As ATP released from astrocytes can modulate many neural signaling systems, the triggers of and pathways for this ATP release are important. Here, the ability of mechanical strain to trigger ATP release through pannexin channels, and the effects of sustained strain on pannexin expression, were examined in rat optic nerve head astrocytes. Astrocytes released ATP when subjected to 5% equibiaxial strain or to hypotonic swelling. While astrocytes expressed mRNA for pannexins 1–3, connexin 43 and VNUT, pharmacological analysis suggested a predominant role for pannexins in mechanosensitive ATP release, with Rho kinases contributing. Astrocytes from panx1−/− mice had reduced baseline and stimulated levels of extracellular ATP, confirming the role for pannexins. Swelling astrocytes triggered a regulatory volume decrease that was inhibited by apyrase or probenecid. The swelling–induced rise in calcium was inhibited by P2X7 receptor antagonists A438079 and AZ10606120, in addition to apyrase and carbenoxelone. Extended stretch of astrocytes in vitro upregulated expression of panx1 and panx2 mRNA. A similar upregulation was observed in vivo in optic nerve head tissue from the Tg-MYOCY437H mouse model of chronic glaucoma; genes for panx1, panx2 and panx3 were increased while immunohistochemistry confirmed increased expression of pannexin 1 protein. In summary, astrocytes released ATP in response to mechanical strain, with pannexin 1 the predominant efflux pathway. Sustained strain upregulated pannexins in vitro and in vivo. Together these findings provide a mechanism by which extracellular ATP remains elevated under chronic mechanical strain, as found in the optic nerve head of patients with glaucoma.
"In this article we evaluate the accuracy and bias of projections of total population and population by age group for census tracts in three counties in Florida. We use [U.S. census] data from 1970 and 1980 and several simple extrapolation techniques to produce projections for 1990; we then compare these projections with 1990 census counts and evaluate the differences. For the total sample, we find mean absolute errors of 17%-20% for the three most accurate techniques for projecting total population and find no indication of overall bias. For individual age groups, mean absolute errors range from 20%-29%." This is a revised version of a paper presented at the 1993 Annual Meeting of the Population Association of America.
Bangladesh is one of the densely populated countries of South East Asia with children up to the age of sixteen making up nearly half of the population. Like other least developed countries Bangladeshi children are subjected to a large diversity of conditions which may have negative effect on their physical and psychological well-being like poverty, malnutrition, poor living conditions, infectious diseases and illiteracy. There are positive factors in the cultural background, family bondage, caring parents and other members of the extended families and good relationship with siblings and cousins. Globally one in every five children and adolescent suffer from a mental disorder and two out of five who require mental health services do not receive them. It is expected that by 2020 childhood neuropsychiatric disorder will rise to over 50% and will become one of five most common reasons of morbidity, mortality and disability among children. 1 Behavioral problems can occur in children with all ages and very often they start in early life. Many risk factors have been proposed for the occurrence of mental disorders, among which social factors are clearly implicated in the
Synaptic scaffold proteins control the localization of ion channels and receptors, and facilitate molecular associations between signaling components that modulate synaptic transmission and plasticity. Here, we define novel roles for a recently described scaffold protein, Dsychronic (DYSC), at the Drosophila larval neuromuscular junction. DYSC is the Drosophila homolog of whirlin/DFNB31, a PDZ domain protein linked to Usher syndrome, the most common form of human deaf-blindness. We show that DYSC is expressed presynaptically and is often localized adjacent to the active zone, the site of neurotransmitter release. Loss of DYSC results in marked alterations in synaptic morphology and cytoskeletal organization. Moreover, active zones are frequently enlarged and misshapen in dysc mutants. Electrophysiological analyses further demonstrate that dysc mutants exhibit substantial increases in both evoked and spontaneous synaptic transmission. We have previously shown that DYSC binds to and regulates the expression of the Slowpoke (SLO) BK potassium channel. Consistent with this, slo mutant larvae exhibit similar alterations in synapse morphology, active zone size and neurotransmission, and simultaneous loss of dysc and slo does not enhance these phenotypes, suggesting that dysc and slo act in a common genetic pathway to modulate synaptic development and output. Our data expand our understanding of the neuronal functions of DYSC and uncover non-canonical roles for the SLO potassium channel at Drosophila synapses.
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