Foxn1 Is Dynamically Regulated in Thymic Epithelial Cells during Embryogenesis and at the Onset of Thymic Involution

Thymus function requires extensive cross-talk between developing T-cells and the thymic epithelium, which consists of cortical and medullary TEC. The transcription factor FOXN1 is the master regulator of TEC differentiation and function, and declining Foxn1 expression with age results in stereotypical thymic involution. Understanding of the dynamics of Foxn1 expression is, however, limited by a lack of single cell resolution data. We have generated a novel reporter of Foxn1 expression, Foxn1G, to monitor changes in Foxn1 expression during embryogenesis and involution. Our data reveal that early differentiation and maturation of cortical and medullary TEC coincides with precise sub-lineage-specific regulation of Foxn1 expression levels. We further show that initiation of thymic involution is associated with reduced cTEC functionality, and proportional expansion of FOXN1-negative TEC in both cortical and medullary sub-lineages. Cortex-specific down-regulation of Foxn1 between 1 and 3 months of age may therefore be a key driver of the early stages of age-related thymic involution

Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.

BACKGROUND: Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice. RESULTS: Our analysis reveals that the expression levels of most genes are generally preserved in B cell precursors isolated from aged compared with young mice. Nonetheless, age-specific expression changes are observed at numerous genes, including microRNA encoding genes. Importantly, these changes are underpinned by multi-layered alterations in chromatin structure, including chromatin accessibility, histone modifications, long-range promoter interactions, and nuclear compartmentalization. Previous work has shown that differentiation is linked to changes in promoter-regulatory element interactions. We find that aging in B cell precursors is accompanied by rewiring of such interactions. We identify transcriptional downregulation of components of the insulin-like growth factor signaling pathway, in particular downregulation of Irs1 and upregulation of Let-7 microRNA expression, as a signature of the aged phenotype. These changes in expression are associated with specific alterations in H3K27me3 occupancy, suggesting that Polycomb-mediated repression plays a role in precursor B cell aging. CONCLUSIONS: Changes in chromatin and 3D genome organization play an important role in shaping the altered gene expression profile of aged precursor B cells. Components of the insulin-like growth factor signaling pathways are key targets of epigenetic regulation in aging in bone marrow B cell precursors

Evaluation of two different scrap tires as hydrocarbon source by pyrolysis

WOS: 000230940700020The main objective of the present study is to investigate the effect of the polymer types in scrap tires on the pyrolysis products. Two different types of scrap tires (passenger car tire, PCT and truck tire, TT) have been pyrolyzed in a fixed bed reactor at the temperatures of 550, 650 and 800 degrees C under N-2 atmosphere. Pyrolysis products (gas, oil and carbon black) obtained from PCT and TT were investigated comparatively. The gaseous products were analyzed by GC-TCD. The psychical and chemical properties of pyrolytic oils were characterized by means of GC-FID, GC-NIS, H-1 NNIR. In addition, boiling point distributions of hydrocarbons in pyrolytic oils were determined by using simulated distillation curves in comparison with commercial diesel fuel. The production of activated carbon from pyrolytic carbon blacks (CBp) was also carried out. The composition of gaseous products from pyrolysis of PCT and TT were similar and they contained mainly hydrocarbons (C-1-C-4)- Pyrolytic oils were found lighter than diesel but heavier than naphtha. The physical properties of pyrolytic oils from PCT and TT were similar at the same temperature. However, the composition of aromatic and sulphur content from pyrolysis of PCT was higher than that of TT. Furthermore, TT derived pyrolytic carbon black was found more suitable for the production of activated carbon due to its low ash content. (c) 2005 Elsevier Ltd. All rights reserved

Effects of Rituximab on Atherosclerotic Biomarkers in Kidney Transplant Recipients

Introduction. Cardiovascular disease is the leading cause of mortality in kidney transplantrecipients. Rituximab is widely used in kidney transplantation for a variety of situations,and rituximab may inhibit some cytokines and antibodies that may play an active role in theatherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab onatherosclerosis biomarkers in kidney transplant recipients.Methods. All patients, 18 years of age and older, who underwent kidney transplantationand received at least 1 dose of 375 mg/m2 rituximab were considered for participation inthis study. The primary study endpoint was the development of cardiovascular diseasesafter rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV)disease or biopsy-confirmed BK virus nephropathy. In addition, comparison ofatherosclerosis biomarkers was performed between study and control groups.Results. There were no cardiovascular events observed during follow up. Only 8 patientsin the study group suffered from CMV disease during follow up. Serum interleukin 10levels were significantly higher in the rituximab group compared with the control group,although antieoxidized low-density lipoprotein levels were lower in the rituximab groupcompared with the control group, though this did not achieve statistical significance.Discussion. Rituximab treatment may increase the risk of CMV reactivation anddecrease lymphocyte counts and interleukin 10 levels; however, significant decreases in allatherosclerotic-related biomarkers have not been shown in our study