Faculty Bibliography

Inherited retinal degeneration results from many different mutations in either photoreceptor-specific or nonphotoreceptor-specific genes. However, nearly all mutations lead to a common blinding phenotype that initiates with rod cell death, followed by loss of cones. In most retinal degenerations, other retinal neuron cell types survive for long periods after blindness from photoreceptor loss. One strategy to restore light responsiveness to a retina rendered blind by photoreceptor degeneration is to express light-regulated ion channels or transporters in surviving retinal neurons. Recent experiments in rodents have restored light-sensitivity by expressing melanopsin or microbial opsins either broadly throughout the retina or selectively in the inner segments of surviving cones or in bipolar cells. Here, we present an approach whereby a genetically and chemically engineered light-gated ionotropic glutamate receptor (LiGluR) is expressed selectively in retinal ganglion cells (RGCs), the longest-surviving cells in retinal blinding diseases. When expressed in the RGCs of a well-established model of retinal degeneration, the rd1 mouse, LiGluR restores light sensitivity to the RGCs, reinstates light responsiveness to the primary visual cortex, and restores both the pupillary reflex and a natural light-avoidance behavior.

Crocipodin, an unusual benzotropolone pigment, has been isolated from the fruit bodies of the mushroom Leccinum crocipodium. Its structure was determined by spectroscopic methods, particularly 2D NMR spectroscopy. The structure was confirmed by total synthesis, starting from 4-bromocatechol and gallic acid. (C) 2010 Elsevier Ltd. All rights reserved.

DNA-polymer conjugates have been recognized as versatile functional materials in many different fields ranging from nanotechnology to diagnostics and biomedicine. They combine the favorable properties of nucleic acids and synthetic polymers. Moreover, joining both structures with covalent bonds to form bioorganic hybrids allows for the tuning of specific properties or even the possibility of evolving completely new functions. One important class of this type of material is amphiphilic DNA block copolymers, which, due to microphase separation, can spontaneously adopt nanosized micelle morphologies with a hydrophobic core and a DNA corona. These DNA nano-objects have been explored as vehicles for targeted gene and drug delivery, and also as programmable nanoreactors for organic reactions. Key to the successful realization of these potential applications is that (1) DNA block copolymer conjugates can be fabricated in a fully automated fashion by employing a DNA synthesizer; (2) hydrophobic compounds can be loaded within their interior; and (3) they can be site-specifically functionalized by a convenient nucleic acid hybridization procedure. This chapter aims to broaden the range of biodiagnostic and biomedical applications of these materials by providing a comprehensive outline of the preparation and characterization of multifunctional DNA-polymer nanoparticles.

It is still debated how altruistic punishment as one form of strong reciprocity has established during evolution and which motives may underlie such behavior. Recent neuroscientific evidence on the activation of brain reward regions during altruistic punishment in two-person one-shot exchange games suggests satisfaction through the punishment of norm violations as one underlying motive. In order to address this issue in more detail, we used fMRI during a one-shot economic exchange game that warrants strong reciprocity by introducing a third party punishment condition wherein revenge is unlikely to play a role. We report here that indeed, reward regions such as the nucleus accumbens showed punishment-related activation. Moreover, we provide preliminary evidence that genetic variation of dopamine turnover impacts similarly on punishment-related nucleus accumbens activation during both first person and third party punishment. The overall pattern of results suggests a common cognitive-affective-motivational network as the driving force for altruistic punishment, with only quantitative differences between first person and third party perspectives.

BACKGROUND: Body image distortion is a key symptom of eating disorders. In behavioral research two components of body image have been defined: attitudes towards the body and body size estimation. Only few fMRI-studies investigated the neural correlates of body image in bulimia; those are constrained by the lack of a direct distinction between these different body image components. METHODS: The present study investigates the neural correlates of two aspects of the body image using fMRI: satisfaction rating and size estimation of distorted own body photographs in bulimia nervosa patients (15) and controls (16). RESULTS: Patients were less satisfied with their current body shape than controls and preferred to be thinner. The amount of insula activity reflects the pattern of the satisfaction rating for patients and controls. Patients also overestimated their own body size. For control subjects, an activated cluster in lateral occipital cortex was sensitive for body size distortions, whereas bulimic patients did not demonstrate such a modulation. Furthermore, bulimic subjects did not recruit the middle frontal gyrus (MFG) in contrast to controls during the body size estimation task, maybe indicating a reduced spatial manipulation capacity. Therefore, this activation pattern of lateral occipital cortex and MFG might be responsible for body size overestimation in bulimia. CONCLUSIONS: The present results show that bulimic patients exhibit two distinct deficits in body image representations similar to anorectic patients and that specifically associated neuronal correlates can be identified. Concludingly, our study support psychotherapeutic strategies specifically targeting these two aspects of body image distortions.

Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations.

The current publishing system with its merits and pitfalls is a mending topic for debate among scientists of various disciplines. Editors and reviewers alike, both face difficult decisions about the judgment of new scientific findings. Increasing interdisciplinary themes and rapidly changing dynamics in method development of each field make it difficult to be an "expert" with regard to all issues of a certain paper. Although unintended, it is likely that misunderstandings, human biases, and even outright mistakes can play an unfortunate role in final verdicts. We propose a new community-driven publication process that is based on network statistics to make the review, publication, and scientific evaluation process more transparent.