Structural and biochemical characterization of Rv2140c,a phosphatidylethanolamine-binding protein from Mycobacterium tuberculosis

Rv2140c is one of many conserved Mycobacterium tuberculosis proteins for which no molecular function has been identified. We have determined a high-resolution crystal structure of the Rv2140c gene product, which reveals a dimeric complex that shares strong structural homology with the phosphatidylethanolamine-binding family of proteins. Rv2140c forms low-millimolar interactions with a selection of soluble phosphatidylethanolamine analogs, indicating that it has a role in lipid metabolism. Furthermore, the small molecule locostatin binds to the Rv2140c ligand-binding site and also inhibits the growth of the model organism Mycobacterium smegmatis.     

THE GENOMIC TRAJECTORY OF HYBRID SWARMS: OUTCOMES OF REPEATED CROSSES BETWEEN POPULATIONS OF TIGRIOPUS CALIFORNICUS

Introgressive hybridization between genetically divergent populations is an important evolutionary process. The degree to which repeated hybridization events between the same parental taxa lead to similar genomic outcomes is unknown. This study addressed this question by following genomic trajectories of replicate hybrid swarms of the copepod Tigriopus californicus over many generations of free mating. Swarm composition was determined both by differential reproductive success of founder individuals and subsequent selection on hybrid genotypes. For one cross, between two populations showing differential fitness in the laboratory and no hybrid breakdown, the genetic trajectory was highly repeatable: replicates rapidly became dominated by alleles from the fitter parent. In a second cross, between two populations showing similar fitness and significant F2 hybrid breakdown, alleles from alternative populations dominated different replicates. Swarms exhibited a general temporal trend of decreasing cytonuclear mismatch. Some patterns of differential introgression across the genome were strikingly congruent amongst swarm replicates, both within and between cross types, and reflected patterns of segregation distortion previously observed within controlled crosses between the same parental populations. Differences in heterozygosity between the sexes, and evidence for a previously suspected sex‐distortion locus, suggest that complex interactions between sex and genotype influence hybrid swarm outcome.     

Allergenic airborne pollen monitoring of Vigo (NW Spain) in 1995–2001

Pollen data from the atmosphere of Vigo, NW Spain was collected using a Hirst type pollen trap over a seven-year period (1995–2001). A total of 56 different pollen types were identified, among which Urticaceae, Poaceae, Betula and Quercus represent the greatest risk for people suffering from allergic rhinitis (hay fever) or other allergic diseases. Although in the atmosphere of Vigo the presence of allergenic pollen is constant throughout the year, the months of March and April account for 40% of the annual total pollen count. Two main risk periods have been identified for asthma and allergies: (1) March – April, and (2) June – July, the latter is of greater importance due to high concentrations of Poaceae pollen. Correlation analysis with meteorological parameters demonstrates that rainfall, relative humidity, maximum temperature, sun hours and north-easterly winds are the main factors influencing the average daily pollen concentrations in the atmosphere.     

LOV‐domain photoreceptor,encoded in a genomic island,attenuates the virulence of Pseudomonas syringae in light‐exposed Arabidopsis leaves

In Arabidopsis thaliana, light signals modulate the defences against bacteria. Here we show that light perceived by the LOV domain‐regulated two‐component system (Pst–Lov) of Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) modulates virulence against A. thaliana. Bioinformatic analysis and the existence of an episomal circular intermediate indicate that the locus encoding Pst–Lov is present in an active genomic island acquired by horizontal transfer. Strains mutated at Pst–Lov showed enhanced growth on minimal medium and in leaves of A. thaliana exposed to light, but not in leaves incubated in darkness or buried in the soil. Pst–Lov repressed the expression of principal and alternative sigma factor genes and their downstream targets linked to bacterial growth, virulence and quorum sensing, in a strictly light‐dependent manner. We propose that the function of Pst–Lov is to distinguish between soil (dark) and leaf (light) environments, attenuating the damage caused to host tissues while releasing growth out of the host. Therefore, in addition to its direct actions via photosynthesis and plant sensory receptors, light may affect plants indirectly via the sensory receptors of bacterial pathogens.     

Discovery of TAK-960: An orally available small molecule inhibitor of polo-like kinase 1 (PLK1)

Using structure-based drug design, we identified and optimized a novel series of pyrimidodiazepinone PLK1 inhibitors resulting in the selection of the development candidate TAK-960. TAK-960 is currently undergoing Phase I evaluation in adult patients with advanced solid malignancies.     

A road map for molecular ecology

The discipline of molecular ecology has undergone enormous changes since the journal bearing its name was launched approximately two decades ago. The field has seen great strides in analytical methods development, made groundbreaking discoveries and experienced a revolution in genotyping technology. Here, we provide brief perspectives on the main subdisciplines of molecular ecology, describe key questions and goals, discuss common challenges, predict future research directions and suggest research priorities for the next 20 years.     

When to approach novel prey cues? Social learning strategies in frog-eating bats

Animals can use different sources of information when making decisions. Foraging animals often have access to both self-acquired and socially acquired information about prey. The fringe-lipped bat, Trachops cirrhosus, hunts frogs by approaching the calls that frogs produce to attract mates. We examined how the reliability of self-acquired prey cues affects social learning of novel prey cues. We trained bats to associate an artificial acoustic cue (mobile phone ringtone) with food rewards. Bats were assigned to treatments in which the trained cue was either an unreliable indicator of reward (rewarded 50% of the presentations) or a reliable indicator (rewarded 100% of the presentations), and they were exposed to a conspecific tutor foraging on a reliable (rewarded 100%) novel cue or to the novel cue with no tutor. Bats whose trained cue was unreliable and who had a tutor were significantly more likely to preferentially approach the novel cue when compared with bats whose trained cue was reliable, and to bats that had no tutor. Reliability of self-acquired prey cues therefore affects social learning of novel prey cues by frog-eating bats. Examining when animals use social information to learn about novel prey is key to understanding the social transmission of foraging innovations.     

Environmental enrichment promotes neural plasticity and cognitive ability in fish

Different kinds of experience during early life can play a significant role in the development of an animal''s behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such neural and behavioural deficits can be problematic if captive-bred animals are being reared with the intention of releasing them as part of a conservation strategy. Over the last decade, there has been growing interest in the use of environmental enrichment to promote behavioural flexibility in animals that are bred for release. Here, we describe the positive effects of environmental enrichment on neural plasticity and cognition in juvenile Atlantic salmon (Salmo salar). Exposing fish to enriched conditions upregulated the forebrain expression of NeuroD1 mRNA and improved learning ability assessed in a spatial task. The addition of enrichment to the captive environment thus promotes neural and behavioural changes that are likely to promote behavioural flexibility and improve post-release survival.     

Catalytic and regulatory roles of species involved in metal–nucleotide equilibriums in human pyridoxal kinase

Pyridoxal 5′-phosphate is the active form of vitamin B₆ and its deficiency is directly related with several human disorders, which make human pyridoxal kinase (hPLK) an important pharmacologic target. In spite of this, a carefully kinetic characterization of hPLK including the main species that regulates the enzymatic activity is at date missing. Here we analyse the catalytic and regulatory mechanisms of hPLK as a function of a precise determination of the species involved in metal–nucleotide equilibriums and describe new regulatory mechanisms for this enzyme. hPLK activity is supported by several metals, being Zn²⁺ the most effective, although the magnitude of the effect observed is highly dependent on the relative concentrations of metal and nucleotide used. The true substrate for the reaction catalyzed by hPLK is the metal nucleotide complex, while ATP^4? and HATP^3? did not affect the activity. The enzyme presents substrate inhibition by both pyridoxal (PL) and ZnATP^2?, although the latter behaves as a weakly inhibitor. Our study also established, for the first time, a dual role for free Zn²⁺; as an activator at low concentrations (19 μM optimal concentration) and as a potent inhibitor with a IC₅₀ of 37 μM. These results highlighted the importance of an accurate estimation of the actual concentration of the species involved in metal–nucleotide equilibriums in order to obtain reliable values for the kinetic parameters, and for determine the true regulators of the PLK activity. They also help to explain the dissimilar kinetic parameters reported in the literature for this enzyme.