Isolation, characterization and transcriptional regulation of {\it Xenopus myod\/}

I have cloned cDNAs corresponding to two distinct genes, Xlmf1 and Xlmf25, which encode skeletal muscle-specific, transcriptional regulatory proteins. These proteins are members of the helix-loop-helix family of DNA binding factors, and are most homologous to MyoD1. These two genes have disparate temporal expression patterns during early embryogenesis; although, both transcripts are present exclusively in skeletal muscle of the adult. Xlmf1 is first detected 7 hours after fertilization, shortly after the midblastula transition. Xlmf25 is detected in maternal stores of mRNA, during early cleavage stages of the embryo and throughout later development. Both Xlmf1 and Xlmf25 transcripts are detected prior to the expression of other, previously characterized, muscle-specific genes. The ability of Xlmf1 and Xlmf25 to convert mouse 10T1/2 fibroblasts to a myogenic phenotype demonstrates their activity as myogenic regulatory factors. Additionally, Xlmf1 and Xlmf25 can directly transactivate a reporter gene linked to the muscle-specific, muscle creatine kinase (MCK) enhancer. The functional properties of Xlmf1 and Xlmf25 proteins were further explored by investigating their interactions with the binding site in the MCK enhancer. Analysis of dissociation rates revealed that Xlmf25-E12 dimers had a two-fold lower avidity for this site than did Xlmf1-E12 dimers. Clones containing genomic sequence of Xlmf1 and Xlmf25 have been isolated. Reporter gene constructs containing a lac-z gene driven by Xlmf1 regulatory sequences were analyzed by embryo injections and transfections into cultured muscle cells. Elements within $-$200 bp of the transcription start site can promote high levels of muscle specific expression. Embryo injections show that 3500 bp of upstream sequence is sufficient to drive somite specific expression. EMSAs and DNAse I footprint analysis has shown the discrete interaction of factors with several cis-elements within 200 bp of the transcription start site. Mutation of several of these elements shows a positive requirement for two CCAAT boxes and two E boxes. It is evident from the work performed with this promoter that Xlmf1 is tightly regulated during muscle cell differentiation. This is not surprising given the fact that its gene product is crucial to the determination of cell fate choices. ^

Knockdown of Kiaa0319 Reduces Dendritic Spine Density

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to exhibit differential spatial-temporal expression patterns in the brain throughout development, which suggests that the polycystic kidney disease (PKD) domain encoded by KIAA0319 facilitates cell-cell adhesion to enable neuronal precursors to crawl up the radial glia during neuronal migration. With the knowledge of KIAA0319 involvement in early neurogenesis, we were interested in determining how different KIAA0319 expression may impact cortical neurons in layer II and III during early adulthood. We show that KIAA0319 knockdown in cortical pyramidal neurons significantly reduces the dendritic spine density. Studies have shown that changes in dendritic spine morphology and density affect properties of neural circuitry. Henceforth, this finding may reveal a link between the Kiaa0319 gene and the deficit of the neural processing task of reading due to reduced spines density. Finding a correlation between Kiaa0319 expression and its influence on dendritic spine development may lead to a greater insight of a direct link between the dyslexia susceptibility gene and the biological mechanism that causes dyslexia.

A community-based assessment of the spatiotemporal distribution of influenza in a U.S.-Mexico border county during the spring 2009 novel H1N1 swine-origin influenza A pandemic

This study retrospectively evaluated the spatial and temporal disease patterns associated with influenza-like illness (ILI), positive rapid influenza antigen detection tests (RIDT), and confirmed H1N1 S-OIV cases reported to the Cameron County Department of Health and Human Services between April 26 and May 13, 2009 using the space-time permutation scan statistic software SaTScan in conjunction with geographical information system (GIS) software ArcGIS 9.3. The rate and age-adjusted relative risk of each influenza measure was calculated and a cluster analysis was conducted to determine the geographic regions with statistically higher incidence of disease. A Poisson distribution model was developed to identify the effect that socioeconomic status, population density, and certain population attributes of a census block-group had on that area's frequency of S-OIV confirmed cases over the entire outbreak. Predominant among the spatiotemporal analyses of ILI, RIDT and S-OIV cases in Cameron County is the consistent pattern of a high concentration of cases along the southern border with Mexico. These findings in conjunction with the slight northward space-time shifts of ILI and RIDT cluster centers highlight the southern border as the primary site for public health interventions. Finally, the community-based multiple regression model revealed that three factors—percentage of the population under age 15, average household size, and the number of high school graduates over age 25—were significantly associated with laboratory-confirmed S-OIV in the Lower Rio Grande Valley. Together, these findings underscore the need for community-based surveillance, improve our understanding of the distribution of the burden of influenza within the community, and have implications for vaccination and community outreach initiatives.^

Planktic foraminiferal assemblage turnover at the Cretaceous-Tertiary boundary

Three uppermost Cretaceous through basal Paleocene stratigraphic sequences are examined for planktic foraminiferal assemblage stability and temporal succession patterns. These sequences are at mid-latitude South Atlantic DSDP Site 528, then-equatorial Pacific DSDP Site 577 and the Tethyan shelf Ben Gurion section of the Negev, Israel. In order to better estimate biogeographic patterns and habitat preferences, the results of these analyses are compared to previous Cretaceous biogeographic studies and to previous analyses of Cretaceous-Tertiary (K/T) boundary shelf and epicontinental sections. Results indicate that immediately following the K/T boundary, the examined epicontinental and open-ocean sites were exploited primarily by previously epicontinental planktic foraminiferal assemblages. This pattern of K/T boundary assemblage dominance suggests the geologically instantaneous break-down of Late Cretaceous epicontinental and open-ocean biogeographic provincialization. This shift in open-ocean foraminiferal assemblages is not consistent with models of nonselective K/T boundary extinctions, but is consistent with models of extinction resistence and offshore expansion of nearshore taxa. The re-establishment of stable biogeographic differences between open-ocean and epicontinental planktic foraminiferal assemblages occurs by the basal Parvularugoglobigerina eugubina Zone. At open-ocean sites 528 and 577 and the outershelf Ben Gurion section, P0 and P. eugubina Zone faunal records are marked by a pronounced alternation between Paleocene biserial- and non-biserial-dominated assemblages, This alternation appears strongly damped at shelf and epicontinental sections previously examined. The first appearance and peak magnitude of abundant earliest Paleocene trochospiral forms (Parvularugoglobigerina, Eoglobigerina, Morozovella, Globoconusa) also vary from site to site and may depend closely on levels of primary carbonate productivity.

Radiolarian events in the eastern Equatorial Pacific

The development of an orbitally tuned time scale for the ODP leg 138 sites provides biostratigraphers a very high resolution chronostratigraphic framework. With this framework we are better able to define which of the first and last appearances of species appear to be synchronous. In addition, the geographic distribution of sites provides the means with which the detailed spatial patterns of invasion of new species and the extinction of older species can be mapped. These maps not only provide information on the process of evolution, migration, and extinction, they can also be related to water mass distributions and near-surface circulation of the ocean. Of 39 radiolarian events studied at 11 sites in the eastern equatorial Pacific, 28 were found to have a minimum range in their estimated age that exceeded 0.15 m.y. The temporal pattern of first and last appearances of these diachronous events have coherent spatial patterns that indicate shifts in the areas of high oceanographic gradients over the past 10 Ma. These changes in the locations of high gradient regions suggest that the South Equatorial Current (SEC) was north of its present position prior to approximately 7 Ma. There was a southward shift in the northern boundary of this current between approximately 6 and 7 Ma, and the development of a relatively strong gradient between the northeastern and northwestern sites. Between approximately 3.7 and 3.4 Ma, there was a very slight northward shift in the northern boundary of the SEC and the steep gradients between the northeastern and northwestern sites may have disappeared. This change is thought to be associated with the closing of the Isthmus of Panama. The temporal-spatial patterns of diachronous events younger than 3.4 Ma are consistent with patterns of circulation in the modern ocean.

Revision of the early-middle Pleistocene calcareous nannofossil biochronology

The extant nannofossil biostratigraphic and biochronologic framework for the early-middle Pleistocene time interval has been tested through the micropaleontological analysis of globally distributed high-quality low- to mid-latitude deep-sea successions. The quantitative temporal distribution patterns of relative abundances of selected taxa were reconstructed in critical intervals, and the following biohorizons were defined: first occurrence of medium-sized Gephyrocapsa spp. (bmG); last occurrence of Calcidiscus macintyrei (tCm); first occurrence of large Gephyrocapsa spp. (blG); last occurrence of large Gephyrocapsa spp. (tlG); first occurrence of Reticulofenestra asanoi (bRa); re-entrance of medium-sized Gephyrocapsa spp. (reemG) and last occurrence of Reticulofenestra asanoi (tRa). The detailed patterns of abundance change at these biohorizons were used to generate a detailed biostratigraphy, and the biostratigraphic data were transformed into a precise biochronology by means of correlation to isotope stratigraphies and astronomical timescales. The degree of isochrony or diachrony of the biohorizons was evaluated. Biohorizons tlG and tRa are isochronous occurring close to marine isotope stages (MIS)55 and MIS 22, respectively, and bmG and blG are slightly diachronous on the order of 30-40 kyr, whereas biohorizons tCm, reemG and bRa are confirmed as diachronous on the order of 100, 80 and 60 kyr, respectively. Some of the events are clearly controlled by environmental conditions, e.g. the last occurrence of R. asanoi, related to significant environmental changes associated with the first large-amplitude glaciation of the late Quaternary, MIS 22.