The past, present and future challenges in epilepsy related and sudden deaths and biobanking.

Awareness and research on epilepsy-related deaths (ERD), in particular Sudden Unexpected Death in Epilepsy (SUDEP), have exponentially increased over the last two decades. Most publications have focused on guidelines that inform clinicians dealing with these deaths, educating patients, potential risk factors and mechanisms. There is a relative paucity of information available for pathologists who conduct these autopsies regarding appropriate post-mortem practice and investigations. As we move from recognizing SUDEP as the most common form of ERD toward in-depth investigations into its causes and prevention, health professionals involved with these autopsies and post-mortem procedure must remain fully informed. Systematizing a more comprehensive and consistent practice of examining these cases will facilitate 1) more precise determination of cause of death, 2) identification of SUDEP for improved epidemiological surveillance (the first step for an intervention study), and 3) bio-banking and cell-based research. This article reviews how pathologists and healthcare professionals have approached ERD, current practices, logistical problems and areas to improve and harmonize. The main neuropathology, cardiac and genetic findings in SUDEP are outlined, providing a framework for best practices, integration of clinical, pathologic and molecular genetic investigations in SUDEP, and ultimately prevention

p53 and Beclin 1 in Caenorhabditis elegans are involved in cell death and DNA damage repair

p53 is a key regulator of growth arrest, DNA repair, apoptosis, and autophagy in response to cellular stress in animals as diverse as Caenorhabditis elegans and humans. In mammals, p53 functions as a key tumor suppressor protein that promotes removal of potentially tumorigenic cells. p53 is mutated or deleted in over 50% of all mammalian tumors and these tumors are highly resistant to available therapies. Therefore, identifying therapeutic agents and cell death pathways that promote p53-independent cell death is vital to the future of cancer therapy. We are interested in identifying how the alkylating agent, 10-decarbomyl mitomycin C (DMC) promotes p53-indpendent cell death. To answer this question, we used a C. elegans as a model system to identify known and novel cell death genes involved in DMC-induced death. C. elegans have an orthologue of p53, cep-1, that functions in germline cell death in a similar way to p53 in apoptosis. The germline in C. elegans has both mitotic and meiotic cells and displays CEP-1/p53-dependent cell death in response to UV. We examined both germline cell death and transcript levels of CEP-1 target genes in C. elegans. We found that DMC increased CED-1::GFP positive cells and DNA lesions in the absence of CEP-1 while UV required CEP-1 for germline cell death but not nuclear lesion formation. More lesions were seen over time in cep-1(gk138) mutant worms leading to the idea that CEP-1 is involved in DNA repair. Additionally, we examined the role of autophagy in cell death and DNA damage and saw that initially the knockdown of bec-1 required CEP-1 for increases in germ cell death. However in the F1 generation of bec-1 RNAi knockdown animals, the observed increase in cell death was due to a lack of clearance. Furthermore, bec-1 knockdown resulted in the increase of DNA lesions in worms with UV damage

PASSIVE Q-SWITCHING OF A CO2−N2−HeCO_{2}- N_{2}-He LASER WITH C2H4C_{2} H_{4} GAS

Author Institution: Polytechnic Institute of BrooklynStable passive Q-switching of a $CO_{2}- N_{2}-He$ laser operating sequentially on several P branch rotational transitions of the $00^\circ 1\rightarrow 10^\circ 0$ vibrational band of $CO_{2}$, has been achieved using $C_{2} H_{4}$ as a saturable absorber. Pulse widths observed were approximately 2 $\mu$ sec and the time between pulses approximately 20 $\mu$ sec. The pulse width and repetition rate are similar to those obtained with $SF_{6}$ and $CH_{3}Br$ as saturable absorbers. The effect of He on pulse stability, shape and repetition rates was also investigated

Inducible Nitric Oxide Synthase Mediates Prostaglandin H(2) Synthase Nitration and Suppresses Eicosanoid Production

Nitric oxide (NO) modulates the biological levels of arachidonate-derived cell signaling molecules by either enhancing or suppressing the activity of prostaglandin H(2) isoforms (PGHS-1 and PGHS-2). Whether NO activates or suppresses PGHS activity is determined by alternative protein modifications mediated by NO and NO-derived species. Here, we show that inducible NO synthase (iNOS) and PGHS-1 co-localize in atherosclerotic lesions of ApoE(−/−) mouse aortae. Immunoblotting and immunohistochemistry revealed Tyr nitration in PGHS-1 in aortic lesions but markedly less in adjacent nonlesion tissue. PGHS-2 was also found in lesions, but 3-nitrotyrosine incorporation was not detected. 3-Nitrotyrosine formation in proteins is considered a hallmark reaction of peroxynitrite, which can form via NO-superoxide reactions in an inflammatory setting. That iNOS-derived NO is essential for 3-nitrotyrosine modification of PGHS-1 was confirmed by the absence of 3-nitrotyrosine in lesions from ApoE(−/−)iNOS(−/−) mice. Mass spectrometric studies specifically identified the active site residue Tyr385 as a 3-nitrotyrosine modification site in purified PGHS-1 exposed to peroxynitrite. PGHS-mediated eicosanoid (PGE(2)) synthesis was more than fivefold accelerated in cultured iNOS(−/−) versus iNOS-expressing mouse aortic smooth muscle cells, suggesting that iNOS-derived NO markedly suppresses PGHS activity in vascular cells. These results further suggest a regulatory role of iNOS in eicosanoid biosynthesis in human atherosclerotic lesions