328 research outputs found
Electrostatics of ions inside the nanopores and trans-membrane channels
A model of a finite cylindrical ion channel through a phospholipid membrane
of width separating two electrolyte reservoirs is studied. Analytical
solution of the Poisson equation is obtained for an arbitrary distribution of
ions inside the trans-membrane pore. The solution is asymptotically exact in
the limit of large ionic strength of electrolyte on the two sides of membrane.
However, even for physiological concentrations of electrolyte, the
electrostatic barrier sizes found using the theory are in excellent agreement
with the numerical solution of the Poisson equation. The analytical solution is
used to calculate the electrostatic potential energy profiles for pores
containing charged protein residues. Availability of a semi-exact interionic
potential should greatly facilitate the study of ionic transport through
nanopores and ion channels
The Ingredients for a Geomorphological Inversion of Landform Evidence to Reconstruct the Behaviour of the Last British-Irish Ice Sheet
"Go Back to the Land!" Negotiating Space, Framing Governmentality in Lambwe Valley, Kenya 1954-75
Opacity in the upper atmospheres of active stars II. AD Leonis
We present FUV and UV spectroscopic observations of AD Leonis, with the aim
of investigating opacity effects in the transition regions of late-type stars.
The C III lines in FUSE spectra show significant opacity during both the
quiescent and flaring states of AD Leonis, with up to 30% of the expected flux
being lost during the latter. Other FUSE emission lines tested for opacity
include those of O VI, while C IV, Si IV and N V transitions observed with STIS
are also investigated. These lines only reveal modest amounts of opacity with
losses during flaring of up to 20%. Optical depths have been calculated for
homogeneous and inhomogeneous geometries, giving path lengths of ~20-60 km and
\~10-30 km, respectively, under quiescent conditions. However path lengths
derived during flaring are ~2-3 times larger. These values are in excellent
agreement with both estimates of the small-scale structure observed in the
solar transition region, and path lengths derived previously for several other
active late-type stars.Comment: 13 pages, 4 figures, 4 Tabels, accepted A&
Model Channel Ion Currents in NaCl - SPC/E Solution with Applied-Field Molecular Dynamics
Using periodic boundary conditions and a constant applied field, we have
simulated current flow through an 8.125 Angstrom internal diameter, rigid,
atomistic channel with polar walls in a rigid membrane using explicit ions and
SPC/E water. Channel and bath currents were computed from ten 10-ns
trajectories for each of 10 different conditions of concentration and applied
voltage. An electric field was applied uniformly throughout the system to all
mobile atoms. On average, the resultant net electric field falls primarily
across the membrane channel, as expected for two conductive baths separated by
a membrane capacitance. The channel is rarely occupied by more than one ion.
Current-voltage relations are concentration-dependent and superlinear at high
concentrations.Comment: Accepted for publication in Biophysical Journa
MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4
Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically
SoTL Lab: Undergraduate student-faculty collaborative research in teaching and learning in CSD
The University of Wisconsin-Eau Claire Communication Sciences and Disorders SoTL Lab was designed to provide hands-on research experiences to undergraduate students on a large scale. Student reflections on experiences within the SoTL Lab identify the value of collaboration, development of confidence, and exposure to the entire research process as key outcomes. These experiences foster development of research skills and may lead students to consider academic careers
A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection
The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo
Animal welfare along the smallholder pig value chain in Vietnam: Current status, legal perspectives and way forward
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