The first report of RPSA polymorphisms, also called 37/67 kDa LRP/LR gene, in sporadic Creutzfeldt-Jakob disease (CJD)

<p>Abstract</p> <p>Background</p> <p>Although polymorphisms of <it>PRNP</it>, the gene encoding prion protein, are known as a determinant affecting prion disease susceptibility, other genes also influence prion incubation time. This finding offers the opportunity to identify other genetic or environmental factor (s) modulating susceptibility to prion disease. Ribosomal protein SA (<it>RPSA</it>), also called 37 kDa laminin receptor precursor (LRP)/67 kDa laminin receptor (LR), acts as a receptor for laminin, viruses and prion proteins. The binding/internalization of prion protein is dependent for LRP/LR.</p> <p>Methods</p> <p>To identify other susceptibility genes involved in prion disease, we performed genetic analysis of <it>RPSA</it>. For this case-control study, we included 180 sporadic Creutzfeldt-Jakob disease (CJD) patients and 189 healthy Koreans. We investigated genotype and allele frequencies of polymorphism on <it>RPSA </it>by direct sequencing or restriction fragment length polymorphism (RFLP) analysis.</p> <p>Results</p> <p>We observed four single nucleotide polymorphisms (SNPs), including -8T>C (rs1803893) in the 5'-untranslated region (UTR) of exon 2, 134-32C>T (rs3772138) in the intron, 519G>A (rs2269350) in the intron and 793+58C>T (rs2723) in the intron on the <it>RPSA</it>. The 519G>A (at codon 173) is located in the direct PrP binding site. The genotypes and allele frequencies of the <it>RPSA </it>polymorphisms showed no significant differences between the controls and sporadic CJD patients.</p> <p>Conclusion</p> <p>These results suggest that these <it>RPSA </it>polymorphisms have no direct influence on the susceptibility to sporadic CJD. This was the first genetic association study of the polymorphisms of <it>RPSA </it>gene with sporadic CJD.</p

Experimental study of negative photoconductivity in n-PbTe(Ga) epitaxial films

We report on low-temperature photoconductivity (PC) in n-PbTe(Ga) epitaxial films prepared by the hot-wall technique on -BaF_2 substrates. Variation of the substrate temperature allowed us to change the resistivity of the films from 10^8 down to 10_{-2} Ohm x cm at 4.2 K. The resistivity reduction is associated with a slight excess of Ga concentration, disturbing the Fermi level pinning within the energy gap of n-PbTe(Ga). PC has been measured under continuous and pulse illumination in the temperature range 4.2-300 K. For films of low resistivity, the photoresponse is composed of negative and positive parts. Recombination processes for both effects are characterized by nonexponential kinetics depending on the illumination pulse duration and intensity. Analysis of the PC transient proves that the negative photoconductivity cannot be explained in terms of nonequilibrium charge carriers spatial separation of due to band modulation. Experimental results are interpreted assuming the mixed valence of Ga in lead telluride and the formation of centers with a negative correlation energy. Specifics of the PC process is determined by the energy levels attributed to donor Ga III, acceptor Ga I, and neutral Ga II states with respect to the crystal surrounding. The energy level corresponding to the metastable state Ga II is supposed to occur above the conduction band bottom, providing fast recombination rates for the negative PC. The superposition of negative and positive PC is considered to be dependent on the ratio of the densities of states corresponding to the donor and acceptor impurity centers.Comment: 7 pages, 4 figure

Extraribosomal functions associated with the C terminus of the 37/67 kDa laminin receptor are required for maintaining cell viability

The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly. LAMR is important for cell viability; however, it is unclear which of its functions are essential. We developed a silent mutant LAMR construct, resistant to siRNA, to rescue the phenotypic effects of knocking down endogenous LAMR, which include inhibition of protein synthesis, cell cycle arrest, and apoptosis. In addition, we generated a C-terminal-truncated silent mutant LAMR construct structurally homologous to the Archaeoglobus fulgidus S2 ribosomal protein and missing the C-terminal 75 residues of LAMR, which displays more sequence divergence. We found that HT1080 cells stably expressing either silent mutant LAMR construct still undergo arrest in the G1 phase of the cell cycle when treated with siRNA. However, the expression of full-length silent mutant LAMR rescues cell viability, whereas the expression of the C-terminal-truncated LAMR does not. Interestingly, we also found that both silent mutant constructs restore protein translation and localize to the nucleus. Our findings indicate that the ability of LAMR to regulate viability is associated with its C-terminal 75 residues. Furthermore, this function is distinct from its role in cell proliferation, independent of its ribosomal functions, and may be regulated by a nonnuclear localization

Tectonically controlled sedimentation: impact on sediment supply and basin evolution of the Kashafrud Formation (Middle Jurassic, Kopeh-Dagh Basin, northeast Iran)

peer reviewedThe Kashafrud Formation was deposited in the extensional Kopeh-Dagh Basin during the Late Bajocian to Bathonian (Middle Jurassic) and is potentially the most important siliciclastic unit from NE Iran for petroleum geology. This extensional setting allowed the accumulation of about 1,700 m of siliciclastic sediments during a limited period of time (Upper Bajocian–Bathonian). Here, we present a detailed facies analysis combined with magnetic susceptibility (MS) results focusing on the exceptional record of the Pol-e-Gazi section in the southeastern part of the basin. MS is classically interpreted as related to the amount of detrital input. The amount of these detrital inputs and then the MS being classically influenced by sea-level changes, climate changes and tectonic activity. Facies analysis reveals that the studied rocks were deposited in shallow marine, slope to pro-delta settings. A major transgressive–regressive cycle is recorded in this formation, including fluvial-dominated delta to turbiditic pro-delta settings (transgressive phase), followed by siliciclastic to mixed siliciclastic and carbonate shoreface rocks (regressive phase). During the transgressive phase, hyperpycnal currents were feeding the basin. These hyperpycnal currents are interpreted as related to important tectonic variations, in relation to significant uplift of the hinterland during opening of the basin. This tectonic activity was responsible for stronger erosion, providing a higher amount of siliciclastic input into the basin, leading to a high MS signal. During the regressive phase, the tectonic activity strongly decreased. Furthermore, the depositional setting changed to a wave- to tide-dominated, mixed carbonate–siliciclastic setting. Because of the absence of strong tectonic variations, bulk MS was controlled by other factors such as sea-level and climatic changes. Fluctuations in carbonate production, possibly related to sea-level variations, influenced the MS of the siliciclastic/carbonate cycles. Carbonate intervals are characterized by a strong decrease of MS values indicates a gradual reduction of detrital influx. Therefore, the intensity of tectonic movement is thought to be the dominant factor in controlling sediment supply, changes in accommodation space and modes of deposition throughout the Middle Jurassic sedimentary succession in the Pol-e-Gazi section and possibly in the Kopeh-Dagh Basin in general