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PubMed2004

The ghost of Saddam and UN sanctions.

Events in the past 10-15 years have meant that Iraq's once highly sophisticated health-care system has fallen to rack and ruin. To fight the very low morale, Iraqi people are making use of many approaches, some of which are unconventional, such as circus entertainment to raise spirits in paediatric wards. This Reportage looks at the events that have lead to the current health-care crisis in Iraq through the eyes of those living and working there. It is based on interviews done by Jo Wilding, an independent humanitarian activist and writer working on various grassroots rehabilitation and solidarity projects in Iraq, in Al Mansour teaching hospital, Shahid Adnan hospital, the centre for Nuclear Medicine, and the Ministry of Health in Baghdad.

Health Services Accessibility↗
PubMed1995

Crown Prince Frederick of Prussia: Suez and syphilis. Un canard dévoilé.

Frederick III (Crown Prince of Prussia, and Emperor of Germany) died of cancer of the larynx in 1888. In Drame Imperial (1888) journalist Jean de Bonnefon asserted that the disease was not cancer but syphilis which the Crown Prince acquired in 1869 in Suez. What de Bonnefon wrote about the prince does not coincide with the prince's itinerary published in the London Times. This discrepancy is examined and the reason for de Bonefon's claim is considered. The report that Crown Prince Frederick of Prussia caught syphilis in Suez is a canard.

Egypt↗
PubMed2000

Hierarchical protein "un-design": insulin's intrachain disulfide bridge tethers a recognition alpha-helix.

A hierarchical pathway of protein folding can enable segmental unfolding by design. A monomeric insulin analogue containing pairwise substitution of internal A6-A11 cystine with serine [[Ser(A6),Ser(A11),Asp(B10),Lys(B28),Pro(B29)]insulin (DKP[A6-A11](Ser))] was previously investigated as a model of an oxidative protein-folding intermediate [Hua, Q. X., et al. (1996) J. Mol. Biol. 264, 390-403]. Its structure exhibits local unfolding of an adjoining amphipathic alpha-helix (residues A1-A8), leading to a 2000-fold reduction in activity. Such severe loss of function, unusual among mutant insulins, is proposed to reflect the cost of induced fit: receptor-directed restoration of the alpha-helix and its engagement in the hormone's hydrophobic core. To test this hypothesis, we have synthesized and characterized the corresponding alanine analogue [[Ala(A6),Ala(A11),Asp(B10),Lys(B28), Pro(B29)]insulin (DKP[A6-A11](Ala))]. Untethering the A6-A11 disulfide bridge by either amino acid causes similar perturbations in structure and dynamics as probed by circular dichroism and (1)H NMR spectroscopy. The analogues also exhibit similar decrements in thermodynamic stability relative to that of the parent monomer as probed by equilibrium denaturation studies (Delta Delta G(u) = 3.0 +/- 0.5 kcal/mol). Despite such similarities, the alanine analogue is 50 times more active than the serine analogue. Enhanced receptor binding (Delta Delta G = 2.2 kcal/mol) is in accord with alanine's greater helical propensity and more favorable hydrophobic-transfer free energy. The success of an induced-fit model highlights the applicability of general folding principles to a complex binding process. Comparison of DKP[A6-A11](Ser) and DKP[A6-A11](Ala) supports the hypothesis that the native A1-A8 alpha-helix functions as a preformed recognition element tethered by insulin's intrachain disulfide bridge. Segmental unfolding by design provides a novel approach to dissecting structure-activity relationships.

Amino Acid Sequence↗
PubMed2002

pH and ionic strength dependence of protein (un)folding and ligand binding to bovine beta-lactoglobulins A and B.

Formation of complexes between bovine beta-lactoglobulins (BLG) and long-chain fatty acids (FAs), effect of complex formation on protein stability, and effects of pH and ionic strength on both complex formation and protein stability were investigated as a function of pH and ionic strength by electrophoretic techniques and NMR spectroscopy. The stability of BLG against unfolding is sharply affected by the pH of the medium: both A and B BLG variants are maximally stabilized against urea denaturation at acidic pH and against SDS denaturation at alkaline pH. The complexes of BLGB with oleic (OA) and palmitic acid (PA) appear more stable than the apoprotein at neutral pH whereas no differential behavior is observed in acidic and alkaline media. PA forms with BLG more stable complexes than OA. The difference between the denaturant concentration able to bring about protein unfolding in the holo versus the apo forms is larger for urea than for SDS treatment. This evidence disfavors the hypothesis of strong hydrophobic interactions being involved in complex formation. Conversely, a significant contribution to FA binding by ionic interactions is demonstrated by the effect of pH and of chloride ion concentration on the stoichiometry of FA.BLG complexes. At neutral pH in a low ionic strength buffer, one molecule of FA is bound per BLG monomer; this ratio decreases to ca. 0.5 per monomer in the presence of 200 mM NaCl. The polar heads of bound FA appear to be solvent accessible, and carboxyl resonances exhibit an NMR titration curve with an apparent pK(a) of 4.7(1).

Animals↗
PubMed1998

Effect of Protonation on Peroxo-Copper Bonding: Spectroscopic and Electronic Structure Study of [Cu(2)((UN-O-)(OOH)](2+).

Spectroscopic studies of a &mgr;-1,1-hydroperoxo-bridged copper dimer are combined with SCF-Xalpha-SW molecular orbital calculations to describe the vibrational and electronic structure of the hydroperoxo-copper complex and compare it to that of previously studied peroxo-copper species. Four vibrational modes of the Cu(2)OOH unit in the resonance Raman and infrared spectra are assigned on the basis of isotope shifts: nu(O-O) = 892 cm(-)(1), nu(as)(Cu-O) = 506 cm(-)(1), nu(s)(Cu-O) = 322 cm(-)(1), and nu(O-H) = 3495 cm(-)(1). The 892 cm(-)(1) O-O stretch of the &mgr;-1,1-hydroperoxo-bridged copper dimer is 89 cm(-)(1) higher than that of the unprotonated complex. Resonance Raman profiles of the 892 cm(-)(1) O-O stretch are used to assign an electronic absorption band at 25 200 cm(-)(1) (epsilon = 6700 M(-)(1) cm(-)(1)) to a hydroperoxide pi-to-Cu charge transfer (CT) transition. This band is approximately 5000 cm(-)(1) higher in energy than the corresponding transition in the unprotonated complex. The pi-to-Cu CT transition intensity defines the degree of hydroperoxide-to-copper charge donation, which is lower than in the unprotonated complex due to the increased electronegativity of the peroxide with protonation. The lower Cu-O covalency of this hydroperoxo-copper complex shows that the high O-O stretching frequency is not due to increased pi-to-Cu charge donation but rather reflects the direct effect of protonation on intra-peroxide bonding. Density functional calculations are used to describe changes in intra-peroxide and Cu-O bonding upon protonation of the peroxo-copper complex and to relate these changes to changes in reactivity.

Journal Article↗
PubMed2005

Microstructure of un-neutralized hydrophobically modified alkali-soluble emulsion latex in different surfactant solutions.

At low pH conditions and in the presence of anionic, cationic, and nonionic surfactants, hydrophobically modified alkali-soluble emulsions (HASE) exhibit pronounced interaction that results in the solubilization of the latex. The interaction between HASE latex and surfactant was studied using various techniques, such as light transmittance, isothermal titration calorimetry, laser light scattering, and electrophoresis. For anionic surfactant, noncooperative hydrophobic binding dominates the interaction at concentrations lower than the critical aggregation concentration (CAC) (C < CAC). However, cooperative hydrophobic binding controls the formation of mixed micelles at high surfactant concentrations (C > or = CAC), where the cloudy solution becomes clear. For cross-linked HASE latex, anionic surfactant binds only noncooperatively to the latex and causes it to swell. For cationic surfactant, electrostatic interaction occurs at very low surfactant concentrations, resulting in phase separation. With further increase in surfactant concentration, noncooperative hydrophobic and cooperative hydrophobic interactions dominate the binding at low and high surfactant concentrations, respectively. For anionic and cationic surfactant systems, the CAC is lower than the critical micelle concentration (CMC) of surfactants in water. In addition, counterion condensation plays an important role during the binding interaction between HASE latex and ionic surfactants. In the case of nonionic surfactants, free surfactant micelles are formed in solution due to their relatively low CMC values, and HASE latexes are directly solubilized into the micellar core of nonionic surfactants.

Journal Article↗
PubMed2002

Un lugar seguro para sus ninos: development and evaluation of a pesticide education video.

The need exists for culturally appropriate and effective educational interventions to reduce pesticide exposure in migrant and seasonal farm-worker (MSFW) communities. The development of one such intervention was part of a community-based research project which partnered the Oregon Health Sciences University and the Oregon Child Development Coalition (Migrant Head Start). The process involved identifying an optimal educational method and content, evaluating existing educational materials on pesticides, developing the selected educational tool (a video), and assessing the effectiveness of the video as an intervention. Focus groups were conducted with MSFWs to elicit their perceived need for education and desired content, method, and delivery. Four currently used educational tools were evaluated for satisfaction, preference, recall ability and knowledge change. Based on these findings, a pesticide exposure video directed at the protection of children was produced. To determine the effectiveness of the video, knowledge, satisfaction and self-reported behaviors were assessed with MSFWs. A sizeable increase in overall pesticide knowledge was measured after seeing the video (p < 0.0001). MSFWs overall were satisfied with the video and reported increased protective behaviors after seeing the video.

Journal Article↗
PubMed2000

Cell invasion by un-palatable parasites.

While some intracellular pathogens invade and replicate exclusively in phagocytic host cells, others have evolved mechanisms to stimulate their uptake by cells not equipped with a well-developed phagocytic machinery. A common mechanism utilized by bacteria involves the induction of macropinocytosis, or of other F-actin-driven processes which result in engulfment of the pathogen through formation of a plasma membrane-derived vacuole. Interestingly, this type of "induced phagocytosis" mechanism does not appear to be utilized by protozoan parasites, which are significantly larger than bacteria in size (about 5-10 microns in average length). Intracellular protozoa either restrict themselves to infecting "professional" phagocytes (one example is the trypanosomatid Leishmania), or utilize highly unusual mechanisms for gaining access to the intracellular environment. Here we discuss what has been revealed in recent years about the remarkable cell invasion strategies of two highly successful intracellular parasites: Toxoplasma gondii and Trypanosoma cruzi. Toxoplasma utilizes a distinct form of actin/myosin-dependent gliding motility to propel itself into mammalian cells, while T. cruzi invades by subverting a Ca(2+)-regulated lysosomal exocytic pathway.

Actins↗
PubMed2002

The (un)reasonableness of reporting: antecedents and consequences of reporting sexual harassment.

This study places the reporting of sexual harassment within an integrated model of the sexual harassment process. Two structural models were developed and tested in a sample (N = 6,417) of male and female military personnel. The 1st model identifies determinants and effects of reporting; reporting did not improve--and at times worsened--job, psychological, and health outcomes. The authors argue that organizational responses to reports (i.e., organizational remedies, organizational minimization, and retaliation) as well as procedural satisfaction can account for these negative effects. The 2nd model examines these mediating mechanisms; results suggest that these mediators, and not reporting itself, are the source of the negative effects of reporting. Organizational and legal implications of these findings are discussed.

Adaptation, Psychological↗