Developmental Exposure to Endocrine Disrupter DDT Interferes with Age-Related Involution of Thymus

The impact of endocrine-disrupting chemicals on the development and involution of the immune system is a possible reason for the increased incidence of disorders associated with inappropriate immune function. The thymus is a lymphoid and also an endocrine organ, and, accordingly, its development and functioning may be impaired by endocrine disruptors. The aim was to evaluate age-related thymus involution in mature rats exposed to the endocrine disruptor DDT during prenatal and postnatal ontogeny. Methodology included in vivo experiment on male Wistar rats exposed to low doses of DDT during prenatal and postnatal development and morphological assessment of thymic involution, including the immunohistochemical detection of proliferating thymocytes. The study was carried out at the early stage of involution. Results: DDT-exposed rats exhibited a normal anatomy, and the relative weight of the thymus was within the control ranges. Histological and immunohistochemical examinations revealed increased cellularity of the cortex and the medulla, higher content of lymphoblasts, and more intensive proliferation rate of thymocytes compared to the control. Evaluation of thymic epithelial cells revealed a higher rate of thymic corpuscles formation. Conclusion: The data obtained indicate that endocrine disrupter DDT disturbs postnatal development of the thymus. Low-dose exposure to DDT during ontogeny does not suppress growth rate but violates the developmental program of the thymus by slowing down the onset of age-related involution and maintaining high cell proliferation rate. It may result in excessive formation of thymus-dependent areas in peripheral lymphoid organs and altered immune response.     

A Simple Approach for the Formation of Oxides,Sulfides, and Oxide–Sulfide Hybrid Nanostructures

The synthesis of various types of metal oxide and metal sulfide nanostructures through the thermal decomposition of single-source molecular precursors is presented. By varying the reaction conditions, such as solvent, precursor concentration, temperature, and time, we were able to control the shape of Fe₃O₄ (rectangles and belt-like structures), CoO nanofibers, and SnO₂ nanowires. Two sulfides are also presented: CdS filling a vertically aligned ZnO nanowire array (to create a hybrid structure) and SnS wires. The formation of various phases of iron oxide and cobalt oxide is also shown.     

Experience matters: The impact of doing versus watching on infants' subsequent perception of tool-use events.

Prior work suggests that active experience affects infants' understanding of simple actions. The present studies compared the impact of active and observational experience on infants' ability to identify the goal of a novel tool-use event. Infants either received active training and practice in using a cane to retrieve an out-of-reach toy or had matched observational experience before taking part in a habituation paradigm that we used to assess infants' ability to identify the goal of another person's tool-use acts. Active training alone facilitated 10-month-old infants' ability to identify the goal of the tool-use event. Active experience using tools may enable infants to build motor representations of tool-use events that subsequently guide action perception and support action understanding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structural and Dynamical Insight into PPARγ Antagonism: In Silico Study of the Ligand-Receptor Interactions of Non-Covalent Antagonists

The structural and dynamical properties of the peroxisome proliferator-activated receptor γ (PPARγ) nuclear receptor have been broadly studied in its agonist state but little is known about the key features required for the receptor antagonistic activity. Here we report a series of molecular dynamics (MD) simulations in combination with free energy estimation of the recently discovered class of non-covalent PPARγ antagonists. Their binding modes and dynamical behavior are described in details. Two key interactions have been detected within the cavity between helices H3, H11 and the activation helix H12, as well as with H12. The strength of the ligand-amino acid residues interactions has been analyzed in relation to the specificity of the ligand dynamical and antagonistic features. According to our results, the PPARγ activation helix does not undergo dramatic conformational changes, as seen in other nuclear receptors, but rather perturbations that occur through a significant ligand-induced reshaping of the ligand-receptor and the receptor-coactivator binding pockets. The H12 residue Tyr473 and the charge clamp residue Glu471 play a central role for the receptor transformations. Our results also demonstrate that MD can be a helpful tool for the compound phenotype characterization (full agonists, partial agonists or antagonists) when insufficient experimental data are available.     

C?C Hydrolases for Biocatalysis

Although C C bond hydrolases are distributed widely in Nature, they has as yet have received only limited attention in the area of biocatalysis compared to their counterpart the C‐heteroatom hydrolases, such as lipases and proteases. However, the substrate range of C C hydrolases, and their non‐dependence on cofactors, suggest that these enzymes may have considerable potential for applications in synthesis. In addition, hydrolases such as the β‐diketone hydrolase from Rhodococcus (OCH) are known, that catalyse the formation of interesting chiral intermediates. Further enzymes, such as kynureninase and a meta‐cleavage product hydrolase (MhpC), are able to catalyse carbon‐carbon bond formation, suggesting wider applications in biocatalysis than previously envisaged. In this review, the distribution, catalytic characteristics and applications of C C hydrolases are described, with a view to assessing their potentialfor use in biocatalytic processes in the future.     

Definitions of Normal Liver Fat and the Association of Insulin Sensitivity with Acquired and Genetic NAFLD—A Systematic Review

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disease ranging from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) and fibrosis. “Obese/Metabolic NAFLD” is closely associated with obesity and insulin resistance and therefore predisposes to type 2 diabetes and cardiovascular disease. NAFLD can also be caused by common genetic variants, the patatin-like phospholipase domain-containing 3 (PNPLA3) or the transmembrane 6 superfamily member 2 (TM6SF2). Since NAFL, irrespective of its cause, can progress to NASH and liver fibrosis, its definition is of interest. We reviewed the literature to identify data on definition of normal liver fat using liver histology and different imaging tools, and analyzed whether NAFLD caused by the gene variants is associated with insulin resistance. Histologically, normal liver fat content in liver biopsies is most commonly defined as macroscopic steatosis in less than 5% of hepatocytes. In the population-based Dallas Heart Study, the upper 95th percentile of liver fat measured by proton magnetic spectroscopy (¹H-MRS) in healthy subjects was 5.6%, which corresponds to approximately 15% histological liver fat. When measured by magnetic resonance imaging (MRI)-based techniques such as the proton density fat fraction (PDFF), 5% macroscopic steatosis corresponds to a PDFF of 6% to 6.4%. In contrast to “Obese/metabolic NAFLD”, NAFLD caused by genetic variants is not associated with insulin resistance. This implies that NAFLD is heterogeneous and that “Obese/Metabolic NAFLD” but not NAFLD due to the PNPLA3 or TM6SF2 genetic variants predisposes to type 2 diabetes and cardiovascular disease.     

Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury

We assessed the effect of antioxidant therapy using the Food and Drug Administration-approved respiratory drug N-acetylcysteine (NAC) or sulforaphane (SFN) as monotherapies or duotherapy in vitro in neuron-BV2 microglial co-cultures and validated the results in a lateral fluid-percussion model of TBI in rats. As in vitro measures, we assessed neuronal viability by microtubule-associated-protein 2 immunostaining, neuroinflammation by monitoring tumor necrosis factor (TNF) levels, and neurotoxicity by measuring nitrite levels. In vitro, duotherapy with NAC and SFN reduced nitrite levels to 40% (p < 0.001) and neuroinflammation to –29% (p < 0.001) compared with untreated culture. The treatment also improved neuronal viability up to 72% of that in a positive control (p < 0.001). The effect of NAC was negligible, however, compared with SFN. In vivo, antioxidant duotherapy slightly improved performance in the beam walking test. Interestingly, duotherapy treatment decreased the plasma interleukin-6 and TNF levels in sham-operated controls (p < 0.05). After TBI, no treatment effect on HMGB1 or plasma cytokine levels was detected. Also, no treatment effects on the composite neuroscore or cortical lesion area were detected. The robust favorable effect of duotherapy on neuroprotection, neuroinflammation, and oxidative stress in neuron-BV2 microglial co-cultures translated to modest favorable in vivo effects in a severe TBI model.     

Concave π-prismand hydrocarbon [2.2.2]cyclophanes and their crystalline Ag-triflate complexes

New small concave hydrocarbon cyclophanes were prepared via the well-known HD-2SO₂-method. The cyclophanes obtained are isomers of the very well-known [2.2.2]p,p,p-cyclophane, C₂₄H₂₄, a π-prismand efficiently complexing Ag⁺-ion. X-ray crystal structure determinations showed the bis-sulfide 7 (1,10-dithia[3.3.2]m,p,p-cyclophane) to be helically chiral and that the conformation of the parent hydrocarbon cyclophane 13 ([2.2.2]m,p,p-cyclophane) does not change dramatically upon complexation with the Ag⁺-ion. The 16- and 17-membered [2.2.2]m,m,p- and [2.2.2]m,p,p-cyclophane ( 15 and 16 ) also act as π-prismands and form surprisingly similar crystalline 1:1 Ag-triflate complexes (π-prismates) as the well-known 18-membered p,p,p-isomer proved by the X-ray structure analysis.     

A new device to expose cells to changing dose rates of ionising radiation

In many exposure scenarios to ionising radiation, the dose rate is not constant. Despite this, most in vitro studies aimed at investigating the effects of ionising radiation are carried out exposing samples at constant dose rates. Consequently, very little data exist on the biological effects of exposures to changing dose rates. This may be due to technical limitations of standard irradiation facilities, but also to the fact that the importance of research in this area has not been appreciated. We have recently shown that cells exposed to a decreasing dose rate suffer higher levels of cytogenetic damage than do cells exposed to an increasing or a constant dose rate. To further study the effects of changing dose rates, a new device was constructed that permits the exposure of cell samples in tubes, flasks or Petri dishes to changing dose rates of X-rays. This report presents the technical data, performance and dosimetry of this novel device.