Location of Ribosomal Protein Binding Sites on 16S Ribosomal RNA

The distribution of ribosomal protein binding sites on the 16S ribosomal RNA molecule has been analyzed by limited ribonuclease hydrolysis of RNA-protein complexes, as well as by the interaction of individual proteins with RNA fragments purified from partial enzymatic digests. Of the six 30S subunit proteins known to interact directly with 16S RNA, proteins S4, S8, S15, S20, and, probably, S13 bind within a fragment produced by T(1) RNase (12S RNA) that comprises some 900 nucleotides and covers almost the entire 5'-terminal half of the 16S molecule. A fragment of 500-600 nucleotides (8S RNA) that is contiguous with 12S RNA and arises from the 3'-terminal portion of the 16S molecule is believed to contain the binding site for protein S7. Protein S15 interacts specifically with a sequence of about 135 nucleotides (4S RNA) that derives from 12S RNA after more extensive hydrolysis. Protein S4, but none of the other ribosomal proteins, binds to a 500-nucleotide fragment (9S RNA), generated by pancreatic RNase, that lies at the 5'-terminus of 16S RNA and is completely overlapped by the 12S fragment. A preliminary map of the binding sites is presented.     

Alterations of gene profiles in Leydig-cell-regenerating adult rat testis after ethane dimethane sulfonate-treatment

Only occupying about 1%–5% of total testicular cells, the adult Leydig cell (ALC) is a unique endocrine cell that produces androgens. Rat Leydig cells regenerate after these cells in the testis are eliminated with ethane dimethane sulfonate (EDS). In this study, we have characterized Leydig cell regeneration and messenger ribonucleic acids (mRNA) profiles of EDS treated rat testes. Serum testosterone, testicular gene profiling and some steroidogenesis-related proteins were analyzed at 7, 21, 35 and 90 days after EDS treatment. Testicular testosterone levels declined to undetectable levels until 7 days after treatment and then started to recover. Seven days after treatment, 81 mRNAs were down-regulated greater than or equal to two-fold, with 48 becoming undetectable. These genes increased their expression 21 days and completely returned to normal levels 90 days after treatment. The undetectable genes include steroidogenic pathway proteins: steroidogenic acute regulatory protein, Scarb1, Cyp11a1, Cyp17a1, Hsd3b1, Cyp1b1 and Cyp2a1. Seven days after treatment, there were 89 mRNAs up-regulated two-fold or more including Pkib. These up-regulated mRNAs returned to normal 90 days after treatment. Cyp2a1 did not start to recover until 35 days after treatment, indicating that this gene is only expressed in ALCs not in the precursor cells. Quantitative polymerase chain reaction, western blotting and semi-quantitative immunohistochemical staining using tissue array confirmed the changes of several randomly picked genes and their proteins.     

Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study

The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden. Patients were randomly assigned to receive either 12 courses of the chemotherapy regimen CHVP (cyclophosphamide, adriamycin, etoposide, and prednisolone) plus interferon-alpha2a (CHVP+I arm) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m(2) rituximab and interferon for the same time period (R-CHVP+I arm). After a median follow-up of 5 years, event-free survival estimates were, respectively, 37% (95% confidence interval [CI], 29%-44%) and 53% (95% CI, 45%-60%) in the CHVP+I and R-CHVP+I arm (P = .001). Five-year overall survival estimates were not statistically different in the CHVP+I (79%; 95% CI, 72%-84%) and R-CHVP+I (84%; 95% CI, 78%-84%) arms. In a multivariate regression analysis, event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score (hazard ratio = 2.08; 95% CI, 1.6%-2.8%) and the treatment arm (hazard ratio = 0.59; 95% CI, 0.44%-0.78%). With a 5-year follow-up, the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy. This study's clinical trial was registered at the National Institutes of Health website as no. NCT00136552.     

Instability of Trinucleotidic Repeats During Chromatin Remodeling in Spermatids

Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.     

Rationale for the potential use of mesenchymal stromal cells in liver transplantation

Mesenchymal stromal cells(MSCs) are multipotent and self-renewing cells that reside essentially in the bone marrow as a non-hematopoietic cell population, but may also be isolated from the connective tissues of most organs. MSCs represent a heterogeneous population of adult, fibroblast-like cells characterized by their ability to differentiate into tissues of mesodermal lineages including adipocytes, chondrocytes and osteocytes. For several years now, MSCs have been evaluated for their in vivo and in vitro immunomodulatory and ‘tissue reconstruction’ properties, which could make them interesting in various clinical settings, and particularly in organ transplantation. This paper aims to review current knowledge on the properties of MSCs and their use in pre-clinical and clinical studies in solid organ transplantation, and particularly in the field of liver transplantation. The first available clinical data seem to show that MSCs are safe to use, at least in the medium-term, but more time is needed to evaluate the potential adverse effects of long-term use. Many issues must be resolved on the correct use of MSCs. Intensive in vitro and pre-clinical research are the keys to a better understanding of the way that MSCs act, and to eventually lead to clinical success.