Cysteine string protein (CSP) and its role in preventing neurodegeneration

AbstractCysteine string protein (CSP) is a member of the DnaJ/Hsp40 family of co-chaperones that localises to neuronal synaptic vesicles. Its name derives from the possession of a string of 12–15 cysteine residues, palmitoylation of which is required for targeting to post-Golgi membranes. The DnaJ domain of CSP enables it to bind client proteins and recruit Hsc70 chaperones, thereby contributing to the maintenance of protein folding in the presynaptic compartment. Mutation of CSP in flies, worms and mice reduces lifespan and causes synaptic dysfunction and neurodegeneration. Furthermore, recent studies have revealed that the neurodegenerative disease, adult onset neuronal ceroid lipofuscinosis, is caused by mutations in the human CSPα-encoding DNAJC5 gene. Accumulating evidence suggests that the major mechanism by which CSP prevents neurodegeneration is by maintaining the conformation of SNAP-25, thereby facilitating its entry into the membrane-fusing SNARE complex. In this review, we focus on the role of CSP in preventing neurodegeneration and discuss how recent studies of this universal neuroprotective chaperone are being translated into potential novel therapeutics for neurodegenerative diseases

Development of Ground-testable Phase Fresnel Lenses in Silicon

Diffractive/refractive optics, such as Phase Fresnel Lenses (PFL's), offer the potential to achieve excellent imaging performance in the x-ray and gamma-ray photon regimes. In principle, the angular resolution obtained with these devices can be diffraction limited. Furthermore, improvements in signal sensitivity can be achieved as virtually the entire flux incident on a lens can be concentrated onto a small detector area. In order to verify experimentally the imaging performance, we have fabricated PFL's in silicon using gray-scale lithography to produce the required Fresnel profile. These devices are to be evaluated in the recently constructed 600-meter x-ray interferometry testbed at NASA/GSFC. Profile measurements of the Fresnel structures in fabricated PFL's have been performed and have been used to obtain initial characterization of the expected PFL imaging efficiencies.Comment: Presented at GammaWave05: "Focusing Telescopes in Nuclear Astrophysics", Bonifacio, Corsica, September 2005, to be published in Experimental Astronomy, 8 pages, 3 figure

The Gravitational Lens Candidate FBQ 1633+3134

We present our ground-based optical imaging, spectral analysis, and high resolution radio mapping of the gravitational lens candidate FBQ 1633+3134. This z=1.52, B=17.7 quasar appears double on CCD images with an image separation of 0.66 arcseconds and a flux ratio of ~3:1 across BVRI filters. A single 0.27 mJy radio source is detected at 8.46 GHz, coincident to within an arcsecond of both optical components, but no companion at radio wavelengths is detected down to a flux level of 0.1 mJy (3 sigma). Spectral observations reveal a rich metal-line absorption system consisting of a strong Mg II doublet and associated Fe I and Fe II absorption features, all at an intervening redshift of z=0.684, suggestive of a lensing galaxy. Point spread function subtraction however shows no obvious signs of a third object between the two quasar images, and places a detection limit of I > 23.0 if such an object exists. Although the possibility that FBQ 1633+3134 is a binary quasar cannot be ruled out, the evidence is consistent with it being a single quasar lensed by a faint, metal-rich galaxy.Comment: 24 pages, 5 figures. Accepted by AJ. A calibration error affecting B and V band apparent magnitudes has been corrected. The conclusions of the paper are not change

A major role for protein kinase C in calcium-activated exocytosis in permeabilised adrenal chromaffin cells

AbstractThe role of endogenously activated protein kinase C in calcium-activated exocytosis was examined in digitonin-permeabilised bovine adrenal chromaffin cells. Protein kinase C activity was reduced by down-regulation following long-term treatment with PMA or by using the inhibitor sphingosine. Both treatments resulted in a substantial reduction in catecholamine secretion elicited by micromolar calcium, indicating that endogenous activation of protein kinase C is a major requirement for calcium-activated exocytosis in chromaffin cells

From facial mimicry to emotional empathy: A role for norepinephrine?

Tendency to mimic others’ emotional facial expressions predicts empathy and may represent a physiological marker of psychopathy. Anatomical connectivity between amygdala, cingulate motor cortex (M3, M4), and facial nucleus demonstrates a potential neuroanatomical substrate for mimicry, though pharmacological influences are largely unknown. Norepinephrine modulation selectively impairs negative emotion recognition, reflecting a potential role in processing empathy-eliciting facial expressions. We examined effects of single doses of propranolol (beta-adrenoceptor blocker) and reboxetine (selective norepinephrine reuptake inhibitor) on automatic facial mimicry of sadness, anger, and happiness, and the relationship between mimicry and empathy. Forty-five healthy volunteers were randomized to 40 mg propranolol or 4 mg reboxetine. Two hours after drug subjects viewed and rated facial expressions of sadness, anger, and happiness, while corrugator, zygomatic, and mentalis EMG were recorded. Trait emotional empathy was measured using the Balanced Emotional Empathy Scale. EMG confirmed emotion-specific mimicry and the relationship between corrugator mimicry and empathy. Norepinephrine modulation did not alter mimicry to any expression or influence the relationship between mimicry and empathy. Corrugator but not zygomaticus mimicry predicts trait empathy, consistent with greater anatomical connectivity between amygdala and M3 coding upper facial muscle representations. Although influencing emotion perception, norepinephrine does not influence emotional facial mimicry or its relationship with trait empathy