Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance

Complement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa(−/−)) or C3 (C3(−/−)) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa(−/−) or C3(−/−) mice. The rejection of the male grafts correlated with the presence of HY D(b)Uty-specific CD8(+) T cells. Consistent with this, peptide-treated C1qa(−/−) and C3(−/−) female mice rejecting male grafts exhibited more antigen-specific CD8(+)IFN-γ(+) and CD8(+)IL-10(+) cells compared with WT females. This suggests that accumulation of IFN-γ- and IL-10-producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide-treated WT mice, IFN-γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance

Damage function for historic paper. Part I: Fitness for use

Background In heritage science literature and in preventive conservation practice, damage functions are used to model material behaviour and specifically damage (unacceptable change), as a result of the presence of a stressor over time. For such functions to be of use in the context of collection management, it is important to define a range of parameters, such as who the stakeholders are (e.g. the public, curators, researchers), the mode of use (e.g. display, storage, manual handling), the long-term planning horizon (i.e. when in the future it is deemed acceptable for an item to become damaged or unfit for use), and what the threshold of damage is, i.e. extent of physical change assessed as damage. Results In this paper, we explore the threshold of fitness for use for archival and library paper documents used for display or reading in the context of access in reading rooms by the general public. Change is considered in the context of discolouration and mechanical deterioration such as tears and missing pieces: forms of physical deterioration that accumulate with time in libraries and archives. We also explore whether the threshold fitness for use is defined differently for objects perceived to be of different value, and for different modes of use. The data were collected in a series of fitness-for-use workshops carried out with readers/visitors in heritage institutions using principles of Design of Experiments. Conclusions The results show that when no particular value is pre-assigned to an archival or library document, missing pieces influenced readers/visitors’ subjective judgements of fitness-for-use to a greater extent than did discolouration and tears (which had little or no influence). This finding was most apparent in the display context in comparison to the reading room context. The finding also best applied when readers/visitors were not given a value scenario (in comparison to when they were asked to think about the document having personal or historic value). It can be estimated that, in general, items become unfit when text is evidently missing. However, if the visitor/reader is prompted to think of a document in terms of its historic value, then change in a document has little impact on fitness for use

Caracterização de acessos de pimenta-do-reino com base em sistemas enzimáticos.

Setenta e oito acessos de pimenta-do-reino, incluindo algumas espécies silvestres foram submetidos à análise eletroforética de isoenzimas em gel de poliacrilamida, visando distinguir diferenças fenotípicas que auxiliem na discriminação e seleção dos acessos. Foram utilizados os sistemas enzimáticos SKDH, GOT, ACP, ACO, PGI, FUM, 6PGDH e G6PDH. O polimorfismo de isoenzimas foi avaliado pelo número de alozimas com diferentes mobilidades por sistema enzimático, pelas freqüências de alozimas dentro de cada sistema enzimático em relação ao total de bandas do sistema e pela análise da similaridade genética, com base na ausência e presença de bandas. Todos os sistemas enzimáticos utilizados tiveram boa resolução e definição de bandas, com ênfase para SKDH, 6PGDH, PGI e ACP. Em sua totalidade, os sistemas apresentaram polimorfismo capaz de caracterizar e identificar acessos ou grupos de pequeno número de acessos, sendo que o sistema GOT foi o que apresentou maior variabilidade de alozimas e de perfis; e o que apresentou menor variabilidade foi o sistema FUM, com três alozimas e quatro perfis. Cinqüenta e sete por cento das alozimas podem ser usadas para caracterizar e identificar clones ou grupos de clones. Cerca de 64% dos acessos analisados podem ser identificados por um a seis fenótipos individuais de sistemas enzimáticos. A análise da similaridade indicou os grupos G1, G2 e G3 como os mais divergentes da coleção, os quais são indicados para cruzamentos intraespecíficos e interespecíficos visando a obtenção de clones superiores.Título em inglês: Characterization of black pepper accessions using isozymes. Publicado também on-line

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Poland's 2011 Online Election Campaign: New Tools, New Professionalism, New Ways to Win Votes

This article analyzes the use of the online environment within the context of the Polish parliamentary election of 2011. Using traditional methods of content analysis, we find that parties tend to adhere to a professionalized model of campaigning, and adapting online tools to suit the objectives of the campaign. There also appears to be a recognition that their most likely visitors to these online presences would be converts, and so they attempt to mobilize supporters rather than convert browsers. New parties and candidates are more likely to target browsers, with the latter offering a more personalized experience to online visitors. Importantly, when analyzing the outcome of the contest, we find that being online matters for candidates when controlling for all other variables. Equally, the reach the candidate has, which may well influence their vote share, is dependent on offering a more personalized, representational image and having a frequently updated online presence that should encourage repeat visits. Cumulatively, we suggest the future of online campaigning must not only focus on having a presence, but on using it in a way that appeals to a range of visitors, encouraging repeat visits, and that this strategy could have a positive impact on election outcomes. © Taylor & Francis Group, LLC

The Arabidopsis protein phosphatase PP2C38 negatively regulates the central immune kinase BIK1

Plants recognize pathogen-associated molecular patterns (PAMPs) via cell surface-localized pattern recognition receptors (PRRs), leading to PRR-triggered immunity (PTI). The Arabidopsis cytoplasmic kinase BIK1 is a downstream substrate of several PRR complexes. How plant PTI is negatively regulated is not fully understood. Here, we identify the protein phosphatase PP2C38 as a negative regulator of BIK1 activity and BIK1-mediated immunity. PP2C38 dynamically associates with BIK1, as well as with the PRRs FLS2 and EFR, but not with the co-receptor BAK1. PP2C38 regulates PAMP-induced BIK1 phosphorylation and impairs the phosphorylation of the NADPH oxidase RBOHD by BIK1, leading to reduced oxidative burst and stomatal immunity. Upon PAMP perception, PP2C38 is phosphorylated on serine 77 and dissociates from the FLS2/EFR-BIK1 complexes, enabling full BIK1 activation. Together with our recent work on the control of BIK1 turnover, this study reveals another important regulatory mechanism of this central immune component

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.This study was funded by the WT fellowship grant for VV (093705/Z/ 10/Z) and Cambridge NIHR Biomedical Research Centre. VV and NAH are Wellcome Trust (WT) intermediate Clinical Fellows. YW is supported by the Fyssen Fondation and MRC Studentships. PD is supported by the Gatsby Charitable Foundation. JEG has received grants from the National Institute of Drug Abuse and the National Center for Responsible Gaming. TWR and BJS are supported on a WT Programme Grant (089589/Z/09/Z). The BCNI is supported by a WT and MRC grant.This is the final published version. It's also available from Molecular Psychiatry at http://www.nature.com/mp/journal/vaop/ncurrent/full/mp201444a.html