Resveratrol prevents alcohol-induced cognitive deficits and brain damage by blocking inflammatory signaling and cell death cascade in neonatal rat brain

Human prenatal ethanol exposure that occurs during a period of increased synaptogenesis known as the 'brain growth spurt' has been associated with significant impairments in attention, learning and memory. Recent studies have shown that administration of ethanol to infant rats during the synaptogenesis period (first 2 weeks after birth) triggers extensive apoptotic neurodegeneration throughout many regions of the developing brain and results in cognitive dysfunctions as the animal matures. The present study was designed with an aim to investigate the effect of resveratrol, a polyphenolic phytoalexin (trans-3,5,4-trihydroxy stilbene) present in red wine on alcohol-induced cognitive deficits and neuronal apoptosis in rat pups postnatally exposed to ethanol. Pups were administered ethanol (5 g/kg, 12% v/v) by intragastric intubation on postnatal days 7, 8, and 9. Ethanol-exposed pups showed impaired memory performance in both Morris water maze elevated plus maze task recorded by using computer tracking with EthoVision software. Behavioral deficit in ethanol-exposed pups was associated with enhanced acetylcholinesterase activity, increased oxidative-nitrosative stress, cytokine (TNF-α, IL-1β and TGF-β), nuclear factor kappa beta and caspase 3 levels in both cerebral cortex and hippocampus. Chronic treatment with resveratrol (10 and 20 mg/kg) significantly attenuated all the behavioral, biochemical and molecular changes in different brain regions of ethanol administered pups. The major finding of the study is that resveratrol blocks activation of nuclear factor kappa beta pathway and apoptotic signaling and prevents cognitive deficits in rats postnatally exposed to ethanol.     

CK2 signaling in androgen-dependent and -independent prostate cancer

Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell growth and proliferation but is also a potent suppressor of apoptosis. CK2 has been found to be dysregulated in all the cancers that have been examined, including prostate cancer. Investigations of CK2 signaling in the prostate were originally initiated in this laboratory, and these studies have identified significant functional activities of CK2 in relation to normal prostate growth and to the pathobiology of androgen-dependent and -independent prostate cancer. We present a brief overview of these developments in the context of prostate biology. An important outcome of these studies is the emerging concept that CK2 can be effectively targeted for cancer therapy.     

Steroid structural requirements for interaction of ostreolysin, a lipid-raft binding cytolysin, with lipid monolayers and bilayers

Ostreolysin, a cytolytic protein from the edible oyster mushroom (Pleurotus ostreatus), recognizes and binds specifically to membrane domains enriched in cholesterol and sphingomyelin (or saturated phosphatidylcholine). These events, leading to permeabilization of the membrane, suggest that a cholesterol-rich liquid-ordered membrane phase, which is characteristic of lipid rafts, could be its possible binding site. In this work, we present effects of ostreolysin on membranes containing various steroids. Binding and membrane permeabilizing activity of ostreolysin was studied using lipid mono- and bilayers composed of sphingomyelin combined, in a 1/1 molar ratio, with natural and synthetic steroids (cholesterol, ergosterol, β-sitosterol, stigmasterol, lanosterol, 7-dehydrocholesterol, cholesteryl acetate, and 5-cholesten-3-one). Binding to membranes and lytic activity of the protein are both shown to be dependent on the intact sterol 3β-OH group, and are decreased by introducing additional double bonds and methylation of the steroid skeleton or C17-isooctyl chain. The activity of ostreolysin mainly correlates with the ability of the steroids to promote formation of liquid-ordered membrane domains, and is the highest with cholesterol-containing membranes. Furthermore, increasing the cholesterol concentration enhanced ostreolysin binding in a highly cooperative manner, suggesting that the membrane lateral distribution and accessibility of the sterols are crucial for the activity of this new member of cholesterol-dependent cytolysins.     

Effects of a 50 Hz magnetic field on Dictyostelium discoideum (Protista)

Some studies have demonstrated that a few biological systems are affected by weak, extremely low frequency (ELF) electromagnetic fields (EMFs), lower than 10 mT. However, to date there is scanty evidence of this effect on Protists in the literature. Due to their peculiarity as single-cell eukaryotic organisms, Protists respond directly to environmental stimuli, thus appearing as very suitable experimental systems. Recently, we showed the presence of propionylcholinesterase (PrChE) activity in single-cell amoebae of Dictyostelium discoideum. This enzyme activity was assumed to be involved in cell-cell and cell-environment interactions, as its inhibition affects cell aggregation and differentiation. In this work, we have exposed single-cell amoebae of D. discoideum to an ELF-EMF of about 200 microT, 50 Hz, for 3 h or 24 h at 21 degrees C. A delay in the early phase of the differentiation was observed in 3 h exposed cells, and a significant decrease in the fission rate appeared in 24 h exposed cells. The PrChE activity was significantly lower in 3 h exposed cells than in the controls, whereas 24 h exposed cells exhibited an increase in this enzyme activity. However, such effects appeared to be transient, as the fission rate and PrChE activity values returned to the respective control values after a 24 h stay under standard conditions.     

KSRP is critical in governing hepatic lipid metabolism through controlling Per2 expression

Hepatic lipid metabolism is controlled by integrated metabolic pathways. Excess accumulation of hepatic TG is a hallmark of nonalcoholic fatty liver disease, which is associated with obesity and insulin resistance. Here, we show that KH-type splicing regulatory protein (KSRP) ablation reduces hepatic TG levels and diet-induced hepatosteatosis. Expression of period 2 (Per2) is increased during the dark period, and circadian oscillations of several core clock genes are altered with a delayed phase in Ksrp^−/− livers. Diurnal expression of some lipid metabolism genes is also disturbed with reduced expression of genes involved in de novo lipogenesis. Using primary hepatocytes, we demonstrate that KSRP promotes decay of Per2 mRNA through an RNA-protein interaction and show that increased Per2 expression is responsible for the phase delay in cycling of several clock genes in the absence of KSRP. Similar to Ksrp^−/− livers, both expression of lipogenic genes and intracellular TG levels are also reduced in Ksrp^−/− hepatocytes due to increased Per2 expression. Using heterologous mRNA reporters, we show that the AU-rich element-containing 3′ untranslated region of Per2 is responsible for KSRP-dependent mRNA decay. These findings implicate that KSRP is an important regulator of circadian expression of lipid metabolism genes in the liver likely through controlling Per2 mRNA stability.     

Multilocus phylogeography of the Patagonian lizard complex Liolaemus kriegi (Iguania: Liolaemini)

This study presents a detailed phylogeographical analysis of one of the most conspicuous groups of lizards in northwestern Patagonia, the Liolaemus kriegi complex. This region is geographically very complex as a result of Andean orogeny and subsequent volcanism coupled with a long history of glaciations and climatic changes. For 247 individuals we sequenced one mitochondrial gene (cytochrome b) and for a subset we sequenced another mitochondrial gene [12S ribosomal RNA (12S)] and two nuclear fragments [kinesin family member 24 (KIF24) and BA3 ribosomal RNA (BA3)]. We obtained gene trees and mitochondrial and nuclear haploytpe networks, and estimated genetic distances between the main lineages and basic molecular diversity indices. We also performed spatial analysis of molecular variance (SAMOVA) and Bayesian Skyline Plot (BSP) analyses, and concordant patterns from different lines of evidence permitted delimitation of seven lineages: two described species, Liolaemus buergeri and Liolaemus tregenzai; four candidate species, Liolaemus sp. A, Liolaemus sp. B, Liolaemus sp. C, and Liolaemus sp. D; and one lineage that includes all individuals from the geographical range of Liolaemus ceii and L. kriegi, referred to as L. kriegi + L. ceii. We discuss the evolutionary processes that may contribute to the origin of these lineages and their taxonomic and conservation implications. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 256–269.     

The influence of spatial pulsed magnetic field application on neuropathic pain after tibial nerve transection in rat

The purpose of the study was to examine the influence of the spatial variable magnetic field (induction: 150–300?µT, 80–150?µT, 20–80?µT; frequency 40?Hz) on neuropathic pain after tibial nerve transection. The experiments were carried out on 64 male Wistar C rats. The exposure of animals to magnetic field was performed 1?d/20?min., 5?d/week, for 28?d. Behavioural tests assessing the intensity of allodynia and sensitivity to mechanical and thermal stimuli were conducted 1?d prior to surgery and 3, 7, 14, 21 and 28?d after the surgery. The extent of autotomy was examined. Histological and immunohistochemical analysis was performed. The use of extremely low-frequency magnetic fields of minimal induction values (20–80?µT/40?Hz) decreased pain in rats after nerve transection. The nociceptive sensitivity of healthy rats was not changed following the exposition to the spatial magnetic field of the low frequency. The results of histological and immunohistochemical investigations confirm those findings. Our results indicate that extremely low-frequency magnetic field may be useful in the neuropathic pain therapy.     

Anonymous single‐copy nuclear DNA (scnDNA) markers for two endemic log‐dwelling beetles: Apasis puncticeps and Adelium calosomoides (Tenebrionidae: Lagriinae: Adeliini)

Three approaches — microsatellite library screening, consensus primer PCR (polymerase chain reaction) and sequencing with arbitrary primer pairs (SWAPP) — were used to develop single‐copy nuclear DNA (scnDNA) markers for log‐dwelling beetles Apasis puncticeps and Adelium calosomoides. We are unaware of other nuclear markers for Adeliini. We tested > 70 primer pairs per species, but despite exhaustive optimization, we obtained only five polymorphic markers. Nonetheless, the markers are valuable in detection of effects of habitat fragmentation.