I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

GTPases are conserved molecular switches, built according to a common structural design. Rapidly accruing knowledge of individual GTPases--crystal structures, biochemical properties, or results of molecular genetic experiments--support and generate hypotheses relating structure to function in other members of the diverse family of GTPases.

The GTPase superfamily: conserved structure and molecular mechanism

A review of central 5-HT receptors and their function

Publisher Summary This chapter focuses on interleukin-8 (IL-8) and related chemotactic cytokines—namely, CXC and CC chemokines. IL-8 is the best known member of a new class of cytokines that are widely studied because of their ability to attract and activate leukocytes, and their potential role as mediators of inflammation. IL-8 was originally isolated from the culture supernatants of stimulated human blood monocytes and was identified as a protein of 72 amino acids with a molecular weight of 8383. The three-dimensional structure of IL-8 has been studied by nuclear magnetic resonance spectroscopy and X-ray crystallography. In concentrated solution, and on crystallization, IL-8 is present as a dimer. The first CC chemokine was identified after cloning by differential hybridization from human tonsillar lymphocytes and was termed LD78. The CC and CXC chemokines are similar in size and have an overall structure that is characterized by the two intrachain disulfide bonds, short N-terminal and long C-terminal sequences. It discusses the role of chemokines in pathology with skin inflammation because psoriasis was the first disease to be linked to overproduction of IL-8. Several independent studies document the occurrence of high levels of IL-8 in the synovial fluid of inflamed joints of patients with different forms of rheumatic diseases, osteoarthritis, and gout.

Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines.

I Introduction UNTIL 35 yr ago, most scientists did not take research on the pineal gland seriously The decade beginning in 1956, however, provided several discoveries that laid the foundation for what has become a very active area of investigation These important early observations included the findings that, 1), the physiological activity of the pineal is influenced by the photoperiodic environment (1–5); 2), the gland contains a substance, N-acetyl-5-methoxytryptamine or melatonin, which has obvious endocrine capabilities (6, 7); 3), the function of the reproductive system in photoperiodically dependent rodents is inextricably linked to the physiology of the pineal gland (5, 8, 9); 4), the sympathetic innervation to the pineal is required for the gland to maintain its biosynthetic and endocrine activities (10, 11); and 5), the pineal gland can be rapidly removed from rodents with minimal damage to adjacent neural structures using a specially designed trephine (12) Since the mid 1960s, research on t

Pineal Melatonin: Cell Biology of Its Synthesis and of Its Physiological Interactions*

Calcium bursts induced by nanosecond electric pulses.

Irish setter dogs affected with a rod/cone dysplasia (locus designation, rcd1) display markedly elevated levels of retinal cGMP during postnatal development. The photoreceptor degeneration commences approximately 25 days after birth and culminates at about 1 year when the population of rods and cones is depleted. A histone-sensitive retinal cGMP phosphodiesterase (PDE; EC 3.1.4.35) activity, a marker for photoreceptor PDEs, was shown previously to be present in retinal homogenates of immature, affected Irish setters. Here we report that, as judged by HPLC separation, this activity originates exclusively from cone photoreceptors, whereas rod PDE activity is absent. An immunoreactive product the size of the PDE alpha subunit, but none the size of the beta subunit, can be detected on immunoblots of retinal extracts of affected dogs, suggesting a null mutation in the PDE beta-subunit gene. Using PCR amplification of Irish setter retinal cDNA, we determined the complete coding sequence of the PDE beta subunit in heterozygous and affected animals. The affected PDE beta-subunit mRNA contained a nonsense amber mutation at codon 807 (a G-->A transition converting TGG to TAG), which was confirmed to be present in putative exon 21 of the affected beta-subunit gene. The premature stop codon truncates the beta subunit by 49 residues, thus removing the C-terminal domain that is required for posttranslational processing and membrane association. These results suggest that the rcd1 gene encodes the rod photoreceptor PDE beta subunit and that a nonsense mutation in this gene is responsible for the production of a nonfunctional rod PDE and the photoreceptor degeneration in the rcd1/rcd1 Irish setter dogs.

https://www.pnas.org/content/pnas/90/9/3968.full.pdf

Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene.

Pineal N-acetyltransferase (NAT) activity and radioimmunoassayable levels of melatonin were compared in 2-month-old (young), 12-month-old (middle-aged), and 29-month-old (old) female rats killed at 1600 h (during the light) and at 2300 h (4 h after darkness onset) and 0100 h (6 h after darkness onset). During the light period, NAT levels were equivalent in pineals from each age group. With the onset of darkness NAT levels rose sharply and were again equivalent in all groups at 2300 h. At 0100 h pineal NAT values in the old rats were lower than in the other two groups. Melatonin values were low in pineal glands of all animals killed at 1600 h in light. By 4 h after darkness onset pineal melatonin content in the young rats had increased 12-fold compared to a 6-fold rise in the old animals. Melatonin levels in the middle aged rats were intermediate between the other two groups. Similar relationships were observed in the rats killed at 0100 h. By this time the young rats had melatonin levels 17 times higher than during the day while the increase in the old rats was only 7-fold; 12-month-old rats again had intermediate levels. The finding show a marked reduction in pineal melatonin with aging in female rats.

Age-associated reduction in nocturnal pineal melatonin levels in female rats.

The present invention is related to methods in which an electric field pulse is applied to cells and tissue. Several embodiments of the present invention relate to the application of electric field pulses to cells to regulate the physiology and biophysical properties of various cell types, including terminally differentiated and rapidly dividing cells. Methods of regulating transcription of a gene in a cell, marking a cell for diagnostic or therapeutic procedures, determining cellular tolerance to electroperturbation, selectively electroperturbing a population of cells, reducing proliferation of rapidly dividing cells in a patient, and facilitating entry of a diagnostic or therapeutic agent into a cell's intracellular structures are also provided.

Method for intracellular modifications within living cells using pulsed electric fields

Purpose. To investigat the e developing retin oaf norma anl d rd/rd mic teo establis ih f theinherited defec it n the retinal degeneration (rd) gene, encoding the beta subunit of the cascadephosphocliesterase, is associated with rd photoreceptor degeneration by apoptosis.Methods. DNA conten ot f developing norma anl d rd/rd retinas was measured spectrophoto-metrically and analyze fod r differential loss during the cours oef photoreceptor degeneration.Degenerating rd photoreceptors were evaluated by electron microscop for cytoplasmiy c fea -tures and chromosomal condensation. DNA fragmentatio wan analyzes d by agarose gel electro-phoresis at daily intervals durin thge developmental period in which rd/rd cell death occurs.Results. DNA loss from developing rd/rd retinas is maximal between 10 and 15 postnatal days.Photoreceptor cell dise individually throughou th postnataet l perio ofd degeneration , withpyenotic nuclei dispersed among morphologically norma rd photoreceptorsl . DNA fragmenta-tion into 200 base pair multiples occurs maximall in rd/rdy retinas between 1 an0d 15 postna-tal days.Conclusion. Photorcceptor cell i deatn developinh g rd/rd retinas occur bsy a mechanism I hatlinks a defect in the phototransduction cascade with a progra fomr cell death, called apoptosis.Invest. Ophthalmol Vis Sci. 1994;35:358-362.A.I1 retina rol d photoreceptors degenerat in hornoe -zygous rd (retinal degeneration) mice after expressinga mutant gen foer whic h th e translation produc is atdetective componen of tht phosphocliesterase en- ezyme complex that normall thy phototranse serves -duction cascade.

Cheryl M. Craft

Papers

Calcium bursts induced by nanosecond electric pulses.

Irish setter dogs affected with rod/cone dysplasia contain a nonsense mutation in the rod cGMP phosphodiesterase beta-subunit gene.

Age-associated reduction in nocturnal pineal melatonin levels in female rats.

Method for intracellular modifications within living cells using pulsed electric fields

Linkage of photoreceptor degeneration by apoptosis with inherited defect in phototransduction.