Expression of transglutaminase-2 isoforms in normal human tissues and cancer cell lines: dysregulation of alternative splicing in cancer.

The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process.

Novel interactions of TG2 with heparan sulfate proteoglycans: reflection on physiological implications.

This mini-review brings together information from publications and recent conference proceedings that have shed light on the biological interaction between transglutaminase-2 and heparan sulphate proteoglycans. We subsequently draw hypotheses of possible implications in the wound healing process. There is a substantial overlap in the action of transglutaminase-2 and the heparan sulphate proteoglycan syndecan-4 in normal and abnormal wound repair. Our latest findings have identified syndecan-4 as a possible binding and signalling partner of fibronectin-bound TG2 and support the idea that transglutaminase-2 and syndecan-4 act in synergy.

Induced growth of dendrite gold nanostructure by controlling self-assembly aggregation dynamics.

Self-assembly of gold nanoparticles (AuNPs) is an important growth mode for fabricating functional materials. In this work we report a dendrite structure formed by slowing down the aggregation dynamics of AuNPs self-assembly. The obtained results show that the aggregation dynamics is dominated by the Reaction Limited Aggregation Model (RLA) more than the Diffusion Limited Aggregation Model (DLA). In which the repulsion due to electrostatic forces is dominant by the Van Der Walls attraction forces, and low sticking probability of nanoparticles. The aggregation dynamics of AuNPs can be slowed down if the water evaporation of the drop casted colloidal AuNPs on a quartz substrate is slowed. Slowing down the evaporation allows electrostatic repulsion forces to decrease gradually. At certain point, the attraction forces become higher than the electrostatic repulsion and hence cluster aggregation take place slowly. The slow aggregation dynamics allows the nanoparticles to sample all possible orientation in the sticking site, searching for the lowest energy configuration. The size distribution of the nanoparticles in liquid is confirmed using dynamic light scattering based on Stokes-Einstein equation for diffusion coefficient in water. X-ray and photoluminescence (PL) spectra of the sample after aggregation showed a shift which is related to the aggregation compared with non-aggregated colloidal nanoparticles in the solution. The study shows that dendrite self similar structure can be formed by slowing down the aggregation dynamics of nanoparticles as a result of minimizing the Helmholtz free surface energy of the system.

Titanate nanotube coatings on biodegradable photopolymer scaffolds.

Rigid, biodegradable photopolymer scaffolds were coated with titanate nanotubes (TNTs) by using a spin-coating method. TNTs were synthesized by a hydrothermal process at 150 °C under 4.7 bar ambient pressure. The biodegradable photopolymer scaffolds were produced by mask-assisted excimer laser photocuring at 308 nm. For scaffold coating, a stable ethanolic TNT sol was prepared by a simple colloid chemical route without the use of any binding compounds or additives. Scanning electron microscopy along with elemental analysis revealed that the scaffolds were homogenously coated by TNTs. The developed TNT coating can further improve the surface geometry of fabricated scaffolds, and therefore it can further increase the cell adhesion.

Superficial acral fibromyxoma of the toe, with erosion of the distal phalanx. A clinical report.

Superficial acral fibromyxoma (SAFM) is a rare soft tissue tumor most often located in the ungual region of the fingers and toes. This tumor was first described in 2001, and since then very few cases have been reported. We present the case of a 35-year-old male with a SAFM located in the toe, with involvement of the nail and erosion of the distal phalanx. The lesion was surgically removed, and the histopathological study confirmed the diagnosis of SAFM. The differential diagnosis must be established with other myxoid tumors and with those lesions showing a predilection for the distal portions of the limbs. After 2 years, the patient remains disease free, with no disability of any kind.

[Typhoid fever and Salmonella gastroenteritis in children (author's transl)]. / Fiebre tifoidea y gastroenteritis a Salmonella en la infancia

A study on 25 hospitalized children with salmonellosis in the two forms of typhoid fever and gastroenteritis is reported. It confirms the higher incidence of gastroenteritic forms under the age of 3 years, and of typhoid fever in older children. We verify the limited value of the white cell count and the enlargement of the spleen. An appraisal of the serologic tests is made. The direct relationship between group D salmonella and typhoid fever form is pointed out. Finally we analyze the action of ampicillin, chloramphenicol and trimethoprim-sulphamethoxazole, due to the current appearance of resistances to antibiotics.

Antibiotherapy of Serratia marcescens septicemia in children.

The clinical and bacteriological response of 38 treatments performed on 24 children (11 of them neonates) carrying out separate treatments with carbenicillin (2 treatments), gentamicin [4], fosfomycin [6], and associated treatments with gentamicin plus carbenicillin [6], fosfomycin plus gentamicin [18] and fosfomycin plus carbenicillin [2] are considered. The clinical cure was obtained in 21 children (87.5%). The most effective treatment was fosfomycin plus gentamicin; both antibiotics showed synergism in vitro on isolated Serratia strains. A dosage of 75 mg/kg fosfomycin enables serum levels of about 32 mug/ml during 4-5 h, being this level higher to the MIC of all isolated strains of S. marcescens.

A point mutation in a domain of gamma interferon receptor 1 provokes severe immunodeficiency.

Gamma interferon (IFN-gamma) and the cellular responses induced by it are essential for controlling mycobacterial infections. Most patients bearing an IFN-gamma receptor ligand-binding chain (IFN-gammaR1) deficiency present gross mutations that truncate the protein and prevent its expression, giving rise to severe mycobacterial infections and, frequently, a fatal outcome. In this report a new mutation that affects the IFN-gammaR1 ligand-binding domain in a Spanish patient with mycobacterial disseminated infection and multifocal osteomyelitis is characterized. The mutation generates an amino acid change that does not abrogate protein expression on the cellular surface but that severely impairs responses after the binding of IFN-gamma (CD64 and HLA class II induction and tumor necrosis factor alpha and interleukin-12 production). A patient's younger brother, who was also probably homozygous for the mutation, died from meningitis due to Mycobacterium bovis. These findings suggest that a point mutation may be fatal when it affects functionally important domains of the receptor and that the severity is not directly related to a lack of IFN-gamma receptor expression. Future research on these nontruncating mutations will make it possible to develop new therapeutical alternatives in this group of patients.