Nest architecture influences host use by avian brood parasites and is shaped by coevolutionary dynamics.

Brood (social) parasites and their hosts exhibit a wide range of adaptations and counter-adaptations as part of their ongoing coevolutionary arms races. Obligate avian brood parasites are expected to use potential host species with more easily accessible nests, while potential hosts are expected to evade parasitism by building more concealed nests that are difficult for parasites to enter and in which to lay eggs. We used phylogenetically informed comparative analyses, a global database of the world's brood parasites, their host species, and the design of avian host and non-host nests (approx. 6200 bird species) to examine first, whether parasites preferentially target host species that build open nests and, second, whether host species that build enclosed nests are more likely to be targeted by specialist parasites. We found that species building more accessible nests are more likely to serve as hosts, while host species with some of the more inaccessible nests are targeted by more specialist brood parasites. Furthermore, evolutionary-transition analyses demonstrate that host species building enclosed nests frequently evolve to become non-hosts. We conclude that nest architecture and the accessibility of nests for parasitism represent a critical stage of the ongoing coevolutionary arms race between avian brood parasites and their hosts.

Plumage and eggshell colouration covary with the level of sex-specific parental contributions to nest building in birds.

Interspecific variation in sex-specific contributions to prenatal parental care, including avian nest building, is becoming increasingly better understood as we amass more information on more species. We examined whether sex-specific nest building contributions covary with the colouration of parents and their eggs in 521 species of Western Palearctic birds. Having colourful plumage and laying colourful eggs are costly because of the deposition of pigments in feathers and eggs and/or forming costly nanostructural substrates in feathers, and so it might be expected that those costs covary with the costs of nest building at the level of individuals and/or across species to produce of a suite of codivergent traits. Using a phylogenetically informed approach, we tested the hypothesis that species in which females alone invest energy building nests exhibit less sexual plumage dichromatism. However, we found comparative support for the opposite of this prediction. We then tested that species in which females alone build nests lay more colourful, and costlier, eggs because the dual costs of building nests and laying colourful eggs can only be borne by higher quality individuals. As expected, we found that species in which females build nests alone or together with males are more likely to lay colourfully pigmented eggs relative to species in which only males build nests. Finally, stochastic character mapping provided evidence of the repeated evolution of female-only nest building. Interspecific sex differences in plumage colouration therefore covary in a complex manner with female pre- (nest building) and post-copulatory (egg production) investment in reproduction.

A Phase II Study with Lead-In Safety Cohort of 5-Fluorouracil, Oxaliplatin, and Lapatinib in Combination with Radiation Therapy as Neoadjuvant Treatment for Patients with Localized HER2-Positive Esophagogastric Adenocarcinomas.

LESSONS LEARNED: Neoadjuvant 5-fluorouracil, oxaliplatin, and lapatinib in combination with radiation therapy is safe for neoadjuvant treatment for patients with localized human epidermal growth receptor 2-positive esophagogastric adenocarcinoma.Evaluation of this drug combination in a larger patient pool would allow for more accurate analysis of its efficacy. BACKGROUND: The optimal design of neoadjuvant chemoradiation for the treatment of localized esophagogastric cancers is the subject of much debate. In this nonrandomized trial, we evaluated neoadjuvant 5-fluorouracil (5-FU), oxaliplatin, and lapatinib in combination with radiation therapy as neoadjuvant treatment for patients with localized human epidermal growth receptor 2 (HER2)-positive esophagogastric adenocarcinomas. METHODS: Patients received neoadjuvant 5-FU (225 mg/m2 continuous intravenous infusion, days 1-42), oxaliplatin (85 mg/m2 intravenously [IV], days 1, 15, and 29), and lapatinib (six patients, 1,000 mg p.o., days 1-42; six patients, 750 mg p.o., days 1-42) plus radiation (1.8 Gy/day Monday through Friday for 50.4 Gy total). Following restaging, eligible patients underwent definitive resection, and pathologic response to neoadjuvant therapy was assessed. Planned enrollment was 42 patients. The primary endpoint was the pathologic complete response (pCR) rate. RESULTS: Twelve patients (median age 64 years; 67% male) received a median of 5.6 weeks of treatment (range: 1.1-8.4). The pCR rate was 8%; four of the 12 patients underwent tumor resection and one patient had a pCR, with pathologic partial response in the remaining three. The most common lapatinib-related adverse events included (all grades) nausea (67%) and diarrhea (58%), although these were all grade 1 or 2. Enrollment was halted due to low accrual. CONCLUSION: The treatment regimen was determined to be safe. The study was terminated early due to low accrual.

A Phase-2 Trial of Single Agent Axitinib as Maintenance Therapy Following First-Line Treatment With Modified FOLFOX/Bevacizumab in Patients With Metastatic Colorectal Cancer.

This phase-2 trial evaluated the efficacy of axitinib as maintenance therapy for patients with metastatic colorectal cancer (mCRC) following first-line treatment with FOLFOX/bevacizumab. Patients with mCRC received mFOLFOX/bevacizumab followed by axitinib maintenance after four cycles. The primary endpoint was progression-free survival (PFS). Seventy patients were enrolled. Common treatment-related toxicities were fatigue, nausea, diarrhea, and peripheral neuropathy during FOLFOX/bevacizumab treatment; and fatigue, hypertension, diarrhea, and peripheral neuropathy during axitinib treatment. Median PFS was 8.3 months. Treatment with FOLFOX/bevacizumab followed by maintenance axitinib as first-line treatment for mCRC produced a median PFS consistent with historical controls of other first-line regimens.

Stress reactivity, condition, and foraging behavior in zebra finches: effects on boldness, exploration, and sociality.

The arid and semi-arid zones of Australia are characterized by highly variable and unpredictable environmental conditions which affect resources for flora and fauna. Environments which are highly unpredictable in terms of both resource access and distribution are likely to select for a variety of adaptive behavioral strategies, intrinsically linked to the physiological control of behavior. How unpredictable resource distribution has affected the coevolution of behavioral strategies and physiology has rarely been quantified, particularly not in Australian birds. We used a captive population of wild-derived zebra finches to test the relationships between behavioral strategies relating to food access and physiological responses to stress and body condition. We found that individuals that were in poorer body condition and had higher peak corticosterone levels entered baited feeders earlier in the trapping sequence of birds within the colony. We also found that individuals in poorer body condition fed in smaller social groups. Our data show that the foraging decisions which individuals make represent not only a trade-off between food access and risk of exposure, but their underlying physiological response to stress. Our data also suggest fundamental links between social networks and physiological parameters, which largely remain untested. These data demonstrate the fundamental importance of physiological mechanisms in controlling adaptive behavioral strategies and the dynamic interplay between physiological control of behavior and life-history evolution.

Sex steroid profiles in zebra finches: Effects of reproductive state and domestication.

The zebra finch is a common model organism in neuroscience, endocrinology, and ethology. Zebra finches are generally considered opportunistic breeders, but the extent of their opportunism depends on the predictability of their habitat. This plasticity in the timing of breeding raises the question of how domestication, a process that increases environmental predictability, has affected their reproductive physiology. Here, we compared circulating steroid levels in various "strains" of zebra finches. In Study 1, using radioimmunoassay, we examined circulating testosterone levels in several strains of zebra finches (males and females). Subjects were wild or captive (Captive Wild-Caught, Wild-Derived, or Domesticated). In Study 2, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined circulating sex steroid profiles in wild and domesticated zebra finches (males and females). In Study 1, circulating testosterone levels in males differed across strains. In Study 2, six steroids were detectable in plasma from wild zebra finches (pregnenolone, progesterone, dehydroepiandrosterone (DHEA), testosterone, androsterone, and 5α-dihydrotestosterone (5α-DHT)). Only pregnenolone and progesterone levels changed across reproductive states in wild finches. Compared to wild zebra finches, domesticated zebra finches had elevated levels of circulating pregnenolone, progesterone, DHEA, testosterone, androstenedione, and androsterone. These data suggest that domestication has profoundly altered the endocrinology of this common model organism. These results have implications for interpreting studies of domesticated zebra finches, as well as studies of other domesticated species.

Sex steroid profiles and pair-maintenance behavior of captive wild-caught zebra finches (Taeniopygia guttata).

Here, we studied the life-long monogamous zebra finch, to examine the relationship between circulating sex steroid profiles and pair-maintenance behavior in pairs of wild-caught zebra finches (paired in the laboratory for >1 month). We used liquid chromatography-tandem mass spectrometry to examine a total of eight androgens and progestins [pregnenolone, progesterone, dehydroepiandrosterone (DHEA), androstenediol, pregnan-3,17-diol-20-one, androsterone, androstanediol, and testosterone]. In the plasma, only pregnenolone, progesterone, DHEA, and testosterone were above the limit of quantification. Sex steroid profiles were similar between males and females, with only circulating progesterone levels significantly different between the sexes (female > male). Circulating pregnenolone levels were high in both sexes, suggesting that pregnenolone might serve as a circulating prohormone for local steroid synthesis in zebra finches. Furthermore, circulating testosterone levels were extremely low in both sexes. Additionally, we found no correlations between circulating steroid levels and pair-maintenance behavior. Taken together, our data raise several interesting questions about the neuroendocrinology of zebra finches.

Local weather conditions have complex effects on the growth of blue tit nestlings.

Adverse weather conditions are expected to result in impaired nestling development in birds, but empirical studies have provided equivocal support for such a relationship. This may be because the negative effects of adverse weather conditions are masked by parental effects. Globally, ambient temperatures, rainfall levels and wind speeds are all expected to increase in a changing climate and so there is a need for a better understanding of the relationship between weather conditions and nestling growth. Here, we describe a correlative study that examined the relationships between local temperatures, rainfall levels and wind speeds and the growth of individual blue tit (Cyanistes caeruleus) nestlings in relation to their hatching order and sex. We found that changes in a range of morphological characters were negatively related to both temperature and wind speed, but positively related to rainfall. These patterns were further influenced by the hatching order of the nestlings but not by nestling sex. This suggests that the predicted changes in local weather conditions may have complex effects on nestling growth, but that parents may be able to mitigate the adverse effects via adaptive parental effects. We therefore conclude that local weather conditions have complex effects on avian growth and the implications for patterns of avian growth in a changing climate are discussed.

Plastic is a widely used and selectively chosen nesting material for pied flycatchers (Ficedula hypoleuca) in rural woodland habitats.

There is increasing concern about the burgeoning effects of discarded plastic on the earth's biodiversity. Quantifying the presence of plastic and other anthropogenic waste in the environment can be logistically and financially challenging, although it is possible that bird' nests can be used as bioindicators. Many birds in heavily modified terrestrial ecoystems, such as urban environments, incorporate plastic and other anthropogenic materials into their nests but our understanding of the presence of discarded plastic in nests in rural woodlands remains poor. Here, we show that plastic and other anthropogenic materials were present in 35 % of 325 pied flycatcher (Ficedula hypoleuca) nests from 17 rural woodlands throughout Great Britain, although the woodlands did vary in the amount of material incorporated into nests. Then, in an experimental test at one study site, where flycatchers were provided with a choice of two types of natural and two types of anthropogenic nest materials, they preferentially selected one natural and one anthropogenic material. In another test, the flycatchers were provided with plastic of four colours and overwhelmingly selected white and avoided orange, blue and yellow plastic. Although the flycatcher's selectivity for certain material types and colours preclude their nests being a reliable indicator of plastic in the environment, our study nonetheless demonstrates that bird species incorporate anthropogenic materials, such as plastic, into their nests in rural woodlands.

Born without a Silver Spoon: A Review of the Causes and Consequences of Adversity during Early Life.

A huge amount of research attention has focused on the evolution of life histories, but most research focuses on dominant individuals that acquire a disproportionate level of reproductive success, while the life histories and reproductive tactics of subordinate individuals have received less attention. Here, we review the links between early life adversity and performance during adulthood in birds, and highlight instances in which subordinate individuals outperform dominant conspecifics. Subordinate individuals are those from broods raised under high risk of predation, with low availability of food, and/or with many parasites. Meanwhile, the broods of many species hatch or are born asynchronously and mitigation of the asynchrony is generally lacking from variation in maternal effects such as egg size and hormone deposition or genetic effects such as offspring sex or parentage. Subordinate individuals employ patterns of differential growth to attempt to mitigate the adversity they experience during early life, yet they overwhelmingly fail to overcome their initial handicap. In terms of surviving through to adulthood, subordinate individuals employ other "suboptimal" tactics, such as adaptively timing foraging behaviors to avoid dominant individuals. During adulthood, meanwhile, subordinate individuals rely on "suboptimal" tactics, such as adaptive dispersal behaviors and competing for partners at optimal times, because they represent the best options available to them to acquire copulations whenever possible. We conclude that there is a gap in knowledge for direct links between early life adversity and subordination during adulthood, meaning that further research should test for links. There are instances, however, where subordinate individuals employ "suboptimal" tactics that allow them to outperform dominant conspecifics during adulthood.

The evolutionary ecology of nests: a cross-taxon approach.

Nests, including the enormous structures housing colonies of eusocial insects and the elaborately built nests of some fishes, have long fascinated scientists, yet our understanding of the evolutionary ecology of nests has lagged behind our understanding of subsequent reproductive stages. There has, however, been a burgeoning amount of interest in nests over the past decade, and this special issue on 'The evolutionary ecology of nests: a cross-taxon approach' outlines our understanding of the form and function of nests in diverse animal lineages. Papers in 'The function of nests: mechanisms and adaptive benefits' theme examine the various functions of nests, while papers in 'The evolution of nest characteristics' theme examine the evolution of nesting behaviours. Meanwhile, papers in the 'Large communal nests in harsh environments' theme examine how the enormous structures constructed by eusocial insects and social birds enable them to inhabit harsh arid environments, whereas papers in the 'Nests in the Anthropocene' theme examine how adaptive shifts in nest architecture allow animals to adapt to breed in the age of accelerating global human impacts. Finally, the synthesis outlines how the mixture of ideas and approaches from researchers studying different taxa will advance our understanding of this exciting field of research. This article is part of the theme issue 'The evolutionary ecology of nests: a cross-taxon approach'.

Why do some bird species incorporate more anthropogenic materials into their nests than others?

Many bird species incorporate anthropogenic materials (e.g. sweet wrappers, cigarette butts and plastic strings) into their nests. Anthropogenic materials have become widely available as nesting materials in marine and terrestrial environments globally. These human-made objects can provide important benefits to birds such as serving as reliable signals to conspecifics or protecting against ectoparasites, but they can also incur fundamental survival and energetic costs via offspring entanglement and reduced insulative properties, respectively. From an ecological perspective, several hypotheses have been proposed to explain the use of anthropogenic nest materials (ANMs) by birds but no previous interspecific study has tried to identify the underlying mechanisms of this behaviour. In this study, we performed a systematic literature search and ran phylogenetically controlled comparative analyses to examine interspecific variation in the use of ANM and to examine the influence of several ecological and life-history traits. We found that sexual dimorphism and nest type significantly influenced the use of ANMs by birds providing support for the 'signalling hypothesis' that implies that ANMs reflect the quality of the nest builder. However, we found no support for the 'age' and 'new location' hypotheses, nor for a phylogenetic pattern in this behaviour, suggesting that it is widespread throughout birds. This article is part of the theme issue 'The evolutionary ecology of nests: a cross-taxon approach'.

The evolution of nest site use and nest architecture in modern birds and their ancestors.

The evolution of nest site use and nest architecture in the non-avian ancestors of birds remains poorly understood because nest structures do not preserve well as fossils. Nevertheless, the evidence suggests that the earliest dinosaurs probably buried eggs below ground and covered them with soil so that heat from the substrate fuelled embryo development, while some later dinosaurs laid partially exposed clutches where adults incubated them and protected them from predators and parasites. The nests of euornithine birds-the precursors to modern birds-were probably partially open and the neornithine birds-or modern birds-were probably the first to build fully exposed nests. The shift towards smaller, open cup nests has been accompanied by shifts in reproductive traits, with female birds having one functioning ovary in contrast to the two ovaries of crocodilians and many non-avian dinosaurs. The evolutionary trend among extant birds and their ancestors has been toward the evolution of greater cognitive abilities to construct in a wider diversity of sites and providing more care for significantly fewer, increasingly altricial, offspring. The highly derived passerines reflect this pattern with many species building small, architecturally complex nests in open sites and investing significant care into altricial young. This article is part of the theme issue 'The evolutionary ecology of nests: a cross-taxon approach'.

Temperature synchronizes temporal variation in laying dates across European hole-nesting passerines.

Identifying the environmental drivers of variation in fitness-related traits is a central objective in ecology and evolutionary biology. Temporal fluctuations of these environmental drivers are often synchronized at large spatial scales. Yet, whether synchronous environmental conditions can generate spatial synchrony in fitness-related trait values (i.e., correlated temporal trait fluctuations across populations) is poorly understood. Using data from long-term monitored populations of blue tits (Cyanistes caeruleus, n = 31), great tits (Parus major, n = 35), and pied flycatchers (Ficedula hypoleuca, n = 20) across Europe, we assessed the influence of two local climatic variables (mean temperature and mean precipitation in February-May) on spatial synchrony in three fitness-related traits: laying date, clutch size, and fledgling number. We found a high degree of spatial synchrony in laying date but a lower degree in clutch size and fledgling number for each species. Temperature strongly influenced spatial synchrony in laying date for resident blue tits and great tits but not for migratory pied flycatchers. This is a relevant finding in the context of environmental impacts on populations because spatial synchrony in fitness-related trait values among populations may influence fluctuations in vital rates or population abundances. If environmentally induced spatial synchrony in fitness-related traits increases the spatial synchrony in vital rates or population abundances, this will ultimately increase the risk of extinction for populations and species. Assessing how environmental conditions influence spatiotemporal variation in trait values improves our mechanistic understanding of environmental impacts on populations.

Bird populations most exposed to climate change are less sensitive to climatic variation.

The phenology of many species shows strong sensitivity to climate change; however, with few large scale intra-specific studies it is unclear how such sensitivity varies over a species' range. We document large intra-specific variation in phenological sensitivity to temperature using laying date information from 67 populations of two co-familial European songbirds, the great tit (Parus major) and blue tit (Cyanistes caeruleus), covering a large part of their breeding range. Populations inhabiting deciduous habitats showed stronger phenological sensitivity than those in evergreen and mixed habitats. However, populations with higher sensitivity tended to have experienced less rapid change in climate over the past decades, such that populations with high phenological sensitivity will not necessarily exhibit the strongest phenological advancement. Our results show that to effectively assess the impact of climate change on phenology across a species' range it will be necessary to account for intra-specific variation in phenological sensitivity, climate change exposure, and the ecological characteristics of a population.

Conformity to Bergmann's rule in birds depends on nest design and migration.

Ecogeographical rules attempt to explain large-scale spatial patterns in biological traits. One of the most enduring examples is Bergmann's rule, which states that species should be larger in colder climates due to the thermoregulatory advantages of larger body size. Support for Bergmann's rule, however, is not consistent across taxonomic groups, raising questions about what factors may moderate its effect. Behavior may play a crucial, yet so far underexplored, role in mediating the extent to which species are subject to environmental selection pressures in colder climates. Here, we tested the hypothesis that nest design and migration influence conformity to Bergmann's rule in a phylogenetic comparative analysis of the birds of the Western Palearctic, a group encompassing dramatic variation in both climate and body mass. We predicted that migratory species and those with more protected nest designs would conform less to the rule than sedentary species and those with more exposed nests. We find that sedentary, but not short- or long-distance migrating, species are larger in colder climates. Among sedentary species, conformity to Bergmann's rule depends, further, on nest design: Species with open nests, in which parents and offspring are most exposed to adverse climatic conditions during breeding, conform most strongly to the rule. Our findings suggest that enclosed nests and migration enable small birds to breed in colder environments than their body size would otherwise allow. Therefore, we conclude that behavior can substantially modify species' responses to environmental selection pressures.

Widespread translocation from autosomes to sex chromosomes preserves genetic variability in an endangered lark.

Species that pass repeatedly through narrow population bottlenecks (<100 individuals) are likely to have lost a large proportion of their genetic variation. Having genotyped 92 Raso larks Alauda razae, a Critically Endangered single-island endemic whose world population in the Cape Verdes over the last 100 years has fluctuated between about 15 and 130 pairs, we found variation at 7 of 21 microsatellite loci that successfully amplified, the remaining loci being monomorphic. At 6 of the polymorphic loci variation was sex-linked, despite the fact that these microsatellites were not sex-linked in the other passerine birds where they were developed. Comparative analysis strongly suggests that material from several different autosomes has been recently transferred to the sex chromosomes in larks. Sex-linkage might plausibly allow some level of heterozygosity to be maintained, even in the face of persistently small population sizes.

A phase II trial of oxaliplatin and trastuzumab in the treatment of HER2-positive metastatic breast cancer.

We investigated the feasibility/efficacy of oxaliplatin in combination with trastuzumab as first-/second-line treatment of HER2-positive metastatic breast cancer (MBC). Patients received oxaliplatin/trastuzumab every 21 days and were evaluated every 6 weeks using RECIST criteria. The study closed early due to slow accrual. Twenty-five patients were evaluable; of these, 5 (20%) had objective responses to oxaliplatin/trastuzumab. Therapy was well tolerated (no grade-4 and gastrointestinal grade-3 toxicity in 4% of patients), but had only modest activity (median time-to-progression 1.8 months). Substitution of oxaliplatin for cisplatin or carboplatin, in combination with trastuzumab, does not appear to improve first-/second-line therapy in HER2-positive MBC.

Environmental and not maternal effects determine variation in offspring phenotypes in a passerine bird.

Maternal and environmental effects can profoundly influence offspring phenotypes, independent of genetic effects. Within avian broods, both the asymmetric post-hatching environment created by hatching asynchrony and the differential maternal investment through the laying sequence have important consequences for individual nestlings in terms of the allocation of resources to body structures with different contributions to fitness. The purpose of this study was to evaluate the relative importance of post-hatching environmental and maternal effects in generating variation in offspring phenotypes. First, an observational study showed that within blue tit, Cyanistes caeruleus, broods, late-hatched nestlings allocated resources to tarsus development, maintained mass gain and head-bill growth and directed resources away from the development of fourth primary feathers. Second, a hatching order manipulation experiment resulted in nestlings from first-laid eggs hatching last, thereby allowing comparison with both late and early-hatched nestlings. Experimental nestlings had growth patterns which were closer to late-hatched nestlings, suggesting that within-brood growth patterns are determined by post-hatching environmental effects. Therefore, we conclude that post-hatching environmental effects play an important role in generating variation in offspring phenotypes.

Sex-specific patterns of minimal compensation of care during and after short term mate removal in biparental blue tits.

Early theoretical models predicted that over evolutionary timescales, changes in effort by one biparental parent should result in incomplete compensation by the other. Empirical studies, however, report responses ranging from no compensation through to complete compensation which may mean that parents respond to each other's efforts over short time scales, as predicted by some recent theoretical models. Few studies have examined behavioural changes over short time periods which mimic the onset of reduced effort so we removed one blue tit (Cyanistes caeruleus) parent for 20 min during nestling provisioning. We then quantified the provisioning rates of both parents for 60 min 'pre-removal', the non-removed partner during the 20 min 'removal' period and both parents for 60 min 'post-removal'. When compared to pre-removal, both sexes reduced their provisioning rates during the removal stage and also during the post-removal stage. There were, however, sex-specific provisioning patterns in the hour after the parent was returned because after females were released, males began provisioning at a relatively high rate and then maintained that rate across the hour after removal whereas after males were released, females began provisioning at a low rate but significantly increased thereafter. There was no long term effect on offspring fitness, which probably reflects the short time parents were removed and so we conclude that parents with biparental care adjust their provisioning rates to successfully overcome very short term decreases in care.