More than a Rumor Spreads in Parkinson's Disease

As Parkinson's disease progresses, a massive loss of dopaminergic neurons is accompanied by accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies and Lewy neurites. Inclusions first appear in olfactory bulb and enteric neurons then in ascendant neuroanatomical interconnected areas, and finally, in late stages of the disease, Lewy bodies are observed in a substantia nigra pars compacta with clear signs of neuronal loss. It is believed that the spreading of Lewy bodies through the nervous system is a consequence of the cell-to-cell propagation of αSyn, that can occur via sequential steps of secretion and uptake. Certain pathological forms of transmitted αSyn are able to seed endogenous counterparts in healthy recipient cells, thus promoting the self-sustained cycle of inclusion formation, amplification and spreading, that ultimately underlies disease progression. Here we review the cell-to-cell propagation of αSyn focusing on its role in the progression of Parkinson’s disease

Broadband Relaxation-Optimized Polarization Transfer in Magnetic Resonance

Many applications of magnetic resonance are limited by rapid loss of spin coherence caused by large transverse relaxation rates. In nuclear magnetic resonance (NMR) of large proteins, increased relaxation losses lead to poor sensitivity of experiments and increased measurement time. In this paper we develop broadband relaxation optimized pulse sequences (BB-CROP) which approach fundamental limits of coherence transfer efficiency in the presence of very general relaxation mechanisms that include cross-correlated relaxation. These broadband transfer schemes use new techniques of chemical shift refocusing (STAR echoes) that are tailored to specific trajectories of coupled spin evolution. We present simulations and experimental data indicating significant enhancement in the sensitivity of multi-dimensional NMR experiments of large molecules by use of these methods

Identification of quantitative trait loci controlling root and shoot traits associated with drought tolerance in a lentil (Lens culinaris Medik.) recombinant inbred line population

Drought is one of the major abiotic stresses limiting lentil productivity in rainfed production systems. Specific rooting patterns can be associated with drought avoidance mechanisms that can be used in lentil breeding programs. In all, 252 co-dominant and dominant markers were used for Quantitative Trait Loci (QTL) analysis on 132 lentil recombinant inbred lines based on greenhouse experiments for root and shoot traits during two seasons under progressive drought-stressed conditions. Eighteen QTLs controlling a total of 14 root and shoot traits were identified. A QTL-hotspot genomic region related to a number of root and shoot characteristics associated with drought tolerance such as dry root biomass, root surface area, lateral root number, dry shoot biomass and shoot length was identified. Interestingly, a QTL (QRSratioIX-2.30) related to root-shoot ratio, an important trait for drought avoidance, explaining the highest phenotypic variance of 27.6 and 28.9% for the two consecutive seasons, respectively, was detected. This QTL was closed to the co-dominant SNP marker TP6337 and also flanked by the two SNP TP518 and TP1280. An important QTL (QLRNIII-98.64) related to lateral root number was found close to TP3371 and flanked by TP5093 and TP6072 SNP markers. Also, a QTL (QSRLIV-61.63) associated with specific root length was identified close to TP1873 and flanked by F7XEM6b SRAP marker and TP1035 SNP marker. These two QTLs were detected in both seasons. Our results could be used for marker-assisted selection in lentil breeding programs targeting root and shoot characteristics conferring drought avoidance as an efficient alternative to slow and labor-intensive conventional breeding methods

Debye mass and heavy quark potential in a PNJL quark plasma

We calculate the Debye mass for the screening of the heavy quark potential in a plasma of massless quarks coupled to the temporal gluon background governed by the Polyakov loop potential within the PNJL model in RPA approximation. We give a physical motivation for a recent phenomenological fit of lattice data by applying the calculated Debye mass with its suppression in the confined phase due to the Polyakov-loop to a description of the temperature dependence of the singlet free energy for QCD with a heavy quark pair at infinite separation. We compare the result to lattice data.Comment: 6 pages, 1 figure, contribution to Proceedings of the 6th International Conference on "Critical Point and Onset of Deconfinement", to appear in Phys. At. Nucl., vol. 7

Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPSc from sporadic Creutzfeldt-Jakob disease

In recent studies, the amyloid form of recombinant prion protein (PrP) encompassing residues 89–230 (rPrP 89-230) produced in vitro induced transmissible prion disease in mice. These studies showed that unlike “classical” PrPSc produced in vivo, the amyloid fibrils generated in vitro were more proteinase-K sensitive. Here we demonstrate that the amyloid form contains a proteinase K-resistant core composed only of residues 152/153–230 and 162–230. The PK-resistant fragments of the amyloid form are similar to those observed upon PK digestion of a minor subpopulation of PrPSc recently identified in patients with sporadic Creutzfeldt-Jakob disease (CJD). Remarkably, this core is sufficient for self-propagating activity in vitro and preserves a β-sheet-rich fibrillar structure. Full-length recombinant PrP 23-230, however, generates two subpopulations of amyloid in vitro: One is similar to the minor subpopulation of PrPSc, and the other to classical PrPSc. Since no cellular factors or templates were used for generation of the amyloid fibrils in vitro, we speculate that formation of the subpopulation of PrPSc with a short PK-resistant C-terminal region reflects an intrinsic property of PrP rather than the influence of cellular environments and/or cofactors. Our work significantly increases our understanding of the biochemical nature of prion infectious agents and provides a fundamental insight into the mechanisms of prions biogenesis

Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G') and the loss modulus (G″), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation

Evaluating chiral symmetry restoration through the use of sum rules

We pursue the idea of assessing chiral restoration via in-medium modifications of hadronic spectral functions of chiral partners. The usefulness of sum rules in this endeavor is illustrated, focusing on the vector and axial-vector channels. We first present an update on constructing quantitative results for pertinent vacuum spectral functions. These spectral functions serve as a basis upon which the in-medium spectral functions can be constructed. A striking feature of our analysis of the vacuum spectral functions is the need to include excited resonances, dictated by satisfying the Weinberg-type sum rules. This includes excited states in both the vector and axial-vector channels. Preliminary results for the finite temperature vector spectral function are presented. Based on a rho spectral function tested in dilepton data which develops a shoulder at low energies, we find that the rho' peak flattens off. The flattening may be a sign of chiral restoration, though a study of the finite temperature axial-vector spectral function remains to be carried out.Comment: 9 pages, conference proceedings from Resonance Workshop at UT Austin, March 5-7 201

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

Characterisation of sugar beet (Beta vulgaris L. ssp. vulgaris) varieties using microsatellite markers

<p>Abstract</p> <p>Background</p> <p>Sugar beet is an obligate outcrossing species. Varieties consist of mixtures of plants from various parental combinations. As the number of informative morphological characteristics is limited, this leads to some problems in variety registration research.</p> <p>Results</p> <p>We have developed 25 new microsatellite markers for sugar beet. A selection of 12 markers with high quality patterns was used to characterise 40 diploid and triploid varieties. For each variety 30 individual plants were genotyped. The markers amplified 3-21 different alleles. Varieties had up to 7 different alleles at one marker locus. All varieties could be distinguished. For the diploid varieties, the expected heterozygosity ranged from 0.458 to 0.744. The average inbreeding coefficient F_iswas 0.282 ± 0.124, but it varied widely among marker loci, from F_is= +0.876 (heterozygote deficiency) to F_is= -0.350 (excess of heterozygotes). The genetic differentiation among diploid varieties was relatively constant among markers (F_st= 0.232 ± 0.027). Among triploid varieties the genetic differentiation was much lower (F_st= 0.100 ± 0.010). The overall genetic differentiation between diploid and triploid varieties was F_st= 0.133 across all loci. Part of this differentiation may coincide with the differentiation among breeders' gene pools, which was F_st= 0.063.</p> <p>Conclusions</p> <p>Based on a combination of scores for individual plants all varieties can be distinguished using the 12 markers developed here. The markers may also be used for mapping and in molecular breeding. In addition, they may be employed in studying gene flow from crop to wild populations.</p

CIS-based registration of quality of life in a single source approach

Background: Documenting quality of life (QoL) in routine medical care and using it both for treatment and for clinical research is not common, although such information is absolutely valuable for physicians and patients alike. We therefore aimed at developing an efficient method to integrate quality of life information into the clinical information system (CIS) and thus make it available for clinical care and secondary use. Methods: We piloted our method in three different medical departments, using five different QoL questionnaires. In this setting we used structured interviews and onsite observations to perform workflow and form analyses. The forms and pertinent data reports were implemented using the integrated tools of the local CIS. A web-based application for mobile devices was developed based on XML schemata to facilitate data import into the CIS. Data exports of the CIS were analysed with statistical software to perform an analysis of data quality. Results: The quality of life questionnaires are now regularly documented by patients and physicians. The resulting data is available in the Electronic Health Record (EHR) and can be used for treatment purposes and communication as well as research functionalities. The completion of questionnaires by the patients themselves using a mobile device (iPad) and the import of the respective data into the CIS forms were successfully tested in a pilot installation. The quality of data is rendered high by the use of automatic score calculations as well as the automatic creation of forms for follow-up documentation. The QoL data was exported to research databases for use in scientific analysis. Conclusion: The CIS-based QoL is technically feasible, clinically accepted and provides an excellent quality of data for medical treatment and clinical research. Our approach with a commercial CIS and the web-based application is transferable to other sites