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We address a controversy over use of the term “gene drive” to include both natural and synthetic genetic elements that promote their own transmission within a population, arguing that this broad definition is both practical and has advantages for risk analysis.

Genes linked to brahma (brm), a stimulator of homeotic gene expression in Drosophila, were screened to establish possible regulators of Hox gene expression. brg1, a cloned murine gene, may be a DNA-dependent ATPase or a helicase, because it encodes a member of the DEGH proteins family. Hox gene regulation and other regulatory routes may involve the action of brg1.

The Antennapedia Complex (ANT-C) of Drosophila (D) pseudoobscura was cloned to determine the rigidity of its organization and to provide further understanding of its evolutionary changes. Results revealed that the structural characteristics of ANT-C in D pseudoobscura is highly identical with that found in D melanogaster, except that the psudoobscura ANT-C lacks the z2 gene. In addition, in D pseudoobscura, the Deformed gene's orientation is inverted and has a 5' to 3' transcription direction. These indicate that the ANT-C structure is not rigid and can be altered even during a short period of evolutionary divergence.

This document explores the importance of addressing ethical, social, and cultural issues in global health research. It suggests the implementation of consultation services in research ethics to assist researchers and institutions in navigating these challenges. The document proposes key features of these consultation services, including integrating ethical considerations throughout the research process and prioritizing perspectives from the global South. It also acknowledges the difficulties in implementing these features, such as communication barriers and administrative obstacles. Additionally, the document discusses the key features of an Ethics and Social Determinants of Health program for global health research, which aims to integrate ethical considerations into scientific endeavors and prioritize perspectives from the global South. It suggests focusing on specific cases to identify and propose solutions to common issues, such as community engagement, regulatory gaps, and responsible partnerships with the private sector. The document emphasizes the importance of evaluating strategies, activities, and outcomes to enhance the impact of these programs. [Extracted from the article]

Abstract: The Additional sex combs (Asx) gene of Drosophila is required to maintain homeotic gene activation and silencing. Here we characterize the three murine homologs of Asx: Additional sex combs-like (Asxl1, Asxl2, and Asxl3) and identify conserved sequence features. The predicted amino acid sequence of Asxl1 has 16% identity and 40% similarity to Drosophila Asx, and 74% identity and 81% similarity to human ASXL1. Murine Asxl1 contains two regions highly conserved with Drosophila Asx: 1) a conserved amino terminal region of unknown function, termed the ASX homology domain (ASXH) which contains two nuclear receptor (NR) co-regulator binding motifs; and 2) a conserved C-terminal PHD domain. The mammalian Asx-like predicted proteins possess additional conserved sequence features of unknown function not present in Drosophila Asx, including three more NR co-regulator binding motifs. Asxl1and Asxl2 are expressed as multiple transcripts, at varying levels, in adult tissues and in embryonic stem cells analyzed by Northern blot, and exhibit similar expression patterns suggesting they may be co-regulated. Whole mount RNA in situ hybridization revealed that Asxl1 is also expressed in 10.5–11.0 dpc mouse embryos. [Copyright &y& Elsevier]

We have used DNA microarrays to follow Neisseria meningitidis serogroup B (MenB) gene regulation during interaction with human epithelial cells. Host-cell contact induced changes in the expression of 347 genes, more than 30% of which encode proteins with unknown function. The upregulated genes included transporters of iron, chloride, amino acids, and sulfate, many virulence factors, and the entire pathway of sulfur-containing amino acids. Approximately 40% of the 189 upregulated genes coded for peripherally located proteins, suggesting that cell contact promoted a substantial reorganization of the cell membrane. This was confirmed by fluorescence activated cell sorting (FACS) analysis on adhering bacteria using mouse sera against twelve adhesion-induced proteins. Of the 12 adhesion-induced surface antigens, 5 were able to induce bactericidal antibodies in mice, demonstrating that microarray technology is a valid approach for identifying new vaccine candidates and nicely complements other genome mining strategies used for vaccine discovery. [ABSTRACT FROM AUTHOR]

Determines the activation of Wnt/beta-catenin pathway in human colon cancers. Effect of beta-catenin antisense oligodeoxynucleotides on the level of axin2 and human naked cuticle (hnkd) mRNA; Expression of axin2 and hnkd in colon cancer cell lines; Correlation of the increased expression of axin2 and hnkd with truncations in polyposis coli.

The Additional sex combs (Asx) gene of Drosophila is an Enhancer of trithorax and Polycomb (ETP), and is required to maintain activation and silencing of homeotic loci. The molecular basis of this dual function is not understood. Here, we identify a human homolog of Asx, termed ADDITIONAL SEX COMBS-LIKE 1 (ASXL1). Overall, the amino acid sequence of ASXL1 has 21% identity and 41% similarity to Drosophila ASX. The ASXL1 protein contains a 118 amino acid conserved amino terminal region of unknown function that we term the ASX homology domain (ASXH) that contains two LXXLL consensus sequences for nuclear receptor binding. ASXL1 also contains a conserved C-terminal cysteine cluster that is a variant of the PHD domain. Three ASXL1 transcripts of differing size are detected, which are widely expressed in adult tissues. ASXL1 maps to chromosome 20q11, a region frequently amplified in human tumors. Interestingly, ASXL1 is overexpressed in cell lines derived from carcinomas. [Copyright &y& Elsevier]

To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.