Novel RPTPγ and RPTPζ splice variants from mixed neuron-astrocyte hippocampal cultures as well as from the hippocampi of newborn and adult mice.

Receptor protein tyrosine phosphatases γ and ζ (RPTPγ and RPTPζ) are transmembrane signaling proteins with extracellular carbonic anhydrase-like domains that play vital roles in the development and functioning of the central nervous system (CNS) and are implicated in tumor suppression, neurodegeneration, and sensing of extracellular [CO2] and [HCO3 -]. RPTPγ expresses throughout the body, whereas RPTPζ preferentially expresses in the CNS. Here, we investigate differential RPTPγ-RPTPζ expression in three sources derived from a wild-type laboratory strain of C57BL/6 mice: (a) mixed neuron-astrocyte hippocampal (HC) cultures 14 days post isolation from P0-P2 pups; (b) P0-P2 pup hippocampi; and (c) 9- to 12-week-old adult hippocampi. Regarding RPTPγ, we detect the Ptprg variant-1 (V1) transcript, representing canonical exons 1-30. Moreover, we newly validate the hypothetical assembly [XM_006517956] (propose name, Ptprg-V3), which lacks exon 14. Both transcripts are in all three HC sources. Regarding RPTPζ, we confirm the expression of Ptprz1-V1, detecting it in pups and adults but not in cultures, and Ptprz1-V3 through Ptprz1-V7 in all three preparations. We newly validate hypothetical assemblies Ptprz1-X1 (in cultures and pups), Ptprz1-X2 (in all three), and Ptprz1-X5 (in pups and adults) and propose to re-designate them as Ptprz1-V0, Ptprz1-V2, and Ptprz1-V8, respectively. The diversity of RPTPγ and RPTPζ splice variants likely corresponds to distinct signaling functions, in different cellular compartments, during development vs later life. In contrast to previous studies that report divergent RPTPγ and RPTPζ protein expressions in neurons and sometimes in the glia, we observe that RPTPγ and RPTPζ co-express in the somata and processes of almost all HC neurons but not in astrocytes, in all three HC preparations.

Carbon dioxide transport across membranes.

Carbon dioxide (CO2) movement across cellular membranes is passive and governed by Fick's law of diffusion. Until recently, we believed that gases cross biological membranes exclusively by dissolving in and then diffusing through membrane lipid. However, the observation that some membranes are CO2 impermeable led to the discovery of a gas molecule moving through a channel; namely, CO2 diffusion through aquaporin-1 (AQP1). Later work demonstrated CO2 diffusion through rhesus (Rh) proteins and NH3 diffusion through both AQPs and Rh proteins. The tetrameric AQPs exhibit differential selectivity for CO2 versus NH3 versus H2O, reflecting physico-chemical differences among the small molecules as well as among the hydrophilic monomeric pores and hydrophobic central pores of various AQPs. Preliminary work suggests that NH3 moves through the monomeric pores of AQP1, whereas CO2 moves through both monomeric and central pores. Initial work on AQP5 indicates that it is possible to create a metal-binding site on the central pore's extracellular face, thereby blocking CO2 movement. The trimeric Rh proteins have monomers with hydrophilic pores surrounding a hydrophobic central pore. Preliminary work on the bacterial Rh homologue AmtB suggests that gas can diffuse through the central pore and three sets of interfacial clefts between monomers. Finally, initial work indicates that CO2 diffuses through the electrogenic Na/HCO3 cotransporter NBCe1. At least in some cells, CO2-permeable proteins could provide important pathways for transmembrane CO2 movements. Such pathways could be amenable to cellular regulation and could become valuable drug targets.

Effect of Air Pollutant Markers on Multiple Sclerosis Relapses.

BACKGROUND: Multiple Sclerosis (MS) is one of the autoimmune diseases with an unknown cause. The aim of this study was to explore the link between air quality and MS relapses in patients who suffer from MS. METHODS: This time-series study was conducted on patients registered at the Iranian Multiple Sclerosis Society in 2011-2012. They were randomly selected from patients lived in Tehran in the last five years, and had at least one relapse in the last three years. The link between monthly mean air pollutant levels and the relapses of MS in the participants was studied. RESULTS: Among the registered 160 participants, at least 150 had one attack during 2009 and 2012. Most air pollutants such as NO2, NO and CO are in high levels in the rainy season. Others like Pm10 and Nox are in high levels in the dry season. The correlation between NO2 levels of all markers of air quality and MS relapses (P=0.03, r=0.27) is weak. Best ARIMA model (p,d,q; 1,0,1) was determined between number of monthly relapses and living place, although this model was not significant (P=0.3) (AR; P=0.000, MA;P=0.4). CONCLUSIONS: Air pollutants might be regarded as a risk factor for MS relapse.