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At least 73 records · Page 4Linked to original sources

Risk factors for long-term posttraumatic stress reactions in unarmed UN military observers: a four-year follow-up study.

Follow-up data from 187 male Norwegian veteran officers from unarmed UN military observer missions were compared with follow-up data from 211 male veteran officers from Norwegian contingents of the UNIFIL peacekeeping mission in South Lebanon on stress exposure, posttraumatic stress symptoms, level of alcohol consumption, and problems with social adaptation after redeployment from the mission. Observer mission veterans reported exposure to significantly higher levels of war zone stressors than veterans from peacekeeping units did. Observer veterans also reported significantly more posttraumatic stress symptoms at follow-up, higher alcohol consumption levels during service and at follow-up, and more problems with social adaptation to their lives at home in the years after their UN military service. All of these difficulties were most prominent in observers having served in missions with high-intensity stress exposure. Multivariate analyses demonstrated stress exposure during the mission and problems with social adaptation after homecoming to predict posttraumatic stress symptoms at follow-up.

Adult↗

Apoflavodoxin (un)folding followed at the residue level by NMR.

The denaturant-induced (un)folding of apoflavodoxin from Azotobacter vinelandii has been followed at the residue level by NMR spectroscopy. NH groups of 21 residues of the protein could be followed in a series of 1H-15N heteronuclear single-quantum coherence spectra recorded at increasing concentrations of guanidinium hydrochloride despite the formation of protein aggregate. These NH groups are distributed throughout the whole apoflavodoxin structure. The midpoints of unfolding determined by NMR coincide with the one obtained by fluorescence emission spectroscopy. Both techniques give rise to unfolding curves with transition zones at significantly lower denaturant concentrations than the one obtained by circular dichroism spectroscopy. The NMR (un)folding data support a mechanism for apoflavodoxin folding in which a relatively stable intermediate is involved. Native apoflavodoxin is shown to cooperatively unfold to a molten globule-like state with extremely broadened NMR resonances. This initial unfolding step is slow on the NMR chemical shift timescale. The subsequent unfolding of the molten globule is faster on the NMR chemical shift timescale and the limited appearance of 1H-15N HSQC cross peaks of unfolded apoflavodoxin in the denaturant range studied indicates that it is noncooperative.

Apoproteins↗

Molecular characterization of the p(un) allele of the mouse pink-eyed dilution locus.

The mouse pink-eyed dilution locus, p, located on chromosome 7, mediates coat and eye color. The human correlate of this gene may underlie some forms of tyrosinase-positive oculocutaneous albinism. Mutations at the p locus result in a reduction in pigmentation of the eyes and coat. Although most mutant p alleles (including all spontaneous mutations) affect only pigmentation, several mutant alleles (all radiation induced) are also associated with a variety of other phenotypes. We have focused our attention on the p(un) mutant allele, a spontaneous mutation, exhibiting one of the highest reversion frequencies reported for a mammalian mutation. Using a new technique, genome scanning, we have cloned fragments of genomic DNA from the p locus that are associated with a DNA duplication in p(un) DNA. These fragments can now be used to locate the p gene-encoding sequences and aid in the molecular characterization of complex mutant p alleles.

Albinism, Oculocutaneous↗

Experimental validation of novel genes predicted in the un-annotated regions of the Arabidopsis genome.

BACKGROUND: Several lines of evidence support the existence of novel genes and other transcribed units which have not yet been annotated in the Arabidopsis genome. Two gene prediction programs which make use of comparative genomic analysis, Twinscan and EuGene, have recently been deployed on the Arabidopsis genome. The ability of these programs to make use of sequence data from other species has allowed both Twinscan and EuGene to predict over 1000 genes that are intergenic with respect to the most recent annotation release. A high throughput RACE pipeline was utilized in an attempt to verify the structure and expression of these novel genes. RESULTS: 1,071 un-annotated loci were targeted by RACE, and full length sequence coverage was obtained for 35% of the targeted genes. We have verified the structure and expression of 378 genes that were not present within the most recent release of the Arabidopsis genome annotation. These 378 genes represent a structurally diverse set of transcripts and encode a functionally diverse set of proteins. CONCLUSION: We have investigated the accuracy of the Twinscan and EuGene gene prediction programs and found them to be reliable predictors of gene structure in Arabidopsis. Several hundred previously un-annotated genes were validated by this work. Based upon this information derived from these efforts it is likely that the Arabidopsis genome annotation continues to overlook several hundred protein coding genes.

Arabidopsis↗

[Anti-tumor promoting activities and inhibitory effects on Epstein-Barr virus activation of Shi-un-kou and its constituents].

The Kampo-prescription, Shi-un-kou, and its constituent crude drugs [Lithospermum erythrorhizon (1), Macrotomia euchroma (2) and Angelica acutiloba (3)] were assayed for their inhibitory effects on Epstein-Barr virus activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). The crude drugs exhibited inhibitory activity singly and in combinations. In particular, the combination of 2 and 3 yielded enhanced inhibition and lower cytotoxicity. The anti-tumor promoter activity suggested by these results was further investigated in an in vivo study, which demonstrated that Shi-un-kou markedly inhibited TPA-induced skin tumor formation in mice.

9,10-Dimethyl-1,2-benzanthracene↗

Kinetic pathways of beta-hairpin (un)folding in explicit solvent.

We examine the dynamical (un)folding pathways of the C-terminal beta-hairpin of protein G-B1 at room temperature in explicit solvent, by employing transition path sampling algorithms. The path ensembles contain information on the folding kinetics, including solvent motion. We determine the transition state ensembles for the two main transitions: 1), the hydrophobic collapse; and 2), the backbone hydrogen bond formation. In both cases the transition state ensembles are characterized by a layer (1) or a strip (2) of water molecules in between the two hairpin strands, supporting the hypothesis of the solvent as lubricant in the folding process. The transition state ensembles do not correspond with saddle points in the equilibrium free-energy landscapes. The kinetic pathways are thus not completely determined by the free-energy landscape. This phenomenon can occur if the order parameters obey different timescales. Using the transition interface sampling technique, we calculate the rate constants for (un)folding and find them in reasonable agreement with experiments, thus supporting the validation of using all-atom force fields to study protein folding.

Algorithms↗

The in-vitro influence of serum amyloid A isoforms on enzymes that regulate the balance between esterified and un-esterified cholesterol.

The intracellular balance between un-esterified and esterified cholesterol is regulated by two enzyme activities, cholesterol ester hydrolases, which drive the balance in favor of un-esterified cholesterol, and acyl-CoA:cholesterol acyl transferase (ACAT) which acts in the opposite direction. During acute inflammation apo-serum amyloid A (apoSAA) isoforms 1.1 and 2.1 become major constituents of high density lipoprotein and this complex is internalized by macrophages. Mixtures of the two isoforms have been shown to enhance cholesterol esterase activity. Using a purified form of the pancreatic enzyme we have explored the mechanism by which apoSAA may accomplish this stimulation. The pancreatic esterase cleaves cholesteryl-oleate with a Km of 0.255 mM, releasing both cholesterol and oleate. Cholesterol exhibits a product inhibition which is relieved by isoform 2.1 but not 1.1 nor apolipoprotein A-I. The NH2-terminal 16 residues of isoform 2.1 had no effect on the esterase, but the 80 residue peptide constituting its COOH-terminus possessed the stimulatory property. Purified isoforms 1.1, 2.1, 2.2, apolipoprotein A-I, the NH2-terminal 16 residues and COOH-terminal 80 residues of isoform 2.1 were also examined for their effects on macrophage ACAT activity. Isoforms 2.1 and 2.2 produced dose dependent inhibitions of up to 50%, (p<0.001). Isoform 1.1, and apoA-I had no effect on ACAT activity. The NH2-terminal 16 residue peptide of isoform 2.1 reduced the ACAT activity in a dose dependent manner by 74% (p<0.001), whereas the COOH-terminal 80 residues, in contrast to its enhancing effect on the esterase, had no inhibitory effect on ACAT. Such complementary but opposite effects of isoform 2.1 on ACAT and the esterase are consistent with a role for this protein in shifting the balance between unesterified (transportable) and esterified (storage) forms of cholesterol in favor of the latter. They suggest that apoSAA2.1 may mediate cholesterol mobilization at sites of tissue injury.

Animals↗

Humanitarian assistance in UN operations: laboratory and consultative support of a local hospital in Eritrea.

The United Nations Mission to Eritrea and Ethiopia deployed to monitor a cease-fire in a mutually agreed upon Temporary Security Zone. Support for the United Nations (UN) troops included a Field Dressing Station supplied by the Dutch Navy, augmented by Canadian personnel. As with most missions of this type, the health of the deployed Canadian and Dutch soldiers is such that there is time to provide some medical support to local civilian institutions. This article describes this interaction in Eritrea through the illustration of the diagnosis and management of a specific illness through the cooperative use of high-technology laboratory equipment coupled with what we believe to be common sense. Although there was no specific United Nations Mission to Eritrea and Ethiopia humanitarian medical assistance mandate, the expanded use of CIMIC# projects was employed to allow this activity. The guiding principle of sustainability once UN facilities leave is also illustrated in the approach taken to provide this assistance.

Adult↗

Prediction of the size of un-erupted permanent cuspids and bicuspids in a Saudi sample: a pilot study.

The purpose of this study was to produce an estimated equation for the prediction of unerupted cuspids and bicuspids for the Saudi population. In this study, dental casts of 65 Saudi subjects (37 males and 28 females) were used. The subjects' age ranged from 18 to 25 years. The mesiodistal width of all permanent teeth was measured. The data was subjected to regression analysis. Results showed the Tanaka and Johnston equations overestimate the predicted tooth width of the un-erupted cuspids and bicuspids in Saudis. Results showed the predicted tooth width of Saudis (males and females) is closer to the 50% level of confidence in Moyer's chart. Multiple regression equations were estimated including the sex factor. Accordingly, two equations were estimated for the prediction of the tooth width of the un-erupted cuspids and bicuspids for the Saudi males and females. Based on the results, it can be concluded the 50% data is more accurate than the commonly used percentage Moyer's table (75%) when both sexes are combined. Further studies are needed to confirm the findings of this study.

Adolescent↗

UN water action decade: a unique challenge and chance for water engineers.

In the year 2000, the UN General Assembly resolved the Millennium Development Goals (MDGs), and all the Member States of the UN pledged to take any measures to get the MDGs achieved. Concerning water supply and sanitation, a rough calculation clearly tells that it is impossible to meet the MDGs by just copying and pasting the traditional technology as it has been developed in the industrialized countries. Novel concepts and technologies have to be developed, tested and made available which allow fast implementation for a reasonable price, and which provide high treatment efficiency, reliability and robustness. Based on the latest estimates on population growth and migration rates it appears that top priority should be given to investments in the water infrastructure of municipalities. Introduction of water re-use systems should be favoured to avoid over-exploitation of local water resources. Suggested are step changes of the infrastructural system components with emphasis on technology innovation. Many small steps are often more effective than a single big one. In the attempt to quickly improve local situations specific attention should be paid to modern physico-chemical methods based on membrane technology. Decentralized wastewater treatment and re-use methods should be installed simultaneously to the construction of new houses. Further development of methods for separate collection and treatment of particularly composed waste streams should be encouraged. Wastewater should be rated as a source of valuable materials rather than a nuisance. Technology development should proceed hand-in-hand with the development of the societal, economical and political framework. Concerted actions are necessary to make novel technology function. Otherwise, meeting of the MDGs will remain an illusion.

Conservation of Natural Resources↗

[Synthesis and antiinflammatory and anticancer activities of 2-(E)-(un)substituted benzylidene cyclopentanones and their Mannich base hydro chlorides].

It has been known that non-steroidal antiinflammatory drugs (NSAIDs) act by preventing cyclooxygenase products of arachidonic acid. In recent years, research on non-steroid dual inhibitors of cyclooxygenase (CO) and 5-lipoxygenase (5-LO), which should represent a novel class of antiinflammatory drugs with a wider spectrum of activity than classical NSAIDs, has been carried out. In the present paper, a total of 29 compounds including 18 compounds of 2-(E)-(un) substituted benzylidene cyclopentanone (I) derivatives and 11 compounds of 2-(E)-(un)substituted benzylidene-5-dimethylaminomethyl cyclopentanone (II) derivatives were synthesized as dual inhibitors of CO/5-LO. Preliminary pharmacological test showed that I4, I12 and I13 given orally have significant inhibiting effect on carrageenan induced rat paw edema and most compounds of type II exhibited potent effect when given subcutaneously. In particular, II3, which inhibited by 95.8%, 70.34%, and 44.2% at 50, 25, and 12.5 mg/kg respectively, was similar to Ibuprofen. Some compounds of type II exhibited anticancer activity both in vitro (IC50 ranging from 2.93 to 18.06 mumol/L on L1210) and in vivo (maximum increase of life span was 97.5% on EAC in mice).

Animals↗

How the UN is defending human rights.

Today some nurses are themselves victims of human rights violations (ranging from the extreme practice of torture to economic and social discrimination just because they are women), while others are witness to violations of the rights of their people or patients (minorities, indigenous population, AIDS sufferers, the mentally ill or children). But these injustices are not being ignored and nurses can help stop them. Since 40 years ago when the conscience of the world was awakened with the Universal Declaration of Human Rights, international instruments providing the legal clout and pressure to stop the oppressors have been set in motion and are working in some places. Unfortunately violations continue in a number of countries. There are numerous effective channels (see also Inside View), many through the UN. To mark the Declaration's 40th anniversary on December 10 and to give readers a better understanding of what the UN is doing to promote and protect the peoples of the world, INR below answers some questions that nurses may be asking, defines the treaties and shows what international machinery is available to realize those rights.* In a subsequent issue, INR will focus on nurses' involvement in torture and other inhuman treatment and their moral dilemma, giving the views of nurses who have cared for such victims.

Human Rights↗

Comparative X-ray analysis of the un-liganded fosfomycin-target murA.

MurA, an essential enzyme for the synthesis of the bacterial cell wall, follows an induced-fit mechanism. Upon substrate binding, the active site forms in the interdomain cleft, involving movements of the two domains of the protein and a reorientation of the loop Pro112-Pro121. We compare two structures of un-liganded MurA from Enterobacter cloacae: a new orthorhombic form, solved to 1.80 A resolution, and a monoclinic form, redetermined to 1.55 A resolution. In the monoclinic form, the loop Pro112-Pro121 stretches into solvent, while in the new form it adopts a winded conformation, thereby reducing solvent accessibility of the critical residue Cys115. In the interdomain cleft a network of 27 common water molecules has been identified, which partially shields negative charges in the cleft and stabilizes the orientation of catalytically crucial residues. This could support substrate binding and ease domain movements. Near the hinge region an isoaspartyl residue has been recognized, which is the product of post-translational modification of the genetically encoded Asn67-Gly68. The homogeneous population with L-isoaspartate in both structures suggests that the modification in Enterobacter cloacae MurA is not a mere aging defect but rather the result of a specific in vivo process.

Alkyl and Aryl Transferases↗

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery.

Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model.

Adult↗

Inhibition of nuclear factor-kappaB activation un-masks the ability of TNF-alpha to induce human eosinophil apoptosis.

Apoptosis renders eosinophils functionally effete and marks them for "silent" removal from inflamed sites by macrophages. We show, for the first time, that eosinophils exposed to TNF-alpha rapidly lose their cytoplasmic levels of IkappaBalpha, the inhibitory subunit of NF-kappaB. Consequently, TNF-alpha triggers NF-kappaB mobilization from the cytoplasm to the nucleus, as determined by tracking the NF-kappaB subunit p65 by immunofluorescence and Western blot analysis. Inhibition of TNF-alpha-mediated IkappaBalpha degradation and NF-kappaB activation by gliotoxin or the proteasome inhibitor MG-132 un-masks the caspase-dependent pro-apoptotic properties of TNF-alpha. In addition, cycloheximide similarly renders TNF-alpha pro-apoptotic, suggesting that NF-kappaB activation controls the production of a protein(s) that protects eosinophils from the cytotoxic effects of TNF-alpha. Evidence is presented suggesting that TNF-alpha triggered apoptosis is more susceptible to NF-kappaB inhibition than constitutive apoptosis, leading to the possibility of the specific targeting of apoptosis in eosinophil sub-populations. Prior to morphological signs of apoptosis, TNF-alpha-induced IL-8 synthesis is abrogated by inhibition of NF-kappaB. We propose that NF-kappaB activation plays a critical role in controlling eosinophil responsiveness and apoptosis, and speculate that selective inhibitors of eosinophil NF-kappaB activation may ultimately provide alternative therapeutic agents for the treatment of eosinophilic diseases, including asthma and allergic rhinitis.

Apoptosis↗

Synthesis and antibacterial activity of 7 beta-[3-(un)substituted-2-aminopropionamido]-3-vinylcephalosporin s and related compounds.

A series of new 7 beta-[3-(un)substituted-alanyl]-3-vinylcephalosporins and some related compounds, 4a-l is described. They incorporate residues of proteinogenic L-alpha-aminocarboxylic acids, their antimetabolites and enantiomers as well as a dipeptide in the 7 beta-acylamido side chain. The acylation of diphenyl-methyl 7-amino-3-vinyl-3-cephem-4-carboxylate (2: R2 = DPM) with various protected alpha-aminocarboxylic acids 1a-k and the dipeptide 1l is carried out using TBTU as coupling reagent. The compounds, except 4f, are active in vitro against S. aureus and S. lutea, but only 4a, 4k, and 4l inhibit some of the Gram-negative strains.

Anti-Bacterial Agents↗

Intestinal absorption of acidic beta-lactam antibiotics: contribution of ionized and un-ionized forms.

The effect of the pH of dissolutions of weakly acidic beta-lactam antibiotics on their intestinal absorption has been studied by quantification of the contribution of the ionized and un-ionized antibiotic forms to the whole absorptive process. In vivo recirculation in both sexes of adult Wistar rats was performed with buffer solutions at different pH values and samples were analyzed by high-performance liquid chromatography (HPLC).

Animals↗

Genome analysis in Neurospora crassa; cloning of four loci arginine-1 (arg-1), methionine-6 (met-6), unknown-7 (un-7), and ribosome production-1 (rip-1) and associated chromosome walking.

We have cloned four Neurospora crassa genes by complementation analysis. Cloned genes include the arginine-1 (arg-1), methionine-6 (met-6), unknown-7 (un-7), and ribosome production-1 (rip-1) loci. Chromosome walks were initiated in ordered cosmid libraries from the cloned loci. A total of about 700 kb of the Neurospora genome is covered in these walks.

Arginine↗