Rosangela Vieira de Andrade

SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although several clinical characteristics can be associated with worse prognosis, more robust biological markers still remains uncovered. SMYD2, a member of SMYD protein family, regulates the activity of several proteins through methylation. In this study, we performed quantitative real time PCR to compare the expression of SMYD2 in 83 pediatric ALL patients and non-neoplastic bone marrow samples (BMS). The study revealed that SMYD2 expression is altered in ALL BMS and its high expression was correlated with a bad prognosis. Moreover, we also revealed that SMYD2 expression level significantly decreases in patients that respond to chemotherapy treatment.

Altered expression of MLL methyltransferase family genes in breast cancer

The histone lysine methyltransferases contain a SET domain, which catalyzes the addition of methyl groups to specific lysine residues. The MLL family of genes encodes histone-modifying enzymes with histone 3-lysine 4 methyltransferase activity that can regulate gene transcription. The MLL family exists in multi-protein complexes and has been implicated in a variety of processes including normal development and cell growth. Although some of the MLL family members have already been described to be involved in cancer, a clear relationship of these genes with breast cancer is not determined to date. In the present study, we used quantitative PCR to investigate the expression profile of all five MLL genes [MLL (ALL-1), MLL2, MLL3, MLL4 and MLL5] in 7 breast cancer cell lines, 8 breast tumors and adjacent non-tumor tissues and in 12 normal tissues. We observed a diminished expression of all five genes in the breast cancer cell lines when compared to normal breast tissue. We found a significantly decreased expression of MLL2 in the tumor samples compared to the non-tumor controls. In tumor samples, MLL5 also showed a clear suppression tendency. Among the normal tissues analyzed, all genes showed a markedly higher expression in skeletal muscle and brain. Although further studies are required to determine the exact role of these methyltransferases in cancer development, our results indicate that the suppression of MLL genes, especially MLL2 and 5, take part in modulating breast carcinogenesis. Our assessment of the MLL family gene expression patterns in a diverse set of breast cancer cell lines and in a multitude of tissue types and breast tumors should lead to increasingly detailed information on the involvement of these genes in cancer progression.

High molecular mass proteomics analyses of left ventricle from rats subjected to differential swimming training

BackgroundRegular exercises are commonly described as an important factor in health improvement, being directly related to contractile force development in cardiac cells.In order to evaluate the links between swimming exercise intensity and cardiac adaptation by using high molecular mass proteomics, isogenic Wistar rats were divided into four groups: one control (CG) and three training groups (TG’s), with low, moderate and high intensity of exercises.In order to evaluate the links between swimming exercise intensity and cardiac adaptation by using high molecular mass proteomics, isogenic Wistar rats were divided into four groups: one control (CG) and three training groups (TG’s), with low, moderate and high intensity of exercises.ResultsFindings here reported demonstrated clear morphologic alterations, significant cellular injury and increased energy supplies at high exercise intensities. α-MyHC, as well proteins associated with mitochondrial oxidative metabolism were shown to be improved. α-MyHC expression increase 1.2 fold in high intensity training group when compared with control group. α-MyHC was also evaluated by real-time PCR showing a clear expression correlation with protein synthesis data increase in 8.48 fold in high intensity training group. Other myofibrillar protein, troponin , appear only in high intensity group, corroborating the cellular injury data. High molecular masses proteins such as MRS2 and NADH dehydrogenase, involved in metabolic pathways also demonstrate increase expression, respectily 1.5 and 1.3 fold, in response to high intensity exercise.ConclusionsHigh intensity exercise demonstrated an increase expression in some high molecular masses myofibrilar proteins, α-MyHC and troponin. Furthermore this intensity also lead a significant increase of other high molecular masses proteins such as MRS2 and NADH dehydrogenase in comparison to low and moderate intensities. However, high intensity exercise also represented a significant degree of cellular injury, when compared with the individuals submitted to low and moderate intensities.

Use of Targeted Exome Sequencing for Molecular Diagnosis of Skeletal Disorders.

Genetic disorders of the skeleton comprise a large group of more than 450 clinically distinct and genetically heterogeneous diseases associated with mutations in more than 300 genes. Achieving a definitive diagnosis is complicated due to the genetic heterogeneity of these disorders, their individual rarity and their diverse radiographic presentations. We used targeted exome sequencing and designed a 1.4Mb panel for simultaneous testing of more than 4,800 exons in 309 genes involved in skeletal disorders. DNA from 69 individuals from 66 families with a known or suspected clinical diagnosis of a skeletal disorder was analyzed. Of 36 cases with a specific clinical hypothesis with a known genetic basis, mutations were identified for eight cases (22%). Of 20 cases with a suspected skeletal disorder but without a specific diagnosis, four causative mutations were identified. Also included were 11 cases with a specific skeletal disorder but for which there was at the time no known associated gene. For these cases, one mutation was identified in a known skeletal disease genes, and re-evaluation of the clinical phenotype in this case changed the diagnoses from osteodysplasia syndrome to Apert syndrome. These results suggest that the NGS panel provides a fast, accurate and cost-effective molecular diagnostic tool for identifying mutations in a highly genetically heterogeneous set of disorders such as genetic skeletal disorders. The data also stress the importance of a thorough clinical evaluation before DNA sequencing. The strategy should be applicable to other groups of disorders in which the molecular basis is largely known.

Role of exercise intensity on GLUT4 content, aerobic fitness and fasting plasma glucose in type 2 diabetic mice

Type 2 diabetes mellitus (T2D) results in several metabolic and cardiovascular dysfunctions, clinically characterized by hyperglycaemia due to lower glucose uptake and oxidation. Physical exercise is an effective intervention for glycaemic control. However, the effects of exercising at different intensities have not yet been addressed. The present study analysed the effects of 8 weeks of training performed at different exercise intensities on type 4 glucose transporters (GLUT4) content and glycaemic control of T2D (ob/ob) and non‐diabetic mice (ob/OB). The animals were divided into six groups, with four groups being subjected either to low‐intensity (ob/obL and ob/OBL: 3% body weight, three times/week/40 min) or high‐intensity (ob/obH and ob/OBH: 6% body weight, three times per week per 20 min) swimming training. An incremental swimming test was performed to measure aerobic fitness. After the training intervention period, glycaemia and the content of GLUT4 were quantified. Although both training intensities were beneficial, the high‐intensity regimen induced a more significant improvement in GLUT4 levels and glycaemic profile compared with sedentary controls (p < 0·05). Only animals in the high‐intensity exercise group improved aerobic fitness. Thus, our study shows that high‐intensity training was more effective for increasing GLUT4 content and glycaemia reduction in insulin‐resistant mice, perhaps because of a higher metabolic demand imposed by this form of exercise. Copyright

Phospholipase gene expression during Paracoccidioides brasiliensis morphological transition and infection

Phospholipase is an important virulence factor for pathogenic fungi. In this study, we demonstrate the following: (i) the Paracoccidioides brasiliensis pld gene is preferentially expressed in mycelium cells, (ii) the plb1 gene is mostly up-regulated by infection after 6 h of co-infection of MH-S cells or during BALB/c mice lung infection, (iii) during lung infection, plb1, plc and pld gene expression are significantly increased 6-48 h post-infection compared to 56 days after infection, strongly suggesting that phospholipases play a role in the early events of infection, but not during the chronic stages of pulmonary infection by P. brasiliensis.

Rare genetic diseases: update on diagnosis, treatment and online resources

Rare genetic diseases collectively impact a significant portion of the worlds population. For many diseases there is limited information available, and clinicians can find difficulty in differentiating between clinically similar conditions. This leads to problems in genetic counseling and patient treatment. The biomedical market is affected because pharmaceutical and biotechnology industries do not see advantages in addressing rare disease treatments, or because the cost of the treatments is too high. By contrast, technological advances including DNA sequencing and analysis, together with computer-aided tools and online resources, are allowing a more thorough understanding of rare disorders. Here, we discuss how the collection of various types of information together with the use of new technologies is facilitating diagnosis and, consequently, treatment of rare diseases.

Longer Telomere Length in Elite Master Sprinters: Relationship to Performance and Body Composition

Emergent evidence suggests that the long-term healthy lifestyle of master athletes may attenuate aging. We compared telomere length (TL) of high-level master sprinters and non-athlete age-matched controls, and analyzed the relationships of TL with performance and body fat. Elite master sprinters (n=11; aged 50.1±9.2yrs) and healthy untrained controls (n=10; aged 45.4±10.9yrs) had blood samples collected for biochemical and biomolecular analyses. Master sprinters had longer TL, lower body fat and BMI, and a better lipid profile than age-matched controls (p<0.05). A large effect size was verified comparing TL between athletes vs. controls (Cohens d=1.039), with a significant negative correlation between TL and performance decline per decade (r=-0.624, p<0.01) and a positive correlation of TL and actual performance level (r=0.641, p<0.01). In conclusion, TL of elite master sprinters was longer than their untrained peers, and seems to be not only a marker of health status, but also an indicator of sports longevity since both actual performance level and its decrease over years were related to TL. Further research might assess the TL of elite master endurance athletes for comparison with sprinters, and also investigate the underlying mechanisms by which the attenuation of telomere shortening occurs in master athletes.

Training Performed Above Lactate Threshold Decreases p53 and Shelterin Expression in Mice

Telomere shortening is associated to sarcopenia leading to functional impairment during aging. There are mechanisms associated with telomere attrition, as well to its protection and repair. Physical training is a factor that attenuates telomere shortening, but little is known about the effects of different exercise intensities on telomere biology. Thus, we evaluated the effects of exercise intensity (moderate vs. high-intensity domain) on gene expression of senescence markers Checkpoint kinase 2 and tumor suppressor (Chk2 and p53, respectively), shelterin telomere repeat binding 1 and 2 (Trf1/Trf2), DNA repair (Xrcc5), telomerase reverse transcriptase (mTERT) and telomere length in middle aged mice. Three groups were studied: a control group (CTL) and two groups submitted to swimming at intensities below the lactate threshold (LI group) and above the lactate threshold (HI group) for 40 and 20 min respectively, for 12 weeks. After training, the HI group showed reduction in p53 expression in the muscle, and decreased shelterin complex expression when compared to LI group. No differences were observed between groups for mTERT expression and telomere length. Thus, exercise training in high-intensity domain was more effective on reducing markers of senescence and apoptosis. The higher intensity exercise training also diminished shelterin expression, with no differences in telomere length and mTERT expression. Such results possibly indicate a more effective DNA protection for the higher-intensity exercise training.