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.

Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain.

Abstract: The adult CNS contains an abundant population of oligodendrocyte precursor cells (NG2(+) cells) that generate oligodendrocytes and repair myelin, but how these ubiquitous progenitors maintain their density is unknown. We generated NG2-mEGFP mice and used in vivo two-photon imaging to study their dynamics in the adult brain. Time-lapse imaging revealed that NG2(+) cells in the cortex were highly dynamic; they surveyed their local environment with motile filopodia, extended growth cones and continuously migrated. They maintained unique territories though self-avoidance, and NG2(+) cell loss though death, differentiation or ablation triggered rapid migration and proliferation of adjacent cells to restore their density. NG2(+) cells recruited to sites of focal CNS injury were similarly replaced by a proliferative burst surrounding the injury site. Thus, homeostatic control of NG2(+) cell density through a balance of active growth and self-repulsion ensures that these progenitors are available to replace oligodendrocytes and participate in tissue repair.

Opinion: What is the role of protein aggregation in neurodegeneration?

Abstract: Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic. However, several lines of evidence indicate that inclusion bodies are not the main cause of toxicity, and probably represent a cellular protective response. Aggregation is a complex multi-step process of protein conformational change and accretion. The early species in this process might be most toxic, perhaps through the exposure of buried moieties such as main chain NH and CO groups that could serve as hydrogen bond donors or acceptors in abnormal interactions with other cellular proteins. This model implies that the pathogenesis of diverse neurodegenerative diseases arises by common mechanisms, and might yield common therapeutic targets.

Diabetic retinopathy: current understanding, mechanisms, and treatment strategies

Abstract: Diabetic retinopathy (DR) causes significant visual loss on a global scale. Treatments for the vision-threatening complications of diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) have greatly improved over the past decade. However, additional therapeutic options are needed that take into account pathology associated with vascular, glial, and neuronal components of the diabetic retina. Recent work indicates that diabetes markedly impacts the retinal neurovascular unit and its interdependent vascular, neuronal, glial, and immune cells. This knowledge is leading to identification of new targets and therapeutic strategies for preventing or reversing retinal neuronal dysfunction, vascular leakage, ischemia, and pathologic angiogenesis. These advances, together with approaches embracing the potential of preventative or regenerative medicine, could provide the means to better manage DR, including treatment at earlier stages and more precise tailoring of treatments based on individual patient variations.

Primate motor cortex and free arm movements to visual targets in three-dimensional space. I. Relations between single cell discharge and direction of movement.

Abstract: We describe the relations between the neuronal activity in primate motor cortex and the direction of arm movement in three-dimensional (3-D) space. The electrical signs of discharge of 568 cells were recorded while monkeys made movements of equal amplitude from the same starting position to 8 visual targets in a reaction time task. The layout of the targets in 3-D space was such that the direction of the movement ranged over the whole 3-D directional continuum in approximately equal angular intervals. We found that the discharge rate of 475/568 (83.6%) cells varied in an orderly fashion with the direction of movement: discharge rate was highest with movements in a certain direction (the cell's "preferred direction") and decreased progressively with movements in other directions, as a function of the cosine of the angle formed by the direction of the movement and the cell's preferred direction. The preferred directions of different cells were distributed throughout 3-D space. These findings generalize to 3-D space previous results obtained in 2-D space (Georgopoulos et al., 1982) and suggest that the motor cortex is a nodal point in the construction of patterns of output signals specifying the direction of arm movement in extrapersonal space.