Vanderbilt University

About: Vanderbilt University is a education organization based out in Nashville, Tennessee, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 45066 authors who have published 106528 publications receiving 5435039 citations. The organization is also known as: Vandy.

Corneal avascularity is due to soluble VEGF receptor-1

Abstract: Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

Topography of visual cortex connections with frontal eye field in macaque: convergence and segregation of processing streams

Abstract: The primate visual system consists of at least two processing streams, one passing ventrally into temporal cortex that is responsible for object vision, and the other running dorsally into parietal cortex that is responsible for spatial vision How information from these two streams is combined for perception and action is not understood Visually guided eye movements require information about both feature identity and location, so we investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements Multiple anatomical tracers were placed either in parietal and temporal cortex or in different parts of FEF in individual macaque monkeys Convergence from the dorsal and ventral processing streams occurred in lateral FEF but not in medial FEF Certain extrastriate areas with retinotopic visual field organizations projected topographically onto FEF The dorsal bank of the superior temporal sulcus projected to medial FEF; the ventral bank, to lateral FEF, and the fundus, throughout FEF Thus, lateral FEF, which is responsible for generating short saccades, receives visual afferents from the foveal representation in retinotopically organized areas, from areas that represent central vision in inferotemporal cortex and from other areas having no retinotopic order In contrast, medial FEF, which is responsible for generating longer saccades, is innervated by the peripheral representation of retinotopically organized areas, from areas that emphasize peripheral vision or are multimodal and from other areas that have no retinotopic order or are auditory

Frontal brain asymmetry and emotional reactivity: A biological substrate of affective style

Abstract: Individuals differ dramatically in the quality and intensity of their response to affectively evocative stimuli. On the basis of prior theory and research, we hypothesized that these individual differences are related to variation in activation of the left and right frontal brain regions. We recorded baseline brain electrical activity from subjects on two occasions 3 weeks apart. Immediately following the second recording, subjects were exposed to brief positive and negative emotional film clips. For subjects whose frontal asymmetry was stable across the 3-week period, greater left frontal activation was associated with reports of more intense positive affect in response to the positive films, whereas greater right frontal activation was associated with more intense reports of negative affect in response to the negative film clips. The methodological and theoretical implications of these data are discussed.

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.

Perspective: Reproductive isolation caused by natural selection against immigrants from divergent habitats

Abstract: The classification of reproductive isolating barriers laid out by Dobzhansky and Mayr has motivated and structured decades of research on speciation. We argue, however, that this classification is incomplete and that the unique contributions of a major source of reproductive isolation have often been overlooked. Here, we describe reproductive barriers that derive from the reduced survival of immigrants upon reaching foreign habitats that are ecologically divergent from their native habitat. This selection against immigrants reduces encounters and thus mating opportunities between individuals from divergently adapted populations. It also reduces the likelihood that successfully mated immigrant females will survive long enough to produce their hybrid offspring. Thus, natural selection against immigrants results in distinctive elements of premating and postmating reproductive isolation that we hereby dub "immigrant inviability." We quantify the contributions of immigrant inviability to total reproductive isolation by examining study systems where multiple components of reproductive isolation have been measured and demonstrate that these contributions are frequently greater than those of traditionally recognized reproductive barriers. The relevance of immigrant inviability is further illustrated by a consideration of population-genetic theory, a review of selection against immigrant alleles in hybrid zone studies, and an examination of its participation in feedback loops that influence the evolution of additional reproductive barriers. Because some degree of immigrant inviability will commonly exist between populations that exhibit adaptive ecological divergence, we emphasize that these barriers play critical roles in ecological modes of speciation. We hope that the formal recognition of immigrant inviability and our demonstration of its evolutionary importance will stimulate more explicit empirical studies of its contributions to speciation.