Regulation of pro-apoptotic phosphorylation of Kv2.1 K⁺ channels

Caspase activity during apoptosis is inhibited by physiological concentrations of intracellular K+. To enable apoptosis in injured cortical and hippocampal neurons, cellular loss of this cation is facilitated by the insertion of Kv2.1 K+ channels into the plasma membrane via a Zn2+ /CaMKII/SNARE-dependent process. Pro-apoptotic membrane insertion of Kv2.1 requires the dual phosphorylation of the channel by Src and p38 at cytoplasmic N- and C- terminal residues Y124 and S800, respectively. In this study, we investigate if these phosphorylation sites are mutually co-regulated, and whether putative N- and C-terminal interactions, possibly enabled by Kv2.1 intracellular cysteine residues C73 and C710, influence the phosphorylation process itself. Studies were performed with recombinant wild type and mutant Kv2.1 expressed in Chinese hamster ovary (CHO) cells. Using immunoprecipitated Kv2.1 protein and phospho-specific antibodies, we found that an intact Y124 is required for p38 phosphorylation of S800, and, importantly, that Src phosphorylation of Y124 facilitates the action of the p38 at the S800 residue. Moreover, the actions of Src on Kv2.1 are substantially decreased in the non-phosphorylatable S800A channel mutant. We also observed that mutations of either C73 or C710 residues decreased the p38 phosphorylation at S800 without influencing the actions of Src on tyrosine phosphorylation of Kv2.1. Surprisingly, however, apoptotic K+ currents were suppressed only in cells expressing the Kv2.1(C73A) mutant but not in those transfected with Kv2.1(C710A), suggesting a possible structural alteration in the C-terminal mutant that facilitates membrane insertion. These results show that intracellular N-terminal domains critically regulate phosphorylation of the C-terminal of Kv2.1, and vice versa, suggesting possible new avenues for modifying the apoptotic insertion of these channels during neurodegenerative processes

Chemical efficiency of reactive microflows with heterogeneus catalysis: a lattice Boltzmann study

We investigate the effects of geometrical micro-irregularities on the conversion efficiency of reactive flows in narrow channels of millimetric size. Three-dimensional simulations, based upon a Lattice-Boltzmann-Lax-Wendroff code, indicate that periodic micro-barriers may have an appreciable effect on the effective reaction efficiency of the device. Once extrapolated to macroscopic scales, these effects can result in a sizeable increase of the overall reaction efficiency.Comment: 12 pages, 12 figure

Conversion of the random amplified polymorphic DNA (RAPD) marker UBC#116 linked to Fusarium crown and root rot resistance gene (Frl) into a co-dominant sequence characterized amplified region (SCAR) marker for marker-assisted selection of tomato

Fusarium crown and root rot of tomato (Solanum lycopersicum) is the disease caused by the fungal pathogen Fusarium oxysporum f.sp. radicis-lycopersici (FORL). The most effective way to control this disease is to plant resistant varieties. Markers tightly linked to Fusarium crown and root rot could be used in breeding programs to introgress crown rot resistance into new varieties. In this study, we converted the random amplified polymorphic DNA (RAPD) marker UBC#116, linked to the Fusarium crown and root rot resistance gene (Frl), into a co-dominant sequence characterized amplified region (SCAR) marker. A fragment of about 480 bp, linked to the Frl gene, was polymerase chain reaction (PCR) amplified with the use of the UBC#116 primers, cloned and sequenced. A pair of primers were designed and PCR amplification was performed to develop a new SCAR marker for the Frl gene. The new marker was applied for the analysis of 96 tomato genotypes. The RAPD marker UBC#116 was also used and it revealed that the markers were equivalent to each other. However, the development of the new co-dominant SCAR marker has made marker-assisted selection (MAS) more practical, rapid and efficient.Key words: Fusarium oxysporum f. sp. radicis-lycopersicum (FORL), marker-assisted selection (MAS), Solanum lycopersicum, breeding

Chemical characteristics of Pacific tropospheric air in the region of the Intertropical Convergence Zone and South Pacific Convergence Zone

The Pacific Exploratory Mission (PEM)-Tropics provided extensive aircraft data to study the atmospheric chemistry of tropospheric air in Pacific Ocean regions, extending from Hawaii to New Zealand and from Fiji to east of Easter Island. This region, especially the tropics, includes some of the cleanest tropospheric air of the world and, as such, is important for studying atmospheric chemical budgets and cycles. The region also provides a sensitive indicator of the global-scale impact of human activity on the chemistry of the troposphere, and includes such important features as the Pacific "warm pool," the Intertropical Convergence Zone (ITCZ), the South Pacific Convergence Zone (SPCZ), and Walker Cell circulations. PEM-Tropics was conducted from August to October 1996. The ITCZ and SPCZ are major upwelling regions within the South Pacific and, as such, create boundaries to exchange of tropospheric air between regions to the north and south. Chemical data obtained in the near vicinity of the ITCZ and the SPCZ are examined. Data measured within the convergent zones themselves are not considered. The analyses show that air north and south of the convergent zones have different chemical signatures, and the signatures are reflective of the source regions and transport histories of the air. Air north of the ITCZ shows a modest urban/industrialized signature compared to air south of the ITCZ. The chemical signature of air south of the SPCZ is dominated by combustion emissions from biomass burning, while air north of the SPCZ is relatively clean and of similar composition to ITCZ south air. Chemical signature differences of air north and south of the zones are most pronounced at altitudes below 5 km, and, as such, show that the ITCZ and SPCZ are effective low-altitude barriers to the transport of tropospheric air. At altitudes of 8 to 10 km, chemical signatures are less dissimilar, and air backward trajectories (to 10 days) show cross-convergent-zone flow. At altitudes below about 5 km, little cross-zonal flow is observed. Chemical signatures presented include over 30 trace chemical species including ultrafine, fine, and heated-fine (250°C) aerosol. Copyright 1999 by the American Geophysical Union

Glioblastoma multiforme: a rare manifestation of extensive liver and bone metastases

Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumours known collectively as gliomas. Gliomas are graded by their microscopic appearance. As a rule, their behaviour can be predicted from histology: Grade I (pilocytic astrocytomas) and Grade II (benign astrocytomas) tumours are of low grade and grow slowly over many years. Grade IV tumours (GBM) are the most aggressive and, unfortunately, also the most common in humans, growing rapidly, invading and altering brain function. These tumours arise from the supporting glial cells of the brain during childhood and in adulthood

Functional significance of the hepaCAM gene in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).</p> <p>Materials and methods</p> <p>HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.</p> <p>Results</p> <p>HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.</p> <p>Conclusions</p> <p>HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.</p

Constrained analytical interrelations in neutrino mixing

Hermitian squared mass matrices of charged leptons and light neutrinos in the flavor basis are studied under general additive lowest order perturbations away from the tribimaximal (TBM) limit in which a weak basis with mass diagonal charged leptons is chosen. Simple analytical expressions are found for the three measurable TBM-deviants in terms of perturbation parameters appearing in the neutrino and charged lepton eigenstates in the flavor basis. Taking unnatural cancellations to be absent and charged lepton perturbation parameters to be small, interrelations are derived among masses, mixing angles and the amount of CP-violation.Comment: To be published in the Springer Proceedings in the Physics Series under the heading of the XXI DAE-BRNS Symposium (Guwahati, India

Initial validation of Chinese Pain Assessment in Advanced Dementia Scale (C-PAINAD)

2007-2008 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Development of interfering RNA agents to inhibit SARS-associated coronavirus infection and replication.

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