University of California, Irvine

About: University of California, Irvine is a education organization based out in Irvine, California, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 47031 authors who have published 113602 publications receiving 5521832 citations. The organization is also known as: UC Irvine & UCI.

The Arabidopsis lyrata genome sequence and the basis of rapid genome size change

Abstract: We present the 207 Mb genome sequence of the outcrosser Arabidopsis lyrata, which diverged from the self-fertilizing species A. thaliana about 10 million years ago. It is generally assumed that the much smaller A. thaliana genome, which is only 125 Mb, constitutes the derived state for the family. Apparent genome reduction in this genus can be partially attributed to the loss of DNA from large-scale rearrangements, but the main cause lies in the hundreds of thousands of small deletions found throughout the genome. These occurred primarily in non-coding DNA and transposons, but protein-coding multi-gene families are smaller in A. thaliana as well. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome.

The Difference Between “Significant” and “Not Significant” is not Itself Statistically Significant

Abstract: It is common to summarize statistical comparisons by declarations of statistical significance or nonsignificance. Here we discuss one problem with such declarations, namely that changes in statistical significance are often not themselves statistically significant. By this, we are not merely making the commonplace observation that any particular threshold is arbitrary—for example, only a small change is required to move an estimate from a 5.1% significance level to 4.9%, thus moving it into statistical significance. Rather, we are pointing out that even large changes in significance levels can correspond to small, nonsignificant changes in the underlying quantities.The error we describe is conceptually different from other oft-cited problems—that statistical significance is not the same as practical importance, that dichotomization into significant and nonsignificant results encourages the dismissal of observed differences in favor of the usually less interesting null hypothesis of no difference, and that...

Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi

Abstract: Genetic engineering technologies can be used both to create transgenic mosquitoes carrying antipathogen effector genes targeting human malaria parasites and to generate gene-drive systems capable of introgressing the genes throughout wild vector populations. We developed a highly effective autonomous Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated protein 9 (Cas9)-mediated gene-drive system in the Asian malaria vector Anopheles stephensi, adapted from the mutagenic chain reaction (MCR). This specific system results in progeny of males and females derived from transgenic males exhibiting a high frequency of germ-line gene conversion consistent with homology-directed repair (HDR). This system copies an ∼17-kb construct from its site of insertion to its homologous chromosome in a faithful, site-specific manner. Dual anti-Plasmodium falciparum effector genes, a marker gene, and the autonomous gene-drive components are introgressed into ∼99.5% of the progeny following outcrosses of transgenic lines to wild-type mosquitoes. The effector genes remain transcriptionally inducible upon blood feeding. In contrast to the efficient conversion in individuals expressing Cas9 only in the germ line, males and females derived from transgenic females, which are expected to have drive component molecules in the egg, produce progeny with a high frequency of mutations in the targeted genome sequence, resulting in near-Mendelian inheritance ratios of the transgene. Such mutant alleles result presumably from nonhomologous end-joining (NHEJ) events before the segregation of somatic and germ-line lineages early in development. These data support the design of this system to be active strictly within the germ line. Strains based on this technology could sustain control and elimination as part of the malaria eradication agenda.

Pattern regulation in epimorphic fields

Abstract: We have described a formal model for pattern regulation in epimorphic fields in which positional information is specified in terms of polar coordinates in two dimensions. We propose that cells within epimorphic fields behave according to two simple rules, the shortest intercalation rule and the complete circle rule, for both of which there is direct experimental evidence. It is possible to understand a large number of different behaviors of epimorphic fields as a straight-forward consequence of these two rules, and the model therefore provides a context in which to view many of the results of experimental embryology. Although we have confined our discussion to cockroach legs, the imaginal disks of Drosophila, and regenerating and developing amphibian limbs, the fact that the model can explain regulative behavior in such evolutionarily diverse animals suggests that it may have general applicability to epimorphic fields. The predictions which the model makes should make it possible to assess its applicability to other developing systems, and to investigate the cellular mechanisms involved.

A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus

Abstract: Chronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA sequencing in primary human hepatocytes activated with synthetic double-stranded RNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a new transiently induced region that harbors a dinucleotide variant ss469415590 (TT or ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590[ΔG] is a frameshift variant that creates a novel gene, designated IFNL4, encoding the interferon-λ4 protein (IFNL4), which is moderately similar to IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, although it provides comparable information in Europeans and Asians. Transient overexpression of IFNL4 in a hepatoma cell line induced STAT1 and STAT2 phosphorylation and the expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.