The Tnfrh1 (Tnfrsf23) gene is weakly imprinted in several organs and expressed at the trophoblast-decidua interface

BACKGROUND: The Tnfrh1 gene (gene symbol Tnfrsf23) is located near one end of a megabase-scale imprinted region on mouse distal chromosome 7, about 350 kb distant from the nearest known imprinting control element. Within 20 kb of Tnfrh1 is a related gene called Tnfrh2 (Tnfrsf22) These duplicated genes encode putative decoy receptors in the tumor necrosis factor (TNF) receptor family. Although other genes in this chromosomal region show conserved synteny with genes on human Chr11p15.5, there are no obvious human orthologues of Tnfrh1 or Tnfrh2. RESULTS: We analyzed Tnfrh1 for evidence of parental imprinting, and characterized its tissue-specific expression. Tnfrh1 mRNA is detectable in multiple adult and fetal tissues, with highest expression in placenta, where in situ hybridization reveals a distinctive population of Tnfrh1-positive cells in maternal decidua, directly beneath the trophoblast giant cells. In offspring of interspecific mouse crosses, Tnfrh1 shows a consistent parent-of-origin-dependent allelic expression bias, with relative repression, but not silencing, of the paternal allele in several organs including fetal liver and adult spleen. CONCLUSIONS: Genes preferentially expressed in the placenta are predicted to evolve rapidly, and Tnfrh1 appears to be an example of this phenomenon. In view of its strong expression in cells at the fetal-maternal boundary, Tnfrh1 warrants further study as a gene that might modulate immune or trophic interactions between the invasive placental trophoblast and the maternal decidua. The preferential expression of Tnfrh1 from the maternal allele indicates weak functional imprinting of this locus in some tissues

LA SCRITTURA MIGRANTE: LA MIA LINGUA E LA MIA NUOVA LINGUA ITALIANA

Acquisire una nuova lingua non è mai un percorso semplice. Il cammino che il migrante deve compiere per apprendere l'italiano è costellato di difficoltà e di ostacoli dovuti ad emozioni contrastanti, al  trauma causato dall'esperienza della migrazione, dalle condizioni, spesso di forte disagio, di lavoro, del contesto in cui si trova a svolgere una nuova vita, dalla qualità o meno dell'accoglienza, dalle possibilità reali, sul piano sociale, di integrazione. Lo scopo di questo articolo consiste nel mettere in evidenza il passaggio complesso dalla lingua madre alla cosiddetta lingua adottiva, mostrando come in taluni casi l'italiano, imparato nei corsi per stranieri o a scuola dai più giovani sia divenuto uno straordinario strumento grazie al quale poter evocare il paese d'origine e raccontare il proprio vissuto. Lo scrivere in una lingua diversa permette al migrante non solo di narrare fatti ed esperienze che magari preferirebbe non raccontare nella lingua madre, ma di diventare costruttore di cultura.   Learning a new language is never a simple task. The new-comer's experience of learning Italian is marked by difficulties and obstacles caused by contrasting emotions, the trauma from the experience of migration, the often difficult work conditions, the living conditions in the host country, the presence or absence of feeling welcomed, and the real chances for social integration. This paper aims at highlighting the complex passage from the mother tongue to the so-called adopted language, showing how in some cases learning Italian, thanks to courses for foreigners or as children at school, has become a wonderful tool for evoking the home country and telling about life there. Writing in another language allows migrants not only to recount facts and experiences that they might prefer not to tell in their own language, but it is a cultural building block as well

CD117 expression in diffuse large B-cell lymphomas: Fact or fiction?

CD117 (KIT) is expressed in a variety of hematopoietic neo- plasms but there are a paucity of data regarding its expres- sion in diffuse large B-cell lymphomas (DLBCL). The purpose of the present paper was to describe the authors’ experience of two CD117+ DLBCL (one of follicle center-cell origin and one nasal Epstein–Barr virus (EBV)– plasmablas- tic lymphoma associated with lytic bone lesions), as deter- mined by tissue immunohistochemistry and flow cytometry. The CD117 expression in DLBCL was further evaluated using tissue microarrays and seven additional plasma- blastic lymphomas, using two commercially available anti-CD117 antibodies (Ab-1, Oncogene and A4502, Dako- Cytomation). Membranous ± cytoplasmic staining was seen with Ab-1 in 24/65 (37%) DLBCL, including 21/56 microarray DLBCL, two index cases, and 1/7 additional plasmablastic lymphomas, with persistent staining in 13% of microarray DLBCL despite preincubation with KIT peptide. However, A4502 had only membranous staining of the index cases and one additional EBV– plasmablastic lymphoma with medullary disease. The present study suggests that (i) CD117 expression can be detected sporadically in DLBCL of follicle center-cell origin and a subset of plasmablastic lymphomas; (ii) staining for CD117 might help in identifying EBV– plasmablastic lymphomas associated with bone mar- row involvement; and (iii) CD117 antibodies should be care- fully validated prior to use, because non-specific staining, as observed with Ab-1, could lead to false-positive results

The normal and fibrotic mouse lung classified by spatial proteomic analysis

Single cell classification is elucidating homeostasis and pathology in tissues and whole organs. We applied in situ spatial proteomics by multiplex antibody staining to routinely processed mouse lung, healthy and during a fibrosis model. With a limited validated antibody panel (24) we classify the normal constituents (alveolar type I and II, bronchial epithelia, endothelial, muscular, stromal and hematopoietic cells) and by quantitative measurements, we show the progress of lung fibrosis over a 4 weeks course, the changing landscape and the cell-specific quantitative variation of a multidrug transporter. An early decline in AT2 alveolar cells and a progressive increase in stromal cells seems at the core of the fibrotic process

Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B cell lymphomas in mice

Diffuse large B cell lymphomas (DLBCL) derive from germinal center (GC) B cells and display chromosomal alterations deregulating the expression of BCL6, a transcriptional repressor required for GC formation. To investigate the role of BCL6 in DLBCL pathogenesis, we have engineered mice that express BCL6 constitutively in B cells by mimicking a chromosomal translocation found in human DLBCL. These mice display increased GC formation and perturbed post-GC differentiation characterized by a decreased number of post-isotype switch plasma cells. Subsequently, these mice develop a lympho- proliferative syndrome that culminates with the development of lymphomas displaying features typical of human DLBCL. These results define the oncogenic role of BCL6 in the pathogenesis of DLBCL and provide a faithful mouse model of this common disease

Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling

Background and Objectives. In early and polymorphic post-transplant lymphoprolifera- tive disorders (PTLD) Epstein-Barr virus (EBV), through its latency proteins, drives the proliferation of B lymphocytes, a process which in immunocompetent individuals leads to the establishment of latently infected memory B cells. Design and Methods. We analyzed 11 cases, which included early and polymorphic PTLD, and 12 controls for latency of EBV infection and their antigenic profile. Results. We identified a minority of terminally differentiated EBER+ IRTA1+ memory B cells and EBER+ CD138+ PRDM1+ plasma cells in these samples. These elements were identified both in PTLD and in tumor-free tonsils from post-transplant patients but not in EBV– control tonsils. The expression of EBV latency proteins is heterogeneous, and is associated with activation of the NF-κB pathway. EBV signaling (through EBNA2, LMP1 and LMP2A) and NF-κB activation correlated with upregulation of target proteins: cMYC, JunB, CCL22, TRAF1 and IRF4. EBV-infected lymphocytes in early and polymor- phic PTLDs represent a mixture of latencies II, III and, in at least 1/3 of infected cells, of latency 0. Interpretation and conclusions. EBV infection correlates with NF-κB activation, with EBV-dependent cell signaling, and lastly, with the presence of EBV-infected plasma cells and memory cells. Key words: post-transplant lymphoproliferative disorder, Epstein-Barr virus, viral latency, NF-κB signaling, plasma cell, memory B cell