Different forms of the bovine PrP gene have five or six copies of a short, G-C-rich element within the protein-coding exon

Current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (BSE) have to take into account that structural changes in a host-encoded protein (PrP protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. We report here the sequence of different forms of the bovine PrP gene which contain either five or six copies of a short, G-C-rich element which encodes the octapeptide Pro-His-Gly-Gly-Gly-Trp-Gly-Gln or its longer variants Pro-Gln/His-Gly-Gly-Gly-Gly-Trp-Gly-Gln. Out of 12 cattle, we found eight animals homozygous for genes with six copies of the Gly-rich peptide (6:6), while four were heterozygous (6:5). Two confirmed cases of BSE occurred in (6: 6) homozygous animals. Bovine spongiform encephalopathy (BSE) is a transmissible disease (Fraser et al., 1988; Dawson et al., 1990; Barlow & Middleton, 1990) which produces neuropathological lesions in cattle similar to those seen in ovine scrapie (Wells et al., 1987) and the rare human dementias Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str/iussler syndrome (GSS) (Beck & Daniel, 1987). A cellular membrane protein (PrP) has a key role in the transmission and development of these diseases. This protein accumulates in the brain and other tissues during the protracted time course of these diseases and, in a disease-specific, protease-resistant isoform (SAF-PrP), has been purified by subcellular fractionation of scrapie

Density of bulk trap states in organic semiconductor crystals: discrete levels induced by oxygen in rubrene

The density of trap states in the bandgap of semiconducting organic single crystals has been measured quantitatively and with high energy resolution by means of the experimental method of temperature-dependent space-charge-limited-current spectroscopy (TD-SCLC). This spectroscopy has been applied to study bulk rubrene single crystals, which are shown by this technique to be of high chemical and structural quality. A density of deep trap states as low as ~ 10^{15} cm^{-3} is measured in the purest crystals, and the exponentially varying shallow trap density near the band edge could be identified (1 decade in the density of states per ~25 meV). Furthermore, we have induced and spectroscopically identified an oxygen related sharp hole bulk trap state at 0.27 eV above the valence band.Comment: published in Phys. Rev. B, high quality figures: http://www.cpfs.mpg.de/~krellner

Significant differences in incubation times in sheep infected with bovine spongiform encephalopathy result from variation at codon 141 in the PRNP gene

The susceptibility of sheep to prion infection is linked to variation in the PRNP gene, which encodes the prion protein. Common polymorphisms occur at codons 136, 154 and 171. Sheep which are homozygous for the A<sub>136</sub>R<sub>154</sub>Q<sub>171</sub> allele are the most susceptible to bovine spongiform encephalopathy (BSE). The effect of other polymorphisms on BSE susceptibility is unknown. We orally infected ARQ/ARQ Cheviot sheep with equal amounts of BSE brain homogenate and a range of incubation periods was observed. When we segregated sheep according to the amino acid (L or F) encoded at codon 141 of the PRNP gene, the shortest incubation period was observed in LL141 sheep, whilst incubation periods in FF<sub>141</sub> and LF<sub>141</sub> sheep were significantly longer. No statistically significant differences existed in the expression of total prion protein or the disease-associated isoform in BSE-infected sheep within each genotype subgroup. This suggested that the amino acid encoded at codon 141 probably affects incubation times through direct effects on protein misfolding rates

Coarsening in surface growth models without slope selection

We study conserved models of crystal growth in one dimension [$\partial_t z(x,t) =-\partial_x j(x,t)$] which are linearly unstable and develop a mound structure whose typical size L increases in time ($L = t^n$). If the local slope ($m =\partial_x z$) increases indefinitely, $n$ depends on the exponent $\gamma$ characterizing the large $m$ behaviour of the surface current $j$ ($j = 1/|m|^\gamma$): $n=1/4$ for $1< \gamma <3$ and $n=(1+\gamma)/(1+5\gamma)$ for $\gamma>3$.Comment: 7 pages, 2 EPS figures. To be published in J. Phys. A (Letter to the Editor

Photoreceptor vitality in organotypic cultures of mature vertebrate retinas validated by light-dependent molecular movements

AbstractVertebrate photoreceptor cells are polarized neurons highly specialized for light absorption and visual signal transduction. Photoreceptor cells consist of the light sensitive outer segment and the biosynthetic active inner segment linked by a slender connecting cilium. The function of mature photoreceptor cells is strictly dependent on this compartmentalization which is maintained in the specialized retinal environment. To keep this fragile morphologic and functional composition for further cell biological studies and treatments we established organotypic retina cultures of mature mice and Xenopus laevis. The organotypic retina cultures of both model organisms are created as co-cultures of the retina and the pigment epithelium, still attached to outer segments of the photoreceptor cells. To demonstrate the suitability of the culture system for physiological analyses we performed apoptotic cell death analyses and verified photoreceptor viability. Furthermore, light-dependent bidirectional movements of arrestin and transducin in photoreceptors in vivo and in the retinal cultures were indistinguishable indicating normal photoreceptor cell-biologic function in organotypic cultures. Our established culture systems allow the analysis of mature photoreceptor cells and their accessibility to treatments, characteristic for common cell culture. Furthermore, this culturing technique also provides an appropriate system for gene delivery to retinal cells and will serve to simulate gene therapeutic approaches prior to difficult and time-consuming in vivo experiments

THE EFFECT OF DIFFERENT FOOTWEAR ON THE MYOELECTRIC ACTIVITY OF M. TIBIALIS POSTERIOR DURING TREADMILL RUNNING

Overload running injuries of the lower extremity, particularly the knee, are associated with excessive pronation of the foot resulting in tibial rotation (Nigg et al., 1995). M. tibialis posterior (TP) is shown to have an active influence on pronation and the medial longitudinal arch (Kaye & Jahss, 1991). Its functional role during running and interaction with footwear is still not clearly understood (Reber et al., 1993; O’Connor & Hamill, 2004). Therefore the purpose of this study is to investigate the influence of different footwear on the muscle’s EMG pattern

WIRE EMG OF FLEXOR HALLUCIS LONGUS DURING BAREFOOT AND SHOD RUNNING ON A TREADMILL: A PILOT STUDY

Excessive pronation is associated with overload injuries of the lower extremity (Nigg, 1995). The flexor hallucis longus (FHL) acts against the pronation of the calcaneus (Klein, 1996). The influence of different footwear on the activity of the FHL was neither measured in walking nor running. The purpose of this study was to investigate the activity of the FHL during different phases in stance of walking and running in different footwear conditions

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Following a severe outbreak of clinical scrapie in 2006–2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated PrP (PrP$^{\rm d}$), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for PrP$^{\rm d}$ in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrP$^{\rm d}$ accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrP$^{\rm d}$ within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrP$^{\rm d}$ in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrP$^{\rm d}$ different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats

Implications of troponin testing in clinical medicine

During the past decade considerable research has been conducted into the use of cardiac troponins, their diagnostic capability and their potential to allow risk stratification in patients with acute chest pain. Determination of risk in patients with suspected myocardial ischaemia is known to be as important as retrospective confirmation of a diagnosis of myocardial infarction (MI). Therefore, creatine kinase (CK)-MB - the former 'gold standard' in detecting myocardial necrosis - has been supplanted by new, more accurate biomarkers.Measurement of cardiac troponin levels constitute a substantial determinant in assessment of ischaemic heart disease, the presentations of which range from silent ischaemia to acute MI. Under these conditions, troponin release is regarded as surrogate marker of thrombus formation and peripheral embolization, and therefore new therapeutic strategies are focusing on potent antithrombotic regimens to improve long-term outcomes. Although elevated troponin levels are highly sensitive and specific indicators of myocardial damage, they are not always reflective of acute ischaemic coronary artery disease; other processes have been identified that cause elevations in these biomarkers. However, because prognosis appears to be related to the presence of troponins regardless of the mechanism of myocardial damage, clinicians increasingly rely on troponin assays when formulating individual therapeutic plans

Hole dynamics in noble metals

We present a detailed analysis of hole dynamics in noble metals (Cu and Au), by means of first-principles many-body calculations. While holes in a free-electron gas are known to live shorter than electrons with the same excitation energy, our results indicate that d-holes in noble metals exhibit longer inelastic lifetimes than excited sp-electrons, in agreement with experiment. The density of states available for d-hole decay is larger than that for the decay of excited electrons; however, the small overlap between d- and sp-states below the Fermi level increases the d-hole lifetime. The impact of d-hole dynamics on electron-hole correlation effects, which are of relevance in the analysis of time-resolved two-photon photoemission experiments, is also addressed.Comment: 4 pages, 2 figures, to appear in Phys. Rev. Let