Separate Intramolecular Targets for Protein Kinase A Control N-Methyl-d-aspartate Receptor Gating and Ca2+ Permeability

Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca²⁺ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca²⁺ permeability (P_Ca/P_Na) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca²⁺ conductance, because neither Na⁺ conductance nor Ca²⁺-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca²⁺ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca²⁺ permeability.     

Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens

Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.     

Ethnic fertility differentials in Peninsular Malaysia and Singapore

Differences in fertility between the three major ethnic groups (Malays, Chinese and Indians) in Peninsular Malaysia and Singapore have existed since before the onset of fertility decline in the late 1950s and remain today, although the relative positions and the actual differences have changed due to the varying rates of decline. By 1987, the Malays experienced the highest fertility and the Chinese the lowest in both countries but in Singapore the Malay fertility was lower than the Chinese fertility in Peninsular Malaysia. The fertility differentials will lead to changes in the ethnic composition in both countries but more so in Peninsular Malaysia.     

Fruit trees in a Malaysian rain forest

An inventory was made of 50 ha of primary lowland rain forest in Peninsular Malaysia, in which ca. 340,000 trees 1 cm dbh or larger were measured and identified to species. Out of a total plot tree flora of 820 species, 76 species are known to bear edible fruit. Especially diverse were the wild species of mango (Mangifera, Anacardiaceae, 12 spp.), mangosteen (Garcinia, Clusiaceae, 13 spp.), breadfruit (Artocarpus, Moraceae, 10 spp.) and rambutan (Nephelium, Sapindaceae, 5 spp.). Median population size for all species of fruit trees was 3.0 trees per ha and 0.2 adult trees per ha. Direct economic value of wild fruit trees was small; only one species has been very much collected and sold, Parkia speciosa (Fabaceae), amounting to less than US$20 per ha per year. The potential value of the species as genetic resources is very large: 24 species are cultivated, 38 edible species are congeneric with cultivated crops and at least 10 other species bear inedible fruit but are related to cultivated crops. We conclude that the Peninsular Malaysian rain forest is exceedingly rich in wild fruit trees, that these normally live at low densities, and that their principal economic value is as genetic resources.     

Population Differences in Brain Morphology and Microstructure among Chinese,Malay, and Indian Neonates

We studied a sample of 75 Chinese, 73 Malay, and 29 Indian healthy neonates taking part in a cohort study to examine potential differences in neonatal brain morphology and white matter microstructure as a function of ethnicity using both structural T2-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). We first examined the differences in global size and morphology of the brain among the three groups. We then constructed the T2-weighted MRI and DTI atlases and employed voxel-based analysis to investigate ethnic differences in morphological shape of the brain from the T2-weighted MRI, and white matter microstructure measured by fractional anisotropy derived from DTI. Compared with Malay neonates, the brains of Indian neonates’ tended to be more elongated in anterior and posterior axis relative to the superior-inferior axis of the brain even though the total brain volume was similar among the three groups. Although most anatomical regions of the brain were similar among Chinese, Malay, and Indian neonates, there were anatomical variations in the spinal-cerebellar and cortical-striatal-thalamic neural circuits among the three populations. The population-related brain regions highlighted in our study are key anatomical substrates associated with sensorimotor functions.     

Congenital Postero-Lateral Diaphragmatic Hernia in Children

Congenital diaphragmatic hernia must be seriously considered in the differential diagnosis of acute respiratory distress in neonates as well as in older infants who present with chronic progressive gastrointestinal and respiratory symptoms. An x-ray film of the chest is mandatory and is almost always diagnostic. Immediate nasogastric decompression of the stomach, with simultaneous fluid and electrolyte replacement and prompt surgical intervention offers the patient the best chance of survival.     

CaСl2 Salt Signaling in Primary Root Architecture and Lateral Root Emergence in Arabidopsis thaliana

Russian Journal of Plant Physiology - Plant root architecture modulates during developmental stages and adjusts with the environmental condition. The cytosolic calcium which is a ubiquitous...     

Late Quaternary Environmental and Human Impacts on the Mitochondrial DNA Diversity of Four Commensal Rodents in Myanmar

Journal of Mammalian Evolution - We addressed the spatiotemporal characteristics of four commensal rodent species occurring in Myanmar in comparison with other areas of the Indo-Malayan region. We...