Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.

Bovine basic fibroblast growth factor (bFGF) is a potent mitogen isolated from bovine pituitary glands and brain. The addition of homogeneous bFGF to primary cultures of rat cerebral cortical neurons markedly enhances cell survival and elaboration of neurites. These effects are dose-dependent, with optimal stimulation occurring at a concentration of 500 pg/ml. Maintenance of survival and neurite outgrowth require the continuous presence of bFGF. Other growth factors, such as thrombin, platelet-derived growth factor, .3 nerve growth factor, and interleukin 2, have no effect on neuronal survival or process formation. Although the cellular site(s) of bFGF synthesis has not yet been established, these results suggest that bFGF may function as a neurotrophic agent in the central nervous system. Survival and the acquisition of a differentiated phenotype are critical events characteristic of neuronal development. The spectrum of factors and conditions responsible for regulating these processes have not been elucidated. However, with the discovery of nerve growth factor (NGF) it became clear that certain aspects of neuronal development may be mediated by diffusible molecules. NGF is the most completely characterized of these factors, but its activity is best characterized for neurons of the sympathetic and sensory ganglia (reviewed in refs.

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The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.

Conditional image synthesis from layout has recently attracted much interest. Previous approaches condition the generator on object locations as well as class labels but lack fine-grained control over the diverse appearance aspects of individual objects. Gaining control over the image generation process is fundamental to build practical applications with a user-friendly interface. In this paper, we propose a method for attribute controlled image synthesis from layout which allows to specify the appearance of individual objects without affecting the rest of the image. We extend a state-of-the-art approach for layout-to-image generation to additionally condition individual objects on attributes. We create and experiment on a synthetic, as well as the challenging Visual Genome dataset. Our qualitative and quantitative results show that our method can successfully control the fine-grained details of individual objects when modelling complex scenes with multiple objects.