Studying hunting behaviour in the striped field mouse using data compression

We compare predatory behaviour towards a mobile insect in three species of small mammals: the granivorous striped field mouse, the insectivorous common shrew and the Norway rat (a generalist). The striped field mouse displays a surprisingly efficient hunting stereotype. We apply the data compression method (Ryabko et al. Theory Comput Syst 52:133–147, 2013) to compare the complexity of hunting behavioural patterns and to evaluate the flexibility of stereotypes and their succinctness. Norway rats demonstrated the highest level of complexity of hunting behaviour, with the highest proportion of ‘auxiliary’ and ‘noise’ elements and relatively low proportion of ‘key’ elements in their behaviours. The predominance of ‘key’ elements resulted in similarly low levels of complexity of hunting stereotypes in striped field mice and shrews. The similarity between hunting stereotypes of the insectivorous shrew and the granivorous striped field mouse enables us to argue about evolutionary roots of hunting behaviour in small mammals. We show that this method is a useful tool for comparing ethograms as ‘biological texts’.     

A general approach for two-stage analysis of multilevel clustered non-Gaussian data

In this article, we propose a two-stage approach to modeling multilevel clustered non-Gaussian data with sufficiently large numbers of continuous measures per cluster. Such data are common in biological and medical studies utilizing monitoring or image-processing equipment. We consider a general class of hierarchical models that generalizes the model in the global two-stage (GTS) method for nonlinear mixed effects models by using any square-root-n-consistent and asymptotically normal estimators from stage 1 as pseudodata in the stage 2 model, and by extending the stage 2 model to accommodate random effects from multiple levels of clustering. The second-stage model is a standard linear mixed effects model with normal random effects, but the cluster-specific distributions, conditional on random effects, can be non-Gaussian. This methodology provides a flexible framework for modeling not only a location parameter but also other characteristics of conditional distributions that may be of specific interest. For estimation of the population parameters, we propose a conditional restricted maximum likelihood (CREML) approach and establish the asymptotic properties of the CREML estimators. The proposed general approach is illustrated using quartiles as cluster-specific parameters estimated in the first stage, and applied to the data example from a collagen fibril development study. We demonstrate using simulations that in samples with small numbers of independent clusters, the CREML estimators may perform better than conditional maximum likelihood estimators, which are a direct extension of the estimators from the GTS method.     

Effect of Dipyridamole on Membrane Energization and Energy Transfer in Chromatophores of Rba. sphaeroides

Biochemistry (Moscow) - Effect of dipyridamole (DIP) at concentrations up to 1 mM on fluorescent characteristics of light-harvesting complexes LH2 and LH1, as well as on conditions of...     

The egghead gene is required for compartmentalization in Drosophila optic lobe development

The correct targeting of photoreceptor neurons (R-cells) in the developing Drosophila visual system requires multiple guidance systems in the eye-brain complex as well as the precise organization of the target area. Here, we report that the egghead (egh) gene, encoding a glycosyltransferase, is required for a compartment boundary between lamina glia and lobula cortex, which is necessary for appropriate R1-R6 innervation of the lamina. In the absence of egh, R1-R6 axons form a disorganized lamina plexus and some R1-R6 axons project abnormally to the medulla instead of the lamina. Mosaic analysis demonstrates that this is not due to a loss of egh function in the eye or in the neurons and glia of the lamina. Rather, as indicated by clonal analysis and cell-specific genetic rescue experiments, egh is required in cells of the lobula complex primordium which transiently abuts the lamina and medulla in the developing larval brain. In the absence of egh, perturbation of sheath-like glial processes occurs at the boundary region delimiting lamina glia and lobula cortex, and inappropriate invasion of lobula cortex cells across this boundary region disrupts the pattern of lamina glia resulting in inappropriate R1-R6 innervation. This finding underscores the importance of the lamina/lobula compartment boundary in R1-R6 axon targeting.     

The role of the periplasmic loop residue glutamine 65 for MscL mechanosensitivity

The periplasmic loop of MscL, the mechanosensitive channel of large conductance, acts as a spring resisting the opening of the channel. Recently, a high-throughput functional screening of a range of MscL structural mutants indicated that the substitution of residue glutamine (Q) 65 with arginine (R) or leucine (L) leads to a wild-type (WT)-like and a loss-of-function (LOF) phenotype, respectively (Maurer and Dougherty J. Biol. Chem. 278(23):21076–21082, 2003). We used electron paramagnetic resonance (EPR) spectroscopy, single-channel recording and in vivo experiments to investigate further the effect of R and L mutation of Q65 on the gating mechanism of MscL. Structural analysis of Q65R and Q65L was carried out by coupling the site-directed spin labeling (SDSL) with EPR spectroscopy. A SDSL cysteine mutant of the isoleucine 24 residue (I24C-SL) in the first transmembrane domain, TM1, of MscL served as a reporter residue in EPR experiments. This was due to its strong spin–spin interaction with the neighboring I24C-SL residues in the MscL channel pentamer (Perozo et al.Nature 418:942–948, 2002). The effects of bilayer incorporation of lysophosphatidylcholine on the MscL mutants were also investigated. Functional analysis was carried out using patch-clamp recordings from these mutants and WT MscL reconstituted into artificial liposomes. Although our data are largely in agreement with the high-throughput mutational analysis of Maurer and Dougherty, this study shows that Q65R and Q65L form functional channels and that these mutations lead to partial gain-of-function (GOF) and LOF mutation, respectively. Overall, our study confirms and advances the notion that the periplasmic loop plays a role in setting the channel mechanosensitivity.A Proceeding of the 28th Annual Meeting of the Australian Society for Biophysics     

Evolution of host specificity in fleas: is it directional and irreversible?

Evolutionary trends in the evolution of host specificity have been the focus of much discussion but little rigorous empirical testing. On the one hand, specialization is often presumed to lead irreversibly into evolutionary dead ends and little diversification; this would mean that generalists might evolve into specialists, but not vice versa. On the other hand, low host specificity may limit the risk of extinction and provide more immediate fitness benefits to parasites, such that selection may favour evolution toward a generalist strategy. Here, we test for directionality in the evolution of host specificity using a large data set and phylogenetic information on 297 species of fleas parasitic on small mammals. The analyses determined whether host specificity, measured both as the number of host species exploited and their taxonomic diversity, was related to clade rank of the flea species, or the number of branching events between an extant species and the root of the phylogenetic tree (i.e., the total path length from the root of the tree to the species). Based on regression analyses, we found positive relationships between the number of host species used and clade rank across all 297 species, as well as within one (Hystrichopsyllidae) of four large families and one of seven large genera investigated separately; in addition, we found a positive relationship between the taxonomic diversity of host species used and clade rank in another of the seven genera. These results suggest a slight evolutionary trend of decreasing host specificity. Using a much more conservative likelihood ratio test, however, a random walk, or null model, of evolution could not be discarded in favour of the directional trends in all cases mentioned above. Still, these results suggest that host specificity may have tended to decrease in many flea lineages, a process that could have been driven by the benefits of exploiting a wide range of host species.     

Discovery and structural characterization of an allosteric inhibitor of bacterial cis‐prenyltransferase

Undecaprenyl pyrophosphate synthase (UPPs) is an essential enzyme in a key bacterial cell wall synthesis pathway. It catalyzes the consecutive condensations of isopentenyl pyrophosphate (IPP) groups on to a trans-farnesyl pyrophosphate (FPP) to produce a C55 isoprenoid, undecaprenyl pyrophosphate (UPP). Here we report the discovery and co-crystal structures of a drug-like UPPs inhibitor in complex with Streptococcus pneumoniae UPPs, with and without substrate FPP, at resolutions of 2.2 and 2.1 Å, respectively. The UPPs inhibitor has a low molecular weight (355 Da), but displays potent inhibition of UPP synthesis in vitro (IC₅₀ 50 nM) that translates into excellent whole cell antimicrobial activity against pathogenic strains of Streptococcal species (MIC₉₀ 0.4 µg mL⁻¹). Interestingly, the inhibitor does not compete with the substrates but rather binds at a site adjacent to the FPP binding site and interacts with the tail of the substrate. Based on the structures, an allosteric inhibition mechanism of UPPs is proposed for this inhibitor. This inhibition mechanism is supported by biochemical and biophysical experiments, and provides a basis for the development of novel antibiotics targeting Streptococcus pneumoniae.