ED-initiated addiction treatment holds promise for enhancing access to treatment for those with opioid use disorder (OUD). We present a literature review summarizing the evidence for buprenorphine ...induction in the ED including best practices for dosing, follow-up care, and reducing implementation barriers. A literature search of Pubmed, PsychInfo, and Embase identified articles studying OUD treatment in the ED published after 1980. Twenty-five studies were identified including eleven scientific abstracts. Multiple studies suggest that buprenorphine induction improves engagement in substance treatment up to 30 days after ED treatment. Many different induction protocols were presented, but no particular approach was best supported as criteria for induction and initial dosing vary widely. Similarly, transition of care models focused on either a "hub and spoke" model or "warm hand-offs" model, but no studies compared these approaches. Common barriers to implementing induction programs were provider inexperience, discomfort with addiction treatment, and limited time during the ED visit. No studies described the number of EDs offering induction. While ED buprenorphine induction is safe and enhances adherence to addiction treatment, uncertainty persists in how to best identify patients needing treatment, how to initiate buprenorphine, and how to enhance follow-up after ED-initiated treatment.
We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, ...RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.
Deletions of chromosome 6 are a common abnormality in diverse human malignancies including astrocytic tumours, suggesting the presence of tumour suppressor genes (TSG). In order to help identify ...candidate TSGs, we have constructed a chromosome 6 tile path microarray. The array contains 1,780 clones (778 P1-derived artificial chromosome and 1,002 bacterial artificial chromosome) that cover 98.3% of the published chromosome 6 sequences. A total of 104 adult astrocytic tumours (10 diffuse astrocytomas, 30 anaplastic astrocytomas (AA), 64 glioblastomas (GB)) were analysed using this array. Single copy number change was successfully detected and the result was in general concordant with a microsatellite analysis. The pattern of copy number change was complex with multiple interstitial deletions/gains. However, a predominance of telomeric 6q deletions was seen. Two small common and overlapping regions of deletion at 6q26 were identified. One was 1,002 kb in size and contained PACRG and QKI, while the second was 199 kb and harbours a single gene, ARID1B. The data show that the chromosome 6 tile path array is useful in mapping copy number changes with high resolution and accuracy. We confirmed the high frequency of chromosome 6 deletions in AA and GB, and identified two novel commonly deleted regions that may harbour TSGs.
Little is known as to why a large number of human diseases are influenced by the major histocompatibility complex. In some cases, a direct involvement of the products of the polymorphic class I and ...class II, as well as the less variable products of the class III, genes has been proposed. During characterization of the class III region for the presence of additional loci, we have located a duplicated locus encoding the major heat shock protein HSP70 between the complement and tumor necrosis factor genes. The HSP70 loci are 12 kilobases apart and lie 92 kilobases telomeric of the C2 gene. As HSP70 proteins have been linked with a protective role during and after cellular stress, and HSP70 analogues are often presented as antigens in bacterial and protozoal infections, this finding may have major implications with regard to the major histocompatibility complex and associated diseases.
An SNP map of human chromosome 22 Bentley, D. R; Mullikin, J. C; Hunt, S. E ...
Nature (London),
09/2000, Letnik:
407, Številka:
6803
Journal Article
Recenzirano
Odprti dostop
The human genome sequence will provide a reference for measuring DNA sequence
variation in human populations. Sequence variants are responsible for the
genetic component of individuality, including ...complex characteristics such
as disease susceptibility and drug response. Most sequence variants are single
nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP
per kilobase. A sufficiently dense map of SNPs would allow
the detection of sequence variants responsible for particular characteristics
on the basis that they are associated with a specific SNP allele.
Here we have evaluated large-scale sequencing approaches to obtaining SNPs,
and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the
SNPs are within 25 kilobases of a transcribed exon, and are valuable
for association studies. We have scaled up the process, detecting over 65,000
SNPs in the genome as part of The SNP Consortium programme, which is on target
to build a map of 1 SNP every 5 kilobases that is integrated
with the human genome sequence and that is freely available in the public
domain.
The Human Cell Atlas Regev, Aviv; Teichmann, Sarah A; Lander, Eric S ...
eLife,
12/2017, Letnik:
6
Journal Article
Recenzirano
Odprti dostop
The recent advent of methods for high-throughput single-cell molecular profiling has catalyzed a growing sense in the scientific community that the time is ripe to complete the 150-year-old effort to ...identify all cell types in the human body. The Human Cell Atlas Project is an international collaborative effort that aims to define all human cell types in terms of distinctive molecular profiles (such as gene expression profiles) and to connect this information with classical cellular descriptions (such as location and morphology). An open comprehensive reference map of the molecular state of cells in healthy human tissues would propel the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, and also provide a framework for understanding cellular dysregulation in human disease. Here we describe the idea, its potential utility, early proofs-of-concept, and some design considerations for the Human Cell Atlas, including a commitment to open data, code, and community.
Jeffrey Barrett, Ian Dunham and Ewan Birney discuss the initiatives of the newly founded Centre for Therapeutic Target Validation, including a range of approaches to use human genetics to inform drug ...discovery and make better medicines.
Ensembl 2012 Flicek, Paul; Amode, M. Ridwan; Barrell, Daniel ...
Nucleic acids research,
01/2012, Letnik:
40, Številka:
D1
Journal Article
Recenzirano
Odprti dostop
The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and ...zebrafish. Five additional species were added in the last year including gibbon (Nomascus leucogenys) and Tasmanian devil (Sarcophilus harrisii) bringing the total number of supported species to 61 as of Ensembl release 64 (September 2011). Of these, 55 species appear on the main Ensembl website and six species are provided on the Ensembl preview site (Pre!Ensembl; http://pre.ensembl.org) with preliminary support. The past year has also seen improvements across the project.
The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology ...and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome.
The cytidine (C) to uridine (U) editing of apolipoprotein (apo) B mRNA is mediated by tissue-specific, RNA-binding cytidine deaminase APOBEC1. APOBEC1 is structurally homologous to Escherichia coli ...cytidine deaminase (ECCDA), but has evolved specific features required for RNA substrate binding and editing. A signature sequence for APOBEC1 has been used to identify other members of this family. One of these genes, designated APOBEC2, is found on chromosome 6. Another gene corresponds to the activation-induced deaminase (AID) gene, which is located adjacent to APOBEC1 on chromosome 12. Seven additional genes, or pseudogenes (designated APOBEC3A to 3G), are arrayed in tandem on chromosome 22. Not present in rodents, this locus is apparently an anthropoid-specific expansion of the APOBEC family. The conclusion that these new genes encode orphan C to U RNA-editing enzymes of the APOBEC family comes from similarity in amino acid sequence with APOBEC1, conserved intron/exon organization, tissue-specific expression, homodimerization, and zinc and RNA binding similar to APOBEC1. Tissue-specific expression of these genes in a variety of cell lines, along with other evidence, suggests a role for these enzymes in growth or cell cycle control.
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