Mammalian prion amyloid formation in bacteria

Mammalian prion proteins (PrPs) that cause transmissible spongiform encephalopathies are misfolded conformations of the host cellular PrP. The misfolded form, the scrapie PrP (PrP^Sc), can aggregate into amyloid fibrils that progressively accumulate in the brain, evolving to a pathological phenotype. A particular characteristic of PrP^Sc is to be found as different strains, related to the diversity of conformational states it can adopt. Prion strains are responsible for the multiple phenotypes observed in prion diseases, presenting different incubation times and diverse deposition profiles in the brain. PrP biochemical properties are also strain-dependent, such as different digestion pattern after proteolysis and different stability. Although they have long been studied, strain formation is still a major unsolved issue in prion biology. The recreation of strain-specific conformational features is of fundamental importance to study this unique pathogenic phenomenon. In our recent paper, we described that murine PrP, when expressed in bacteria, forms amyloid inclusion bodies that possess different strain-like characteristics, depending on the PrP construct. Here, we present an extra-view of these data and propose that bacteria might become a successful model to generate preparative amounts of prion strain-specific assemblies for high-resolution structural analysis as well as for addressing the determinants of infectivity and transmissibility.     

Developmental change and sexual difference in synaptic modulation produced by oxytocin in rat substantia gelatinosa neurons

We have previously reported that oxytocin produces an inward current at a holding potential of ?70 mV without a change in glutamatergic excitatory transmission in adult male rat spinal lamina II (substantia gelatinosa; SG) neurons that play a pivotal role in regulating nociceptive transmission. Oxytocin also enhanced GABAergic and glycinergic spontaneous inhibitory transmissions in a manner sensitive to a voltage-gated Na⁺-channel blocker tetrodotoxin. These actions were mediated by oxytocin-receptor activation. Such a result was different from that obtained by other investigators in young male rat superficial dorsal horn neurons in which an oxytocin-receptor agonist enhanced glutamatergic and GABAergic but not glycinergic spontaneous transmissions. In order to know a developmental change and also sexual difference in the actions of oxytocin, we examined its effect on spontaneous synaptic transmission in adult female and young male rat SG neurons by using the whole-cell patch-clamp technique in spinal cord slices. In adult female rats, oxytocin produced an inward current at ?70 mV without a change in excitatory transmission. GABAergic and glycinergic transmissions were enhanced by oxytocin, the duration of which enhancement was much shorter than in adult male rats. In young (11–21 postnatal days) male rats, oxytocin produced not only an inward but also outward current at ?70 mV, and presynaptically inhibited or facilitated excitatory transmission, depending on the neurons tested; both GABAergic and glycinergic transmissions were enhanced by oxytocin. The inhibitory transmission enhancements in adult female and young male rats were sensitive to tetrodotoxin. Although the data may not be enough to be estimated, it is suggested that synaptic modulation by oxytocin in SG neurons, i.e., cellular mechanism for its antinociceptive action, exhibits a developmental change and sexual difference.     

What is ‘post-race’ and what does it reveal about contemporary racisms?

ABSTRACT

In this paper, I will critically engage those aspects of Goldberg’s Are We All Postracial Yet that I found to be particularly generative for thinking about contemporary racisms. These foci include the place of post-racial mystification vis-à-vis liberal market capitalism, animalization and synchronic global relationalities. A case will be made for post-race being best understood in terms of how it both incorporates as well as exceeds the explanatory terrain already serviced by the concept of ‘Cultural Racism’ and/or ‘New Racism’. A unique connection to Chamayou’s recent Manhunts will also be advanced. I will read contemporary processes of post-racial animalization via Chamayou’s key contention that Power is always about who is to be the object of force, who shall do the enforcing and how is it to be enforced – a historically contingent force that results in particular technologies of classification, hunting, surveillance, internment, killing and fortification.     

Collaboration between Sami and non-Sami formal and family caregivers in rural municipalities

The aim of this study was to explore how caregivers experience collaboration in rural municipalities in northern Norway. We conducted fieldwork with a dementia team in addition to seventeen qualitative in-depth interviews with formal and family caregivers. The caregivers had ethnic Sami and ethnic Norwegian affiliation. The theme ‘negotiating ethnic and ethno-political positions’ was identified through thematic analysis and developed using positioning theory. Ethnicity involves dynamic and situated personal affiliations, and participants negotiate each other's ethnic positions in practice. Negotiations of ethnic positions hamper collaboration between formal and family caregivers, and ethno-political positions reinforce stereotyped ethnic positions. This study contributes to the understanding of and the debate over positions on ethno-cultural collaboration in health care. In practice, participants negotiate the health policy concept of ‘cultural facilitation’, which must be broadened to ensure equal healthcare services.     

Theoretical insight into three disease-related benefits of migration

Migration (seasonal round-trip movement across relatively large distances) is common within the animal kingdom. This behaviour often incurs extreme costs in terms of time, energy, and/or survival. Climate, food, predation, and breeding are typically suggested as factors favouring the evolution of migration. Although disease regulation has also been considered, few studies consider it as the primary selective pressure for migration. Our aim was to determine, theoretically, under what conditions migration could reduce the long-term disease prevalence within a population, assuming the only benefits of migration are infection-related. We created two mathematical models, one where the population migrates annually and one where the entire population remains on the breeding ground year-round. In each we simulated disease transmission (frequency-dependent and density-dependent) and quantified eventual disease prevalence. In the migration model we varied the time spent migrating, disease-related migration mortality, and the overall migration mortality. When we compared results from the two models, we found that migration generally lowered disease prevalence. We found a population was healthier if it: (1) spent more time migrating (assuming no disease transmission during migration), (2) had higher disease-induced migration mortality, and (3) had an overall higher mortality when migrating (compared to not migrating). These results provide support for two previously proposed mechanisms by which migration can reduce disease prevalence (migratory escape and migratory cull), and also demonstrate that non-selective mortality during migration is a third mechanism. Our findings indicate that migration may be evolutionarily advantageous even if the only migratory benefit is disease control.     

Study on the interaction between pelargonidin‐3‐O‐glucoside and bovine serum albumin using spectroscopic,transmission electron microscopy and molecular modeling techniques

The aim of this study is to evaluate the binding behavior between pelargonidin‐3‐O‐glucoside (P3G) and bovine serum albumin (BSA) using multi‐spectroscopic, transmission electron microscopy (TEM) and molecular docking methods under physiological conditions. Fluorescence spectroscopy and time‐resolved fluorescence showed that the fluorescence of BSA could be quenched remarkably by P3G via a static quenching mechanism, and there is a single class of binding site on BSA. In addition, the thermodynamic functions ΔH and ΔS were –21.69 kJ/mol and 24.46 J/mol/K, indicating that an electrostatic interaction was a main acting force. The distance between BSA and P3G was 2.74 nm according to Förster's theory, illustrating that energy transfer occurred. In addition, the secondary structure of BSA changed with a decrease in the α‐helix content from 66.2% to 64.0% as seen using synchronous fluorescence, UV/vis, circular dichroism and Fourier transform infrared spectroscopies, whereas TEM images showed that P3G led to BSA aggregation and fibrillation. Furthermore, site marker competitive experiments and molecular docking indicated that P3G could bind with subdomain IIA of BSA. The calculated results of the equilibrium fraction showed that the concentration of free P3G in plasma was high enough to be stored and transported from the circulatory system to its target sites to provide therapeutic effects. Copyright © 2015 John Wiley & Sons, Ltd.     

Paternal‐specific S‐allele transmission in sweet cherry (Prunus avium L.): the potential for sexual selection

Homomorphic self‐incompatibility is a well‐studied example of a physiological process that is thought to increase population diversity and reduce the expression of inbreeding depression. Whereas theoretical models predict the presence of a large number of S‐haplotypes with equal frequencies at equilibrium, unequal allele frequencies have been repeatedly reported and attributed to sampling effects, population structure, demographic perturbation, sheltered deleterious mutations or selection pressure on linked genes. However, it is unclear to what extent unequal segregations are the results of gametophytic or sexual selection. Although these two forces are difficult to disentangle, testing S‐alleles in the offspring of controlled crosses provides an opportunity to separate these two phenomena. In this work, segregation and transmission of S‐alleles have been characterized in progenies of mixed donors and fully compatible pollinations under field conditions in Prunus avium. Seed set patterns and pollen performance have also been characterized. The results reveal paternal‐specific distorted transmission of S‐alleles in most of the crosses. Interestingly, S‐allele segregation within any given paternal or maternal S‐locus was random. Observations on pollen germination, pollen tube growth rate, pollen tube cohort size, seed set dynamics and transmission patterns strongly suggest post‐pollination, prezygotic sexual selection, with male–male competition as the most likely mechanism. According to these results, post‐pollination sexual selection takes precedence over frequency‐dependent selection in explaining unequal S‐haplotype frequencies.     

Germline Competent Pluripotent Mouse Stem Cells Generated by Plasmid Vectors

We developed nonintegrated methods to reprogram mouse embryonic fibroblast (MEF) cells into induced pluripotent stem cells (iPSCs) using pig pOct4, pSox2, and pc-Myc as well as human hKLF4, hAID, and hTDG that were carried by plasmid vectors. The 4F method employed pOct4, pSox2, pc-Myc, and hKLF4 to derive iPSC clones with naive embryonic stem cell (ESC)-like morphology. These 4F clones expressed endogenous mouse Nanog protein and could generate chimeras. In addition to the four conventional reprogramming factors used in the 4F method, hAID and hTDG were utilized in a 6F method to increase the conversion efficiency of reprogramming by approximately five-fold. One of the 6F plasmid derived iPSC (piPSC) clones was shown to be germline transmission competent.     

文化景观作为区域景观研究概念——德国图林根州文化景观研究、教学与规划实践

近20 年来,对风景园林的文化阐释成为埃尔夫特应用科技大学文化景观研究组持续以来的关注焦点。期间,该研究组系统地分析了决定图林根州文化景观的各种文化因素和要素,深入了解文化和自然环境中的复杂相互作用,以此来表述和研究图林根州的区域景观系统。首先,阐述了当下德国风景园林学术语境中“文化景观”的含义,强调文化对于景观质量的价值。继而,论述了对景观进行优化、保护和设计中无法否定和回避的文化与经济因素。这样既要发展经济又要保护文化的矛盾性质,是文化景观概念所理解的人类生存的重要性质所在。文化景观研究能够在看似统一的地理区域中,形成和发展为具有可识别性的、差异化的动态结构。此外,文化景观研究还涉及其他因素,诸如生物多样性与文化多样性的丧失、生态系统服务功能滞后、经济价值的低估、国土空间连接性以及缺少实质性评价的人文特征。对历史性文化景观价值的认知给风景园林学带来了机遇,对历史景观不仅要保护,而且要创造并提供各种富有成效的展示,以参与文化景观的未来发展。维护和整合风景园林规划设计中文化景观遗产的研究实践,可以通过基础设施项目的环境影响评估到建成区的景观设计整体过程中得以贯彻。更好地理解文化景观,有助于在空间规划和发展中对其更加谨慎地进行处理,以提高文化景观研究的科学和策略意识。