Glyphosate-based herbicide induces long-lasting impairment in neuronal and glial differentiation.

Glyphosate-based herbicides (GBH) are among the most sold pesticides in the world. There are several formulations based on the active ingredient glyphosate (GLY) used along with other chemicals to improve the absorption and penetration in plants. The final composition of commercial GBH may modify GLY toxicological profile, potentially enhancing its neurotoxic properties.

A patent review of the antimicrobial applications of lectins: Perspectives on therapy of infectious diseases.

Patents of lectins with antiviral, antibacterial and antifungal applications were searched and reviewed. Lectins are proteins that reversibly bind to specific carbohydrates and have the potential for therapy of infectious diseases as biopharmaceuticals, biomedical tools or in drug design. Given the rising concerns over drug resistance and epidemics, our patent review aims to add information, open horizons and indicate our view of the future perspectives about the antimicrobial applications of lectins.

Analyzing the toxicity of bisphenol-A to microalgae for ecotoxicological applications.

Bisphenol-A (BPA) is a chemical used in the production of polycarbonate plastic and epoxy resins that may be related to the occurrence of human endocrine disorders. The present study aims to indicate a microalgae for use in ecotoxicological tests concerning BPA contamination of aquatic environments by analyzing its toxicity for the freshwater species Pseudokirchneriella subcapitata, and the two marine species Tetraselmis chuii and Skeletonema costatum. The standardization of the test involved determination of suitable nominal concentrations of BPA and the most appropriate species for use as biomarkers.

Production and characterization of Spirulina sp. LEB 18 cultured in reused Zarrouk's medium in a raceway-type bioreactor.

The objective was to evaluate the effect of reusing Zarrouk's medium on a Spirulina sp. LEB 18 culture by determining kinetic parameters, chemical composition, biofuels, and thermal characterization. Cultivation was performed in a raceway bioreactor for 7 days, the supernatant was reused for four cycles.

Estrogen and Thyroid Hormone Receptor Activation by Medicinal Plants from Bahia, Brazil.

: A number of medicinal plants are traditionally used for metabolic disorders in Bahia state, Brazil. The aim of this study was to evaluate the estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts prepared from 20 plants. : Species were extracted and assayed for receptor activation through both ER and TR gene-reporter assays, using 17β-estradiol and triiodothyronine (T3), respectively, as the positive controls.

The oligomeric state of thyroid receptor regulates hormone binding kinetics.

We previously reported that mutations in the thyroid hormone receptor (TR) surface that mediates dimer and heterodimer formation do not alter affinity for cognate hormone (triiodothyronine (T(3))) yet dramatically enhance T(3) association and dissociation rates. This study aimed to show that TR oligomeric state influences binding and dissociation kinetics. We performed binding assays using marked hormone ((125)I-T(3)) and TRs expressed and purified by different methods.

Differential effects of TR ligands on hormone dissociation rates: evidence for multiple ligand entry/exit pathways.

Some nuclear receptor (NR) ligands promote dissociation of radiolabeled bound hormone from the buried ligand binding cavity (LBC) more rapidly than excess unlabeled hormone itself. This result was interpreted to mean that challenger ligands bind allosteric sites on the LBD to induce hormone dissociation, and recent findings indicate that ligands bind weakly to multiple sites on the LBD surface. Here, we show that a large fraction of thyroid hormone receptor (TR) ligands promote rapid dissociation (T(1/2)<2h) of radiolabeled T(3) vs.

Thyroxine-thyroid hormone receptor interactions.

Thyroid hormone (TH) actions are mediated by nuclear receptors (TRs alpha and beta) that bind triiodothyronine (T(3), 3,5,3'-triiodo-l-thyronine) with high affinity, and its precursor thyroxine (T(4), 3,5,3',5'-tetraiodo-l-thyronine) with lower affinity. T(4) contains a bulky 5' iodine group absent from T(3). Because T(3) is buried in the core of the ligand binding domain (LBD), we have predicted that TH analogues with 5' substituents should fit poorly into the ligand binding pocket and perhaps behave as antagonists.

Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor.

Selective therapeutics for nuclear receptors would revolutionize treatment for endocrine disease. Specific control of nuclear receptor activity is challenging because the internal cavities that bind hormones can be virtually identical. Only one highly selective hormone analog is known for the thyroid receptor, GC-24, an agonist for human thyroid hormone receptor beta.

Design of thyroid hormone receptor antagonists from first principles.

It is desirable to obtain TR antagonists for treatment of hyperthyroidism and other conditions. We have designed TR antagonists from first principles based on TR crystal structures. Since agonist ligands are buried in the fold of the TR ligand binding domain (LBD), we reasoned that ligands that resemble agonists with large extensions should bind the LBD, but would prevent its folding into an active conformation.

Two resistance to thyroid hormone mutants with impaired hormone binding.

Resistance to hormones is commonly due to mutations in genes encoding receptors. Resistance to thyroid hormone is due mostly to mutations of the beta-form of the human (h) thyroid hormone receptor (hTRbeta). We determined x-ray crystal structures of two hTRbeta ligand-binding domains (LBDs), Ala 317 Thr and Arg 316 His.

Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain.

Resistance to thyroid hormone (RTH) syndrome is associated with mutations in the human thyroid hormone receptor-beta (hTRbeta), many of which show marked reduction in hormone binding. Here, we investigated the structural consequences of two RTH mutants (A234T and R243Q), residing in the flexible N-terminal portion of the ligand binding domain (LBD), which exhibit modestly reduced hormone binding with impaired release of corepressor. X-ray crystallography analyses revealed that these two RTH mutants modulate the position of this flexible region by either altering the movement of helix 1 (A234T) or disrupting a salt bridge (R243Q).

Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment.

Recent efforts have focused on the design and synthesis of thyroid hormone (T(3)) antagonists as potential therapeutic agents and chemical probes to understand hormone-signaling pathways. We previously reported the development of novel first-generation T(3) antagonists DIBRT, HY-4, and GC-14 using the "extension hypothesis" as a general guideline in hormone antagonist design.(1-3) These compounds contain extensions at the 5'-position (DIBRT, GC-14) of the outer thyronine ring or from the bridging carbon (HY-4).