Molecular responce of Atlantic cod's (Gadus morhua L.) cypia, prolactin and Zona radiata genes upon exposure to polychlorinated biphenyls

A molecular response study was conducted to determine whether Polychlorinated Biphenyl or PCB (Clophen A40) had an effect on the induction of the zona radiata, prolactin and cytochrome P4501A (CYP1A) mRNAs in matured Atlantic cod (Gadus morhua). A total of 127 fishes were maintained under natural photoperiod in tanks and fed with wet pellets containing Clophen A40. RNA samples were taken from the gonads, pituitary and the liver from day 0, 48 and 105 after sacrificing the fish and stored at -20OC prior to analysis. Analysis of gene induction by Northern hybridization assay showed the induction of prolactin and CYP1A in the pituitary and the liver tissues respectively after PCB treatment. The induction was found to be sex, age and seasonal specific. Males had greater gene expression than the females. There was however, no observed differences between the controlled and exposed fishes in terms of zona radiata gene expression. Although the picture is far from complete, the findings demonstrate the potential of using gene induction as a biomarker of aquatic pollution.Keywords: Cytochrome P4501A, Biomarker, Gene expressio

Spectral fluctuations of tridiagonal random matrices from the beta-Hermite ensemble

A time series delta(n), the fluctuation of the nth unfolded eigenvalue was recently characterized for the classical Gaussian ensembles of NxN random matrices (GOE, GUE, GSE). It is investigated here for the beta-Hermite ensemble as a function of beta (zero or positive) by Monte Carlo simulations. The fluctuation of delta(n) and the autocorrelation function vary logarithmically with n for any beta>0 (1<<n<<N). The simple logarithmic behavior reported for the higher-order moments of delta(n) for the GOE (beta=1) and the GUE (beta=2) is valid for any positive beta and is accounted for by Gaussian distributions whose variances depend linearly on ln(n). The 1/f noise previously demonstrated for delta(n) series of the three Gaussian ensembles, is characterized by wavelet analysis both as a function of beta and of N. When beta decreases from 1 to 0, for a given and large enough N, the evolution from a 1/f noise at beta=1 to a 1/f^2 noise at beta=0 is heterogeneous with a ~1/f^2 noise at the finest scales and a ~1/f noise at the coarsest ones. The range of scales in which a ~1/f^2 noise predominates grows progressively when beta decreases. Asymptotically, a 1/f^2 noise is found for beta=0 while a 1/f noise is the rule for beta positive.Comment: 35 pages, 10 figures, corresponding author: G. Le Cae

Biokonsentrasi dan Bioakumulasi Mercury (Hg) Pada Lamun Enhalus Acoroides Di Teluk Kayeli Kabupaten Buru Provinsi Maluku

Gold reserves on Gunung Botak (Bald Mountain), Buru Island, were discovered in 2011. Since then, thousands of illegal miners have used amalgamation methods to extract gold in the areas of Gunung Botak and Gogrea, Buru Island. The resulting waste is disposed of into the environment directly without any treatment process so it is very dangerous for humans and the environment. This research was conducted to determine the ability of the Enhalus acoroides type of seagrass to accumulate heavy metal mercury (Hg) in the aquatic environment. This research shows that the heavy metal mercury has been distributed in the water sediments along Kayeli Bay. Mercury bio-concentration (accumulation) Gunung Botak, Kayeli Bay, Mercury (Hg), bioconcenstration, Seagrass, Enhalus acoroides, Kayeli Baywas found in Enhalus acoroides seagrass, in leaves (0.0243-0.0373 mg/Kg), and in rhizomes (0.0453-0.0663 mg/Kg). This result shows that the Kayeli Bay ecosystem has been contaminated with mercury

A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions [version 1; referees: 2 approved with reservations]

The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity. Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

Hedgehog signaling is necessary and sufficient to mediate craniofacial plasticity in teleosts

Phenotypic plasticity, the ability of a single genotype to produce multiple phenotypes under different environmental conditions, is critical for the origins and maintenance of biodiversity; however, the genetic mechanisms underlying plasticity as well as how variation in those mechanisms can drive evolutionary change remain poorly understood. Here, we examine the cichlid feeding apparatus, an icon of both prodigious evolutionary divergence and adaptive phenotypic plasticity. We first provide a tissue-level mechanism for plasticity in craniofacial shape by measuring rates of bone deposition within functionally salient elements of the feeding apparatus in fishes forced to employ alternate foraging modes. We show that levels and patterns of phenotypic plasticity are distinct among closely related cichlid species, underscoring the evolutionary potential of this trait. Next, we demonstrate that hedgehog (Hh) signaling, which has been implicated in the evolutionary divergence of cichlid feeding architecture, is associated with environmentally induced rates of bone deposition. Finally, to demonstrate that Hh levels are the cause of the plastic response and not simply the consequence of producing more bone, we use transgenic zebrafish in which Hh levels could be experimentally manipulated under different foraging conditions. Notably, we find that the ability to modulate bone deposition rates in different environments is dampened when Hh levels are reduced, whereas the sensitivity of bone deposition to different mechanical demands increases with elevated Hh levels. These data advance a mechanistic understanding of phenotypic plasticity in the teleost feeding apparatus and in doing so contribute key insights into the origins of adaptive morphological radiations

Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro

The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier