Differential effects of testosterone,dihydrotestosterone and estradiol on carotenoid deposition in an avian sexually selected signal

Recent studies have demonstrated that carotenoid-based traits are under the control of testosterone (T) by up-regulation of carotenoid carriers (lipoproteins) and/or tissue-specific uptake of carotenoids. T can be converted to dihydrotestosterone (DHT) and estradiol (E2), and variation in conversion rate may partly explain some contradictory findings in the literature. Moreover, most studies on the effect of T on sexual signals have focused on the male sex only, while in many species females show the same signal, albeit to a lesser extent. We studied the effects of T, DHT, and E2 treatment in male and female diamond doves Geopelia cuneata in which both sexes have an enlarged red eye ring, which is more pronounced in males. We first showed that this periorbital ring contains very high concentration of carotenoids, of which most are lutein esters. Both T and DHT were effective in enhancing hue, UV-chroma and size in both sexes, while E2 was ineffective. However, E2 dramatically increased the concentration of circulating lipoproteins. We conclude that in both sexes both color and size of the secondary sexual trait are androgen dependent. The action of androgens is independent of lipoproteins regulation. Potential mechanisms and their consequences for trade-off are discussed.     

HDACs, histone deacetylation and gene transcription： from molecular biology to cancer therapeutics

Histone deacetylases （HDACs） and histone acetyl transferases （HATs） are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.     

The evolution of the Cercopithecini: a (post)modern synthesis

The Cercopithecini, or African guenon monkeys, are one of the most diverse clades of living primates and comprise the most species‐rich clade of Catarrhini. Species identity is announced by flamboyant coloration of the facial and genital regions and, more cryptically, by vigorous chromosomal rearrangements among taxa. Beneath the skin, however, these animals are skeletally conservative and show low levels of genetic sequence divergence consonant with recent divergence between congeneric species. The guenons clearly demonstrate that morphological, cytogenetic, and reproductive differentiation proceed at different rates during speciation. We review diverse kinds of data in an effort to understand this conundrum.     

Safety and Tolerability of Conserved Region Vaccines Vectored by Plasmid DNA,Simian Adenovirus and Modified Vaccinia Virus Ankara Administered to Human Immunodeficiency Virus Type 1-Uninfected Adults in a Randomized,Single-Blind Phase I Trial

Trial Design

HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.

Methods

Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.

Results

Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern.

Conclusions

These data demonstrate safety and good tolerability of the pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines and together with their high immunogenicity support their further development towards efficacy studies.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01151319","term_id":"NCT01151319"}}NCT01151319     

Polymorphism of a new Ty1-copia retrotransposon in durum wheat under salt and light stresses

Long terminal repeat retrotransposons are the most abundant mobile elements in the plant genome and play an important role in the genome reorganization induced by environmental challenges. Their success depends on the ability of their promoters to respond to different signaling pathways that regulate plant adaptation to biotic and abiotic stresses. We have isolated a new Ty1-copia-like retrotransposon, named Ttd1a from the Triticum durum L. genome. To get insight into stress activation pathways in Ttd1a, we investigated the effect of salt and light stresses by RT-PCR and S-SAP profiling. We screened for Ttd1a insertion polymorphisms in plants grown to stress and showed that one new insertion was located near the resistance gene. Our analysis showed that the activation and mobilization of Ttd1a was controlled by salt and light stresses, which strengthened the hypothesis that stress mobilization of this element might play a role in the defense response to environmental stresses.     

Cell Penetrating Apidaecin Peptide Interactions with Biomimetic Phospholipid Membranes

Apidaecin peptides from Apis mellifera hemolymph are believed to attack intracellular bacterial targets. Our in vivo results for apidaecins 1a and 1b confirm that bacterial activity is non-lytic, however, the manner in which these peptides pass through the cell membrane to exert this activity is unknown. These data are combined with fluorescence (dye leakage) and quartz crystal microbalance studies to investigate the membrane interaction for these two wildtype peptides. It was found that the peptides penetrate the membrane in a trans-membrane manner. The amount of peptide uptake by the membrane is proportional to the concentration of the peptide, however, this appears to be a dynamic equilibrium which can be almost completely reversed by addition of buffer medium. Interestingly, a small residual mass remains within the membrane and the amount of peptide remaining in the membrane is a function of the buffer-salt concentration viz. in high salt, the residual peptide mass remaining is small whereas at low salt concentration, a larger mass of peptide remains bound. These results support a direct membrane penetration mechanism by the wild type apidaecins 1a and 1b. In both cases the peptide–membrane interaction has a negligible effect on the membrane, although, in high salt a permanent change in the membrane does occur at the highest peptide concentration which does not recover following peptide removal. Stefania Piantavigna and Patricia Czihal contributed equally to this article.     

Proteomic profiling during atherosclerosis progression: Effect of nebivolol treatment

There is a great need for the identification of biomarkers for the early diagnosis of atherosclerosis and the agents to prevent its progression. The aim of this study was to explore the effect of 24 week of nebivolol (a third-generation vasodilatory beta-blocker) treatment on serum protein profiles in Apo E^?/? mice during atherosclerosis progression. Nebivolol treated and non-treated (the control group) groups consisted of 10 genetically modified homozygous Apo E^?/? mice. Proteomic analyses were performed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) in the serum samples from the nebivolol treated and non-treated Apo E^?/? mice. The protein profiles obtained using three different chips, CM10 (weak cation-exchange), H50 (reverse phase), and IMAC30-Cu²⁺ (immobilized metal affinity capture) were statistically analyzed using the ProteinChip data manager 3.0 program. At the end of 24 week of nebivolol-treatment period, a total of 662 protein/peptide clustering peaks were detected using 12 different conditions and reading with high and low intensity laser energy. The highest total number of protein/peptide clusters was found on H50 chip array. The peak intensities of 95 of the 662 protein/peptide clusters were significantly different in the nebivolol-treated atherosclerotic group in comparison to the non-treated control mice groups (P < 0.05). Forty-three protein/peptides were up-regulated (high signal intensity) while 52 protein/peptides had lower signal intensity (down-regulated) in the nebivolol-treated atherosclerotic group. The proteomic profiles of nebivolol-treated Apo E^?/? mice were different than the control group indicating a potential role of nebivolol in atherosclerosis. Our study contributes to understand the efficacy of nebivolol on serum protein/peptide profiles during atherosclerosis development.     

Regulation of Gdnf expression by retinoic acid in Sertoli cells

Glial cell line‐derived neurotrophic factor (GDNF) and retinoic acid (RA) are two molecules crucial for the regulation of the spermatogonial compartment of the testis. During the cycle of the seminiferous epithelium, their relative concentration oscillates with lower GDNF levels in stages where RA levels are high. It has been recently shown that RA negatively regulates Gdnf expression but the mechanisms behind are so far unknown. Here, we show that RA directly downregulates Gdnf mRNA levels in primary murine Sertoli cells through binding of RARα to a novel DR5‐RARE on Gdnf promoter. Pharmacological inhibition and chromatin immunoprecipitation–quantitative polymerase chain reaction analysis suggested that the underlying mechanism involved histone deacetylase activity and epigenetic repression of Gdnf promoter upon RA treatment.     

Ubiquitin Carboxy-Terminal Hydrolase L1 (UCH-L1) is increased in cerebrospinal fluid and plasma of patients after epileptic seizure

ABSTRACT: BACKGROUND: Clinical and experimental studies have demonstrated that seizures can cause molecular and cellular responses resulting in neuronal damage. At present, there are no valid tests for assessing organic damage to the brain associated with seizure. The aim of this study was to investigate cerebrospinal fluid (CSF) and plasma concentrations of Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a sensitive indicator of acute injury to brain neurons, in patients with tonic--clonic or partial secondarily generalized seizures due to various etiologies. METHODS: CSF and plasma concentrations of UCH-L1 were assessed in 52 patients within 48 hours after epileptic seizure and in 19 controls using ELISA assays. RESULTS: CSF obtained within 48 hours after seizure or status epilepticus (SE) presented significantly higher levels of UCH-L1 compared to controls (p = 0.008). Plasma UCH-L1 concentrations were negatively correlated with time to sample withdrawal. An analysis conducted using only the first 12 hours post-seizure revealed significant differences between concentrations of UCH-L1 in plasma and controls (p = 0.025). CSF and plasma concentrations were strongly correlated with age in patients with seizure, but not in control patients. Plasma UCH-L1 levels were also significantly higher in patients after recurrent seizures (n = 4) than in those after one or two seizures (p = 0.013 and p = 0.024, respectively). CONCLUSION: Our results suggest that determining levels of neuronal proteins may provide valuable information on the assessment of brain damage following seizure. These data might allow clinicians to make more accurate therapeutic decisions, to identify patients at risk of progression and, ultimately, to provide new opportunities for monitoring therapy and targeted therapeutic interventions.