Congenital iodide transport defect: recent advances and future perspectives

Iodide is an irreplaceable component of thyroid hormones; therefore, a key requirement for thyroid hormone synthesis is that iodide is actively accumulated in the thyroid. The ability of thyroid follicular cell to concentrate iodide relies on the functional expression of the sodium/iodide symporter (SIS) at the plasma membrane. Underscoring the significance of SIS for thyroid physiology, naturally occurring loss-of-function SIS mutations cause iodide transport defect (ITD) autosomalrecessive disorders in which iodide accumulation is severely or totally impaired, leading to dyshormonogenic congenital hypothyroidism. Up to date, sixteen different loss-of-function mutations in the gene encoding SIS have been reported. Surprisingly, marked clinical heterogeneity between patients harboring the different (or even the same) SIS mutation without a clear genotype–phenotype correlation has been observed. Residual mutant SIS activity and iodide intake levels have been proposed to explain the difference in the age of onset on hypothyroidism and the development of goiter. Significantly, genetic screening is highly recommended in patients with severely reduced radioiodide accumulation even in the absence of goiter. The identification of mutations in SIS may allow subsequent preclinical diagnoses of younger members of the family as patients with delayed onset on hypothyroidism had already signs of developmental delay at time of diagnosis. Moreover, iodide supplementation can improve thyroid function in patients with residual SIS activity and should be considered. This review summarizes the current knowledge regarding the molecular basis of ITD, as well as the clinical and biochemical presentation of patients with ITD. Moreover, we explore the latest advances in the molecular characterization of ITD-causing slc5a5 mutants whose study has yielded invaluable information into the molecular mechaSISm of SIS and the perspectives of understanding naturally occurring SIS mutants to improve radioiodide therapy in thyroid cancer as well as SIS-based gene therapy.Fil: Martín, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Renouncing the body. Hegel and thebodily dialectics of self-consciousness

Los lazos políticos y sociales comienzan desde el cuerpo. Contra las lecturas ancladas en la primera Fenomenología del espíritu, este artículo analiza la naturaleza material y corporal del espíritu como segunda naturaleza y su emplazamiento en el desarrollo de la autoconciencia a través de una interpretación inmanente de la Enciclopedia de las Ciencias Filosóficas de Hegel. Se demuestra que la experiencia de la autoconciencia atraviesa dos dialécticas corporales que habilitan la vida política y social: el encuentro mimético entre cuerpos y su colisión en una lucha que culmina en la desigualdad.The body provides the beginning of social and political bonds. Against the interpretations that stay in the first Phenomenology of the spirit, this article analyses the material and bodily nature of the spirit as second nature and its correlation in the development of self-consciousness, by performing an immanent reading of Hegel’s Encyclopaedia of the Philosophical Sciences. The article demonstrates that the self-consciousness’ experience goes through two bodily dialectics that enable social and political life: the mimetic encounter between bodies and its subsequent clash in a struggle that ends in inequality.Fil: de Nicola, Juan Pablo. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The Molecular Basis for Radioiodine Therapy

Radioactive iodine (radioiodine) therapy is a standard and effective therapeutic approach for high-risk differentiated thyroid carcinomas, based on the unique ability of the thyroid follicular cell to accumulate iodide through the sodium/iodide symporter (NIS). However, a recurrent limitation of radioiodine therapy is the development of radioiodine-refractory differentiated thyroid carcinomas, which are associated with a worse prognosis. Loss of radioiodine accumulation in thyroid carcinomas has been attributed to cell dedifferentiation, resulting in reduced NIS expression and NIS intracellular retention involving transcriptional and posttranscriptional or posttranslational mechanisms, respectively. Emerging therapies targeting the oncogene-activated signal pathways potentially involved in thyroid carcinogenesis have been able to recover radioiodine accumulation in radioiodine-refractory tumors, which constitutes the rationale of redifferentiation therapies. Here, we will comprehensively discuss the molecular mechanisms underlying radioiodine therapy, refractoriness to radioiodine therapy in differentiated thyroid carcinomas, and novel strategies for restoring radioiodine accumulation in radioiodine-refractory thyroid carcinomas

Corporations in Modern Political Theory: Positions from Hobbes and Hegel

Nuestro interés en el presente trabajo es, efectivamente, enfocarnos en la temática de las corporaciones, pero centrándonos en dos autores en particular: Thomas Hobbes y Georg Wilhelm Friedrich Hegel. Como se verá, mientras que Hobbes referirá a las corporaciones como empresas, Hegel las aludirá como asociaciones (encargadas de anexar la sociedad civil con el Estado). Es a estos fines que estructuraremos el presente trabajo en tres tiempos. En primer lugar, explicaremos cómo las corporaciones surgen de acuerdo a las teorías de ambos autores. Luego elucidaremos la forma en que las mismas funcionan y se encuentran conformadas. Finalmente, en tercera instancia dilucidaremos la relación que las corporaciones mantienen con el Estado tanto en Hobbes como en Hegel.Our interest in the present work is, indeed, to focus on the subject of corporations, but focusing on two authors in particular: Thomas Hobbes and Georg Wilhelm Friedrich Hegel. As will be seen, while Hobbes will refer to corporations as corporations, Hegel will refer to them as guilds. It is for this purpose that we will structure this paper in three stages. First, we will explain how corporations arise according to the theories of both authors. Then we will elucidate the way in which they function and are formed. Finally, in the third instance, we will elucidate the relationship between corporations and the state in both Hobbes and Hegel.Fil: Ricci Cernadas, Gonzalo. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin

Hegel and Spinoza: A Possible Encounter Regarding Freedom

Este trabajo analiza una posible vinculación entre los pensamientos políticos de Spinoza y Hegel, utilizando como piedra de toque a la noción de la libertad. Su estructura está puesta en función de un estudio comparativo de acuerdo a tres ejes: la crítica de la libertad entendida como libre arbitrio, la concepción de la libertad como autodeterminación y el vínculo inextricable de la libertad con el Estado. En lugar de la propuesta de Pierre Macherey, que exclama "Hegel o Spinoza", nosotros proclamamos "Hegel y Spinoza".This paper examines a possible bond between the political idea of Spinoza and Hegel, focusing on the notion of freedom as a cornerstone. It is structured in the terms of a comparative study according to three dimensions: the critique of freedom understood as free will, the conception of freedom as self-determination, and the inextricable link between freedom and the State. Instead of Pierre Macherey’s proposal, who claims “Hegel or Spinoza”, we affirm “Hegel and Spinoza”.Fil: Ricci Cernadas, Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales; ArgentinaFil: de Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones "Gino Germani"; Argentin

The expansion of adult stem/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy

Extensive evidence has revealed variations in the number of hormone-producing cells in the pituitary gland, which occur under physiological conditions such as gestation and lactancy. It has been proposed that new hormone-producing cells differentiate from stem cells. However, exactly how and when this takes place is not clear. In this work, we used immunoelectron microscopy to identify adult pituitary stem/progenitor cells (SC/P) localized in the marginal zone (MZ), and additionally, we detected GFRa2-, Sox2-, and Sox9-positive cells in the adenoparenchyma (AP) by fluorescence microscopy. Then, we evaluated fluctuations of SC/P mRNA and protein level markers in MZ and AP during gestation and lactancy. An upregulation in stemness markers was shown at term of gestation (AT) in MZ, whereas there were more progenitor cell markers in the middle of gestation and active lactancy. Concerning committed cell markers, we detected a rise in AP at beginning of lactancy (d1L). We performed a BrdU uptake analysis in MZ and AP cells. The highest level of BrdU uptake was observed in MZ AT cells, whereas in AP this was detected in d1L, followed by a decrease in both the MZ and AP. Finally, we detected double immunostaining for BrdU-GFRa2 in MZ AT cells and BrdU-Sox9 in the AP d1L cells. Taken together, we hypothesize that the expansion of the SC/P niche took place mainly in MZ from pituitary rats in AT and d1L. These results suggest that the SC niche actively participates in pituitary plasticity during these reproductive states, contributing to the origin of hormone cell populations.Fil: Vaca, Alicia Maldré del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Guido, Carolina Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Mukdsi, Jorge Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Torres, AIicia Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentin

S-nitrosylation of NF-kB p65 inhibits TSH-induced Na+/I- symporter expression

Nitric oxide (NO) is a ubiquitous signaling molecule involved in a wide variety of cellular physiological processes. In thyroid cells, NO-synthase III-endogenously produced NO reduces thyrotropin (TSH)-stimulated thyroid specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Further studies indicate that NO induces thyroid dedifferentiation, as NO donors repress TSH-stimulated I- uptake. Here, we investigated the molecular mechanism underlying the NO inhibited Na+/I- Symporter (NIS)-mediated I- uptake in thyroid cells. We showed that NO donors reduce I- uptake in a concentration-dependent manner, which correlates with decreased NIS protein expression. NO-reduced I- uptake results from transcriptional repression of NIS gene rather than post-translational modifications reducing functional NIS expression at the plasma membrane. We observed that NO donors repress TSH-induced NIS gene expression by reducing the transcriptional activity of the NF-κB subunit p65. NO-promoted p65 S-nitrosylation reduces p65-mediated transactivation of the NIS promoter in response to TSH stimulation. Overall, our data are consistent with the notion that NO plays a role as an inhibitory signal to counterbalance TSH-stimulated NF-κB activation, thus modulating thyroid hormone biosynthesis.Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Peyret, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Nazar, Magalí. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Romero, Jorge Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Lucero, Ariel Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montesinos, Maria del Mar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Bocco, Jose Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pellizas, Claudia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Masini, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentin

The ERα membrane pool modulates the proliferation of pituitary tumours

The molecular mechanisms underlying the ERα nuclear/cytoplasmic pool that modulates pituitary cell proliferation have been widely described, but it is still not clear how ERα is targeted to the plasma membrane. The aim of this study was to analyse ERα palmitoylation and the plasma membrane ERα (mERα) pool, and their participation in E2-triggered membrane-initiated signalling in normal and pituitary tumour cell growth. Cell cultures were prepared from anterior pituitaries of female Wistar rats and tumour GH3 cells, and treated with 10 nM of oestradiol (E2). The basal expression of ERα was higher in tumour GH3 than in normal pituitary cells. Full-length palmitoylated ERα was observed in normal and pituitary tumour cells, demonstrating that E2 stimulation increased both, ERα in plasma membrane and ERα and caveolin-1 interaction after short-term treatment. In addition, the Dhhc7 and Dhhc21 palmitoylases were negatively regulated after sustained stimulation of E2 for 3 h. Although the uptake of BrdU into the nucleus in normal pituitary cells was not modified by E2, a significant increase in the GH3 tumoural cell, as well as ERK1/2 activation, with this effect being mimicked by PPT, a selective antagonist of ERα. These proliferative effects were blocked by ICI 182780 and the global inhibitor of palmitoylation. These findings indicate that ERα palmitoylation modulated the mERα pool and consequently the ERK1/2 pathway, thereby contributing to pituitary tumour cell proliferation. These results suggest that the plasma membrane ERα pool might be related to the proliferative behaviour of prolactinoma and may be a marker of pituitary tumour growth.Fil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Picech, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Chumpen Ramirez, Sabrina Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Pérez, Pablo Aníbal. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Valdez Taubas, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; ArgentinaFil: Guitierrez, Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; ArgentinaFil: Torres, Alicia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Microscopía Electrónica; Argentin

First report of Meloidogyne arenaria parasitizing lettuce in southern Spain

During the 2005-2006 autumn to winter lettuce-growing (Lactuca sativa cv. Iceberg) season, severely stunted and yellowing lettuce plants with disease incidence ranging from 80 to 100% were observed in four commercial, fall-sown fields at Almodóvar del Río (Córdoba Province) in southern Spain. Early symptoms consisted of severely reduced growth of the plants that continued with extensive leaf yellowing and the absence of tight-head formation. Attacks by the disease were estimated to cause near complete loss of the crop yields since the lettuce head produced in affected fields were unmarketable. Observations of affected lettuce plants revealed high parasitism of the root system by a root-knot nematode (Meloidogyne sp.) in the main and feeder roots as well as heavy soil infestations by the nematode. The nematode was identified by the female perineal pattern, esterases phenotype, and a sequence-characterized amplified region polymerase chain reaction (SCAR-PCR) technique. Measurements and morphological observations of 20 second-stage juveniles (J2s) (body length = 463 ± 28 μm, dorsal gland orifice from stylet base = 2.8 ± 0.6 μm, stylet length = 10.4 ± 0.5 μm, tail length = 54.4 ± 0.6 μm; hyaline tail terminus = 9.4 ± 0.6 μm) and 10 adult females (stylet length = 14.5 ± 0.7 μm, dorsal gland orifice from stylet base = 4.7 ± 0.5 μm, and perineal pattern with low and rounded dorsal arch with coarse striae) conformed to the description of Meloidogyne arenaria. On the basis of the characteristics of the perineal pattern, the 2-band esterase phenotype, and the 420-bp SCAR fragment, the causal agent was identified as the peanut root-knot nematode M. arenaria. Nematodes were extracted from soil and root samples by standard procedures and their populations quantified. M. arenaria was detected in nearly all soil and root samples assessed, with nematode population densities ranging from 206 to 1,072 eggs and J2s per 5 g of fresh roots. Different Meloidogyne spp. have been reported parasitizing lettuce roots, especially M. hapla in northern areas (2); however, to our knowledge this is the first time that M. arenaria is reported parasitizing lettuce roots in Spain and elsewhere.Peer reviewe

Metabolic Profiling of Alpine and Ecuadorian Lichens

Non-targeted H-1-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA) were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g.,due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS) sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis