Exploring the dark genome: implications for precision medicine

Mammalian Genome - The increase in the number of both patients and healthcare practitioners who grew up using the Internet and computers (so-called “digital natives”) is likely to...     

Characteristics of immunomodulating effect of histamine in inbred strain mice]

The activity of 5'-nucleotidase of peritoneal exudate in subcutaneous injection of histamine in a dose of 1.0-100 microliters was studied in mice of different lines (CBA, C57, B1/6, Balb/c, NFS/n, NFR/n). There were interline differences in the influence of histamine on this metabolic index.     

Characterization of the neutral aminopeptidase activity associated to the mouse thymocyte-activating molecule

We previously characterized a dimeric, Mr = 115,000, developmentally regulated mouse T cell-activating molecule (THAM). We show in this report that the THAM-specific mAb H194-112 exhibits strong reactivity with several nonlymphoid tissues including polarized enterocytes from small intestine, kidney cortical tubuli, and liver bile ductuli, as well as kidney glomeruli and lung alveoloar pneumocytes. Both the tissue distribution and the structural features of THAM made it likely that this molecule belongs to the ectoenzyme family. This was confirmed by the following experimental evidence: 1) the H194-112+ molecules from enterocyte brush borders (BB) or M14.T thymoma cells were recognized by several antisera specific for intestinal aminopeptidase N (AP-N); 2) mAb H194-112 was found to immunodeplete the AP-N activity from both thymic or enterocyte BB detergent extracts; 3) the hydrophilic, Mr = 115,000 form obtained by papain treatment of thymoma or enterocyte BB could be immunopurified on H194-112 column and exhibited, after hypotonic elution, strong enzymatic activity on the AP-N substrates (i.e., leucyl or alanyl beta-derivatives); 4) mAb H194-112 was found to inhibit the AP-N activity when assayed on alanyl but not leucyl beta-naphthylamide substrate; and 5) preincubation of AP-N with mAb H194-112 prevented the inhibiting effects of bestatin and D,L-methionyl hydroxamate on AP-N activity. These data add a new member to the list of functional ectoenzymatic markers of lymphoid cells (i.e., CD10, CD13, CD26, CD55, and CD73). In view of the known immunomodulating properties of bestatin, one may speculate that the T cell-activating effects of mAb H194-112 is related to an impairment of a surface enzymatic function regulating lymphoid cell activation.     

Enzymic activity of salivary amylase when bound to the surface of oral streptococci

The enzymatic activity of salivary amylase bound to the surface of several species of oral streptococci was determined by the production of acid from starch and by the degradation of maltotetraose to glucose in a coupled, spectrophotometric assay. Most strains able to bind amylase exhibited functional enzyme on their surface and produced acid from the products of amylolytic degradation. These strains were unable to utilise starch in the absence of salivary amylase. Two strains failed to produce acid from starch, despite the presence of functional salivary amylase, because they could not utilise maltose. Strains that could not bind salivary amylase failed to produce acid from starch. In no case was all the bound salivary amylase active, and two strains of Streptococcus mitis which bound amylase did not exhibit any enzyme activity on their cell surface. The ability to bind amylase may confer a survival advantage on oral bacteria which inhabit hosts that consume diets containing starch.     

Associated Liver Partition and Portal Vein Ligation (ALPPS) vs Selective Portal Vein Ligation (PVL) for Staged Hepatectomy in a Rat Model. Similar Regenerative Response?

Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage hepatectomy technique which can be associated with a hypertrophic stimulus on the future liver remnant (FLR) stronger than other techniques–such as portal vein ligation (PVL). However, the reason of such hypertrophy is still unclear, but it is suggested that liver transection combined with portal vein ligation (ALPPS) during the first stage of this technique may play a key role. The aim of this study is to compare the hypertrophic stimulus on the FLR and the clinical changes associated with both ALPPS and PVL in a rat surgical model. For this purpose, three groups of SD rats were used, namely ALPPS (n = 30), PVL (n = 30) and sham-treated (n = 30). The second stage of ALPPS (hepatectomy of the atrophic lobes), was performed at day 8. Blood and FLR samples were collected at 1, 24, 48 hours, 8 days and 12 weeks after the surgeries. ALPPS provoked a greater degree of hypertrophy of the FLR than the PVL at 48 hours and 8 days (p<0.05). The molecular pattern was also different, with the highest expression of IL-1β at 24h, IL-6 at 8 days, and HGF and TNF-α at 48 hours and 8 days (p<0.05). ALPPS also brought about a mild proliferative stimulus at 12 weeks, with a higher expression of HGF and TGF-β (p<0.05) than PVL. Clinically, ALPPS caused a significant liver damage during the first 48 hours, with a recovery of liver function at day 8. In conclusion, ALPPS seems to induce higher functional hypertrophy on the FLR than PVL at day 8. Such regenerative response seems to be leaded by a complex interaction between pro-mitogenic (IL-6, HGF, TNF-α) and antiproliferative (IL1-β and TGF-β) cytokines.     

Karyotype evolution in Curimatidae (Teleostei, Characiformes) from the Amazon region. II. Centric fissions in the genus Potamorhina

Using cytogenetic analysis following Giemsa staining, nucleolar organizer region (NOR) staining, and C-banding, three distinct karyotypes in three species of curimatids belonging to the fish genus Potamorhina were identified: 2n = 54/44 M + 10 SM (P. pristigaster), 2n = 56/52 M + 2 SM + 2 ST (P. latior), and 2n = 102/2 M + 2 SM + 98 A (P. altamazonica). A 2n = 54 was considered to be the ancestral diploid number and the different karyotypes were probably the result of centric fissions. Both the NOR pattern and constitutive heterochromatin pattern are species specific.