A first-generation X-inactivation profile of the human X chromosome

In females, most genes on the X chromosome are generally assumed to be transcriptionally silenced on the inactive X as a result of X inactivation. However, particularly in humans, an increasing number of genes are known to “escape” X inactivation and are expressed from both the active (Xa) and inactive (Xi) X chromosomes; such genes reflect different molecular and epigenetic responses to X inactivation and are candidates for phenotypes associated with X aneuploidy. To identify genes that escape X inactivation and to generate a first-generation X-inactivation profile of the X, we have evaluated the expression of 224 X-linked genes and expressed sequence tags by reverse-transcription–PCR analysis of a panel of multiple independent mouse/human somatic cell hybrids containing a normal human Xi but no Xa. The resulting survey yields an initial X-inactivation profile that is estimated to represent ≈10% of all X-linked transcripts. Of the 224 transcripts tested here, 34 (three of which are pseudoautosomal) were expressed in as many as nine Xi hybrids and thus appear to escape inactivation. The genes that escape inactivation are distributed nonrandomly along the X; 31 of 34 such transcripts map to Xp, implying that the two arms of the X are epigenetically and/or evolutionarily distinct and suggesting that genetic imbalance of Xp may be more severe clinically than imbalance of Xq. A complete X-inactivation profile will provide information relevant to clinical genetics and genetic counseling and should yield insight into the genomic and epigenetic organization of the X chromosome.

Multiple four-stranded conformations of human telomere sequence d(CCCTAA) in solution

By detailed NMR analysis of a human telomere repeating unit, d(CCCTAA), we have found that three distinct tetramers, each of which consists of four symmetric single-strands, slowly exchange in a slightly acidic solution. Our new finding is a novel i-motif topology (T-form) where T4 is intercalated between C1 and C2 of the other duplex. The other two tetramers have a topology where C1 is intercalated between C2 and C3 of the other parallel duplex, resulting in the non-stacking T4 residues (R-form), and a topology where C1 is stacked between C3 and T4 of the other duplex (S-form). From the NMR denaturation profile, the R-form is the most stable of the three structures in the temperature range of 15–50°C, the S-form the second and the T-form the least stable. The thermodynamic parameters indicate that the T-form is the most enthalpically driven and entropically opposed, and its population is increased with decreasing temperature. The T-form structure determined by restrained molecular dynamics calculation suggests that inter-strand van der Waals contacts in the narrow grooves should contribute to the enthalpic stabilization of the T-form.

Studies of the lamin proteinase reveal multiple parallel biochemical pathways during apoptotic execution.

Although specific proteinases play a critical role in the active phase of apoptosis, their substrates are largely unknown. We previously identified poly(ADP-ribose) polymerase (PARP) as an apoptosis-associated substrate for proteinase(s) related to interleukin 1 beta-converting enzyme (ICE). Now we have used a cell-free system to characterize proteinase(s) that cleave the nuclear lamins during apoptosis. Lamin cleavage during apoptosis requires the action of a second ICE-like enyzme, which exhibits kinetics of cleavage and a profile of sensitivity to specific inhibitors that is distinct from the PARP proteinase. Thus, multiple ICE-like enzymes are required for apoptotic events in these cell-free extracts. Inhibition of the lamin proteinase with tosyllysine "chloromethyl ketone" blocks nuclear apoptosis prior to the packaging of condensed chromatin into apoptotic bodies. Under these conditions, the nuclear DNA is fully cleaved to a nucleosomal ladder. Our studies reveal that the lamin proteinase and the fragmentation nuclease function in independent parallel pathways during the final stages of apoptotic execution. Neither pathway alone is sufficient for completion of nuclear apoptosis. Instead, the various activities cooperate to drive the disassembly of the nucleus.

e_LIPID: Characterisation of the Lipid Profile in the Portuguese Population

AIM: Cardiovascular disease (CVD), particularly coronary heart disease and stroke, are the leading cause of morbidity and mortality worldwide. The common forms of CVD have a complex etiology in which interactions between multiple genetic and environmental factors play an important role. Dyslipidaemia is one of many independent cardiovascular risk factors that have been identified for CVD, and its correct identification is of great importance in order to implement specific interventions, especially for CVD prevention. The aim of this study was the construction of population specific lipid percentiles and the to present the characterization of the dyslipidaemia in the Portuguese population.

Biochemical investigation of multicorer sediment profile PS74/109-2

To detect and track the impact of large-scale environmental changes in a the transition zone between the northern North Atlantic and the central Arctic Ocean, and to determine experimentally the factors controlling deep-sea biodiversity, the Alfred- Wegener-Institute for Polar and Marine Research (AWI) established the deep-sea long-term observatory HAUSGARTEN, which constitutes the first, and until now only open-ocean long-term station in a polar region. Virtually undisturbed sediment samples have been taken using a video-guided multiple corer (MUC) at 13 HAUSGARTEN stations along a bathymetric (1,000 - 4,000 m water depth) and a latitudinal transect in 2,500 m water depth as well as two stations at 230 and 1,200 m water depth within the framework of the KONGHAU project. Various biogenic sediment compounds were analyzed to estimate the input of organic matter from phytodetritus sedimentation, benthic activities (e.g. bacterial exoenzymatic activity), and the total biomass of the smallest sediment-inhabiting organisms (size range: bacteria to meiofauna).

Biochemical investigation of multicorer sediment profile PS74/113-2

To detect and track the impact of large-scale environmental changes in a the transition zone between the northern North Atlantic and the central Arctic Ocean, and to determine experimentally the factors controlling deep-sea biodiversity, the Alfred- Wegener-Institute for Polar and Marine Research (AWI) established the deep-sea long-term observatory HAUSGARTEN, which constitutes the first, and until now only open-ocean long-term station in a polar region. Virtually undisturbed sediment samples have been taken using a video-guided multiple corer (MUC) at 13 HAUSGARTEN stations along a bathymetric (1,000 - 4,000 m water depth) and a latitudinal transect in 2,500 m water depth as well as two stations at 230 and 1,200 m water depth within the framework of the KONGHAU project. Various biogenic sediment compounds were analyzed to estimate the input of organic matter from phytodetritus sedimentation, benthic activities (e.g. bacterial exoenzymatic activity), and the total biomass of the smallest sediment-inhabiting organisms (size range: bacteria to meiofauna).

Biochemical investigation of multicorer sediment profile PS74/118-2

To detect and track the impact of large-scale environmental changes in a the transition zone between the northern North Atlantic and the central Arctic Ocean, and to determine experimentally the factors controlling deep-sea biodiversity, the Alfred- Wegener-Institute for Polar and Marine Research (AWI) established the deep-sea long-term observatory HAUSGARTEN, which constitutes the first, and until now only open-ocean long-term station in a polar region. Virtually undisturbed sediment samples have been taken using a video-guided multiple corer (MUC) at 13 HAUSGARTEN stations along a bathymetric (1,000 - 4,000 m water depth) and a latitudinal transect in 2,500 m water depth as well as two stations at 230 and 1,200 m water depth within the framework of the KONGHAU project. Various biogenic sediment compounds were analyzed to estimate the input of organic matter from phytodetritus sedimentation, benthic activities (e.g. bacterial exoenzymatic activity), and the total biomass of the smallest sediment-inhabiting organisms (size range: bacteria to meiofauna).

Multiple imputation of missing blood alcohol concentration (BAC) values in FARS.

National Highway Traffic Safety Administration, Washington, D.C.

Reauthorization of GSA and multiple award program : hearing before the Committee on Governmental Affairs, United States Senate, One Hundred Second Congress, second session, on S. 1958 ... and S. 2619 ... June 11, 1992.

"S. 1958, to authorize functions and activities under the Federal Property and Administrative Services Act of 1949, to amend laws relating to federal procurement, and for other purposes and S. 2619, to amend the Federal Property and Amdinistrative Services Act of 1949 to enact provisions governing the negotiation and award of contracts under the multiple award schedule program of the Feneral Services Administration"

A system for diagnosis, referral, and rehabilitation of persons convicted of driving while intoxicated: a special rehabilitation program for multiple offenders. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Understanding multiple endocrine neoplasia type 1.

Mode of access: Internet.