Role of Zinc in Hemostasis: A Review

Zinc is a multi-functional element that is found in almost 300 enzymes where it performs catalytic, co-catalytic, and/or structural functions. In 1982, Gordon et al. (Am J Clin Ntr 35:849–857, 1982) found that a low zinc diet caused poor platelet aggregation and increased bleeding tendency in adult males. This fact drew interest to the role of zinc in blood clotting. It has been shown that hyperzincemia predisposes to increased coagulability, and hypozincemia to poor platelet aggregation and increased bleeding time. The blood clotting disturbances can be regressed by appropriate zinc intake management. Considering the importance of zinc as an essential element, its participation in regulation of the equilibrium between pro- and anti-thrombotic factors originating in platelets and endothelium prompted further investigations.     

Superfamily of plant monomeric GTP-binding proteins: 2. Rab proteins are the regulators of vesicles trafficking and plant responses to stresses

In plants, Rab proteins represent the largest family of monomeric GTP-binding proteins (mG-proteins). As distinct from animal cells comprising 40 subfamilies of Rab proteins, which are the key regulators of intracellular vesicular transport, numerous Rab proteins in Arabidopsis and other plant species could be grouped in only eight subfamilies on the basis of their functional properties. The available data concerning the involvement of these mG-proteins in the control of vesicle trafficking agree generally with the paradigms accepted for other eukaryotes. On the other hand, these proteins play an important role in plant responses to abiotic and biotic factors, indicating specific for plants functions of Rab proteins.     

Expression of FGF2 and TGFalpha and testis morphology during testicular hypertrophy subsequent to hemicastration in the neonatal boar

The objective was to ascertain fibroblast growth factor-2 (FGF2), epidermal growth factor (EGF), and transforming growth factor-alpha (TGFalpha) mRNA expression and testis morphology during accelerated testicular growth after hemicastration in the neonatal boar. On Day 10 after birth (Day 0), boars were assigned to control (n = 28), no treatment; hemicastrated (n = 28), left testis removed. The right testis in both groups (n = 7) was removed on Days 5, 10, 15, and 20. Expression of mRNA for FGF2, EGF, and TGFalpha was determined by qRT-PCR using TaqMan. Testicular morphology was determined on Day 15. On Day 10, hemicastrated boars had a greater (P = 0.01) testis weight (6.2 +/- 0.8 g; mean +/- SEM) than controls (4.3 +/- 0.4 g) and on Day 15 testis weight in hemicastrated boars (8.8 +/- 0.8 g) was twice (P < 0.01) that of control boars (4.2 +/- 0.3 g). Seminiferous tubule volume was approximately doubled in hemicastrated boars (P < 0.01) and was associated with an increase (P < 0.01) in Sertoli cell number. Interstitial compartment volume was greater (P < 0.01) in hemicastrated boars. Leydig cell numbers were similar (P = 0.14) but volume was greater (P < 0.01) for hemicastrates. There were no differences (P > 0.05) between control and hemicastrated boars in TGFalpha or FGF2 expression on Day 5 or Day 10, and EGF was not detected. It was concluded that upregulation of TGFalpha or FGF2 expression is not a pre-requisite for enhanced testicular growth and increased Sertoli cell proliferation that occurs subsequent to hemicastration in the neonatal boar.     

Different downstream pathways for Notch signaling are required for gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells

We examined the roles of Notch signaling and fibroblast growth factors (FGFs) in the gliogenesis of mouse mesencephalic neural crest cells. The present study demonstrated that Notch activation or FGF treatment promotes the differentiation of glia expressing glial fibrillary acidic protein. Notch activation or FGF2 exposure during the first 48 h in culture was critical for glial differentiation. The promotion of gliogenesis by FGF2 was significantly suppressed by the inhibition of Notch signaling using Notch-1 siRNA. These data suggest that FGFs activate Notch signaling and that this activation promotes the gliogenic specification of mouse mesencephalic neural crest cells. Notch activation and FGF treatment have been shown to participate in the chondrogenic specification of these cells [Nakanishi, K., Chan, Y.S., Ito, K., 2007. Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 124, 190–203]. Therefore, we analyzed whether or not there were differences between gliogenic and chondrogenic specifications in the downstream pathway of the Notch receptor. Whereas the activation of only the Deltex-mediated pathway was sufficient to promote glial specification, the activation of both RBP-J- and Deltex-dependent pathways was required for chondrogenic specification. These results suggest that the different downstream pathways of the Notch receptor participate in the gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells.     

Assignment of Staphylococcus aureus isolates to clonal complexes based on microarray analysis and pattern recognition

A DNA microarray was designed for the rapid genotyping of Staphylococcus aureus. It covers 185 distinct genes and about 300 alleles thereof, including species-specific controls, accessory gene regulator (agr) alleles, genes encoding virulence factors, and microbial surface components recognizing adhesive matrix molecules, capsule type-specific genes, as well as resistance determinants. It was used to examine 100 clinical isolates and reference strains. Relationships of leukocidin and ssl/set (staphylococcal superantigen-like or exotoxin-like) genes were reviewed considering these experimental results as well as published sequences. A good correlation of overall hybridization pattern and multilocus sequence typing was found. Analysis of hybridization profiles thus allowed not only to assess virulence and drug resistance, but also to assign isolates to strains and to clonal complexes. Hybridization data were used to construct a split network tree and to analyse relationships between strains. Allelic variations of a number of genes indicate a division of S. aureus into three major branches that are not in accordance to agr group or capsule-type affiliations. Additionally, there are some isolated lineages, such as ST75, ST93, or ST152. These strains produce aberrant hybridization profiles, indicating that only a part of the gene pool of S. aureus has been investigated yet.     

NUCEL (Cell and Molecular Therapy Center): A Multidisciplinary Center for Translational Research in Brazil

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil’s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.