Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Body mass patterns of little stints at different latitudes during incubation and chick-rearing

Due to the 'double-clutch' mating system found in the arctic-breeding Little Stint Calidris minuta, each parent cafes for a clutch and brood alone. The resulting constraint on feeding time, combined with the cold climate and a small body size, may cause energetic bottlenecks. Based on the notion that mass stores in birds serve as an 'insurance' for transient periods of negative energy balance, but entail certain costs as well, body mass may vary in relation to climatic conditions and stage of the breeding cycle. We studied body mass in Little Stints in relation to breeding stage and geographical location, during 17 expeditions to 12 sites in the Eurasian Arctic, ranging from north Norway to north-east Taimyr. Body mass was higher during incubation than during chick-rearing. Structural size, as estimated by wing length, increased with latitude. This was probably caused by relatively more females (the larger sex) incubating further north, possibly after leaving a first clutch to be incubated by a male further south. Before and after correction for structural size, body mass was strongly related to latitude during both incubation and chick-rearing. In analogy to a similar geographical pattern in overwintering shorebirds, we interpret the large energy stores of breeding Little Stints as an insurance against periods of cold weather which are a regular feature of arctic summers. Climate data showed that the risk of encountering cold spells lasting several days increases with latitude over the species' breeding range, and is larger in June than in July. Maintaining these stores is therefore less necessary at southern sites and during the chick-rearing period than in the incubation period. When guarding chicks, feeding time is less constrained than during incubation, temperatures tend to be higher than in the incubation period, reducing energy expenditure, and the availability of insect prey reaches a seasonal maximum. However, the alternative interpretation that the chick-tending period is more energetically stressful than the incubation period, resulting in a negative energy balance for the parent, could not be rejected on the present evidence

Travelling on a budget: predictions and ecological evidence for bottlenecks in the annual cycle of long-distance migrants

Long-distance migration, and the study of the migrants who undertake these journeys, has fascinated generations of biologists. However, many aspects of the annual cycles of these migrants remain a mystery as do many of the driving forces behind the evolution and maintenance of the migrations themselves. In this article we discuss nutritional, energetic, temporal and disease-risk bottlenecks in the annual cycle of long-distance migrants, taking a sandpiper, the red knot Calidris canutus, as a focal species. Red knots have six recognized subspecies each with different migratory routes, well-known patterns of connectivity and contrasting annual cycles. The diversity of red knot annual cycles allows us to discuss the existence and the effects of bottlenecks in a comparative framework. We examine the evidence for bottlenecks focusing on the quality of breeding plumage and the timing of moult as indicators in the six subspecies. In terms of breeding plumage coloration, quality and timing of prealternate body moult (from non-breeding into breeding plumage), the longest migrating knot subspecies, Calidris canutus rogersi and Calidris canutus rufa, show the greatest impact of bottlenecking. The same is true in terms of prebasic body moult (from breeding into non-breeding plumage) which in case of both C. c. rogersi and C. c. rufa overlaps with southward migration and may even commence in the breeding grounds. To close our discussion of bottlenecks in long-distance migrants, we make predictions about how migrants might be impacted via physiological ‘trade-offs’ throughout the annual cycle, using investment in immune function as an example. We also predict how bottlenecks may affect the distribution of mortality throughout the annual cycle. We hope that this framework will be applicable to other species and types of migrants, thus expanding the comparative database for the future evaluation of seasonal selection pressures and the evolution of annual cycles in long-distance migrants. Furthermore, we hope that this synthesis of recent advancements in the knowledge of red knot annual cycles will prove useful in the ongoing attempts to model annual cycles in migratory birds

Spatial and temporal variation in the breeding of Masked Lapwings (Vanellus miles) in Australia

Spatial and temporal variation in the breeding of Masked Lapwings (Vanellus miles) in Australia were examined using data from Birds Australia&rsquo;s Nest Record Scheme (NRS; 1957&ndash;2002), the Atlas of Australian Birds (1998&ndash;2006), and climatic data (1952&ndash;2006). Breeding in north-western Australia was concentrated in summer, while in other regions the peak of breeding occurred during spring. Breeding success varied between regions and years but was generally highest in Tasmania. Clutch-size (mean 3.57 eggs &plusmn; 0.033 s.e., n = 549 clutches) did not vary regionally or temporally. In the north-east, breeding became earlier over time (~1.9 days per year, NRS), while in the south-east, breeding became later (~0.9 days per year); in other regions temporal trends were not evident. Only Tasmania showed a significant temporal change in breeding success (decrease of ~1.5% per year). All regions experienced warming climates, and annual rainfall increased in north-western regions and decreased in eastern regions. There were weak or no relationships between the amount or success of breeding, clutch-size and the climatic variables considered (with the possible exception of Tasmania), suggesting either that data limitations precluded us from detecting subtle effects or that Masked Lapwings have been little influenced or are resilient to changes in climate over most of their range.<br /

Near panmixia at the distribution‐wide scale but evidence of genetic differentiation in a geographically isolated population of the Terek Sandpiper Xenus cinereus

Abstract Populations from different parts of a species range may vary in their genetic structure, variation and dynamics. Geographically isolated populations or those located at the periphery of the range may differ from those located in the core of the range. Such peripheral populations may harbour genetic variation important for the adaptive potential of the species. We studied the distribution‐wide population genetic structure of the Terek Sandpiper Xenus cinereus using 13 microsatellite loci and the mitochondrial DNA (mtDNA) control region. In addition, we estimated whether genetic variation changes from the core towards the edge of the breeding range. We used the results to evaluate the management needs of the sampled populations. Distribution‐wide genetic structure was negligible; the only population that showed significant genetic differentiation was the geographically isolated Dnieper River basin population in Eastern Europe. The genetic variation of microsatellites decreased towards the edge of the distribution, supporting the abundant‐centre hypotheses in which the core area of the distribution preserves the most genetic variation; however, no such trend could be seen with mtDNA. Overall genetic variation was low and there were signs of past population contractions followed by expansion; this pattern is found in most northern waders. The current effective population size (Ne) is large, and therefore global conservation measures are not necessary. However, the marginal Dnieper River population needs to be considered its own management unit. In addition, the Finnish population warrants conservation actions due to its extremely small size and degree of isolation from the main range, which makes it vulnerable to genetic depletion