El carcinoma diferenciado incidental de tiroides es menos prevalente en la enfermedad de Graves que en el bocio multinodular

ObjectiveRisk factors for differentiated thyroid carcinoma (DTC) are poorly understood, but serum TSH levels, thyroid nodularity, and presence of autoimmunity are well-recognized factors that modulate DTC prevalence. TSH stimulates proliferation of both normal and neoplastic follicular cells. Consequently, thyroid-stimulating immunoglobulins (TSI), because of its TSH-like action, should induce DTC progression in patients with Graves’ disease (GD). The study objective was to compare the prevalence of incidental DTC in patients undergoing thyroidectomy for benign thyroid disease.MethodsThe pathology reports of 372 patients with preoperative diagnosis of euthyroid multinodular goiter (EMG) or hyperthyroidism were reviewed. Scintigraphy results and serum TSI levels were used to diagnosed either GD or hyperactive MG (HMG) to hyperthyroid subjects. Prevalence of DTC in each category was calculated using a Chi-square test.ResultsEMG, GD, and HMG were diagnosed in 221, 125, and 26 patients. There were 58 DTCs, distributed as follows [n (%)]: EMG, 49 (22.2%); GD, 8 (6.4%), and HMG, 1 (3.8%). Difference in prevalence of incidental DTC between the groups was statistically significant (p < 0.001). After adjustment for age, patients with EMG had a greater DTC prevalence than GD patients, with an OR of 4.17 (p < 0.001). Tumor size (mm, mean ± SD) was 6.92 ± 11.26, 1.97 ± 1.85, and 9.0 for EMG, GD and HMG respectively (p = 0.017).ConclusionsIncidental DTC was less prevalent in GD as compared to EMG irrespective of age. This finding may suggest a predisposition to develop DTC in patients with thyroid nodular disease and/or a potential effect of autoimmunity to protect against development of neoplastic disease.     

Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity

The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies.     

Signaling pathways of immobilized FGF-2 on silicon-substituted hydroxyapatite

Therapeutic strategies for bone regeneration involve the selection of suitable biomaterials, growth factors, and cell types to mimic the cellular microenvironment where molecular and mechanical signals control the reconstruction of bone tissue. The immobilization of basic fibroblast growth factor (FGF-2) on powdered silicon-substituted hydroxyapatite (Si-HA) allows to prepare a biofunctional biomaterial able to interact with bone cells in a very specific way. The biological activity of FGF-2/Si-HA, evaluated in Saos-2 osteoblasts and MC3T3-E1 preosteoblasts through the PLCγ and MAPK/ERK signal transduction pathways, shows that FGF-2 immobilized on Si-HA provides the right signals to cells stimulating crucial intracellular mechanisms of osteoblast proliferation and differentiation.     

The Pleistocene glacial cycles shaped the historical demography and phylogeography of a pine fungal endophyte

The fungal endophyte Lophodermium nitens is an obligate symbiont of soft pines inhabiting only two pine species in Mexico with a broad distribution of geographically isolated populations. A previous study for the hosts indicated a main east–west subdivision with recurrent gene flow within these regions and demographic expansion of populations. We took these patterns as null hypotheses to test for the demography and phylogeographical patterns of the fungus, given the obligatory relationship of the endophyte to the host and its reduced capacity for long-distance dispersal. For this purpose, we employed two nuclear DNA loci, fragments of the actin and chitin synthase I genes. Both loci showed high genetic variation, consisting of private single-copy alleles, as well as few ones at high frequency that were shared among almost all populations. In order to distinguish between shared polymorphism due to incomplete lineage sorting and gene flow posterior to population divergence, we applied the coalescent-based Isolation–Migration (IM) model. We found patterns of gene flow and isolation similar to those of the hosts as well as signs of population expansion. Mean migration time and divergence time estimates fell within the Pleistocene, previous to Last Glacial Maximum. The results presented here for L. nitens emphasize the potential use of endophytic fungi to deepen the knowledge of historical patterns and processes of their host plants.     

Advanced photobioreactor LED illumination system: Scale‐down approach to study microalgal growth kinetics

A newly designed and constructed LED illumination device for commercial cylindrical bioreactors is presented for application in microalgal cultivations and investigation of growth kinetics. An ideally illuminated volume is achieved by focusing the light toward the center of the reactor and thereby compensating the mutual shading of the cells. The relevant biomass concentration for homogeneous illumination depending on reactor radius was determined by light distribution measurements for Chlamydomonas to 0.2 g/L (equal 0.435 optical density at 750 nm). It is shown that cultivation experiments with the newly designed illumination device operated in batch mode can be successfully applied for determination of growth rates and photo conversion efficiencies. The exact knowledge of physiological reactions of specific strain(s) and the estimation of relevant parameters for scale‐up can be used for construction of economic pilot plant photobioreactors. The determination of light‐dependent kinetics of growth and product formation is the first necessary step to achieve this. A wide variety of different parameters can be examined like the effect of different illumination conditions (light intensity, frequency of day/night cycles, flashing light, light color…) and thereby for each single application specific, relevant, and interesting parameters will be examined.     

Cranial morphology of the Early Permian mesosaurid Mesosaurus tenuidens and the evolution of the lower temporal fenestration reassessed

The Early Permian mesosaurids are the oldest known aquatic amniotes with an exclusively Gondwanan distribution. Although several hundred of complete skeletons have been discovered and intensively studied, the anatomy and taxonomic composition of the group, as well as its phylogenetic relationships remain controversial. Several well-preserved mesosaurid specimens found in Uruguay justify a new anatomical reconstruction of the skull of Mesosaurus tenuidens, differing from earlier ones especially in the presence of a lower temporal fenestra. The significance of this structure for the evolution of temporal fenestration in amniotes is evaluated according to the two most recent phylogenetic hypotheses, in which mesosaurids are basalmost sauropsids or basalmost parareptiles. A synapsid-like fenestration may be the primitive condition for Amniota, and it may be also a basal condition for parareptiles, because recent phylogenies suggest a basal position for mesosaurids and lanthanosuchoids within that group, and both possess a lower temporal fenestra. Our results also give a moderately strengthened support for diapsid affinities of turtles.     

The p38 MAPK-MK2 Axis Regulates E2F1 and FOXM1 Expression after Epirubicin Treatment

E2F1 is responsible for the regulation of FOXM1 expression, which plays a key role in epirubicin resistance. Here, we examined the role and regulation of E2F1 in response to epirubicin in cancer cells. We first showed that E2F1 plays a key role in promoting FOXM1 expression, cell survival, and epirubicin resistance as its depletion by siRNA attenuated FOXM1 induction and cell viability in response to epirubicin. We also found that the p38-MAPK activity mirrors the expression patterns of E2F1 and FOXM1 in both epirubicin-sensitive and -resistant MCF-7 breast cancer cells, suggesting that p38 has a role in regulating E2F1 expression and epirubicin resistance. Consistently, studies using pharmacologic inhibitors, siRNA knockdown, and knockout mouse embryonic fibroblasts (MEF) revealed that p38 mediates the E2F1 induction by epirubicin and that the induction of E2F1 by p38 is, in turn, mediated through its downstream kinase MK2 [mitogen-activated protein kinase (MAPK)-activated protein kinase 2; MAPKAPK2]. In agreement, in vitro phosphorylation assays showed that MK2 can directly phosphorylate E2F1 at Ser-364. Transfection assays also showed that E2F1 phosphorylation at Ser-364 participates in its induction by epirubicin but also suggests that other phosphorylation events are also involved. In addition, the p38-MK2 axis can also limit c-jun-NH(2)-kinase (JNK) induction by epirubicin and, notably, JNK represses FOXM1 expression. Collectively, these findings underscore the importance of p38-MK2 signaling in the control of E2F1 and FOXM1 expression as well as epirubicin sensitivity. Mol Cancer Res; 10(9); 1189-202. ?2012 AACR.