A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53

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Cross talk between angiotensin-(1–7)/Mas axis and sirtuins in adipose tissue and metabolism of high-fat feed mice

Angiotensin-(1–7) and resveratrol have been described as new potential therapeutic tools on treating and preventing metabolic disorders. In the present study we aimed to evaluate the effect of an oral formulation of angiotensin-(1–7) [Ang-(1–7)] included in HPB-cyclodextrin and resveratrol (RSV), in modulation of sirtuin and renin-angiotensin system (RAS) in adipose tissue of mice treated with a high-fat diet (HFD). We observed that HFD + Ang-(1–7) and HFD + RSV groups presented marked decrease in the adipose tissue mass. Furthermore, these animals showed improved insulin-sensitivity and glucose tolerance as well as lower plasma levels of fasting glucose and lipids. The RT-PCR analysis revealed decreased expression of ACE and an increase of ACE2 [Ang-(1–7) marker] in group treated with resveratrol and also an increased expression of SIRT1 in groups that received Ang-(1–7). We showed for the first time that improved metabolic profile is associated with increased expression of GLUT4 and high expression of AMPK/FOXO1/PPAR-γ pathway in adipose-tissue. Finally, adipocyte primary cell-culture incubated with and without sirtuin and Ang-(1–7)/Mas antagonists pointed out for a cross-talking between RAS and sirtuins. We conclude that oral administration of Ang-(1–7) and RSV improved metabolic profile through a cross-modulation between RAS and Sirtuins.     

Antigens Associated with N- and L-Type Calcium Channels in Lambert-Eaton Myasthenic Syndrome

Abstract: In Lambert-Eaton myasthenic syndrome neurotransmitter release is reduced by an autoimmune response directed against the calcium channel complex of the nerve terminal. Autoantibodies were detected by immunoprecipitation assays using solubilized receptors labeled with ligands selective for N-type (¹²⁵I-ω conotoxin GVIA) and L-type ([³H]PN200-110) calcium channels. Sera with a high antibody titer (>3 n M ) against rat brain N-type channels contained autoantibodies that immunoprecipitated neuronal and muscle L-type channels. These IgG fractions stained a 55-kDa protein in immunoblots of purified skeletal muscle dihydropyridine receptor, suggesting that they contain autoantibodies against the β subunit of the calcium channel. A distinct antibody population in the same fractions reacted with a nerve terminal 65-kDa protein that is unrelated to the β subunit and displays properties similar to those of synaptotagmin.     

Quantification de l’activité dopaminergique striatale en TEP à la 18F-DOPA : quels paramètres choisir en routine ?

Aim of the studyFunctional assessment of the nigrostriatal dopaminergic pathway (NSDP) is still largely dominated by SPECT imaging of presynaptic dopamine transporters. Because of greater performance characteristics and a potential medico-economic added value, 18F-DOPA PET may advantageously replace SPECT procedures. Clinical analysis of 18F-DOPA PET images is mainly based on visual assessment, a parameter which may be empirically affected by a low reproducibility. We assessed several reproducible semi-quantitative parameters applicable in clinical routine.Material and methodsSeventy-two patients (18 control subjects, 55.2 ± 13.4 years; 54 patients without confirmed Parkinson's disease (no-PD patients): 74.0 ± 9.9 years) were prospectively referred for a 18F-DOPA PET brain study. 18F-DOPA striatal uptake, which reflects the activity level of L-DOPA decarboxylase (DDC), was quantified using calculation methods of SUV in several striatal VOI. Background activity in occipital VOI (non specific uptake) was taken into consideration to assess specific uptake.ResultsDespite the absence of standard of truth regarding the medical status of no-PD patients, the most effective quantitative parameter to assess specific striatal dopaminergic activity was the putamen-to-occipital ratio. According to our data, activity level of DCC might decrease with age.ConclusionAn accurate and early in-vivo detection of NSDP alteration is a critical issue at the earliest stages of PD. Despite limits of this preliminary study, simple semi-quantitative parameters appear to be valuable tools to address problems of classification reproducibility in clinical practice.     

EGF and TGFα modulate structural and functional differentiation of the mammary gland from pregnant mice in vitro: Possible role of the arachidonic acid pathway

Epidermal growth factor (EGF) has been suggested to be involved in mammary gland development by mitogenic stimulation of the ductal and alveolar epithelium in virgin mice. The present studies demonstrate that also in late-pregnant mice EGF leads to proliferation of the ductal, ductular, and alveolar epithelium. The mitogenic effect is associated with structural and functional dedifferentiation of alveolar cells as revealed by analysis of morphology, expression of cytosolic and secretory proteins, and fatty acid synthesis. Using a combination of metabolic inhibitors, the dedifferentiating effect of EGF could be blocked while the mitogenic action was not influenced. This finding demonstrates that the signal transduction pathway leading to dedifferentiation and mitosis can be separated, and that the dedifferentiating effect of EGF is independent of its mitogenic properties, but is probably mediated by activation of the arachidonic acid-dependent pathways (cyclo- and lipoxygenase pathways). Release of arachidonic acid from the endogenous phospholipid pool was found to be an early response of the explants to EGF. Accordingly, arachidonic acid itself proved to be capable of inducing epithelial dedifferentiation but failed to stimulate proliferation. TGFα showed qualitatively similar effects as EGF but was generally a stronger agonist. It is suggested that EGF and TGFα also play a role in mammary gland physiology during pregnancy by final developing and maintanance of the lobulo-alveolar structure in the mammary gland and prevention of premature onset of lactation, and that this is mediated through the PLA₂-arachidonic acid signalling cascade.     

The stimulatory effect of testosterone propionate and 17β-estradiol on 5′-methylthioadenosine phosphorylase activity in rat target tissues

The effect of castration and subsequent administration of 17β-estradiol and testosterone propionate on 5′-methylthioadenosine phosphorylase activity in rat target tissues was studied. Castration 34 days earlier resulted in a 95 reduction in ventral prostate 5′-methylthioadenosine phosphorylase activity and 16 days earlier in a 67% reduction in uterine 5′-methylthiodenosine phosphorylase activity. Four days of testosterone propionate administration stimulated ventral prostate 5′-methylhioadenosine phosphorylase activity 32% above castrate levels, which represented more than 50% of the intact control levels. 17β-Estradiol on the other hand stimulated uterine 5′-methylthioadenosine phosphorylase activity of 35% above castrate controls within 24h and with 3 days of continuous hormone treatment to within 97% of the intact control levels. However, castration and subsequent 17β-estradiol administration did not affect 5′-methylthioadenosine phosphorylase activity in rat liver and lung. Both prostate and uterine 5′-methylthioadenosine phosphorylase were shown to metabolize 5′-methylthioadenosine to 5′-methylthioribose through a 5′-methythiribose 1-phosphate intermediate. The data suggest that 5′-methylthioadenosine is not allowed to accumulate in rat target tissues even under conditions which are known to stimulate polyamine synthesis.     

Loop‐mediated isothermal amplification combined with colorimetric nanogold for detection of the microsporidian Enterocytozoon hepatopenaei in penaeid shrimp

Aims

Enterocytozoon hepatopenaei is an emerging microsporidian parasite that has been linked to recent losses caused by white faeces syndrome (WFS) in cultivated giant or black tiger shrimp Penaeus (Penaeus) monodon and whiteleg shrimp Penaeus (Litopenaeus) vannamei in Asia. To more accurately assess its impact on shrimp production and to determine reservoir carriers for control measures, our objective was to establish a loop‐mediated isothermal amplification (LAMP) assay combined with colorimetric nanogold (AuNP) for rapid, sensitive and inexpensive detection of this parasite.

Methods and Results

A set of six specific primers was designed to successfully detect the SSU rRNA gene of E. hepatopenaei by a LAMP reaction of 45 min at 65°C combined with visual detection of the amplification product via hybridization at 65°C for 5 min with a ssDNA‐labelled nanogold probe, followed by salt‐induced AuNP aggregation (total assay time, approximately 50 min). This method gave similar results to LAMP followed by electrophoresis or spectrophotometric detection, and it was more sensitive (0·02 fg total DNA) than a conventional nested PCR (0·2 fg total DNA). The new method gave negative results with shrimp DNA templates extracted from diseased shrimp containing other pathogens, indicating that the LAMP‐AuNP assay was specific for E. hepatopenaei.

Conclusions

Without sacrificing sensitivity or specificity, the new LAMP‐AuNP assay significantly reduced the time, ease and cost for molecular detection of E. hepatopenaei in shrimp.

Significance and Impact of the study

The new method employs simple, inexpensive equipment and involves simple steps making it applicable for small field laboratories. Wider application of the method to screen broodstock before use in a hatchery, to screen postlarvae before stocking shrimp ponds, to test for natural carriers and to monitor shrimp in rearing ponds would help to assess and reduce the negative impact of this parasite in shrimp farming.     

Gender and Age Differences in the Suppressive Effect of a 50 Hz Electric Field on the Immobilization-Induced Increase of Plasma Glucocorticoid in Mice

We developed an experimental system to characterize the suppressive effect of extremely low-frequency (ELF) electric fields (EFs) on the stress response. We assessed differences in the EF effects by age and gender. Control, EF-alone, immobilization-alone, and co-treated groups were subjected to an EF (50 Hz, 10 kV/m). Co-treated mice were exposed to the EF for 60 min, with immobilization during the latter half. Our results indicate that the suppressive effects of ELF EFs on the stress response in immobilized mice occur regardless of gender or age. As stress plays an important role in the onset and progression of various diseases, these findings may have broad implications for understanding the efficacy of EFs in animal, and perhaps human, health. Bioelectromagnetics. 2020;41:156–163. © 2019 Bioelectromagnetics Society.     

Neuronal non-CG methylation is an essential target for MeCP2 function

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