Preface to the Princeton Landmarks in Biology Edition vii Preface xi Symbols Used xiii 1. The Importance of Islands 3 2. Area and Number of Speicies 8 3. Further Explanations of the Area-Diversity Pattern 19 4. The Strategy of Colonization 68 5. Invasibility and the Variable Niche 94 6. Stepping Stones and Biotic Exchange 123 7. Evolutionary Changes Following Colonization 145 8. Prospect 181 Glossary 185 References 193 Index 201

The Theory of Island Biogeography

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

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

/pdf/how-do-glucocorticoids-influence-stress-responses-4egr3fa2k0.pdf

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction

In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

Stress and the brain: from adaptation to disease

The mechanisms of receptor- and cell-specific effects of the adrenal corticosteroid hormones via mineralo- (MRs) and glucocorticoid receptors (GRs) are still poorly understood. Because the expression levels of two splice variants of the steroid receptor coactivator-1 (SRC-1) 1a and 1e, can differ significantly in certain cell populations, we tested the hypothesis that their relative abundance could determine cell- and receptor-specific effects of corticosteroid receptor-mediated transcription. In transient transfections, we demonstrate three novel types of SRC-1a- and SRC-1e-specific effects for corticosteroid receptors. One is promoter dependence: SRC-1e much more potently coactivated transcription from several multiple response element-containing promoters. Mammalian 1-hydrid studies indicated that this likely does not involve promoter-specific coactivator recruitment. Endogenous phenylethanolamine-N-methyltransferase mRNA induction via GRs was also differentially affected by the splice variants. Anothe...

/pdf/steroid-receptor-coactivator-1-splice-variants-1oea4h5i7x.pdf

Steroid receptor coactivator-1 splice variants differentially affect corticosteroid receptor signaling.

Juvenile neuronal ceroid lipofuscinosis (JNCL), Batten disease, is an autosomal recessive lysosomal storage disease associated with mutations in CLN3 .C LN3 has no known homology to other proteins and a function has not yet been described. The predominant mutation in CLN3 is a 1.02 kb genomic deletion that accounts for nearly 85% of the disease alleles. In this mutation, truncation of the protein by a premature stop codon results in the classical phenotype. Additional missense and nonsense mutations have been described. Some missense substitutions result in a protracted phenotype, with delays in the onset of classical clinical features, whereas others lead to classical JNCL. In this study, we examined the effect of naturally occurring point mutations on the intracellular localization of CLN3 and their ability to complement the CLN3deficient yeast, btn1-∆. We also examined a putative farnesylation motif thought to be involved in CLN3 trafficking. All of the point mutations, like wild-type CLN3, were highly associated with lysosomeassociated membrane protein II in non-neuronal cells and with synaptophysin in neuronal cell lines. In the yeast functional assay, point mutations correlating with a mild phenotype also demonstrated CLN3 activity, whereas the mutations associated with severe disease failed to restore CLN3 function completely. CLN3 with a mutation in the farnesylation motif trafficked normally but was functionally impaired. These data suggest that these clinically relevant point mutations, causative of Batten disease, do not affect protein trafficking but rather exert their effects by impairing protein function.

Batten disease: evaluation of CLN3 mutations on protein localization and function

Quantitative determination of rapid water and solute transport and solute reflection coefficients by light-scattering methods is complicated by dependence of vesicle or cell light scattering on nonvolume factors including solution refractive index, cell motion, and membrane aggregation. To overcome these difficulties, a fluorescence technique has been developed to measure accurately (1) osmotic water permeability (Pf), (2) solute permeability (Ps), and (3) solute reflection coefficient (sigma). The time course of vesicle volume is determined by the self-quenching of entrapped fluorescein sulfonate (FS), the best of a series of dyes screened for self-quenching, brightness, and vesicle loading/trapping. To validate the method, rabbit renal brush border vesicles (BBV) were loaded with 1-10 mM FS for 12 h at 4 degrees C and washed to remove extravesicular FS. FS leakage occurred over greater than 6 h at 4 degrees C and greater than 30 min at 23 degrees C. FS fluorescence vs vesicle volume was calibrated from the time course of fluorescence decrease (excitation 470 nm, emission greater than 515 nm) in response to a series of inward osmotic gradients in a stopped-flow apparatus. At 23 degrees C Pf was 0.005 +/- 0.001 cm/s, independent of osmotic gradient size, and inhibited 67% by 0.5 mM HgCl2. Urea Ps was 2 x 10(-6) cm/s with sigma 0.95-1.00 on the basis of the fluorescence time course analysis and the extravesicular [urea] required to obtain zero initial volume flow (null method) when vesicles were loaded with sucrose.(ABSTRACT TRUNCATED AT 250 WORDS)

Membrane water and solute permeability determined quantitatively by self-quenching of an entrapped fluorophore

Although the CLN3 gene for Batten disease, the most common inherited neurovisceral storage disease of childhood, was identified in 1995, the function of the corresponding protein still remains elusive. We previously cloned the Saccharomyces cerevisiae homologue to the human CLN3 gene, designated BTN1, which is not essential and whose product is 39% identical and 59% similar to Cln3p. We report that btn1-Δ deletion yeast strains are more resistant to d-(−)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (denoted ANP), a phenotype that is complemented in yeast by the human CLN3 gene. Furthermore, the severity of Batten disease in humans and the degree of ANP resistance in yeast are related when the equivalent amino acid replacements in Cln3p and Btn1p are compared. These results indicate that yeast can be used as a model for the study of Batten disease.

https://www.pnas.org/content/pnas/95/12/6915.full.pdf

A yeast model for the study of Batten disease

Ion transport in epithelia is regulated by a variety of hormonal and nonhormonal factors, including mineralocorticoids, insulin, shear stress and osmotic pressure. In mammals, the mineralocorticoid aldosterone is the principal regulator of sodium homeostasis and hence is central to the control of extracellular fluid volume and blood pressure. Aldosterone acts through a member of the nuclear receptor superfamily, the mineralocorticoid receptor (MR), to control the transcriptional activity of specific target genes. Recently, a serine/threonine kinase, SGK1 (serum and glucocorticoid-regulated kinase isoform 1) was identified as a candidate mediator of aldosterone action in the colon and distal nephron. The aldosterone-activated MR increases SGK1 gene transcription and SGK1, in turn, strongly stimulates the activity of the epithelial sodium channel (ENaC). Interestingly, other factors appear to regulate SGK1 gene expression and kinase activity. Insulin, for example, stimulates SGK1 activity (but not gene transcription) through its effects on phosphatidylinositol-3-kinase and osmotic shock appears to stimulate both SGK1 activity and gene transcription. Hence, SGK1 might integrate the effects of multiple hormonal and nonhormonal regulators of Na + transport in tight epithelia and thereby play a key role in volume homeostasis. It is interesting to speculate that SGK1 might be implicated in medical conditions, such as the insulin resistance syndrome, hypertension and congestive heart failure.

David A. Pearce

Papers

Steroid receptor coactivator-1 splice variants differentially affect corticosteroid receptor signaling.

Batten disease: evaluation of CLN3 mutations on protein localization and function

Membrane water and solute permeability determined quantitatively by self-quenching of an entrapped fluorophore

A yeast model for the study of Batten disease

The role of SGK1 in hormone-regulated sodium transport.