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Brain development is critically dependent on the timely supply of thyroid hormones. The thyroid hormone transporters are central to the action of thyroid hormones in the brain, facilitating their passage through the blood-brain b arrier. Mutations of the monocarboxylate transporter 8 (MCT8) cause the Allan-Herndon-Dudley syndrome, with altered thyroid hormone concentrations in the blood and profound neurological impairment and intellectual deficit. Mouse disease models have r evealed interplay between transport, deiodination, and availability of T3 to rece ptors in specific cells. However, the mouse models are not satisfactory, given the funda mental differences between the mouse and human brains. The goal of the present work is to review human neocortex development in the context of thyroid pathophysiology. Recent developments in single-cell transcriptomic approaches aimed at the human brain make it possible to profile the expression of thyroid hormone regulators in single-c ell RNA-Seq datasets of the developing human neocortex. The data provide novel insig hts into the specific cellular expression of thyroid hormone transporters, deiodinases, and receptors., Work in the laboratoriess of the authors has been supported by the Programa Estatal de Investigacion, Desarrollo e Innovación Orientada a los Retos de la Sociedad, and the Center for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III.

Rubber-soil mixtures are known to have mechanical properties that enable their use in backfills, road construction or geotechnical seismic isolation systems. The complexity of these mixtures comes from adding soft (i.e. rubber) particles that increases the number of particle properties to consider when studying the macroscopic behaviour. The distinction between sand-like and rubber-like behaviour is normally presented in relation to the rubber content and size ratio between particles. It is however unknown how the change on the mixture gradation affects the mechanical behaviour of RSm. Entropy coordinates condense the entire particle size distribution (PSD) to a single point on a Cartesian plane, accounting for all the information in the gradation. Grading entropy coordinates have been used to study typical geotechnical behaviours of mostly incompressible (i.e. sand) soils. In this study, entropy coordinates are used to analyse the correlation between the small-strain stiffness and liquefaction susceptibility of RSm and their PSDs. The results suggest that entropy coordinates can be used effectively on RSm as an alternative means of assessment of typical soil behaviours, being also able to distinguish between sand-like and rubber-like behaviours. Based on the 30 PSDs analysed, it is also evidenced that internal stability criterion proposed by Lőrincz (1986) can be used to predict the liquefaction susceptibility of RSm. The normalised base entropy (A) has also been shown to increase with the rubber content, which is linked to a lower liquefaction susceptibility, due to the supporting effect of rubber particles on strong-force chains formed of sand particles.

Bernal-Soriano, Mari Carmen/0000-0002-9174-0068; Berbel, Pere/0000-0001-6124-6037, WOS: 000555874000001, PubMed: 32498666, Background:Thyroxine (T4) to triiodothyronine (T3) deiodination in the hypothalamus/pituitary is mediated by deiodinase type-2 (D2) activity.Dio2((-/-))mice show central resistance to exogenous T4. Patients with resistance to exogenous thyroxine (RETH) have not been described. the aim of this study was to identify hypothyroid patients with thyrotropin (TSH) unresponsiveness to levothyroxine (LT4) and to characterize the clinical, hormonal, and genetic features of human RETH. Methods:We investigated hypothyroid patients with elevated TSH under LT4 treatment at doses leading to clinical and/or biochemical hyperthyroidism. TSH and free T4 (fT4) were determined by chemiluminescence, and total T4, T3, and reverse T3 (rT3) by radioimmunoassay. TSH/fT4 ratio at inclusion and T3/T4, rT3/T4, and T3/rT3 ratios at follow-up were compared with those from patients with resistance to thyroid hormone (RTH) due to thyroid hormone receptor-beta (THRB) mutations.DIO2,including the Ala92-D2 polymorphism, selenocysteine binding protein 2 (SECISBP2), andTHRBwere fully sequenced. Results:Eighteen hypothyroid patients (nine of each sex, 3-59 years) treated with LT4 showed elevated TSH (15.5 +/- 4.7 mU/L; reference range [RR]: 0.4-4.5), fT4 (20.8 +/- 2.4 pM; RR: 9-20.6), and TSH/fT4 ratio (0.74 +/- 0.25; RR: 0.03-0.13). Despite increasing LT4 doses from 1.7 +/- 1.0 to 2.4 +/- 1.7 mu g/kg/day, TSH remained elevated (6.9 +/- 2.7 mU/L). Due to hyperthyroid symptoms, LT4 doses were reduced, and TSH increased again to 7.9 +/- 3.2 mU/L. in the euthyroid/hyperthyrotropinemic state, T3/T4 and T3/rT3 ratios were decreased (9.2 +/- 2.4, RR: 11.3-15.3 and 2.5 +/- 1.4, RR: 7.5-8.5, respectively) whereas rT3/T4 was increased (0.6 +/- 0.2; RR: 0.43-0.49), suggesting reduced T4 to T3 and increased T4 to rT3 conversion. These ratios were serum T4-independent and were not observed in RTH patients. Genetic testing was normal. the Ala92-D2 polymorphism was present in 7 of 18 patients, but the allele dose did not correlate with RETH. Conclusions:Human RETH is characterized by iatrogenic thyrotoxicosis and elevated TSH/fT4 ratio. in the euthyroid/hyperthyrotropinemic state, it is confirmed by decreased T3/T4 and T3/rT3 ratios, and elevated rT3/T4 ratio. This phenotype may guide clinicians to consider combined T4+T3 therapy in a targeted fashion. the absence of germlineDIO2mutations suggests that aberrant post-translational D2 modifications in pituitary/hypothalamus or defects in other genes regulating the T4 to T3 conversion pathway could be involved in RETH., Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos IIIInstituto de Salud Carlos III [PI16/00830]; Rare Diseases Networking Biomedical Research Centre (CIBERER), This work was supported by funding from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (grant PI16/00830 to J.C.M.) and by the Rare Diseases Networking Biomedical Research Centre (CIBERER).

Thyroid hormones (TH) are crucial for brain development; their deficiency during neurodevelopment impairs neural cell differentiation and causes irreversible neurological alterations. Understanding TH action, and in particular the mechanisms regulating TH availability in the prenatal human brain is essential to design therapeutic strategies for neurological diseases due to impaired TH signaling during neurodevelopment. We aimed at the identification of cells involved in the regulation of TH availability in the human brain at fetal stages. To this end, we studied the distribution of the TH transporters monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1), as well as the TH-metabolizing enzymes types 2 and 3 deiodinases (DIO2 and DIO3). Paraffin-embedded human brain sections obtained from necropsies of thirteen fetuses from 14 to 38 gestational weeks were analyzed by immunohistochemistry and in situ hybridization. We found these proteins localized along radial glial cells, in brain barriers, in Cajal-Retzius cells, in migrating fibers of the brainstem and in some neurons and glial cells with particular and complex spatiotemporal patterns. Our findings point to an important role of radial glia in controlling TH delivery and metabolism and suggest two additional novel pathways for TH availability in the prenatal human brain: the outer, and the inner cerebrospinal fluid–brain barriers. Based on our data we propose a model of TH availability for neural cells in the human prenatal brain in which several cell types have the ability to autonomously control the required TH content., The IdiPAZ Biobank is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Retic RD09/0076/00073) and Farmaindustria, through the Cooperation Program in Clinical and Translational Research of the Community of Madrid. We thank Drs. Soledad Bárez-López, José Miguel Cosgaya, Estrella Rausell and Ana Montero-Pedrazuela for the careful reading of the manuscript and their helpful suggestions, and Javier Pérez for his help on the artwork. This work was supported by Grants from the Spanish Plan Nacional de I+D+i (Grant numbers SAF2014-54919-R and SAF2017-86342-R to A.GF and J.B), and the Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos III, Madrid, Spain and the Sherman Foundation (OTR02211 to A.GF). D.LE is a recipient of a fellowship from “Fellowship Training Program for Advanced Human Capital, BECAS CHILE” from the National Commission for Scientific and Technological Research (CONICYT), Gobierno de Chile. The cost of this publication has been paid in part by FEDER funds.

Polyaniline (PANI) composites have gained momentum as supercapacitive materials due to their high energy density and power density. However, some drawbacks in their performance remain, such as the low stability after hundreds of charge-discharge cycles and limitations in the synthesis scalability. Herein, we report for the first time PANI-Graphitic oxidized carbon nitride composites as potential supercapacitor material. The biomimetic polymerization of aniline assisted by hematin, supported by phosphorous and oxygen-modified carbon nitrides (g-POCN and g-OCN, respectively), achieved up to 89% yield. The obtained PAI/g-POCN and PANI/g-OCN show enhanced electrochemical properties, such as conductivity of up to 0.0375 S/cm, specific capacitances (Cs) of up to 294 F/g (at high current densities, 5 A/g) and a stable operation after 500 charge-discharge cycles (at 3 A/g). In contrast, the biomimetic synthesis of Free PANI, assisted by stabilized hematin in cosolvents, exhibited lower performance properties (65%). Due to their structural differences, the electrochemical properties of Free PANI (conductivity of 0.0045 S/cm and Cs of up to 82 F/g at 5 A/g) were lower than those of nanostructured PANI/g-POCN and g-OCN supports, which provide stability and improve the properties of biomimetically synthesized PANI. This work reveals the biomimetic synthesis of PANI, assisted by hematin supported by modified carbon nitrides, as a promising strategy to produce nanostructured supercapacitors with high performance.

Given a set of images we propose an algorithm that approximates all images simultaneously. The algorithm finds the best common partition of the images' domain at each step, this is accomplished by maximizing an appropriate inner product. The algorithm is a pursuit algorithm constrained to build a tree, the optimization is done over a large dictionary of wavelet-like functions. The approximations are given by vector valued discrete martingales that converge to the input set of images. Several computational and mathematical techniques are developed in order to encode the information needed for the reconstruction. Properties of the algorithm are illustrated through many examples, comparisons with JPEG2000 and MPEG4-3 are also provided.

[Background]: Mutations of the thyroid hormone (TH)-specific cell membrane transporter, monocarboxylate transporter 8 (MCT8), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits. Studies of brain from a 30-week-old MCT8-deficient embryo indicated that brain abnormalities were already present during fetal life. [Methods]: A carrier woman with an affected male child (MCT8 A252fs268*), pregnant with a second affected male embryo, elected to carry the pregnancy to term. We treated the fetus with weekly 500 μg intra-amniotic instillation of levothyroxine (LT4) from 18 weeks of gestation until birth at 35 weeks. Thyroxine (T4), T3, and thyrotropin (TSH) were measured in the amniotic fluid and maternal serum. Treatment after birth was continued with LT4 and propylthiouracil. Follow-up included brain magnetic resonance imaging (MRI) and neurodevelopmental evaluation, both compared with the untreated brother. [Results]: During intrauterine life, T4 and T3 in the amniotic fluid were maintained above threefold to twofold the baseline and TSH was suppressed by 80%, while maternal serum levels remained unchanged. At birth, the infant serum T4 was 14.5 μg/dL and TSH 8 mU/L, respectively. MRI at six months of age showed near-normal brain myelination compared with much reduced in the untreated brother. Neurodevelopmental assessment showed developmental quotients in receptive language and problem-solving, and gross motor and fine motor function ranged from 12 to 25 at 31 months in the treated boy and from 1 to 7 at 58 months in the untreated brother. [Conclusions]: This is the first demonstration that prenatal treatment improved the neuromotor and neurocognitive function in MCT8 deficiency. Earlier treatment with TH analogues that concentrate in the fetus when given to the mother may further rescue the phenotype., This work was supported by grants from the National Institutes of Health, USA, DK15070 to Samuel Refetoff and DK110322 to Alexandra M. Dumitrescu, and by funds from the Esformes Thyroid Research Fund to Roy E. Weiss.

The trace element iodine (I) is essential for the synthesis of thyroid hormones. Premature babies need >30 µg I / kg /day (ICCIDD recommendations). Neonates and especially preterm infants are a population at risk of suffering the consequences of iodine deficiency, because of the impact of neonatal hypothyroxinemia on brain development. The main aim of this project is to prevent the mental retardation and increased risk of cerebral palsy of premature infants, which is partially caused by neonatal hypothyroxinemia. We gave Oral iodine supplementation in very premature babies during the neonatal period. Population: we included 94 infants born

© Diego Diez et al., 2021; Published by Mary Ann Liebert, Inc., [Background]: Thyroid hormones are crucial for brain development, acting through the thyroid hormone nuclear receptors (TR)α1 and β to control gene expression. Triiodothyronine (T3), the receptor-ligand, is transported into the brain from the blood by the monocarboxylate transporter 8 (MCT8). Another source of brain T3 is from the local deiodination of thyroxine (T4) by type 2 deiodinase (DIO2). While these mechanisms are very similar in mice and humans, important species-specific differences confound our understanding of disease using mouse models. To fill this knowledge gap on thyroid hormone action in the human fetal brain, we analyzed the expression of transporters, DIO2, and TRs, which we call thyroid hormone effectors, at single-cell resolution. [Methods]: We analyzed publicly available single-cell transcriptome data sets of isolated cerebral cortex neural cells from three different studies, with expression data from 393 to almost 40,000 cells. We generated Uniform Manifold Approximation and Projection scatterplots and cell clusters to identify differentially expressed genes between clusters, and correlated their gene signatures with the expression of thyroid effectors. [Results]: The radial glia, mainly the outer radial glia, and astrocytes coexpress SLCO1C1 and DIO2, indicating close cooperation between the T4 transporter OATP1C1 and DIO2 in local T3 formation. Strikingly, THRB was mainly present in two classes of interneurons: a majority expressing CALB2/calretinin, from the caudal ganglionic eminence, and in somatostatin-expressing interneurons from the medial ganglionic eminence. By contrast, many cell types express SLC16A2 and THRA. [Conclusions]:SLCO1C1 and DIO2 coexpression in the outer radial glia, the universal stem cell of the cerebral cortex, highlights the likely importance of brain-generated T3 in neurogenesis. The unique expression of THRB in discrete subsets of interneurons is a novel finding whose pathophysiological meaning deserves further investigation., This study was supported by grant #SAF2017-86342-R (Programa Estatal de Investigacion, Desarrollo e Innovacio´n Orientada a los Retos de la Sociedad), and the Center for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III. The cost of this publication has been paid in part by FEDER funds.

[Background] The monocarboxylate transporter 8 (Mct8) protein is a primary thyroxine (T4) and triiodothyronine (T3) (thyroid hormone [TH]) transporter. Mutations of the MCT8-encoding, SLC16A2 gene alter thyroid function and TH metabolism and severely impair neurodevelopment (Allan-Herndon-Dudley syndrome [AHDS]). Mct8-deficient mice manifest thyroid alterations but lack neurological signs. It is believed that Mct8 deficiency in mice is compensated by T4 transport through the Slco1c1-encoded organic anion transporter polypeptide 1c1 (Oatp1c1). This allows local brain generation of sufficient T3 by the Dio2-encoded type 2 deiodinase, thus preventing brain hypothyroidism. The Slc16a2/Slco1c1 (MO) and Slc16a2/Dio2 (MD) double knockout (KO) mice lacking T4 and T3 transport, or T3 transport and T4 deiodination, respectively, should be appropriate models of AHDS. Our goal was to compare the cerebral hypothyroidism of systemic hypothyroidism (SH) caused by thyroid gland blockade with that present in the double KO mice., [Methods] We performed RNA sequencing by using RNA from the cerebral cortex and striatum of SH mice and the double KO mice on postnatal days 21–23. Real-time polymerase chain reaction was used to confirm RNA-Seq results in replicate biological samples. Cell type involvement was assessed from cell type-enriched genes. Functional genomic differences were analyzed by functional node activity based on a probabilistic graphical model., [Results] Each of the three conditions gave a different pattern of gene expression, with partial overlaps. SH gave a wider and highest variation of gene expression than MD or MO. This was partially due to secondary gene responses to hypothyroidism. The set of primary transcriptional T3 targets showed a tighter overlap, but quantitative gene responses indicated that the gene responses in SH were more severe than in MD or MO. Examination of cell type-enriched genes indicated cellular differences between the three conditions., [Conclusions] The results indicate that the neurological impairment of AHDS is too severe to be fully explained by TH deprivation only., This work was supported by the Center for Biomedical Research on Rare Diseases, Instituto de Salud Carlos III, as well as the BMBF under the framework of E-Rare-2, the ERA-Net for Research on Rare Diseases (project acronym THYRONERVE). It was also supported by grant #SAF2017-86342-R (Programa Estatal de Investigacion, Desarrollo e Innovación Orientada a los Retos de la Sociedad) and by Fundación Inocente, Inocente. The cost of this publication has been paid in part by FEDER funds.

Background: Mutations of the thyroid hormone (TH)-specific cell membrane transporter, monocarboxylate transporter 8 (MCT8), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits. Studies of brain from a 30-week-old MCT8-deficient embryo indicated that brain abnormalities were already present during fetal life. Methods: A carrier woman with an affected male child (MCT8 A252fs268*), pregnant with a second affected male embryo, elected to carry the pregnancy to term. We treated the fetus with weekly 500 μg intra-amniotic instillation of levothyroxine (LT4) from 18 weeks of gestation until birth at 35 weeks. Thyroxine (T4), T3, and thyrotropin (TSH) were measured in the amniotic fluid and maternal serum. Treatment after birth was continued with LT4 and propylthiouracil. Follow-up included brain magnetic resonance imaging (MRI) and neurodevelopmental evaluation, both compared with the untreated brother. Results: During intrauterine life, T4 and T3 in the amniotic fluid were maintained above threefold to twofold the baseline and TSH was suppressed by 80%, while maternal serum levels remained unchanged. At birth, the infant serum T4 was 14.5 μg/dL and TSH 8 mU/L, respectively. MRI at six months of age showed near-normal brain myelination compared with much reduced in the untreated brother. Neurodevelopmental assessment showed developmental quotients in receptive language and problem-solving, and gross motor and fine motor function ranged from 12 to 25 at 31 months in the treated boy and from 1 to 7 at 58 months in the untreated brother. Conclusions: This is the first demonstration that prenatal treatment improved the neuromotor and neurocognitive function in MCT8 deficiency. Earlier treatment with TH analogues that concentrate in the fetus when given to the mother may further rescue the phenotype.

Light-induced deposits of carbon nanotubes (CNTs) are obtained in multimodal interference (MMI) fiber tips. Differences between deposits obtained with solutions with and without surfactant were observed.

This article reviews recent advances made during the past two years on transport, metabolism and action of thyroid hormone (TH) in the brain. Facilitated transport through the BBB is a first step in the control of TH concentrations in brain. The critical role of the BBB has been confirmed using an in vitro model of the BBB. Further control of brain TH concentrations is exerted by deiodinases. Deiodinase gene inactivation in mice leads to altered behavior, highlighting the importance of local T3 formation and degradation for brain function. T3 action in brain involves binding to nuclear receptors and the control of gene expression. Genomic approaches have been directed at the identification of many genes controlled by T3 which are important in cerebral cortex development.

Systematic acarological surveys are useful tools in assessing risk to tick-borne infections, especially in areas where consistent clinical surveillance for tick-borne disease is lacking. Our goal was to identify environmental predictors of tick burdens on dogs and tick-borne infectious agents in dog-derived ticks in the Chiriquí Province of western Panama to draw inferences about spatio-temporal variation in human risk to tick-borne diseases. We used a model-selection approach to test the relative importance of elevation, human population size, vegetative cover, and change in landuse on patterns of tick parasitism on dogs. We collected 2074 ticks, representing four species (Rhipicephalus sanguineus, R. microplus, Amblyomma ovale, and Ixodes boliviensis) from 355 dogs. Tick prevalence ranged from 0 to 74% among the sites we sampled, and abundance ranged from 0 to 20.4 ticks per dog with R. sanguineus s.l. being the most commonly detected tick species (97% of all ticks sampled). Whereas elevation was the best single determinant of tick prevalence and abundance on dogs, the top models also included predictor variables describing vegetation cover and landuse change. Specifically, low-elevation areas associated with decreasing vegetative cover were associated with highest tick occurrence on dogs, potentially because of the affinity of R. sanguineus for human dwellings. Although we found low prevalence of tick-borne pathogen genera (two Rickettsia-positive ticks, no R. rickettsia or Ehrlichia spp.) in our study, all of the tick species we collected from dogs are known vectors of zoonotic pathogens. In areas where epidemiological surveillance infrastructure is limited, field-based assessments of acarological risk can be useful and cost-effective tools in efforts to identify high-risk environments for tick-transmitted pathogens.

Carbon nanotubes have been used as scaffolds for tissue engineering. However, the identification of these nanomaterials disperses in biological solutions and their direct interaction with nerve cells is still controversial. The aim of this work is to characterize the topographic and ultra-structural distribution of the composite made of multi wall carbon nanotubes-polyvinylpyrrolidone (MWCNTs-PVP) deposited on the Helix aspersa neurons and over glass coverslip. Scanning Electron Microscopy (SEM) and Confocal Microscopy (CM) studies were done to analyze the properties of such MWCNTs-PVP composite. The cerebral ganglion of Helix aspersa was treated and incubated with MWCNTs-PVP, fixing it in paraformaldehyde at 4% and was observed with SEM and CM. Although the nanotubes were not labeled or stained with fluorescent compounds, the MWCNTs-PVP deposited on glass and on nerve cells, was observed by the confocal microscope in the reflection mode. In SEM studies, it was observed that MWCNTs-PVP was attached to the surface on neurons. Moreover, in CM studies, it was possible to observe that MWCNTs-PVP was attached to the neuronal membrane, crossing the cell membrane and getting into the cytoplasm. These results support the hypothesis that carbon nanotubes interact with the neuronal cell membrane and can be useful for neuronal tissue engineering. In addition, these results open new alternatives for toxicological studies, in order to elucidate the cytotoxicity of MWCNTs-PVP composite in neurons and other excitable cells.

The integration of carbon nanotubes (CNTs) into optical fibers allows the application of their unique properties in robust and versatile devices. Here, we present a laser-induced technique to obtain the deposition of CNTs onto the fiber optics tips of multimode interference (MMI) devices. An MMI device is constructed by splicing a section of no-core fiber (NCF) to a single-mode fiber (SMF). The tip of the MMI device is immersed into a liquid solution of CNTs and laser light is launched into the MMI device. CNTs solutions using water and methanol as solvents were tested. In addition, the use of a polymer dispersant polyvinylpyrrolidone (PVP) in the CNTs solutions was also studied. We found that the laser-induced deposition of CNTs performed in water-based solutions generates non-uniform deposits. On the other hand, the laser-induced deposition performed with methanol solutions generates uniform deposits over the fiber tip when no PVP is used and deposition at the center of the fiber when PVP is present in the CNTs solution. The results show the crucial role of the solvent on the spatial features of the laser-induced deposition process. Finally, we register and study the reflection spectra of the as-fabricated CNTs deposited MMI devices.

In this paper we report that electrodes made of multi wall carbon nanotubes (MWCNTs) incorporated on Polyvinylidene fluoride (PVDF) filters can be used for recording and sensing bio-electrical signals. We measured the electrical properties of MWCNTs incorporated on membranes made of cellulose (bond-paper) and PVDF filters. In addition, we performed Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM) studies with the purpose to characterize the ultra-structural properties and distribution of MWCNTs on PVDF filters. We found that the electrodes made of MWCNTs on PVDF filters, have lower resistance and consequently better conductivity compared with other typical electro-conductive materials. We also found that the topographic distribution of the MWCNTs on the PVDF filter is chaotic and non-aligned; nevertheless, MWCNTs on PVDF filters showed a linear electrical resistance without rectification. Electrodes made of MWCNTs on PVDF filters were able to record electrocardiograms in humans with similar resolution than the ones recorded with silver electrodes. The relevance and application of these findings are discussed.

In this paper we provide experimental evidence to demonstrate that multi walled carbon nanotubes (MWCNTs) are sensitive to laser irradiation and this stimulus reduces systematically their intrinsic electrical resistance. MWCNTs were obtained by spray pyrolysis, functionalized by acidic treatment, dispersed in water solution and deposited on different surface materials such as polyvinylidene fluoride (PVDF) filters, bond papers and glass-coverslips. Scanning electron microscopy studies were done to evaluate the dispersion and topographic distribution of MWCNTs deposited on PVDF filters. In addition, we measured the electrical resistance of MWCNTs in control conditions and when a continuous near infrared (nIR) laser beam at 650 nm, was applied. MWCNTs showed a consistent value of electrical resistance depending on the amount of nanotubes applied. The average resistance of the MWCNTs on PVDF filters was as follows (in ohms): 23.78, 307.55 and 22,750 at 1, 1:10 and 1:100 dilutions of stock solution (5 mg/mL), respectively. After the application of nIR-laser, the electrode resistance was transiently reduced by approximately 10% to 45%. In addition, a small increase of temperature (from 0.20 to 3.20 °C) was observed during laser irradiation. Our results presented here, support the hypothesis that nIR-Laser irradiation of MWCNTs modulates with high sensitivity the intrinsic electrical and thermal properties of MWCNTs. Therefore, the laser irradiation on MWCNTs could be synergistically applied in the biomedical field as a therapeutic alternative for hyperthermia cancer treatment.

In the present work, multiple-wall carbon nanotubes (MWCNTs) were surface modified in an environmentally friendly way, using low-frequency ultrasonic energy. This type of modification was carried-out using two different types of organic acids, citric acid (CA) and oxalic acid (OA). The modification of the MWCNTs was confirmed by Fourier-transform infrared spectroscopy (FTIR), where functional groups such as OH, C=O, O&ndash, C=O and COOH were detected. By means of Raman spectroscopy, an increase in carbon surface defects was found. On the other hand, using X-ray photoelectron spectroscopy (XPS), oxidation was evidenced on the surface of the modified MWCNT. In both Raman spectroscopy and XPS, the results indicate a greater modification when CA is used, possibly due to the fact that CA has a larger number of functional groups. MWCNT-CA showed good dispersion in methanol, while MWCNT-OA showed good stability in methanol and ethanol. Finally, a 20% removal of creatinine efficiency improvement was found with respect to the unmodified MWCNTs, while no improvement was found in the case of urea and uric acid.

The actions of thyroid hormones on brain development and function are due primarily to regulation of gene expression. Identification of direct transcriptional responses requires cell culture approaches given the difficulty of in vivo studies. Here, we describe the use of primary cells in culture obtained from embryonic mouse cerebral cortex, to identify the set of genes regulated directly and indirectly by T3 using RNA-Seq.

The actions of thyroid hormones on brain development and function are due primarily to regulation of gene expression. Identification of direct transcriptional responses requires cell culture approaches given the difficulty of in vivo studies. Here, we describe the use of primary cells in culture obtained from embryonic mouse cerebral cortex, to identify the set of genes regulated directly and indirectly by T3 using RNA-Seq., Supported by grants SAF2014-54919-R from the Plan Estatal de Investigación Científica y Técnica y de Innovación, Spain and by the Center for Research on Rare Dieseases (Ciberer) under the frame of E-Rare-2, the ERA-Net for Research on rare Diseases.

A specific type of centrifugal fan named the “squirrel-cage” is broadly used in parallel configurations within an evaporator unit of HVAC systems for public transport. In these units, interaction effects arise, both between fans themselves and between fans and the structural elements. Blockage effects, such as the electrical motor, the evaporator gate and some aesthetic covering may also appear when these external elements are located very close to the fans aspiration nozzles.In this work, an experimental study of different configurations enables the determination of the minimum distances between the elements of the multi-fan unit, in order to minimise these interaction effects and, as a consequence, the problems related to them. Also, the quantitative influence of different motor sizes, covering solutions and the evaporator gate on the fans performance have been determined. Appreciable performance losses were found due to these blockage effects, thus recommendations to avoid the location of any e...

Estudiar los posibles efectos citotóxicos de los NTCPM sobre las señales eléctricas de las neuronas del caracol de jardin Helix aspersa . Específicamente, estudiar si los NTCPM bloquean o modifican la permeabilidad de canales iónicos dependientes del voltaje (canal de calcio y canal de potasio que dependen del calcio) y su efecto sobre canales iónicos dependientes de agonista químico o neurotransmisores (acetilcolina, dopamina y L-glutamato), que subyacen a los potenciales de acción y a los potenciales sinápticos de las neuronas de Helix aspersa . 6 i-3) Material y métodos. Nanotubos de carbono de pared múltiple (NTCPM) usados en este proyecto. Los NTCPM fueron sintetizados por el método de pirólisis de aspersión y fueron funcionalizados con soluciones ácidas de ácido nítrico - ácido sulfúrico; fueron dispersados en soluciones acuosas: agua desionizada y solución Ringer de caracol, usando polivinilpirrolidona (PVP) como agente dispersante. Los NTCPM ya dispersados en PVP fueron sometidos a ultrasonido y con ello se aseguró la homogeneidad de la dispersión. Propiedades ultraestructurales de NTCPM. Los NTCPM dispersados en soluciones acuosas fueron colocados sobre distintos materiales: papel bond, vidrio, filtros de PVDF y láminas de cobre. También los NTCPM se depositaron sobre las neuronas de Helix aspersa . Sus propiedades morfológicas y ultraestructurales se caracterizaron mediante el uso de diversos estudios: microscopía óptica, microscopía electrónica de barrido, microscopía electrónica de transmisión, microscopía confocal y microscopía de fuerza atómica. Además se demostró que los electrodos de NTCPM pueden utilizarse para el registro y detección de señales bioeléctricas, ya que dichos electrodos fueron capaces de registrar señales electrocardiográficas en humanos con resolución y eficiencia similar a los registrados con electrodos convencionales de plata. d). En otra serie de experimentos se obtuvieron resultados que demuestran que los NTCPM son sensibles a la irradiación del láser y que este estímulo reduce sistemáticamente su resistencia eléctrica intrínseca. La resistencia eléctrica de los NTCPM se midió en condiciones de control y cuando se les aplicó un haz de láser 8 continuo cercano al infrarrojo (nIR-láser) a una longitud de onda de 650 nm. Se encontró que los NTCPM mostraron un valor constante de la resistencia eléctrica y dicho valor de resistencia fue dependiente de la cantidad de nanotubos aplicada sobre los filtros de PVDF. La resistencia media de los NTCPM sobre filtros de PVDF fue como sigue (en ohms): 23, 307 y 2275 en diluciones 1, 1:10 y 1:100 de la solución madre de NTCPM (5 mg/mL) respectivamente. Se demostró que nIR-láser disminuyó la resistencia eléctrica en forma transitoria, ya que al suspender la irradiación láser dicho valor de resistencia se recuperó a valores normales. Además se observó un pequeño aumento de la temperatura (1.2 a 3.2 °C) durante la irradiación con láser. Los resultados aquí presentados apoyan la hipótesis de que la irradiación láser modula, con una alta sensibilidad, las propiedades eléctricas y térmicas intrínsecas de los NTCPM. Se encontró que el receptor colinérgico en neurona 1F es de tipo muscarínico M1-M3, ya que la despolarización membranal activada por carbacol es inhibida por atropina y pirenzepina y es incrementada con oxotremorina. En el caso de la hiperpolarización activada por dopamina se encontró que dicha hiperpolarización es regulada por receptores dopaminérgicos tipo D2, ya que los fármacos metoclopramida y ergometrina (antagonistas específicos de los receptores dopaminérgicos D2) bloquean la respuesta de la dopamina. En el caso de la respuesta glutamatérgica se encontró que la despolarización activada por glutamato es moderadamente sensible a bloqueadores tipo ampa-kainato. Se encontró que esta respuesta muscarínica, glutamatérgica y dopaminérgica de la neurona 1F no es bloqueada por los NTCPM a concentraciones de hasta 0.5 mg/mL. De esta serie de experimentos se concluye que los NTCPM no bloquean los canales iónicos dependientes de agonistas. 10 h). Se evaluaron los efectos de NTCPM en otras preparaciones biológicas (células de protistas y de mamíferos) con el propósito de corroborar la no toxicidad y la biocompatibilidad de los NTCPM usados en este trabajo de tesis. Se encontró que los NTCPM son incorporados al interior del citoplasma del Paramecium; no por simple difusión, sino por un proceso membranal de endocitosis. Estos nanotubos no modificaron la sobrevida ni el nado normal del Paramecium; sin embargo, a altas concentraciones de NTCPM, de más de 200 µg/mL, se modificó la conducta de galvanotaxis del ciliado. En otra serie de experimentos se estudió el posible efecto citotóxico de NTCPM en neuronas del hipocampo de mamífero. En dichos experimentos, se encontró que las neuronas de hipocampo de rata cultivadas y depositadas sobre un andamio o “scaffold” hecho con los NTCPM presentaron propiedades electrofisiológicas similares a las neuronas cultivadas sobre cubreobjetos de vidrio sin NTCPM. Antecedentes y justificación. Los nanotubos de carbono (NTC) son materiales desarrollados por la nanotecnología. Los NTC tienen la característica de poder adquirir y transmitir señales bioeléctricas debido a sus dimensiones nanométricas, a su alta capacidad de conducción eléctrica y a su capacidad de adherirse a las membranas celulares. Se han usado distintos nanotubos de carbono de pared simple (NTCPS) y nanotubos de carbono de pared múltiple (NTCPM) como andamios o “scafolds” para cultivo de células nerviosas y se han reportado resultados controversiales en cuanto a su toxicidad, biocompatibilidad celular y crecimiento neuronal. No está claro si los NTC tienen un efecto bloqueante sobre los canales iónicos que subyacen a las señales bioeléctricas neuronales, tales como potenciales de acción y potenciales sinápticos. En particular no se ha demostrado ni evaluado la posible toxicidad de los NTCPM sobre los canales iónicos dependientes de voltaje (canales de calcio y canales de potasio) ni sobre los canales iónicos dependientes de agonista (canales acoplados al receptor de L-glutamato, acetilcolina y dopamina). Más aún, no se ha demostrado si los NTCPM pueden conectar eléctricamente a dos o más neuronas entre sí. i-2) Objetivos. a). Estudiar las propiedades ultraestructurales de los NTCPM dispersos en soluciones acuosas y depositados sobre distintos materiales incluyendo los depositados sobre las neuronas del ganglio del caracol de jardín Helix aspersa. b). Estudiar las propiedades eléctricas de los NTCPM depositados sobre distintos materiales. Habiendo demostrado que los NTCPM se adhieren a la membrana celular y pueden atravesar dicha membrana, se realizaron experimentos de registro intracelular en la configuración de fijación de corriente con el propósito de evaluar el posible efecto de NTCPM sobre: i). La amplitud y la duración del potencial de acción normal, ii). La hiperpolarización postetánica y iii). La duración del potencial de acción de calcio (PA-Ca 2+) en las neuronas de Helix aspersa . En estos experimentos se encontró que los NTCPM no bloquearon ni modificaron la amplitud ni la mofología de los potenciales de acción normales y potenciales de acción cálcicos; tampoco modificaron la hiperpolarización postetánica. Por lo anterior se puede inferir que los NTCPM no bloquean los canales de sodio, ni de potasio, ni de calcio dependientes de voltaje presentes en la membrana neuronal de las neuronas de Helix aspersa . g). En otra serie de experimentos se estudiaron los posibles efectos tóxicos de los NTCPM sobre la permeabilidad iónica de los canales ionicos activados por agonistas y neurotransmisores. La técnica convencional de registro intracelular en el modo de fijación de corriente fue la utilizada para evaluar las propiedades electrofisiológicas de los canales ionicos activados por dopamina, L- glutamato y carbacol en la neurona 1F. En estos experimentos electrofisiológicos se caracterizaron la presencia de estos receptores membranales en las neuronas de Helix aspersa, así como sus propiedades farmacológicas. Se observó que la transmisión sináptica entre pares de neuronas no fue inhibida; más aún, dicha actividad sináptica se vio incrementada. i-5) Conclusiones y perspectivas. En los experimentos realizados para este trabajo de tesis, se logró una dispersión eficiente de NTCPM en soluciones acuosas. Los NTCPM tienen las siguientes características: i). Presentan una baja resistencia eléctrica y consecuentemente una alta conductividad, ii). No tienen un efecto deletéreo o tóxico sobre las propiedades eléctricas de las neuronas de caracol, iii). No bloquean los canales iónicos dependientes de voltaje, y iv). No bloquean los canales iónicos dependientes de agonista. Se demostró que los NTCPM se pueden usar como electrodos de registro para sensar y registrar señales bioeléctricas, tales como el electrocardiograma en humanos. Además se demostró que la resistencia intrínseca de los NTCPM se disminuye al exponer dichos NTCPM a la irradiación láser cercano al infrarrojo. Sin embargo, queda aún pendiente el demostrar que los NTCPM incorporados a electrodos de registro puedan registrar la actividad eléctrica neuronal. También será necesario estudiar si los NTCPM pueden conectar eléctricamente a dos o más neuronas entre sí. Considerando la alta sensibilidad de los NTCPM al láser, estos materiales podrán ser usados en futuros experimentos como alternativa terapéutica para el cáncer, al aplicarse dichos NTCPM en procesos tumorales para lograr ablación tumoral usando el método de hipertermia inducida por láser en tumores cancerosos. Preparación biológica. Las neuronas identificadas del invertebrado caracol de jardín Helix aspersa fueron utilizadas como modelo biológico en este trabajo de tesis. Estas neuronas presentan propiedades bioeléctricas y canales iónicos similares a los que existen en neuronas de mamífero, por lo que estas neuronas de invertebrado han sido utilizadas como modelos biológicos en múltiples estudios en el campo de la investigación básica en neurociencias. Las neuronas del caracol Helix aspersa son fácilmente identificables, tanto morfológica como electrofisiológicamente; presentan actividad eléctrica espontánea y su membrana celular posee canales iónicos de K+ y Ca2+, así como canales iónicos acoplados a receptores membranales como dopamina, L-glutamato y acetilcolina. Experimentos electrofisiológicos de registro intracelular. En el desarrollo experimental de este proyecto se utilizaron técnicas electrofisiológicas convencionales de registro intracelular con microelectrodos en el modo de fijación de corriente. En estos experimentos se monitorearon señales bioeléctricas neuronales tales como: i). Potencial de membrana, ii). Actividad eléctrica espontánea, iii). Hiperpolarización postetánica, iv). Potencial de acción cálcico, v). Despolarización membranal activada por glutamato y carbacol y vi). Hiperpolarización membranal activada por dopamina. Existen reportes controversiales respecto a la toxicidad de los NTC en las células neuronales y su posible efecto de bloqueo de permeabilidad de canales iónicos presentes en neuronas y otras células excitables. En este trabajo de tesis se evaluó el posible efecto bloqueante de NTCPM sobre las permeabilidades iónicas dependientes de voltaje de las neuronas de Helix aspersa . Se realizaron estudios de microscopía óptica, electrónica de barrido y microscopía confocal para demostrar que los NTCPM aplicados sobre las neuronas están dispersados adecuadamente; pueden adherirse a las membranas neuronales y eventualmente podrían bloquear las permeabilidades de canales iónicos localizados en la membrana celular. En experimentos iniciales, los NTCPM fueron marcados con isotiaocianato de fluoresceína (FITC) y con técnicas de microscopía confocal, y se estudió la posible interacción de estos nanotubos fluorescentes con la membrana celular de neuronas del caracol Helix aspersa . En otra serie de experimentos se analizaron neuronas íntegras y cortes histológicos de neuronas del ganglio de Helix aspersa con técnicas de microscopía óptica y microscopía electrónica de barrido, así como microscopía confocal, en donde las neuronas fueron tratadas con NTCPM sin marcaje con fluoresceína. Se pudo demostrar que los NTCPM se adhieren a la membrana celular, atraviesan dicha membrana y tienden a acumularse al interior del citoplasma y sobre el núcleo. Resultados experimentales. a). Se estudiaron distintos compuestos para lograr una dispersión adecuada de los NTCPM en soluciones acuosas. Entre los diferentes compuestos ensayados se encontró que dimetilformamida es un buen dispersante, pero es tóxico para las células. Pluronic F-127 no era tóxico para las células, pero no se dispersaban eficientemente los NTCPM. La Polivinilpirrolidona (PVP) fue el mejor dispersante encontrado para NTCPM y no tiene ningún efecto tóxico en las neuronas y células estudiadas. Se demostró que la manipulación mecánica por sonicación de NTCPM, así como el uso de dispersantes biocompatibles, mejoran la dispersión de NTCPM en soluciones acuosas. b). Mediante el uso de estudios de microscopía óptica, microscopía electrónica de barrido, microscopía electrónica de transmisión, microscopía confocal y microscopía de fuerza atómica, se caracterizaron las propiedades ultraestructurales de los NTCPM depositados en distintos materiales: papel bond, vidrio, filtros de fluoruro de polivinilideno (PVDF) y laminas de cobre; así como los aplicados sobre las neuronas de Helix aspersa . c). En este trabajo de tesis se encontró que los electrodos hechos con NTCPM y depositados sobre papel bond y filtros de PVDF tienen una menor resistencia; por consiguiente una mejor conductividad en comparación con otros materiales electroconductores, tales como la plata y la pintura de grafeno. Se realizaron estudios de microscopía de fuerza atómica (AFM) y estudios de microscopía electrónica de barrido (SEM) con el fin de caracterizar las propiedades ultraestructurales y de distribución de NTCPM en filtros de PVDF. Se observó que los electrodos hechos con NTCPM colocados sobre filtros de PVDF tienen una distribución topográfica caótica y éstos no están alineados; sin embargo, los NTCPM depositados sobre los filtros de PVDF mostraron una resistencia eléctrica lineal sin rectificación.

Resena Santos, Boaventura de Sousa (2015). La universidad en el siglo XXI. Mexico: Siglo XXI, 173 paginas

[Background]: The possibility that the intrinsic genomic activity of thyroxine (T4) is of physiological relevance has been frequently hypothesized. It might explain gene expression patterns in the brain found in type 2-deiodinase (Dio2)-deficient mice. These mice display normal expression of most thyroid hormone–dependent genes, despite decreased brain triiodothyronine (T3)., [Methods]: The relative effects of T4 and T3 on gene expression were analyzed in mouse neuro-2a (N2a) cells stably expressing the thyroid hormone receptor α1, and in primary mouse cerebrocortical cells enriched in astrocytes or in neurons. Cortical cells were derived from Dio2-deficient mice to prevent conversion of T4 to T3. T4 and T3 were measured in the media at the beginning and end of incubation, and T4 and T3 antibodies were used to block T4 and T3 action., [Results]: In all cell types, T4 had intrinsic genomic activity. In N2a cells, T4 activity was higher on negative regulation (1/5th of T3 activity) than on positive regulation (1/40th of T3 activity). T4 activity on positive regulation was dependent on the cell context, and was higher in primary cells than in N2a cells., [Conclusion]: T4 has intrinsic genomic activity. Positive regulation depends on the cell context, and primary cells appear much more sensitive than neuroblastoma cells. In all cells, negative regulation is more sensitive to T4 than positive regulation. These properties may explain the mostly normal gene expression in the brain of Dio2-deficient mice., This work was supported by the Center for Biomedical Research on Rare Diseases (Ciberer) under the frame of E-Rare-2 (project acronym THYRONERVE), the ERA-Net for Research on Rare Diseases; grant SAF2014-54919R from Plan Estatal de Investigación Científica, Técnica y de Innovación, Ministerio de Economía y Competititividad, and FEDER funds.

The male of Ixodes tapirus Kohls, 1956 (Acari: Ixodidae) is described for the first time and the female is redescribed in greater detail. Adults of I. tapirus are similar to those of Ixodes guatemalensis Kohls, 1956, Ixodes lasallei Méndez & Ortiz, 1958, Ixodes montoyanus Cooley, 1944 and Ixodes venezuelensis Kohls, 1953 but can be distinguished by their overall size, the amount of sclerotisation of the conscutum and accessory plates, the shape of the scutum, the number of punctations and their pattern on the conscutum and scutum, the depth of the punctations on the basis capituli dorsally, the shape and size of the porose areas and the size and shape of the auriculae. Adults of I. tapirus were collected from tapirs and vegetation in the mountains of Colombia, Panama and recorded from Costa Rica for the first time. El macho de Ixodes tapirus Kohls, 1956 (Acari: Ixodidae) se describe por primera vez y la hembra se redescribe con mayor detalle. Los adultos de I. tapirus son similares a los de Ixodes guatemalensis Kohls, 1956, Ixodes lasallei Méndez y Ortiz, 1958, Ixodes montoyanus Cooley, 1944 e Ixodes venezuelensis Kohls, 1953, pero pueden distinguirse por su tamaño total, la cantidad de esclerotización de la conscutum y placas accesorias, la forma del scutum, el número de punciones y su patrón en el conscutum y el scutum, la profundidad de las punciones en la base capitular dorsalmente, la forma y el tamaño de las áreas porosas y el tamaño y la forma del aurículas. Se recolectaron adultos de I. tapirus de tapires y vegetación en las montañas de Colombia, Panamá y se registraron en Costa Rica por primera vez. Universidad Nacional, Costa Rica Universidad Nacional, Costa Rica

espanolLas plantas hospedantes de huevos y ninfas de Bemisia tabaci (Gennadius), totalizaron 16 especies agrupadas en 11 familias, las que fueron muestreadas y recolectadas en areas adyacentes a las parcelas de produccion de tomate. Este estudio se realizo en la localidad de "La Mesa de San Martin", en la region este de Panama, mediante evaluaciones trimestrales realizadas entre mayo de 2013 y junio de 2014. Se realizaron muestreos aleatorios que constaron de 15 puntos de recoleccion de 1 m², evaluandose el numero de huevos y ninfas de este insecto vector de begomovirus, en cinco hojas o foliolos en los estratos superior, medio e inferior de las plantas. La superficie total muestreada por hoja o foliolo de la planta hospedante fue de 1.000 cm². La mayor incidencia de huevos y ninfas de B. tabaci se registro en Guazuma ulmifolia Lam., Jatropha gossypifolia L., Solanum torvum Sw., Jatropha urens L. y Physalis angulata L. Se discutio el papel de las plantas hospedantes de B. tabaci en la diseminacion de begomovirus y el manejo de esta interaccion biotica en las areas de produccion de tomate. EnglishThe hosts plants of eggs and nymphs of Bemisia tabaci (Gennadius), totaled 16 species grouped in 11 families, which were sampled and collected in adjacent areas to the plots of tomato production. This study was conducted in the locality of "La Mesa de San Martin", in the East region of Panama, through quarterly assessments carried out between May of 2013 and June 2014. Is per-formed random sampling that consisted of 15 points of 1 m², assessing the numbers of eggs and the nymphs of this insect vector of begomovirus, in five leaves or leaflets in the upper, medium and lower level of the plants. The total area sampled by leaf or leaflet of the host plant was 1,000 cm². The greater incidence of eggs and nymphs of B. tabaci is recorded in Guazuma ulmifolia Lam., Jatropha gossypifolia L., Solanum torvum Sw., Jatropha urens L. and Physalis angulata L. Discussed the role of the host plants of B. tabaci in the begomovirus spread and the management of this biotic interaction in the areas of tomato production.

et al., Monocarboxylate transporter 8 (MCT8) deficiency causes severe X-linked intellectual and neuropsychological impairment associated with abnormal thyroid function tests (TFTs) producing thyroid hormone (TH) deprivation in brain and excess in peripheral tissues. The TH analog diiodothyropropionic acid (DITPA) corrected the TFTs abnormalities and hypermetabolism of MCT8- deficient children but did not improve the neurological phenotype. The latter result was attributed to the late initiation of treatment. Therefore, we gave DITPA to pregnant mice carrying Mct8- deficient embryos to determine whether DITPA, when given prenatally, crosses the placenta and affects the serum TFTs and cerebral cortex of embryos. After depletion of the endogenous TH, Mct8-heterozygous pregnant dams carrying both wild-type (Wt) and Mct8-deficient (Mct8KO) male embryos were given DITPA. Effects were compared with those treated with levothyroxine (L-T4). With DITPA treatment, serum DITPA concentration was not different in the two genotypes, which produced equal effect on serum TSH levels in both groups of pups. In contrast, with L-T4treatment, TSH did not normalize in Mct8KO pups whereas it did in the Wt littermates and dams despite higher concentration of serum T4. Finally, both treatments similarly modulated the expression of the TH-dependent genes Shh, Klf9, and Aldh1a3 in brain. Thus, the ability of DITPA to cross the placenta, its thyromimetic action on the expression of TH-dependent genes in brain, and its better accessibility to the pituitary than L-T4, as assessed by serum TSH, make DITPA a candidate for the prenatal treatment of MCT8 deficiency., This work was supported in part by Grants DK15070 from the National Institute of Diabetes and Digestive and Kidney Diseases; the Sherman family, Grant SAF2011–25608, Ciberer IS Carlos III, Spain and Esformes Endowment. A.M.F. receives support from “5 per mille” Istituto Oncologico Veneto, Padova, Italy. A.M.D. was supported by a National Institutes of Health Grant F32 DK,91016, and P.G.-I. was a recipient of a Junta de Ampliación de Estudios (JAE), Consejo Superior de Investigaciones Cientificas (CSIC), Spain.

The physiological and developmental effects of thyroid hormones are mainly due to the control of gene expression after interaction of T with the nuclear receptors. To understand the role of thyroid hormones on cerebral cortex development, knowledge of the genes regulated by T during specific stages of development is required. In our laboratory, we previously identified genes regulated by T in primary cerebrocortical cells in culture. By comparing these data with transcriptomics of purified cell types from the developing cortex, the cellular targets of T can be identified. In addition, many of the genes regulated transcriptionally by T have defined roles in cortex development, from which the role of T can be derived. This review analyzes the specific roles of T-regulated genes in the different stages of cortex development within the physiological frame of the developmental changes of thyroid hormones and receptor concentrations in the human cerebral cortex during fetal development. These data indicate an increase in the sensitivity to T during the second trimester of fetal development. The main cellular targets of T appear to be the Cajal-Retzius and the subplate neurons. On the other hand, T regulates transcriptionally genes encoding extracellular matrix proteins, involved in cell migration and the control of diverse signaling pathways., Supported with grants SAF2014-54919-R from the Ministry of Economy and Competitivity and the Center for Biomedical Research on Rare Diseases (CIBERER) under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, and by FEDER funds.