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991.
Background
Progress toward meeting Millennium Development Goal 5, which aims to improve maternal and reproductive health outcomes, is behind schedule. This is despite ever increasing volumes of official development aid targeting the goal, calling into question the distribution and efficacy of aid. The 2005 Paris Declaration on Aid Effectiveness represented a global commitment to reform aid practices in order to improve development outcomes, encouraging a shift toward collaborative aid arrangements which support the national plans of aid recipient countries (and discouraging unaligned donor projects).Methods and Findings
We conducted a systematic review to summarise the evidence of the impact on MDG 5 outcomes of official development aid delivered in line with Paris aid effectiveness principles and to compare this with the impact of aid in general on MDG 5 outcomes. Searches of electronic databases identified 30 studies reporting aid-funded interventions designed to improve maternal and reproductive health outcomes. Aid interventions appear to be associated with small improvements in the MDG indicators, although it is not clear whether changes are happening because of the manner in which aid is delivered. The data do not allow for a meaningful comparison between Paris style and general aid. The review identified discernible gaps in the evidence base on aid interventions targeting MDG 5, notably on indicators MDG 5.4 (adolescent birth rate) and 5.6 (unmet need for family planning).Discussion
This review presents the first systematic review of the impact of official development aid delivered according to the Paris principles and aid delivered outside this framework on MDG 5 outcomes. Its findings point to major gaps in the evidence base and should be used to inform new approaches and methodologies aimed at measuring the impact of official development aid. 相似文献992.
During brain development, billions of neurons organize into highly specific circuits. To form specific circuits, neurons must build the appropriate types of synapses with appropriate types of synaptic partners while avoiding incorrect partners in a dense cellular environment. Defining the cellular and molecular rules that govern specific circuit formation has significant scientific and clinical relevance because fine scale connectivity defects are thought to underlie many cognitive and psychiatric disorders. Organizing specific neural circuits is an enormously complicated developmental process that requires the concerted action of many molecules, neural activity, and temporal events. This review focuses on one class of molecules postulated to play an important role in target selection and specific synapse formation: the classic cadherins. Cadherins have a well-established role in epithelial cell adhesion, and although it has long been appreciated that most cadherins are expressed in the brain, their role in synaptic specificity is just beginning to be unraveled. Here, we review past and present studies implicating cadherins as active participants in the formation, function, and dysfunction of specific neural circuits and pose some of the major remaining questions. 相似文献
993.
994.
The interstitial fluid spaces are filled with a mat of collagen fibers, and the interstices of this mat contain a mucopolysaccharide gel ground substance. Both the collagen fibers and the gel are elastic structures that can be expanded or compacted. In the expanded state the collagen fibers are pushed far apart and pockets of free fluid develop witin the gel. In the compacted state the elastic recoil of the compressed collagen fibers and gel reticular fibrillae seems to cause suction on the fluid within the tissue spaces, thus creating a subatmospheric pressure. Measurements of interstitial fluid pressure using a perforated capsule method indicate that this is normally slightly negative (subatmospheric) in most soft tissues. However, even very slight extra filtration of fluid into the tissue spaces increases the interstitial fluid pressure toward more positive values, which in turn increases lymph flow. The increased lymph flow then decreases the interstitial fluid volume and pressure back toward normal because of two mechanism, 1) direct removal of fluid from the tissue spaces in the lymph, and 2) removal of protein from the interstitial fluid in the lymph, thus decreasing the interstitial fluid colloid osmotic pressure and allowing more effective osmosis of fluid directly from the interstitial spaces back into the capillaries. 相似文献
995.
Identification of a TcpC-TcpQ outer membrane complex involved in the biogenesis of the toxin-coregulated pilus of Vibrio cholerae 总被引:3,自引:0,他引:3 下载免费PDF全文
The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation studies revealed that the protein is not localized to the periplasm but is associated predominantly with the outer membrane fraction. An analysis of the amount of TcpQ present in the series of tcp mutants demonstrated the inverse of the TcpC result (absence of TcpQ in a tcpC deletion strain). Complementation of the tcpQ deletion restored TcpC levels and TCP formation, and similarly, complementation of tcpC restored TcpQ. Metal affinity pull-down experiments performed using His-tagged TcpC or TcpQ demonstrated a direct interaction between TcpC and TcpQ. In the presence of TcpQ, TcpC was found to form a high-molecular-weight complex that is stable in 2% sodium dodecyl sulfate and at temperatures below 65°C, a characteristic of secretin complexes. Fractionation studies in which TcpC was overexpressed in the absence of TcpQ showed that TcpQ is also required for proper localization of TcpC to the outer membrane. 相似文献
996.
In the absence of MgATP, the catalytic subunit of cAMP-dependent protein kinase is irreversibly inhibited by the hydrophobic carbodiimide dicyclohexylcarbodiimide, and this inhibition is most likely due to the formation of a cross-link between a carboxyl group and a lysine residue in the active site (Toner-Webb & Taylor, 1987). In order to identify these cross-linked residues, the catalytic subunit was modified by dicyclohexylcarbodiimide and then treated with acetic anhydride and digested with trypsin. The resulting peptides were resolved by high-performance liquid chromatography. One major absorbing tryptic peptide and one smaller peptide consistently and reproducibly showed a decrease in absorbance after the catalytic subunit had been treated with DCCD. These peptides correspond to residues 166-190 and 57-93, respectively. A unique peptide was isolated from the modified catalytic subunit, and the sequence of this peptide established that the cross-linking occurred between Asp-184 and Lys-72. The cross-linking of these two residues, which were both identified previously as essential residues, confirms the likelihood that each plays a role in the functioning of this enzyme. The fact that Asp-184 and Lys-72 appear to be invariant in all protein kinases further supports the hypothesis that these two residues, located close to one another at the active site of the enzyme, play essential roles in catalysis. 相似文献
997.
Crystal structures of mitochondrial processing peptidase reveal the mode for specific cleavage of import signal sequences 总被引:4,自引:0,他引:4
Taylor AB Smith BS Kitada S Kojima K Miyaura H Otwinowski Z Ito A Deisenhofer J 《Structure (London, England : 1993)》2001,9(7):615-625
BACKGROUND: Mitochondrial processing peptidase (MPP) is a metalloendopeptidase that cleaves the N-terminal signal sequences of nuclear-encoded proteins targeted for transport from the cytosol to the mitochondria. Mitochondrial signal sequences vary in length and sequence, but each is cleaved at a single specific site by MPP. The cleavage sites typically contain an arginine at position -2 (in the N-terminal portion) from the scissile peptide bond in addition to other distal basic residues, and an aromatic residue at position +1. Mitochondrial import machinery recognizes amphiphilic helical conformations in signal sequences. However, it is unclear how MPP specifically recognizes diverse presequence substrates. RESULTS: The crystal structures of recombinant yeast MPP and a cleavage-deficient mutant of MPP complexed with synthetic signal peptides have been determined. MPP is a heterodimer; its alpha and beta subunits are homologous to the core II and core I proteins, respectively, of the ubiquinol-cytochrome c oxidoreductase complex. Crystal structures of two different synthetic substrate peptides cocrystallized with the mutant MPP each show the peptide bound in an extended conformation at the active site. Recognition sites for the arginine at position -2 and the +1 aromatic residue are observed. CONCLUSIONS: MPP bound two mitochondrial import presequence peptides in extended conformations in a large polar cavity. The presequence conformations differ from the amphiphilic helical conformation recognized by mitochondrial import components. Our findings suggest that the presequences adopt context-dependent conformations through mitochondrial import and processing, helical for recognition by mitochondrial import machinery and extended for cleavage by the main processing component. 相似文献
998.
Global organellar proteomics 总被引:21,自引:0,他引:21
Cataloging the proteomes of single-celled microorganisms, cells, biological fluids, tissue and whole organisms is being undertaken at a rapid pace as advances are made in protein and peptide separation, detection and identification. For metazoans, subcellular organelles represent attractive targets for global proteome analysis because they represent discrete functional units, their complexity in protein composition is reduced relative to whole cells and, when abundant cytoskeletal proteins are removed, lower abundance proteins specific to the organelle are revealed. Here, we review recent literature on the global analysis of subcellular organelles and briefly discuss how that information is being used to elucidate basic biological processes that range from cellular signaling pathways through protein-protein interactions to differential expression of proteins in response to external stimuli. We assess the relative merits of the different methods used and discuss issues and future directions in the field. 相似文献
999.
Novak AE Jost MC Lu Y Taylor AD Zakon HH Ribera AB 《Journal of molecular evolution》2006,63(2):208-221
Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms
that shaped the vertebrate sodium channel α-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, compared to ten in another vertebrate lineage, mammals. Prior phylogenetic analyses have indicated that the genomes
of both teleosts and tetrapods contain four monophyletic groups of SCNA genes, and that tandem duplications expanded the number of genes in two of the four mammalian groups. However, the number
of genes in each group varies between teleosts and tetrapods, suggesting different evolutionary histories in the two vertebrate
lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analyses of other closely mapped genes in D. rerio as well as of SCNA genes from several teleost species all support the hypothesis that a whole-genome duplication was involved in expansion of
the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation
of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
[Reviewing Editor: Dr. Axel Meyer] 相似文献
1000.
The effect of streptozotocin-induced diabetes on phenylalanine hydroxylase expression in rat liver. 总被引:2,自引:0,他引:2 下载免费PDF全文
The impact of experimentally induced diabetes on the expression of rat liver phenylalanine hydroxylase has been investigated. A significant elevation in maximal enzymic activity was observed in diabetes. This was associated with significant increases in the amount of enzyme, the phenylalanine hydroxylase-specific translational activity of hepatic RNA and the abundance of phenylalanine hydroxylase-specific mRNA. These changes in phenylalanine hydroxylase expression were not observed when diabetes was controlled by daily injections of insulin. These results are discussed in relation to the hormonal control of phenylalanine hydroxylase gene expression. 相似文献