Protein misfolding underlies the pathology of a large number of human disorders, many of which are age-related. An exception to this is preeclampsia, a leading cause of pregnancy-associated morbidity ...and mortality in which misfolded proteins accumulate in body fluids and the placenta. We demonstrate that pregnancy zone protein (PZP), which is dramatically elevated in maternal plasma during pregnancy, efficiently inhibits in vitro the aggregation of misfolded proteins, including the amyloid beta peptide (Aβ) that is implicated in preeclampsia as well as with Alzheimer’s disease. The mechanism by which this inhibition occurs involves the formation of stable complexes between PZP and monomeric Aβ or small soluble Aβ oligomers formed early in the aggregation pathway. The chaperone activity of PZP is more efficient than that of the closely related protein alpha-2-macroglobulin (α₂M), although the chaperone activity of α₂M is enhanced by inducing its dissociation into PZP-like dimers. By immunohistochemistry analysis, PZP is found primarily in extravillous trophoblasts in the placenta. In severe preeclampsia, PZP-positive extravillous trophoblasts are adjacent to extracellular plaques containing Aβ, but PZP is not abundant within extracellular plaques. Our data support the conclusion that the up-regulation of PZP during pregnancy represents a major maternal adaptation that helps to maintain extracellular proteostasis during gestation in humans. We propose that overwhelming or disrupting the chaperone function of PZP could underlie the accumulation of misfolded proteins in vivo. Attempts to characterize extracellular proteostasis in pregnancy will potentially have broad-reaching significance for understanding disease-related protein misfolding.
Seeing thrombin in real time. Quantum‐dot aptamer beacons provide for the sensitive detection of protein targets, such as thrombin, as well as nucleic acid targets and offer the promise of ...simplified, multiplex detection.
We used a combination of surveys of natural vegetation and seed-sowing and seedling transplant experiments to determine the relative importance of competition and microenvironmental modification as ...mechanisms by which understory vegetation influences the establishment of tree seedlings in an Alaskan postfire boreal forest. Seedlings of white spruce (Picea glauca) and paper birch (Betula papyrifera) became established more frequently than expected in patches that were dominated by horsetail (Equisetum arvense), and less frequently than expected in patches of bluestem (Calamagrostis canadensis) and other vegetation. Similarly, birch and spruce, whether sown directly or transplanted as seedlings into horsetail-dominated patches generally showed greater survivorship, growth, and nitrogen accumulation (for birch only) than did those transplanted into bluestem or quaking aspen (Populus tremuloides) patches. Clipping experiments demonstrated that the presence of aboveground vegetation reduced survivorship (for birch only), growth (for both species), and nitrogen accumulation (for spruce only) in all patch types. Thus, the understory vegetation in all patch types competed with tree seedlings. However, patch × clipping interactions were either absent or could not explain the greater inhibition of seedling establishment by bluestem or aspen than by horsetail. The strong inhibitory effect of bluestem and aspen on the establishment of spruce and birch seedlings is best explained by the unfavorable temperature and moisture microenvironments in these patches, rather than by differential competition in patches of bluestem, horsetail, or aspen. Many asymmetrical species interactions that are thought to drive successional change may result more from the contrasting effects that species have on their environment than from resource competition among species.
Let U be a locally compact Hausdorff space that is not compact. Let L(U) denote the family of continuous real valued functions on U such that for each f ∈ L(U) there is a nonzero number p (depending ...on f) for which f - p vanishes at infinity. Then L(U) is obviously a lattice under the usual ordering of functions. In this paper we prove that L(U), as a lattice alone, characterizes the locally compact space U. Let S be a locally compact Hausdorff space. Define T(S) to be L(S) if S is not compact, and T(S) to be C(S) if S is compact. We prove that any locally compact Hausdorff spaces S^sub 1^ and S^sub 2^ are homeomorphic if and only if their associated lattices T(S^sub 1^) and T(S^sub 2^) are isomorphic. PUBLICATION ABSTRACT
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We prove that for any continuous real valued function f on a, b there exists a continuous function K such that K-f has bounded variation and (K-f)' = 0 almost everywhere on a, b and such that in any ...subinterval of a, b, K has right derivative ∞ at continuum many points, K has left derivative ∞ at continuum many points, K has right derivative -∞ at continuum many points, and K has left derivative -∞ at continuum many points. Furthermore, functions K with these properties are dense in Ca, b. We can assume the infinite derivatives of K are bilateral if f is of bounded variation on a, b or if f satisfies Lusin's condition (N). PUBLICATION ABSTRACT
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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