Molecular, functional and modeling study of cystic fibrosis transmembrane conductance regulator (CFTR) modulation of chloride homeostasis in the rat lumbar spinal cord during postnatal development

In the mature central nervous system (CNS) GABA and glycine are the major inhibitory neurotransmitters. They act via shunting incoming excitatory currents and via moving the membrane potential away from the action potential threshold. However, during development, the action of GABA or glycine can be depolarizing and become even excitatory. This phenomenon plays a significant role in the maturation of the CNS, including neuronal migration and growth, synapse formation and plasticity of GABA synapses (Ben-Ari, 2002). Since synaptic inhibition operate mainly through Cl- fluxes, developmental regulation of this anion is crucial for the establishment of GABA/glycine inhibition

Structural Degradation and Swelling of Lipid Bilayer under the Action of Benzene

Benzene and other nonpolar organic solvents can accumulate in the lipid bilayer of cellular membranes. Their effect on the membrane structure and fluidity determines their toxic properties and antibiotic action of the organic solvents on the bacteria. We performed molecular dynamics simulations of the interaction of benzene with the dimyristoylphosphatidylcholine (DMPC) bilayer. An increase in the membrane surface area and fluidity was clearly detected. Changes in the acyl chain ordering, tilt angle, and overall bilayer thickness were, however, much less marked. The dependence of all computed quantities on the benzene content showed two regimes separated by the solubility limit of benzene in water. When the amount of benzene exceeded this point, a layer of almost pure benzene started to grow between the membrane leaflets. This process corresponds to the nucleation of a new phase and provides a molecular mechanism for the mechanical rupture of the bilayer under the action of nonpolar compounds

The Reduced Level of Inorganic Polyphosphate Mobilizes Antioxidant and Manganese-Resistance Systems in <i>Saccharomyces cerevisiae</i>

Inorganic polyphosphate (polyP) is crucial for adaptive reactions and stress response in microorganisms. A convenient model to study the role of polyP in yeast is the Saccharomyces cerevisiae strain CRN/PPN1 that overexpresses polyphosphatase Ppn1 with stably decreased polyphosphate level. In this study, we combined the whole-transcriptome sequencing, fluorescence microscopy, and polyP quantification to characterize the CRN/PPN1 response to manganese and oxidative stresses. CRN/PPN1 exhibits enhanced resistance to manganese and peroxide due to its pre-adaptive state observed in normal conditions. The pre-adaptive state is characterized by up-regulated genes involved in response to an external stimulus, plasma membrane organization, and oxidation/reduction. The transcriptome-wide data allowed the identification of particular genes crucial for overcoming the manganese excess. The key gene responsible for manganese resistance is PHO84 encoding a low-affinity manganese transporter: Strong PHO84 down-regulation in CRN/PPN1 increases manganese resistance by reduced manganese uptake. On the contrary, PHM7, the top up-regulated gene in CRN/PPN1, is also strongly up-regulated in the manganese-adapted parent strain. Phm7 is an unannotated protein, but manganese adaptation is significantly impaired in &#916;phm7, thus suggesting its essential function in manganese or phosphate transport

Two decades of active layer thickness monitoring in northeastern Asia

This study summarizes seasonal thawing data collected in different permafrost regions of northeast Asia over the 1995–2018 period. Empirical observations were undertaken under the Circumpolar Active Layer Monitoring (CALM) program at a range of sites across the permafrost landscapes of the Yana-Indigirka and Kolyma lowlands and the Chukotka Peninsula, and supplemented with 10 years of observations from volcanic mountainous areas of the Kamchatka Peninsula. Thaw depth observations, taken using mechanical probing at the end of the thawing season, and ground temperature measurements, were analyzed with respect to air temperatures trends. The data from 24 sites (16 in the Indigirka-Kolyma region, 5 in Chukotka and 3 in Kamchatka) reveal different reactions of the active layer thickness (ALT) to recent changes in atmospheric climate. In general, there is a positive relation between ALT and summer air temperatures. Since the early 2000s positive ALT anomalies (compared with mean data from all sites) prevail in the Kolyma and Chukotka area, with only one alas site showing a negative ALT trend. The only active site in the Kamchatka Mountains shows no significant thaw depth changes over the period of observation. Two other Kamchatka sites were affected during a volcanic eruption in 2012

Adolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration

Summary: Adolescent smoking is associated with pathological drinking later in life, but the biological basis for this vulnerability is unknown. To examine how adolescent nicotine exposure influences subsequent ethanol intake, nicotine was administered during adolescence or adulthood, and responses to alcohol were measured 1 month later. We found that adolescent, but not adult, nicotine exposure altered GABA signaling within the ventral tegmental area (VTA) and led to a long-lasting enhancement of alcohol self-administration. We detected depolarizing shifts in GABAA reversal potentials arising from impaired chloride extrusion in VTA GABA neurons. Alterations in GABA signaling were dependent on glucocorticoid receptor activation and were associated with attenuated dopaminergic neuron responses to alcohol in the lateral VTA. Importantly, enhancing chloride extrusion in adolescent nicotine-treated animals restored VTA GABA signaling and alcohol self-administration to control levels. Taken together, this work suggests that adolescent nicotine exposure increases the risk profile for increased alcohol drinking in adulthood. : Thomas et al. show that nicotine treatments during adolescence, but not adulthood, cause a long-term increase in alcohol self-administration in adult rodents. Adolescent nicotine exposure shifts GABAA receptor signaling within the ventral tegmental area circuitry, thereby altering subsequent responses to alcohol. Keywords: alcohol use disorder, reward, mesolimbic, nucleus accumbens, self-administration, chloride gradient, KCC2, glucocorticoid, gateway, dopamin