The amplitude and origin of sea-level variability during the Pliocene epoch.

Earth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'1, when atmospheric carbon dioxide concentrations were about 400 parts per million, global sea level oscillated in response to orbital forcing2,3 and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value4,5. For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 ± 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy3 (as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession6 between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere3,6. Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century.

Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome.

Adolescent stress can impact health and well-being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long-term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala-a critical region in the control of emotional states-in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for 2 weeks during adolescence and were used to produce two generations of offspring. Male and female offspring and grandoffspring were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. RNA-seq analysis of the amygdala from male offspring and grandoffspring identified differentially expressed genes (DEGs) in mice derived from fathers exposed to CUS. The DEGSs clustered into numerous pathways, and the "notch signaling" pathway was the most significantly altered in male grandoffspring. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.

Eastern Caribbean family psychology with conduct-disordered adolescents from the Virgin Islands.

Family psychology is a new and relatively undeveloped discipline in much of the English-speaking Caribbean, particularly in the U.S. Virgin Islands. Family structure and youth behavior in the region have changed dramatically over the past few decades. Given the family-oriented nature of the culture, it is posited that the use of family psychology as an approach to research and intervention may prove to be a rich method to address this cultural metamorphosis. This article examines the potential effectiveness of interventions at the family level when mental health providers are working with youth with conduct disorder in the Virgin Islands. This article is offered as a microcosm of the global changes in family structure and the youth culture that are occurring particularly in the developing world, in part due to the rapid development of telecommunications. Possible roles of the family psychologist in this global transformation are presented.

Two-color dual-beam backscatter laser Doppler velocimeter.

A laser Doppler velocimeter has been developed that uses two of the colors emitted from an argon-ion laser for the simultaneous measurement of orthogonal velocities. Designed for use in a 2.13-m by 3.05-m wind tunnel, it is capable of traversing its focal volume across spatially unstable flows at scan speeds of up to 1.5 m/sec. Its optical layout and principles of operation are discussed, and the data from a typical traversal of a trailing wing-tip vortex are presented.

Optical devices to increase photocathode quantum efficiency.

Maximum quantum efficiencies attainable with commercially available semitransparent photocathodes are near 30% (for blue light). Work in the Instrumentation Division at Ames Research Center, NASA, has achieved quantum efficiencies as high as 58% with these same photocathodes through the use of optical enhancement. Improvement ratios in the red and near ir are even larger, but of course, the original sensitivities are smaller at these wavelengths. In addition to simply improving sensitivity, effort is also directed toward extending the applicability of the technique. A new class of devices recently conceived at Ames Research Center will allow application of optical enhancement to TV camera tubes, image intensifiers, and other imaging detectors. This paper describes the optical enhancement work in detail with major emphasis on results in the areas mentioned above.

Maintaining data integrity in microarray data management.

Gene expression microarrays are a relatively new technology, dating back just a few years, yet they have already become a very widely used tool in biology, and have evolved to a wide range of applications well beyond their original design intent. However, while the use of microarrays has expanded, and the issues of performance optimization have been intensively studied, the fundamental issue of data integrity management has largely been ignored. Now that performance has improved so greatly, the shortcomings of data integrity control methods constitute a greater percent of the stumbling blocks for investigators. Microarray data are cumbersome, and the rule up to this point has mostly been one of hands-on transformations, leading to human errors which often have dramatic consequences. We show in this review that the time lost on such mistakes is enormous and dramatically affects results; therefore, mistakes should be mitigated in any way possible. We outline the scope of the data integrity issue, to survey some of the most common and dangerous data transformations, and their shortcomings. To illustrate, we review some case studies. We then look at the work done by the research community on this issue (which admittedly is meager up to this point). Some data integrity issues are always going to be difficult, while others will become easier-one of our goals is to expedite the use of integrity control methods. Finally, we present some preliminary guidelines and some specific approaches that we believe should be the focus of future research.

Significance testing for direct identity-by-descent mapping.

Direct identity-by-descent mapping is a technique for narrowing down the location of the gene or genes responsible for a given genetic disease to small segments of the genome. The technique involves DNA comparisons between pairs of affected individuals. The data generated are in the form of matching segments of the genome, representing regions likely to be identical-by-descent (IBD). Regions in the genome over which there are significantly more segments aligned than is expected by chance are taken as candidate regions for the disease gene or genes. Due to the complex geometric nature of the data, significance testing involves certain mathematical difficulties. We present here a new method for measuring this significance. This method introduces a novel statistic and is appropriate whether or not the relationships between the paired individuals are known. We give examples that we have calculated by implementing this method, including an application to real data.

Generation of patterns from gene expression data by assigning confidence to differentially expressed genes.

MOTIVATION: A protocol is described to attach expression patterns to genes represented in a collection of hybridization array experiments. Discrete values are used to provide an easily interpretable description of differential expression. Binning cutoffs for each sample type are chosen automatically, depending on the desired false-positive rate for the predictions of differential expression. Confidence levels are derived for the statement that changes in observed levels represent true changes in expression. We have a novel method for calculating this confidence, which gives better results than the standard methods. Our method reflects the broader change of focus in the field from studying a few genes with many replicates to studying many (possibly thousands) of genes simultaneously, but with relatively few replicates. Our approach differs from standard methods in that it exploits the fact that there are many genes on the arrays. These are used to estimate for each sample type an appropriate distribution that is employed to control the false-positive rate of the predictions made. Satisfactory results can be obtained using this method with as few as two replicates. RESULTS: The method is illustrated through applications to macroarray and microarray datasets. The first is an erythroid development dataset that we have generated using nylon filter arrays. Clones for genes whose expression is known in these cells were assigned expression patterns which are in accordance with what was expected and which are not picked up by the standards methods. Moreover, genes differentially expressed between normal and leukemic cells were identified. These included genes whose expression was altered upon induction of the leukemic cells to differentiate. The second application is to the microarray data by Alizadeh et al. (2000). Our results are in accordance with their major findings and offer confidence measures for the predictions made. They also provide new insights for further analysis.

RAD and the RAD Study-Annotator: an approach to collection, organization and exchange of all relevant information for high-throughput gene expression studies.

MOTIVATION: Gene expression array technology has become increasingly widespread among researchers who recognize its numerous promises. At the same time, bench biologists and bioinformaticians have come to appreciate increasingly the importance of establishing a collaborative dialog from the onset of a study and of collecting and exchanging detailed information on the many experimental and computational procedures using a structured mechanism. This is crucial for adequate analyses of this kind of data. RESULTS: The RNA Abundance Database (RAD; http://www.cbil.upenn.edu/RAD) provides a comprehensive MIAME-supportive infrastructure for gene expression data management and makes extensive use of ontologies. Specific details on protocols, biomaterials, study designs, etc. are collected through a user-friendly suite of web annotation forms. Software has been developed to generate MAGE-ML documents to enable easy export of studies stored in RAD to any other database accepting data in this format (e.g. ArrayExpress). RAD is part of a more general Genomics Unified Schema (http://www.gusdb.org), which includes a richly annotated gene index (http://www.allgenes.org), thus providing a platform that integrates genomic and transcriptomic data from multiple organisms. This infrastructure enables a large variety of queries that incorporate visualization and analysis tools and have been tailored to serve the specific needs of projects focusing on particular organisms or biological systems.