Specific B cell tolerance is induced by cyclosporin A plus donor-specific blood transfusion pretreatment: prolonged survival of MHC class I disparate cardiac allografts

Donor-specific blood transfusion (DST), designed to prolong allograft survival, sensitized recipients of the high-responder PVG-RT1u strain, resulting in accelerated rejection of MHC-class I mismatched (PVG-R8) allografts. Rejection was found to be mediated by anti-MHC class I (Aa) alloantibody. By pretreating recipients 4 wk before grafting with cyclosporin A (CsA) daily (x7), combined with once weekly (x4) DST, rejection was prevented. The investigation explores the mechanism for this induced unresponsiveness. CD4 T cells purified from the thoracic duct of CsA/DST-pretreated RT1u rats induced rejection when transferred to R8 heart-grafted RT1u athymic nude recipients, indicating that CD4 T cells were not tolerized by the pretreatment. To determine whether B cells were affected, nude recipients were pretreated, in the absence of T cells, with CsA/DST (or CsA/third party blood) 4 wk before grafting. The subsequent transfer of normal CD4 T cells induced acute rejection of R8 cardiac allografts in third party- but not DST-pretreated recipients; prolonged allograft survival was reversed by the cotransfer of B cells with the CD4 T cells. Graft survival correlated with reduced production of anti-MHC class I (Aa) cytotoxic alloantibody. The results indicated that the combined pretransplant treatment of CsA and DST induced tolerance in allospecific B cells independently of T cells. The resulting suppression of allospecific cytotoxic Ab correlated with the survival of MHC class I mismatched allografts. The induction of B cell tolerance by CsA has important implications for clinical transplantation.     

Quercetin and vitamin E ameliorate cardio-apoptotic risks in diabetic rats

Molecular and Cellular Biochemistry - Apoptosis is upregulated in all forms of diabetes, and the mitochondria act as target in diabetes pathophysiology. Quercetin and vitamin E have both shown...     

Review: life-cycle assessment,water footprinting,and carbon footprinting in Portugal

Purpose

A review of readily available quantitative environmental data was conducted in order to determine the state of sustainability reporting and identify possible future research areas in Portugal.

Methods

Internet searches of articles written in English and published between 2001 and 2015 were conducted using the keywords “life-cycle assessment,” “LCA,” “water footprint,” “carbon footprint,” and “Portugal.” Additionally, reports from the Global Reporting Initiative (2015 only) were included in the search.

Results and discussion

It was found that 79% of reports found were published in the period 2011–2015. Several reports were found for the forestry, paper and pulp, food and beverage, energy and electricity, waste management, and automotive industries, while no reports were found for the textile, footwear and clothing, and base metal and mineral industries. As such, these are industries on which future studies might focus. No reports found were published by governmental organizations, although it is thought that expanding the search to include Portuguese language results would yields more results. The majority (68%) of companies reporting to the GRI adhered to the relevant guidelines.

Conclusions

A total of 72 reports were found (41 LCAs, water- or carbon footprints, and 31 GRI reports). It is unclear if there are other reports that may be restricted to “hidden” datasets or company specific archives. The aim of this report was to highlight those that were available to a non-specialist or international audiences trying to gain a greater understanding of the LCA space in Portugal.

     

DNA methylation analysis of murine hematopoietic side population cells during aging

Stem cells have been found in most tissues/organs. These somatic stem cells produce replacements for lost and damaged cells, and it is not completely understood how this regenerative capacity becomes diminished during aging. To study the possible involvement of epigenetic changes in somatic stem cell aging, we used murine hematopoiesis as a model system. Hematopoietic stem cells (HSCs) were enriched for via Hoechst exclusion activity (SP-HSC) from young, medium-aged and old mice and subjected to comprehensive, global methylome (MeDIP-seq) analysis. With age, we observed a global loss of DNA methylation of approximately 5%, but an increase in methylation at some CpG islands. Just over 100 significant (FDR < 0.2) aging-specific differentially methylated regions (aDMRs) were identified, which are surprisingly few considering the profound age-based changes that occur in HSC biology. Interestingly, the polycomb repressive complex -2 (PCRC2) target genes Kiss1r, Nav2 and Hsf4 were hypermethylated with age. The promoter for the Sdpr gene was determined to be progressively hypomethylated with age. This occurred concurrently with an increase in gene expression with age. To explore this relationship further, we cultured isolated SP-HSC in the presence of 5-aza-deoxycytdine and demonstrated a negative correlation between Sdpr promoter methylation and gene expression. We report that DNA methylation patterns are well preserved during hematopoietic stem cell aging, confirm that PCRC2 targets are increasingly methylated with age, and suggest that SDPR expression changes with age in HSCs may be regulated via age-based alterations in DNA methylation.