Cranial form differences in goats by breed and domestic status

Domestic goats (Capra hircus) are globally represented by over 300 breeds, making them a useful model for investigating patterns of morphological change related to domestication. However, they have been little studied, likely due to their poor representation in museum collections and the difficulty in obtaining truly wild goat (Capra aegagrus, the bezoar) samples. Similar studies on other species reveal that domestication correlates with craniofacial alterations in domestics, which are non-uniform and often species-specific. Here, we use three-dimensional geometric morphometric methods (3DGMM) to describe and quantify cranial shape variation in wild (n = 21) versus domestic (n = 54) goats. We find that mean cranial shapes differ significantly between wild and domestic goats as well as between certain breeds. The detected differences are lower in magnitude than those reported for other domestic groups, possibly explained by the fewer directions of artificial selection in goat breeding, and their low global genetic diversity compared to other livestock. We also find tooth-row length reduction in the domestics, suggestive of rostral shortening—a prediction of the “domestication syndrome” (DS). The goat model thus expands the array—and combinations of—morphological changes observed under domestication, notably detecting alterations to the calvarium form which could be related to the ~ 15% brain size reduction previously reported for domestic compared to wild goats. The global success of domestic goats is due more to their ability to survive in a variety of harsh environments than to systematized human management. Nonetheless, their domestication has resulted in a clear disruption from the wild cranial form, suggesting that even low-intensity selection can lead to significant morphological changes under domestication

Singular patterns of skull shape and brain size change in the domestication of South American camelids

Patterns of selection in South American camelids (Lamini) and their unique demographic history establish the llama and alpaca as remarkable cases of domestication among large herd animals. Skull shape is implicated in many changes reported between wild and domestic taxa. We apply 3D geometric morphometric methods to describe skull shape, form, and size, differences among the four species of Lamini. In so doing, we test if domesticated Lamini exhibit changes similar to those in other domesticated groups: not only in the skull, but also in brain and body size. In contrast to other domesticated artiodactyls, very little change has occurred in domestic alpacas and llamas compared to their wild counterparts. Nevertheless, their differences are statistically significant and include a flatter cranium, inclined palate and increased airorhynchy in the domestics. Selection pressures that contrast with those on other herd animals, as well as recent population bottlenecks, likely have influenced the morphological patterns we note in Lamini. High-resolution 3D morphospace allows skull size, shape, and form (shape + size), to discriminate all four species, with form providing the greatest separation. These results help differentiate morphologically the Lamini, which in nature are distinguished mainly by body size, and provide an additional tool to archaeologists for distinction of wild and domestic remains. Most of our shape analyses suggest a marginally closer relationship between the alpaca and vicuña, to the exclusion of the guanaco, supporting the genetic relationships for this group. The expected brain size change between wild and domestic populations is lower than previously thought, with a 15.4% reduction in llama, and 6.8% reduction in alpaca. This is the lowest reduction in brain size thus far reported among domesticated Artiodactyla

PI3Kinase signaling in glioblastoma

Glioblastoma (GBM) is the most common primary tumor of the CNS in the adult. It is characterized by exponential growth and diffuse invasiveness. Among many different genetic alterations in GBM, e.g., mutations of PTEN, EGFR, p16/p19 and p53 and their impact on aberrant signaling have been thoroughly characterized. A major barrier to develop a common therapeutic strategy is founded on the fact that each tumor has its individual genetic fingerprint. Nonetheless, the PI3K pathway may represent a common therapeutic target to most GBM due to its central position in the signaling cascade affecting proliferation, apoptosis and migration. The read-out of blocking PI3K alone or in combination with other cancer pathways should mainly focus, besides the cytostatic effect, on cell death induction since sublethal damage may induce selection of more malignant clones. Targeting more than one pathway instead of a single agent approach may be more promising to kill GBM cells

Quantitative characterization of metabolism and metabolic shifts during growth of the new human cell line AGE1.HN using time resolved metabolic flux analysis

For the improved production of vaccines and therapeutic proteins, a detailed understanding of the metabolic dynamics during batch or fed-batch production is requested. To study the new human cell line AGE1.HN, a flexible metabolic flux analysis method was developed that is considering dynamic changes in growth and metabolism during cultivation. This method comprises analysis of formation of cellular components as well as conversion of major substrates and products, spline fitting of dynamic data and flux estimation using metabolite balancing. During batch cultivation of AGE1.HN three distinct phases were observed, an initial one with consumption of pyruvate and high glycolytic activity, a second characterized by a highly efficient metabolism with very little energy spilling waste production and a third with glutamine limitation and decreasing viability. Main events triggering changes in cellular metabolism were depletion of pyruvate and glutamine. Potential targets for the improvement identified from the analysis are (i) reduction of overflow metabolism in the beginning of cultivation, e.g. accomplished by reduction of pyruvate content in the medium and (ii) prolongation of phase 2 with its highly efficient energy metabolism applying e.g. specific feeding strategies. The method presented allows fast and reliable metabolic flux analysis during the development of producer cells and production processes from microtiter plate to large scale reactors with moderate analytical and computational effort. It seems well suited to guide media optimization and genetic engineering of producing cell lines

The mammalian brain under domestication: Discovering patterns after a century of old and new analyses

Comparisons of wild and domestic populations have established brain reduction as one of the most consistent patterns correlated with domestication. Over a century of scholarly work has been devoted to this subject, and yet, new data continue to foster its debate. Current arguments, both for and against the validity of brain reduction occurring in domestic taxa, have repeatedly cited a small set of reviews on this subject. The original works, their sampling, methodological details, and nuances of results that would be key to establishing validity, particularly in light of new data, have not been investigated. To facilitate and encourage a more informed discussion, we present a comprehensive review of original brain reduction literature for four mammalian clades: Artiodactyla, Perissodactyla, Carnivora, and Glires. Among these are studies that generated the most cited brain reduction values in modern domestication literature. In doing so, we provide a fairer stage for the critique of traits associated with domestication. We conclude that while brain reduction magnitudes may contain error, empirical data collectively support the reduction in brain size and cranial capacity for domestic forms. KEYWORDS allometry, Artiodactyla, encephalization, skul

Singular patterns of skull shape and brain size change in the domestication of South American camelids

International audienceAbstract Patterns of selection in South American camelids (Lamini) and their unique demographic history establish the llama and alpaca as remarkable cases of domestication among large herd animals. Skull shape is implicated in many changes reported between wild and domestic taxa. We apply 3D geometric morphometric methods to describe skull shape, form, and size, differences among the four species of Lamini. In so doing, we test if domesticated Lamini exhibit changes similar to those in other domesticated groups: not only in the skull, but also in brain and body size. In contrast to other domesticated artiodactyls, very little change has occurred in domestic alpacas and llamas compared to their wild counterparts. Nevertheless, their differences are statistically significant and include a flatter cranium, inclined palate and increased airorhynchy in the domestics. Selection pressures that contrast with those on other herd animals, as well as recent population bottlenecks, likely have influenced the morphological patterns we note in Lamini. High-resolution 3D morphospace allows skull size, shape, and form (shape + size), to discriminate all four species, with form providing the greatest separation. These results help differentiate morphologically the Lamini, which in nature are distinguished mainly by body size, and provide an additional tool to archaeologists for distinction of wild and domestic remains. Most of our shape analyses suggest a marginally closer relationship between the alpaca and vicuña, to the exclusion of the guanaco, supporting the genetic relationships for this group. The expected brain size change between wild and domestic populations is lower than previously thought, with a 15.4% reduction in llama, and 6.8% reduction in alpaca. This is the lowest reduction in brain size thus far reported among domesticated Artiodactyla

Intensive human contact correlates with smaller brains: differential brain size reduction in cattle types

Cattle are one of the most intensively bred domestic animals, providing humans with a multitude of products and uses. Using data from the fossil record, we test if their domestication, as for other taxa, has resulted in a reduction of their brain size. We not only conclude that Bos taurus (domestic cattle) have smaller brains than their wild ancestor, Bos primigenius (aurochs), but that brain size varies significantly by breed, with some having much smaller brains than others. Differences in husbandry practices between several breed categories align with a range of human engagement, which also aligns with the degree of selection for docility. Sampling 317 domestics from 71 breeds, we investigate if differences in brain size correlate with the intensity of human contact. A clear pattern emerges whereby a brain reduction gradient parallels a gradient in behavioural selection. Bullfighting cattle, which are bred for fighting and aggressive temperament, have much larger brains than dairy breeds, which are intensively selected for docility. Our results add to a fundamental aspect of animal domestication theory: the interplay between basic features of the domestic environment—selection for docility, absence of predators and human provision of resources—seems to explain differences in brain size