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

Myelin basic protein isoform expression: A comparison of developing rat brain and myelinating and remyelinating rat brain aggregate cell cultures

Recent evidence suggests myelin basic protein (MBP) exon-2 containing isoforms play a significant role in the onset of myelination as they are more abundant during early development. The pattern of expression of MBP exon-2 containing forms was studied in rat brain aggregate cultures during myelination in order to draw comparisons with the developing brain and upon remyelination following demyelinative treatment. The pattern of MBP isoform expression in the aggregate cultures was found to be similar to that of the brain and was recapitulated following demyelination with anti-myelin antibodies. Macrophage enrichment, resulting in increased accumulation of total MBP in the cultures, did not alter the isoform distribution. Both control and enriched cultures expressed a 16 kDa protein (26 +/- 9.8% of total MBP for control samples) which reacted with MBP antisera at the onset of myelination (day in vitro 14) but was barely detectable by day in vitro 21. The expression of this protein, also present in postnatal day 11 rat brain but no longer by day 15, has been predicted by RT-PCR; however, detection of a corresponding protein with the same developmental pattern and appropriate molecular weight has not been previously reported. The results of this study reinforce the value of the aggregate culture system as a versatile yet accurate model of myelination and remyelination

Impact of Low-Level Viremia on Clinical and Virological Outcomes in Treated HIV Infected Patients

Electronic coverage as of Dec. 30, 2003: Vol. 1, no. 1 (spring 2001)-; Description based on: Vol. 2, issue 1 (winter 2003); title from caption (viewed Dec. 30, 2003).; Harvested from the web on 10/25/0

Determinants of restoration of CD4 and CD8 cell counts and their ratio in HIV-1 positive individuals with sustained virological suppression on antiretroviral therapy

Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV uninfected individuals more likely and whether restoration depends on gender, age and other individual characteristics. Methods: We determined median and quartile reference values for CD4 and CD8 cell count and their ratio using cross-sectional data from 2,309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed effects models. Results: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first two years median CD8 cell counts converged towards median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with <250 CD4 cells/mm3. Median CD4:CD8 trajectories did not reach median reference values, even when ART was started at 500 cells/mm3. Discussion: Starting ART with a CD4 cell count of ≥500 cells/mm3 makes reaching median reference CD4 cell counts more likely. However, median CD4:CD8 ratio trajectories remained below the median levels of HIV-negative individuals, because of persisting high CD8 cell counts. To what extent these subnormal immunological responses have impact on specific clinical endpoints requires further investigation