Drug resistance and methylation in myelodysplastic syndrome.

Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder that presents a poor survival for patients treated with standard therapies other than stem-cell transplantation. Multi-drug resistance (MDR) to simultaneous drugs used in chemotherapy is a major concern in the treatment of cancer and also in MDS. ATP-binding cassette (ABC) transporters are involved in the main mechanism that confers drug resistance to cells.

Lesions associated with Mycobacterium tuberculosis complex infection in the European wild boar.

Information on lesion distribution and characteristics is essential to determine the significance of a species as a reservoir host for tuberculosis (TB). Herein, we describe the extension and distribution of lesions in 127 Mycobacterium tuberculosis Complex culture positive European wild boars (Sus scrofa), and use this information to discuss the role of this wildlife species in TB epidemiology in Mediterranean Spain. Macroscopic TB-compatible lesions were detected in 105 of 127 wild boars (82.

Sense-antisense pairs in mammals: functional and evolutionary considerations.

Background: A significant number of genes in mammalian genomes are being found to have natural antisense transcripts (NATs). These sense-antisense (S-AS) pairs are believed to be involved in several cellular phenomena.

Results: Here, we generated a catalog of S-AS pairs occurring in the human and mouse genomes by analyzing different sources of expressed sequences available in the public domain plus 122 massively parallel signature sequencing (MPSS) libraries from a variety of human and mouse tissues.

Structure-based discovery of new small molecule inhibitors of low molecular weight protein tyrosine phosphatase.

The application of a fully integrated and automated virtual screening method for identifying potential and novel inhibitors of bovine lmwPTP is described. The protocol makes extensive use of our recently introduced LINGO tools, which allow the extraction of the implicit chemical information present in SMILES representations. Nine out of 34 compounds selected from a database of almost 500,000 commercially available compounds were experimentally confirmed to be competitive inhibitors of lmwPTP, two of them showing K(i) values around 10microM.

Sex pheromone of Lonomia obliqua: daily rhythm of production, identification, and synthesis.

The sex pheromone of Lonomia obliqua Walker (Lepidoptera: Saturniidae) was studied in the laboratory. All female calling occurred during the scotophase. Most females (70.

Contribution of toxins to the pathogenesis of inhalational anthrax.

Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially as a potential bioterrorism agent. Progress is gradually being made towards understanding the mechanisms used by Bacillus anthracis to escape the immune system and to induce severe septicaemia associated with toxaemia and leading to death. Recent advances in fundamental research have revealed previously unsuspected roles for toxins in various cell types.

Protein kinase activity in Cucumis sativus cotyledons: effect of calcium and light.

Light signals received by phytochromes in plants may be transduced through protein phosphorylation. Ca(2+) as second messenger was involved in phytochrome-mediated cellular events. Our experiments with Cucumis sativus cotyledons, treated with red (R) and far-red (FR) light, showed a stimulatory effect on in vitro protein phosphorylation of histone, added as exogenous substrate to the cotyledon extracts, and also modified the phosphorylation of endogenous polypeptides.

Aujeszky's disease virus infection patterns in European wild boar.

Evidence of exposure (i.e. seroprevalence) to Aujeszky's disease virus (ADV) is high among wild boars from south-central Spain.

Proteomic and transcriptomic analyses of differential stress/inflammatory responses in mandibular lymph nodes and oropharyngeal tonsils of European wild boars naturally infected with Mycobacterium bovis.

Differential stress/inflammatory responses were characterized at the mRNA and protein levels in mandibular lymph nodes (MLN) and oropharyngeal tonsils of European wild boars (Sus scrofa), naturally infected with Mycobacterium bovis. Suppression-subtractive hybridization combined with immunohistochemistry and/or quantitative real-time RT-PCR were used to identify and characterize abundant stress/inflammatory gene sequences differentially expressed in tuberculous (TB+) wild boars. Genes identified in MLN and tonsils corresponded to serum amyloid A, arginase I, osteopontin, lysozyme, annexin I, and heat shock proteins, respectively.

Transfer of lead from shot pellets to game meat during cooking.

We evaluated the transfer of Pb from shot to meat during the preparation of breasts of quails with 0, 1, 2 or 4 embedded Pb shot. A traditional Spanish recipe was used which utilizes vinegar during cooking to enhance the long-term preservation of the meat. The effect of the acidic conditions generated by the vinegar on Pb transfer was compared with the same recipe when the vinegar was substituted with water.

Seroprevalence of Neospora caninum in non-carnivorous wildlife from Spain.

Serum samples from 1034 non-carnivorous wildlife from Spain were tested for antibodies to Neospora caninum by competitive screening enzyme linked immunosorbent assay (ELISA) and confirmed by an indirect fluorescent antibody test (IFAT). High agreement was observed between results in both techniques (kappa value higher than 0.9).

Torque teno virus (TTV) is highly prevalent in the European wild boar (Sus scrofa).

The present study represents the first survey of Torque teno virus (TTV) prevalence in European wild boar (Sus scrofa). The prevalence of two distinct TTV genogroups in 178 Spanish wild boar sera from different geographic regions, management conditions, gender and age was determined by a nested PCR method. The overall prevalence of TTV genogroups was 84% (58% for genogroup 1 and 66% for genogroup 2), and differences between genogroup prevalence were observed depending on the geographical region analysed.

Aberrant methylation in pediatric myelodysplastic syndrome.

Background: Aberrant methylation of gene promoter region is responsible for inappropriate gene silencing, and it has been associated to initiation and progression of cancer. Aberrant promoter methylation is frequently observed in adult patients with myelodysplastic syndrome (MDS), but in pediatric patients it has been poorly investigated.

Methods: We examined the promoter methylation status of 13 genes in bone marrow cells collected at diagnosis of 21 pediatric patients with MDS (subtype RAEB or RAEB-t).

[Anthrax revisited: Bacillus anthracis toxins as novel actors of immune escape?].

The recent bioterrorist attacks have stressed the need of a better knowledge of Bacillus anthracis infection pathophysiology. We present here the increasing interests of B. anthracis studies in term of bio-defense, the main pathogen characteristics, the main clinical features of inhalational anthrax (the pulmonary form of the disease), and recent aspects of its physiopathology.

Resident CD11c+ lung cells are impaired by anthrax toxins after spore infection.

Bacillus anthracis secretes 2 toxins: lethal toxin (LT) and edema toxin (ET). We investigated their role in the physiopathologic mechanisms of inhalational anthrax by evaluating murine lung dendritic cell (LDC) functions after infection with B. anthracis strains secreting LT, ET, or both or with a nontoxinogenic strain.

Topical imiquimod: mechanism of action and clinical applications.

Imiquimod is a synthetic imidazoquinoline heterocyclic amine of 240.3 Da (C14H16N4). Imiquimod is a cytokine inducer and a modifier of the innate immune response, as well as acquired antiviral and antitumor immune responses.

Hypermethylation of CpG island in the promoter region of CALCA in acute lymphoblastic leukemia with central nervous system (CNS) infiltration correlates with poorer prognosis.

Promoter hypermethylation occurs early in leukemogenesis and seems to be associated with poor prognosis in acute lymphoblastic leukemia (ALL). The methylation status of the promoter region of six genes was analyzed in 71 children with ALL using methylation specific PCR (MSP). Calcitonin (CALCA) and E-cadherin (CDH1) were the most frequently methylated genes in this group of patients.

A novel search engine for virtual screening of very large databases.

Virtual screening of large chemical databases using the structure of the receptor can be computationally very demanding. We present a novel strategy that combines exhaustive similarity searches directly in SMILES format with the docking of flexible ligands, whose 3D structure is generated on the fly from the SMILES representation. Our strategy makes use of the recently developed LINGO tools to extract implicit chemical information from SMILES strings and integrates LINGO similarities into a pseudo-evolutionary algorithm.

Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha.

Genistein and apigenin are phytoestrogens present in commercial preparations used for the treatment of postmenopausal symptoms. In this study, we assessed the influence of these compounds on mammary tumor growth. Both compounds stimulate the proliferation of MCF-7 and T47D cells [estrogen receptor alpha (ERalpha-positive)], but do not stimulate the proliferation of an ERalpha-negative cell line (MDA-MB-435 cells).

Comparative sediment quality guideline performance for predicting sediment toxicity in southern California, USA.

Several types of sediment quality guidelines (SQGs) are used by multiple agencies in southern California (USA) to interpret sediment chemistry data, yet little information is available to identify the best approaches to use. The objective of this study was to evaluate the predictive ability of five SQGs to predict the presence and absence of sediment toxicity in coastal southern California: the effects range-median quotient (ERMq), consensus moderate effect concentration (consensus MEC), mean sediment quality guideline quotient (SQGQ1), apparent effects threshold (AET), and equilibrium partitioning (EqP) for organics. Large differences in predictive ability among the SQGs were obtained when each approach was applied to the same southern California data set.

Attempted passive prophylaxis with a monoclonal anti-Burkholderia pseudomallei exopolysaccharide antibody in a murine model of melioidosis.

Melioidosis is a severe gram-negative infection caused by the facultative intracellular bacterium Burkholderia pseudomallei, which is responsible for a broad spectrum of symptoms in both humans and animals. No licensed vaccine currently exists. This study evaluated the protective effect of a monoclonal antibody (Mab Ps6F6) specific to B.

Prevalence of Toxoplasma gondii antibodies in red deer (Cervus elaphus) and other wild ruminants from Spain.

Serum samples from 441 red deer (Cervus elaphus) and 161 other wild ruminant species, collected between 1993 and 2005 from six regions of Spain were tested for antibodies against Toxoplasma gondii by the modified agglutination test (MAT). Antibodies to T. gondii (MAT 1:25 or higher) were detected in 15.

Thymectomy in myasthenia gravis: comparison of outcome in Santiago, Cuba and Nottingham, UK.

Objectives: We compared the outcome of thymectomy for myasthenia gravis (MG) in two healthcare systems. In Nottingham, UK, thymectomy is performed for thymic enlargement and considered in acetylcholine receptor (AchR) antibody positive patients. In Santiago, Cuba, thymectomy is considered in all generalised MG patients irrespective of their radiological findings or AchR antibodies.