A third immunoglobulin class in amphibians

A new class of immunoglobulin (IgX) has been found in the South African frog, Xenopus laevis, and other related species. IgX can be immunoprecipitated by monoclonal antibodies directed against determinants found on Xenopus light chain, or on variable regions of heavy chains. Reagents specific for the heavy chain of IgM or the amphibian IgG equivalent, IgY, failed to react with IgX. IgX, which exists in serum as a polymer, is composed of subunits of disulfide-bonded heavy chains of 80,000 daltons and light chains of 25,000 to 29,000 daltons. Like mu, the heavy chain of IgX carries a large amount of asparagine-linked carbohydrate, but the partial peptide maps of the two are different. Although the concentration of IgX varies greatly in the serum of individual frogs, it is always secreted in cultures of cells from the spleen and intestinal mucosae.     

Dietary protein restriction during lactation in primiparous sows with different live weights at farrowing: II. Consequences on reproductive performance and interactions with metabolic status

The hypothesis that the restriction of dietary protein during lactation has different impacts on reproductive performance in light and heavy sows at farrowing was investigated, as well as the relationships between reproductive parameters and sow metabolic data. At farrowing, 38 primiparous sows were assigned to one of three groups: sows weighing 180 kg not restricted in dietary protein during lactation (180CP); sows weighing 180 or 240 kg restricted in protein (180LP and 240LP). Twenty-four sows were catheterized and serial blood samples were collected 1 d before and 1 d after weaning. The sows were inseminated at the first estrus after weaning and slaughtered at d 30 of gestation. Protein restriction reduced the proportion of sows that returned to estrus within 8 d after weaning in the 180LP sows (P < 0.03), but not in the 240LP sows. It also induced a reduction in ovulation rate in the 180LP sows (P < 0.05) and, to a lesser extent, in the 240LP sows (P = 0.12). When the sows were categorized according to return to estrus (WOI < or = 8 or > 8 d), basal and mean concentrations of LH increased after weaning only in sows with a short WOI. Sows with a delayed estrus exhibited a higher ratio of plasma tyrosine to large neutral amino acids (AA, P < 0.01). In conclusion, large body reserves at farrowing buffer, at least in part, the detrimental effect of a strongly negative nitrogen balance on reproduction. We suggest that the alteration of AA profiles induced by dietary protein restriction and body protein loss alters LH secretion via modifications of the neurotransmitters involved in GnRH secretion.     

The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis

Human immunodeficiency virus (HIV) infection and the progression to AIDS are characterized by the depletion of CD4(+) T-cells. HIV-1 infection leads to apoptosis of uninfected bystander cells and the direct killing of HIV-infected cells. This is mediated, in part, by the HIV-1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells. We chemically synthesized two 86-residue subtype D Tat proteins, Ug05RP and Ug11LTS, from two Ugandan patients who were clinically categorized as either rapid progressor or long-term survivor, with non-conservative mutations located essentially in the glutamine-rich region. Structural heterogeneities were revealed by CD, which translate into differing trans-activational and apoptotic effects. CD data analysis and molecular modeling indicated that the short alpha-helix observed in subtype D Tat proteins from rapid progressor patients such as Tat Mal and Tat Ug05RP is not present in Ug11LTS. We show that Tat Ug05RP is more efficient than Tat Ug11LTS in its trans-activational role and in inducing apoptosis in binding tubulin via the mitochondrial pathway. The glutamine-rich region of Tat appears to be involved in the Tat-mediated apoptosis of T-cells.     

D-penicillamine-induced autoimmunity in Brown-Norway rats. Similarities with HgCl2-induced autoimmunity

D-penicillamine (DP) has been previously shown to induce an autoimmune disease in Brown-Norway (BN) rats, characterized by a dermatitis, by the production of antinuclear antibodies, by the formation fo circulating immune complexes, and by linear IgG deposits along the glomerular basement membrane. These manifestations are quite similar to those observed in mercuric chloride (HgCl2)-induced autoimmunity. The mechanism of the latter disease has been recently partly elucidated. The aim of this study was to compare DP and HgCl2-induced autoimmunity in BN rats and to compare the mechanisms involved in both situations. A transient increase in the number of spleen cells, affecting B cells and CD4+ T cells, and an increase in serum IgE concentration, previously reported in HgCl2-induced autoimmunity, were observed during DP treatment. Autoreactive anti-class II T cells able to proliferate not only in the presence of autologous B cells but also in the presence of syngeneic normal B cells were found in DP-treated BN rats. Spontaneous regulation occurred, associated with the disappearance of autoreactive T cells. Suppressor CD8+ T cells were not involved in this phenomenon. Mechanisms involved in both the induction and the regulation of DP-induced autoimmunity seem to be quite similar to those reported in HgCl2-induced autoimmunity.     

Increased adenylate cyclase catalytic activity explains how estrogens "in vivo" promote lipolytic activity in rat white fat cells

Estradiol administration (5 micrograms per day x 4 days) to ovariectomized rats resulted in a 60-70% increase in the maximal lipolytic response of their white adipocytes to isoproterenol, epinephrine, IBMX and forskolin. These altered lipolytic responses were accompanied by parallel changes in the intracellular cyclic AMP levels found in response to 1 mM IBMX alone (+ 106%) or combined with submaximal concentrations of isoproterenol (+205%), epinephrine (+190%) and forskolin (235%). Studies of the adenylate cyclase activity revealed an overall increase in the stimulatory responsiveness of the enzyme (+150 to +200%) after the estradiol-treatment, regardless of the stimulatory agents tested (GTP, GppNHp, fluoride, isoproterenol, ACTH, forskolin). Finally, the finding of a 2-fold enhancement of the Mn2+ (+/- GDP beta S)-stimulated adenylate cyclase activity after the estradiol-treatment strongly suggests that increased activity of the catalytic subunit of this enzyme is the likely mechanism whereby estrogens promote lipolysis in rat fat cells.     

Endothelial Cells Provide a Notch-Dependent Pro-Tumoral Niche for Enhancing Breast Cancer Survival,Stemness and Pro-Metastatic Properties

Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44^HighCD24^Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.