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

MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes.

IntroductionMCP-1 and eotaxin-1 are encoded on chromosome 17 and have been shown to reduce hippocampal neurogenesis in mice. We investigated whether these chemokines selectively associate with memory in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia.MethodsMCP-1 and eotaxin-1 were assayed in controls, MCI, and AD dementia patients with varying phenotypes (n = 171). A subset of 55 individuals had magnetic resonance imaging (MRI) scans available. Composite scores for cognitive variables were created, and medial temporal lobe volumes were obtained.ResultsAn interaction was noted between MCP-1 and eotaxin-1, such that deleterious associations with memory were seen when both chemokines were elevated. These associations remained significant after adding APOE genotype and comparison (non-chromosome 17) chemokines into the model. These chemokines predicted left medial temporal lobe volume and were not related to other cognitive domains.DiscussionThese results suggest a potentially selective role for MCP-1 and eotaxin-1 in memory dysfunction in the context of varied MCI and AD dementia phenotypes

MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes.

IntroductionMCP-1 and eotaxin-1 are encoded on chromosome 17 and have been shown to reduce hippocampal neurogenesis in mice. We investigated whether these chemokines selectively associate with memory in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia.MethodsMCP-1 and eotaxin-1 were assayed in controls, MCI, and AD dementia patients with varying phenotypes (n = 171). A subset of 55 individuals had magnetic resonance imaging (MRI) scans available. Composite scores for cognitive variables were created, and medial temporal lobe volumes were obtained.ResultsAn interaction was noted between MCP-1 and eotaxin-1, such that deleterious associations with memory were seen when both chemokines were elevated. These associations remained significant after adding APOE genotype and comparison (non-chromosome 17) chemokines into the model. These chemokines predicted left medial temporal lobe volume and were not related to other cognitive domains.DiscussionThese results suggest a potentially selective role for MCP-1 and eotaxin-1 in memory dysfunction in the context of varied MCI and AD dementia phenotypes

The Duration of Zidovudine Benefit in Persons With Asymptomatic HIV Infection: Prolonged Evaluation of Protocol 019 of the AIDS Clinical Trials Group

Objective.—To determine the durability of zidovudine-induced delay in clinical progression of asymptomatic human immunodeficiency virus (HIV) disease and to assess the relationship between this effect and the entry CD4+ cell count.Design and Interventions.—Extended follow-up data from subjects participating in protocol 019 of the AIDS [acquired immunodeficiency syndrome] Clinical Trials Group were examined. Subjects were offered a total daily dose of 500 mg of open-label zidovudine after the unblinding of the original randomized trial in 1989. Original treatment groups included placebo, 500 mg of zidovudine, or 1500 mg of zidovudine daily in divided doses. Three distinct analyses were conducted to assess the duration of zidovudine's effect on progression to AIDS or death: (1) analysis of all follow-up information from all subjects, (2) analysis of all subjects but with follow-up of original placebo-assigned subjects censored at the time open-label zidovudine was initiated, and (3) analysis of the effect of initiating zidovudine in subjects initially assigned to receive placebo.Setting.—University-based and university-affiliated AIDS research clinics participating in AIDS Clinical Trials Group protocol 019.Patients.—A total of 1565 asymptomatic HIV-infected subjects with entry CD4+ cell counts less than 0.50×109/L (500/μL).Main Outcome Measure.—Time to progression to AIDS or death.Results.—During follow-up of up to 4.5 years (mean, 2.6 years), 232 subjects progressed to AIDS or died. In each of the three analyses described herein, zidovudine was associated with a significant (P=.008,.004,.007) decrease in the risk of such progression. However, each of these analyses also indicated a decreasing placebo:zidovudine relative risk with duration of use (P=.002,.08,.04), suggesting a nonpermanent effect. The duration of benefit appeared to be related to entry CD4+ cell count, with greater benefit in those with higher counts at entry. No significant differences in survival were found between those originally randomized to zidovudine or placebo.Conclusions.—Zidovudine at 500 mg/d caused a significant delay in progression to AIDS or death, but its earlier use in asymptomatic disease was not associated with an additional prolongation of survival compared with delayed initiation. The delay in progression diminished over time especially in subjects with entry CD4+ cell counts less than 0.30×109/L (300/μL). Treatment strategies that alter drug regimens before the loss of zidovudine benefit should be explored.(JAMA. 1994;272:437-442

Mega-events and the Preservation of Urban Heritage: Literature Gaps, Potential Overlaps, and a Call for Further Research

Despite mega-events being long perceived as great opportunities by urban policy makers, several cities have recently withdrawn bids for the Olympic games. The disconnect between the planning of mega-events and the urban environment is a reoccurring argument in public debate, but missing in research. In this article, we consider how the relationship between mega-events and urban heritage has been discussed in literature, examining the gaps and potential overlaps, why they exist, and further argue the need to bridge disciplines. In conclusion, we outline new perspectives for studying and learning from the crossroad of the two policy fields, namely, cultural mega-events