The eukaryotic cofactor for the human immunodeficiency virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12–p13: three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2

The eukaryotic initiation factor 5A (eIF-5A) has been identified as an essential cofactor for the HIV-1 trans-activator protein Rev. Rev plays a key role in the complex regulation of HIV-1 gene expression and thereby in the generation of infectious virus particles. Expression of eIF-5A is vital for Rev function, and inhibition of this interaction leads to a block of the viral replication cycle. In humans, four different eIF-5A genes have been identified. One codes for the eIF-5A protein and the other three are pseudogenes. Using a panel of somatic rodent—human cell hybrids in combination with fluorescence in situ hybridization analysis, we show that the four genes map to threedifferent chromosomes. The coding eIF-5A gene (EIF5A) maps to 17p12–p13, and the three pseudogenes EIF5AP1, EIF5AP2, and EIF5AP3 map to 10q23.3, 17q25, and 19q13.2, respectively. This is the first localization report for a eukaryotic cofactor for a regulatory HIV-1 protein.     

Anticataleptic potencies of glutamate-antagonists

Summary The anticataleptic effects of non-competitive and competitive NMDA antagonists as well as those of an agonist at the allosteric glycine binding site of the NMDA receptor were tested in the catalepsy model. Some of these drugs were further tested in a reaction time task demanding rapid locomotor initiation. The results show that the non-competitive NMDA antagonists dizocilpine and memantine as well as the competitive antagonists CGP 39551, CGP 37849 and CPPene antagonized dopamine D2 receptor mediated catalepsy induced by haloperidol. D-cycloserine, a partial glycine agonist per se had no effects, but it enhanced the anticataleptic effects of dizocilpine when coadministered. However, the effects of CGP 37849 were abolished. Dopamine D1 receptor mediated catalepsy induced by SCH 23390 was antagonized by dizocilpine, memantine, CPPene, but not by CGP 37849. In the reaction time task dizocilpine, memantine and CGP 37849 were tested for their anti-akinetic and anti-bradykinetic potencies. All these compounds improved haloperidolinduced slowing of reaction time. However, they acted differentially on haloperidol-induced slowing of movement execution and decreased initial acceleration. Thus, antagonists at the NMDA receptor may have a therapeutic potential in the treatment of Parkinson's disease. Their potency can be manipulated specifically at the glycine binding site.     

PEtab—Interoperable specification of parameter estimation problems in systems biology

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been—so far—no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.