Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression

Kinetic regulation of multi-ligand binding proteins

Background: Second messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation. Results: In this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated. Conclusions: The developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion

Investigation of microstructure and mechanical properties of titanium alloy sheet using low power Nd-YAG laser welding process

© 2018 Institute of Materials and Machine Mechanics, Slovak Academy of Sciences. All rights reserved. In the present investigation, welding of 1 mm thick Ti-6Al-4V sheet has been done by Pulsed Wave (PW) Nd-YAG laser with a variation of laser power from 100 to 400W and welding speed from 4 to 6 mm s -1 . The microstructure and microhardness of the fusion zone indicate that the finely serrated and regular plate-shaped microstructures and the resultant hardness in the welds are the key factors behind the enhanced tensile strength of all joints. The weld bead size increases with decreasing welding speed and vice versa. The hardness increases around the heat affected zone as compared to that of the parent metal, and it is the maximum at the centre of the welded region. In the investigation, the tensile strength of specimen with different process parameters has been found to be approximately equal to the tensile strength of the parent metal. In XRD analysis, the weld zone has been found to consist of 78 % a and 22 % ß peaks where two ß-titanium peaks (bcc) 100 occur at 39.5110° and 56.9120°

Environmental impact of the 73 ka Toba super-eruption in South Asia

Copyright © 2009 Elsevier B.V. All rights reserved.The cooling effects of historic volcanic eruptions on world climate are well known but the impacts of even bigger prehistoric eruptions are still shrouded in mystery. The eruption of Toba volcano in northern Sumatra some 73,000 years ago was the largest explosive eruption of the past two million years, with a Volcanic Explosivity Index of magnitude 8, but its impact on climate has been controversial. In order to resolve this issue, we have analysed pollen from a marine core in the Bay of Bengal with stratified Toba ash, and the carbon isotopic composition of soil carbonates directly above and below the ash in three sites on a 400 km transect across central India. Pollen evidence shows that the eruption was followed by initial cooling and prolonged desiccation, reflected in a decline in tree cover in India and the adjacent region. Carbon isotopes show that C3 forest was replaced by wooded to open C4 grassland in central India. Our results demonstrate that the Toba eruption caused climatic cooling and prolonged deforestation in South Asia, and challenge claims of minimal impact on tropical ecosystems and human populations. © 2009 Elsevier B.V. All rights reserved.Martin A.J. Williams, Stanley H. Ambrose, Sander van der Kaars, Carsten Ruehlemann, Umesh Chattopadhyaya, Jagannath Pal and Parth R. Chauha

Reply to the comment on 'Environmental impact of the 73 ka Toba super-eruption in South Asia' by M. A. J. Williams, S. H. Ambrose, S. van der Kaars, C. Ruehlemann, U. Chattopadhyaya, J. Pal, P. R. Chauhan

Haslam and Petraglia raise three broad questions concerning our paper ‘Environmental impact of the 73 ka Toba super-eruption in South Asia’, by Martin A. J. Williams, Stanley H. Ambrose, Sander van der Kaars, Carsten Ruehlemann, Umesh Chattopadhyaya, Jagannath Pal, Parth R. Chauhan [Palaeogeography, Palaeoclimatology, Palaeoecology 284 (2009) 295–314]. (a) What was the relationship between the 73 ka Toba eruption and the cold stade between the Dansgaard–Oeschger interstades 20 and 19? (b) What was the regional impact of the eruption on vegetation? (c) What was the possible effect of the eruption upon humans and mammals? In response to questions (a) and (b) we note that the 73 ka Toba eruption was followed by several centuries of intense cooling and wind-blown dust accession in the Greenland GISP2 ice core, by a change from forest to grassland or open woodland in central India (carbon isotopic analysis) and in the wider region (pollen analysis of a marine sediment core in the Bay of Bengal). In regard to (c), the genetic evidence is as yet too imprecisely dated to demonstrate causality as is the archaeological evidence cited by Haslam and Petraglia in favour of minimal impact. Future work supported by higher resolution chronologies than are presently available is needed to provide a less equivocal picture of the environmental impact of the 73 ka Toba eruption.Martin A.J. Williams, Stanley H. Ambrose, Sander van der Kaars, Carsten Ruehlemann, Umesh Chattopadhyaya, Jagannath Pal and Parth R. Chauha