Feasibility and Pilot Efficacy Results from the Multi-site Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) Study

The true benefit of pharmacological intervention to improve cognition in schizophrenia may not be evident without regular cognitive enrichment. Clinical trials assessing the neurocognitive effects of new medications may require engagement in cognitive remediation exercises to stimulate the benefit potential. However, the feasibility of large-scale multi-site studies using cognitive remediation at clinical trials sites has not been established

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Woman, community and conflict: Rethinking the metaphor of female adultery in Hosea 1-2

This dissertation will argue that the dominant reading of female adultery in Hosea 1-2 as a metaphor for religious apostasy in a syncretistic fertility cult proceeds from an interpretative framework that spiritualizes the meaning of religion, uncritically imports Western assumptions about gender meanings, and presupposes the individual as the basic unit of human meaning. Reading within this interpretive frame, commentators generally agree that the great point of Hosea\u27s female sexual imagery is the articulation of a theological position in which spirit is raised above matter. This dissertation will show that this conclusion is a product of hermeneutical premises which already presuppose the matter/spirit dichotomy, and will offer a very different reading of the metaphor by setting it within the context of an alternative interpretative framework that presupposes no such dichotomy. Rather than reading Hosea\u27s figure of the \u27 eset zenuni m ( woman of fornications ) through the lens of stereotypical Western associations of woman with nature, sexual temptation and sin, this dissertation will read female sexual transgression in Hosea in light of the repeated association of sexual transgression and social violence which is found in the biblical narratives. Thus female adultery in Hosea will be read as a commentary upon the structural violence in Israelite society which accompanied the eighth century boom in agribusiness and attendant processes of land consolidation. Further, rather than reading Hosea\u27s religious allusions against the background of scholarly fantasies concerning a popular fertility or sex cult, the religious issues relevant to Hosea 1-2 will be identified as relating to the disruption of the socio-sacral order of traditional highland life that accompanied the progressive transformation of Israel\u27s subsistence economy into a commercial economy driven by interregional trade. From this perspective, Hosea\u27s marriage metaphor will be reread as a family metaphor which draws upon the centrality of the family in traditional Israelite life as a way of speaking to the disintegration of that way of life brought about by the avaricious economic practices of Israel\u27s elite establishment. Finally, the symbolism of woman in Hosea will be reconsidered in light of this rereading

Filamin B restricts vaccinia virus spread and is targeted by vaccinia virus protein C4.

UNLABELLED: Vaccinia virus (VACV) is a large DNA virus that encodes scores of proteins that modulate the host immune response. VACV protein C4 is one such immunomodulator known to inhibit the activation of both the NF-κB signaling cascade and the DNA-PK-mediated DNA sensing pathway. Here, we show that the N-terminal region of C4, which neither inhibits NF-κB nor mediates interaction with DNA-PK, still contributes to virus virulence. Furthermore, this domain interacts directly and with high affinity to the C-terminal domain of filamin B (FLNB). FLNB is a large actin-binding protein that stabilizes the F-actin network and is implicated in other cellular processes. Deletion of FLNB from cells results in larger VACV plaques and increased infectious viral yield, indicating that FLNB restricts VACV spread. These data demonstrate that C4 has a new function that contributes to virulence and engages the cytoskeleton. Furthermore, we show that the cytoskeleton performs further previously uncharacterized functions during VACV infection. IMPORTANCE: Vaccinia virus (VACV), the vaccine against smallpox and monkeypox, encodes many proteins to counteract the host immune response. Investigating these proteins provides insights into viral immune evasion mechanisms and thereby indicates how to engineer safer and more immunogenic VACV-based vaccines. Here, we report that the N-terminal domain of VACV protein C4 interacts directly with the cytoskeletal protein filamin B (FLNB), and this domain of C4 contributes to virus virulence. Furthermore, VACV replicates and spreads better in cells lacking FLNB, thus demonstrating that FLNB has antiviral activity. VACV utilizes the cytoskeleton for movement within and between cells; however, previous studies show no involvement of C4 in VACV replication or spread. Thus, C4 associates with FLNB for a different reason, suggesting that the cytoskeleton has further uncharacterized roles during virus infection