Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

The Hedgehog response network: sensors, switches, and routers.

Abstract: The Hedgehog (Hh) signaling pathway is intimately linked to cell growth and differentiation, with normal roles in embryonic pattern formation and adult tissue homeostasis and pathological roles in tumor initiation and growth. Recent advances in our understanding of Hh response have resulted from the identification of new pathway components and new mechanisms of action for old pathway components. The most striking new finding is that signal transmission from membrane to cytoplasm proceeds through recruitment, by the seven-transmembrane protein Smoothened, of an atypical kinesin, which routes pathway activation by interaction with other components of a complex that includes the latent zinc finger transcription factor, Ci.

The telomere syndromes

Abstract: There has been mounting evidence of a causal role for telomere dysfunction in a number of degenerative disorders. Their manifestations encompass common disease states such as idiopathic pulmonary fibrosis and bone marrow failure. Although these disorders seem to be clinically diverse, collectively they comprise a single syndrome spectrum defined by the short telomere defect. Here we review the manifestations and unique genetics of telomere syndromes. We also discuss their underlying molecular mechanisms and significance for understanding common age-related disease processes.

Mediation by a CREB Family Transcription Factor of NGF-Dependent Survival of Sympathetic Neurons

Abstract: Nerve growth factor (NGF) and other neurotrophins support survival of neurons through processes that are incompletely understood. The transcription factor CREB is a critical mediator of NGF-dependent gene expression, but whether CREB family transcription factors regulate expression of genes that contribute to NGF-dependent survival of sympathetic neurons is unknown. CREB-mediated gene expression was both necessary for NGF-dependent survival and sufficient on its own to promote survival of sympathetic neurons. Moreover, expression of Bcl-2 was activated by NGF and other neurotrophins by a CREB-dependent transcriptional mechanism. Overexpression of Bcl-2 reduced the death-promoting effects of CREB inhibition. Together, these data support a model in which neurotrophins promote survival of neurons, in part through a mechanism involving CREB family transcription factor-dependent expression of genes encoding prosurvival factors.

The other side of the engram: experience-driven changes in neuronal intrinsic excitability.

Abstract: Modern theories of memory storage have largely focused on persistent, experience-dependent changes in synaptic function such as long-term potentiation and depression But in addition to these synaptic changes, certain learning tasks produce enduring changes in the intrinsic excitability of neurons by changing the function of voltage-gated ion channels, a change that can produce broader, even neuron-wide changes in synaptic throughput We will consider the evidence for persistent changes in intrinsic neuronal excitability — what we will call intrinsic plasticity — that is produced by training in behaving animals and by artificial patterns of activation in brain slices and neuronal cultures These intrinsic changes might function as part of the engram itself, or as a related phenomenon such as a trigger for the consolidation or adaptive generalization of memories

Diffusion Tensor Imaging and Beyond

Abstract: The diffusion of water molecules inside organic tissues is often anisotropic (1) Namely, if there are aligned structures in the tissue, the apparent diffusion coefficient (ADC) of water may vary depending on the orientation along which the diffusion-weighted (DW) measurements are taken In the late 1980s, diffusion-weighted imaging (DWI) became possible by combining MR diffusion measurements with imaging, enabling the mapping of both diffusion constants and diffusion anisotropy inside the brain and revealing valuable information about axonal architectures (2-14) In the beginning of the 1990s, the diffusion tensor model was introduced to describe the degree of anisotropy and the structural orientation information quantitatively (15,16) This diffusion tensor imaging (DTI) approach provided a simple and elegant way to model this complex neuroanatomical information using only six parameters Since then, we have witnessed a tremendous amount of growth in this research field, including more sophisticated nontensor models to describe diffusion properties and to extract finer anatomical information from each voxel Three-dimensional (3D) reconstruction technologies for white matter tracts are also developing beyond the initial deterministic line-propagation models (17-20) As these new reconstruction methods are an area of very active research, it is important to remember that the theory cannot be dissociated from practical aspects of the technology Importantly, DWI is inherently a noise-sensitive and artifact-prone technique (Fig 1) Thus, we cannot overemphasize the importance of image quality assurance and robust image analysis techniques Last but not least, data acquisition technologies have also been steadfastly evolving In this article, we review the recent advances in these areas since 2000 FIG 1 Examples of typical artifacts: (i) signal/slice dropouts, (ii) eddy-current induced geometric distortions, (iii) systematic vibration artifacts, and (iv) ghosting (insufficient/incorrect fat-suppression)