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Knapp, A.

Publications and source records attributed to Knapp, A..

9 recordsLinked to original sources

Avian cranial evolution is influenced by trade-offs in shape between hard and soft tissue traits.

Changes in the structure and relative size of the brain are thought to be key transformations in the origins and continued evolution of birds, reflecting innovations and diversity of neurosensory and cognitive capabilities. However, these neuro-anatomical and functional changes do not occur in isolation, being accompanied by a host of other derived morphological characteristics associated with the evolution of flight. In the avian head alone, these include the evolution of a toothless beak, increase in relative eye size, and reduction and restructuring of jaw muscles. Several hypothesized developmental trade-offs have been proposed to explain the interrelationships among the hard and soft tissues of the head. How these developmental patterns translate into evolutionary trade-offs in other cranial traits is poorly understood, despite brain shape evolution being well documented in birds. Here, we use two-block partial least squares analyses and Ornstein-Uhlenbeck models of adaptive trait evolution to explore the phenotypic evolution of hard and soft cranial tissues and test hypotheses of correlated trait evolution. In pairwise analyses we found that all traits (endocast shape, neurocranium shape, rostrum shape, jaw muscle shape and residual orbit diameter) are significantly correlated. We found strongest support for a modular hypothesis of trait evolution across the whole head, with the rostrum and jaw muscles forming one module and brain, neurocranium, and eye forming the other. Within modules, traits are tightly integrated, but integration is relaxed between modules, allowing them to develop and evolve with a degree of independence. Together, these results highlight the integrated nature of the avian head and reveal that rather than being driven overwhelmingly by selection on a single trait, the shape of the avian head is a result of multiple interactions among hard and soft tissue traits.

evolutionary biology↗

Divergent morphologies with convergent performance in the mandible of pelagiarian fishes

Mandibles represent a key evolutionary innovation that enabled jawed vertebrates to adapt and diversify in response to a range of food sources. Using a phylogenetic comparative approach, we explore the phenotypic disparity and mechanical properties of the lower jaw in Pelagiaria, a morphologically diverse but relatively small clade of open-ocean fishes which are hypothesized to have radiated near the Cretaceous/Paleogene (K/Pg) mass extinction event. We found that body elongation and diet are not significantly correlated with jaw shape, but that habitat depth and tooth type are. Mechanical advantage (MA) is significantly correlated with mandible shape, with jaw-closing MA being most strongly correlated. Pelagiarian jaw shapes fall broadly into six morphotypes, of which two show significantly higher closing MA than other groups, despite differing substantially in shape. The high morphological disparity of pelagiarian mandible shape was established very early in their evolutionary history, and high levels of disparity have been maintained over tens of millions of years; this is consistent with the hypothesis that Pelagiaria represents an ancient adaptive radiation. Our results demonstrate both the mechanical and morphological diversity of the pelagiarian mandible and highlight the crucial role that morphological diversification has played in the trophic radiation of this clade.

evolutionary biology↗

Carrion converging: Skull shape is predicted by feeding ecology in vultures

The link between skull shape and dietary ecology in birds at macroevolutionary scales has recently been called into question by analyses of 3D shape that reveal that cranial anatomy is mainly influenced by other factors such as allometry. It is still unknown whether this form-function disconnect also exists at smaller evolutionary scales, for example within specialized ecological guilds. Vultures are a diverse guild of 23 extant species in two families (Accipitridae and Cathartidae) that exhibit phenotypic convergence as a result of highly-specialized feeding ecology. Vultures are the only known obligate scavengers among vertebrates and are usually grouped together under this single dietary category, but within this specialized diet there are three distinct, species-specific feeding strategies termed ripper, gulper, and scrapper. We use three-dimensional geometric morphometrics to quantify the relative contributions of feeding ecology, allometry, and phylogeny on vulture skull shape, along with several non-vulture raptors of similar size, range and ecology. Families show clear separation in shape, but phylogenetic signal is comparatively weak (Kmult = 0.33). Taking into account the influence of phylogeny, skull shape is not significantly correlated with either skull size or feeding type, but there are examples of strong, significant convergence and parallel shape evolution across feeding groups. Furthermore, skull shape performs strongly in predicting feeding ecology in a phylogenetic discriminant function analysis. These findings highlight the importance of detailed assessment of feeding behavior in studies of ecomorphology, rather than broader dietary categories alone, and reveal that ecology can be readily inferred from form given appropriate information.

evolutionary biology↗

How to tuna fish: constraint, convergence and integration in the neurocranium of pelagiarian fishes.

Morphological evolution of the vertebrate skull has been explored across a wide range of tetrapod clades, but teleost fishes, accounting for roughly half of all vertebrate species, have largely been overlooked. Here we present the results of a study investigating three-dimensional morphological evolution across 114 species of Pelagiaria, a morphologically diverse clade of open-ocean teleost fishes that includes tuna and mackerel. Despite showing high shape disparity, the majority of taxa are concentrated in fairly restricted regions of morphospace, with taxa from all families falling into three distinct clusters. Phylogenetic signal in shape data is significant but low (Kmult = 0.27, p = 0.001) and a single-rate Ornstein-Uhlenbeck model of evolution is supported, revealing convergence in shape within and between families. Shape is significantly correlated with body elongation (R2 = 0.35, p =0.001), but correlation with size, diet, and habitat depth is weak. Integration of the neurocranium is high, supporting the hypothesis that high integration may promote the evolution of more extreme morphologies. Taken together, these results suggest that shape evolution in the pelagiarian neurocranium is constrained by a number of factors, resulting in the repeated evolution of a restricted range of morphologies.

evolutionary biology↗

Sexual selection leads to positive allometry but not sexual dimorphism in the expression of horn shape in the blue wildebeest, Connochaetes taurinus.

Sexual selection is thought to be an important driver of adaptation, speciation and extinction. Empirically testing these predictions across macroevolutionary timescales first requires an understanding of the morphology of secondary sexual traits in extant taxa. We used three-dimensional geometric morphometrics to analyse a large sample of the skull of the blue wildebeest, Connochaetes taurinus, in which horns are found in both sexes but only used in intrasexual competition in males. We show that the horns fit several predictions of secondary sexual traits; overall skull shape is significantly correlated with size (R2 = 0.38, p = 0.001), and the sexually selected horns show drastically higher growth rates and variation than any other skull element, supporting previous findings. We also find that despite showing significant sexual dimorphism in shape and size (R2 = 0.21, p = 0.001), allometric growth trajectories of sexes are identical (R2 = 0.01, p = 0.635) and dimorphism is not readily detectable without prior knowledge of sex, and is not possible when shape is corrected for size. Our results show that even with strong sexual selection operating in only one sex, the expression of secondary sexual traits may show characteristic and indistinguishable patterns of growth and variance in both sexes.

evolutionary biology↗

Differential genetic variation underlying Ammonium and Nitrate responses in Arabidopsis thaliana

Nitrogen is an essential element required for plant growth and productivity. Understanding the mechanisms and natural genetic variation underlying nitrogen use in plants will facilitate engineering plant nitrogen use to maximize crop productivity while minimizing environmental costs. To understand the scope of natural variation that may influence nitrogen use, we grew 1135 Arabidopsis thaliana natural genotypes on two nitrogen sources, nitrate and ammonium, and measured both developmental and defense metabolite traits. By using different environments and focused on multiple traits, we identified a wide array of different nitrogen responses. These responses are associated with a large number of genes, most of them not previously associated with nitrogen responses. Only a small portion of these genes appear to be shared between environments or traits while most of the detected genes are predominantly specific to a developmental or defense trait under a specific nitrogen source. Finally, by using a large population we were able to identify unique nitrogen responses, like preferring ammonium or nitrate, that appear to be generated by combinations of loci rather than a few large effect loci. This suggests that it may be possible to obtain novel phenotypes in complex nitrogen responses by manipulating sets of genes with small effects rather than solely focusing on large effect single gene manipulations. One Sentence SummaryUsing a large collection of natural genotypes, and studying both developmental and metabolic responses, we found a large number of genes that are involved in the plants nitrogen response.

plant biology↗

Computational modeling of macrophage iron sequestration during host defense against Aspergillus

Iron is essential to the virulence of Aspergillus species, and restricting iron availability is a critical mechanism of antimicrobial host defense. Macrophages recruited to the site of infection are at the crux of this process, employing multiple intersecting mechanisms to orchestrate iron sequestration from pathogens. To gain an integrated understanding of how this is achieved in invasive aspergillosis, we generated a transcriptomic time-series of the response of human monocyte-derived macrophages to Aspergillus and used this and the available literature to construct a mechanistic computational model of iron handling of macrophages during this infection. We found an overwhelming macrophage response beginning 2-4 hours after exposure to the fungus, which included upregulated transcription of iron import proteins transferrin receptor-1, divalent metal transporter-1, and ZIP family transporters, and downregulated transcription of the iron exporter ferroportin. The computational model, based on a discrete dynamical systems framework, consisted of 21 3-state nodes, and was validated with additional experimental data that were not used in model generation. The model accurately captures the steady state and the trajectories of most of the quantitatively measured nodes. In the experimental data, we surprisingly found that transferrin receptor-1 upregulation preceded the induction of inflammatory cytokines, a feature that deviated from model predictions. Model simulations suggested that direct induction of TfR1 after fungal recognition, independent of the Iron Regulatory Protein - Labile Iron Pool system, explains this finding. We anticipate that this model will contribute to a quantitative understanding of iron regulation as a fundamental host defense mechanism during aspergillosis. ImportanceInvasive pulmonary aspergillosis is a major cause of death among immunosuppressed individuals despite the best available therapy. Depriving the pathogen of iron is an essential component of host defense in this infection, but the mechanisms by which the host achieves this are complex. To understand how recruited macrophages mediate iron deprivation during the infection, we developed and validated a mechanistic computational model that integrates the available information in the field. The insights provided by this approach can help in designing iron modulation therapies as anti-fungal treatments.

immunology↗

The Innate Immune Response to Invasive Pulmonary Aspergillosis: A Systems Modeling Approach

Aspergillus species are ubiquitous environmental molds, the spores of which are inhaled daily by most humans. Immunocompromised hosts can develop an invasive infection resulting in high mortality. There is, therefore, a pressing need for host-centric therapeutics for this infection. To address this need, we created a multi-scale computational model of the infection, focused on its interaction with the innate immune system and iron, a critical nutrient for the pathogen. The model, parameterized using published data, was found to recapitulate a wide range of biological features and was experimentally validated in vivo. Conidial swelling was identified as critical in fungal strains with high growth, whereas the siderophore secretion rate is an essential prerequisite for establishment of the infection in low-growth strains. In immunocompetent hosts, high growth, high swelling probability, and impaired leukocyte activation lead to a high conidial germination rate. Similarly, in neutropenic mice, high fungal growth was achieved through synergy between high growth rate, high swelling probability, slow leukocyte activation, and high siderophore secretion. In summary, the model reveals a small set of parameters related to fungal growth, iron acquisition, and leukocyte activation as key determinants of the fate of the infection.

systems biology↗

The a-isoform of VEGFA165 is a Significantly Stronger Activator of Human Retinal Endothelial Cells compared to the b-isoform

PurposeThere are reports that a b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of some diseased eyes. While these isoforms appear to have a different ability to activate the VEGF-Receptor-2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signalling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signalling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA165 target genes in primary human retinal microvascular endothelial cells (HRMECs). MethodsTo determine full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2, direct in-cell western assays were developed using primary Human Retinal Microvascular Endothelial Cells (HRMECs). Potential differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1 and SELE) and tight-junctions (CLDN5 and OCLN) were tested by quantitative-PCR. ResultsActivation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. MAPK activation in primary HRMECs displayed a sigmoidal dose-response to a range of VEGFA165a concentrations spanning 10-250 pM, which shifted higher into the 100-5,000 pM range with VEGFA165b. Similar maximum activation of MAPK was achieved by both isoforms at high concentration. Maximum activation of AKT by VEGFA165b was only half of the maximum activation from VEGFA165a. At a lower intermediate dose, where VEGFA165a activated intracellular signalling stronger than VEGFA165b, the changes to VEGFA target gene expression was generally greater with VEGFA165a. ConclusionsIn primary HRMECs, VEGFA165a could maximally activate MAPK and AKT at lower concentrations where VEGFA165b had relatively little effect. The timing for maximal activation of MAPK was similar for both isoforms, which is different than reprorted for non-retinal endothelial cells. While VEGFA165a and VEGFA165b are limited to the sequence of their six C-terminal six amino acids, this results in a large difference in their ablility to activate at least two key intracellular signalling pathways and potentially VEGF target gene expression in primary human retinal endothelial cells.

cell biology↗