Frequent expansion of Plasmodium vivax Duffy Binding Protein in Ethiopia and its epidemiological significance.

Plasmodium vivax invasion of human erythrocytes depends on the Duffy Binding Protein (PvDBP) which interacts with the Duffy antigen. PvDBP copy number has been recently shown to vary between P. vivax isolates in Sub-Saharan Africa. However, the extent of PvDBP copy number variation, the type of PvDBP multiplications, as well as its significance across broad samples are still unclear. We determined the prevalence and type of PvDBP duplications, as well as PvDBP copy number variation among 178 Ethiopian P. vivax isolates using a PCR-based diagnostic method, a novel quantitative real-time PCR assay and whole genome sequencing. For the 145 symptomatic samples, PvDBP duplications were detected in 95 isolates, of which 81 had the Cambodian and 14 Malagasy-type PvDBP duplications. PvDBP varied from 1 to >4 copies. Isolates with multiple PvDBP copies were found to be higher in symptomatic than asymptomatic infections. For the 33 asymptomatic samples, PvDBP was detected with two copies in two of the isolates, and both were the Cambodian-type PvDBP duplication. PvDBP copy number in Duffy-negative heterozygotes was not significantly different from that in Duffy-positives, providing no support for the hypothesis that increased copy number is a specific association with Duffy-negativity, although the number of Duffy-negatives was small and further sampling is required to test this association thoroughly

Surface Incompressibility from Semiclassical Relativistic Mean Field Calculations

By using the scaling method and the Thomas-Fermi and Extended Thomas-Fermi approaches to Relativistic Mean Field Theory the surface contribution to the leptodermous expansion of the finite nuclei incompressibility has been self-consistently computed. The validity of the simplest expansion, which contains volume, volume-symmetry, surface and Coulomb terms, is examined by comparing it with self-consistent results of the finite nuclei incompressibility for some currently used non-linear sigma-omega parameter sets. A numerical estimate of higher-order contributions to the leptodermous expansion, namely the curvature and surface-symmetry terms, is made.Comment: 18 pages, REVTeX, 3 eps figures, changed conten

The Celestial Reference Frame at 24 and 43 GHz. II. Imaging

We have measured the sub-milli-arcsecond structure of 274 extragalactic sources at 24 and 43 GHz in order to assess their astrometric suitability for use in a high frequency celestial reference frame (CRF). Ten sessions of observations with the Very Long Baseline Array have been conducted over the course of $\sim$5 years, with a total of 1339 images produced for the 274 sources. There are several quantities that can be used to characterize the impact of intrinsic source structure on astrometric observations including the source flux density, the flux density variability, the source structure index, the source compactness, and the compactness variability. A detailed analysis of these imaging quantities shows that (1) our selection of compact sources from 8.4 GHz catalogs yielded sources with flux densities, averaged over the sessions in which each source was observed, of about 1 Jy at both 24 and 43 GHz, (2) on average the source flux densities at 24 GHz varied by 20%-25% relative to their mean values, with variations in the session-to-session flux density scale being less than 10%, (3) sources were found to be more compact with less intrinsic structure at higher frequencies, and (4) variations of the core radio emission relative to the total flux density of the source are less than 8% on average at 24 GHz. We conclude that the reduction in the effects due to source structure gained by observing at higher frequencies will result in an improved CRF and a pool of high-quality fiducial reference points for use in spacecraft navigation over the next decade.Comment: 63 pages, 18 figures, 6 tables, accepted by the Astronomical Journa

Narrowing the window for millicharged particles by CMB anisotropy

We calculate the cosmic microwave background (CMB) anisotropy spectrum in models with millicharged particles of electric charge q\sim 10^{-6}-10^{-1} in units of electron charge. We find that a large region of the parameter space for the millicharged particles exists where their effect on the CMB spectrum is similar to the effect of baryons. Using WMAP data on the CMB anisotropy and assuming Big Bang nucleosynthesis value for the baryon abundance we find that only a small fraction of cold dark matter, Omega_{mcp}h_0^2 < 0.007 (at 95% CL), may consists of millicharged particles with the parameters (charge and mass) from this region. This bound significantly narrows the allowed range of the parameters of millicharged particles. In models without paraphoton millicharged particles are now excluded as a dark matter candidate. We also speculate that recent observation of 511 keV gamma-rays from the Galactic bulge may be an indication that a (small) fraction of CDM is comprised of the millicharged particles.Comment: 10 pages, 3 figures; v2: journal version, references adde

Structural Mechanism for the Specific Assembly and Activation of the Extracellular Signal Regulated Kinase 5 (ERK5) Module

Mitogen-activated protein kinase (MAPK) activation depends on a linear binding motif found in all MAPK kinases (MKK). In addition, the PB1 (Phox and Bem1) domain of MKK5 is required for extracellular signal regulated kinase 5 (ERK5) activation. We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the PB1 domain and the linear binding motif. We show that ERK5 has distinct protein-protein interaction surfaces compared with ERK2, which is the closest ERK5 paralog. The two MAPKs have characteristically different physiological functions and their distinct protein-protein interaction surface topography enables them to bind different sets of activators and substrates. Structural and biochemical characterization revealed that the MKK5 PB1 domain cooperates with the MAPK binding linear motif to achieve substrate specific binding, and it also enables co-recruitment of the upstream activating enzyme and the downstream substrate into one signaling competent complex. Studies on present day MAPKs and MKKs hint on the way protein kinase networks may evolve. In particular, they suggest how paralogous enzymes with similar catalytic properties could acquire novel signaling roles by merely changing the way they make physical links to other proteins

Nuclear matter incompressibility coefficient in relativistic and nonrelativistic microscopic models

We systematically analyze the recent claim that nonrelativistic and relativistic mean field (RMF) based random phase approximation (RPA) calculations for the centroid energy E_0 of the isoscalar giant monopole resonance yield for the nuclear matter incompressibility coefficient, K_{nm}, values which differ by about 20%. For an appropriate comparison with the RMF based RPA calculations, we obtain the parameters for the Skyrme force used in the nonrelativistic model by adopting the same procedure as employed in the determination of the NL3 parameter set of an effective Lagrangian used in the RMF model. Our investigation suggest that the discrepancy between the values of K_{nm} predicted by the relativistic and nonrelativistic models is significantly less than 20%.Comment: Revtex file (13 pages), appearing in PRC-Rapid Com

Combined effects of time spent in physical activity, sedentary behaviors and sleep on obesity and cardio-metabolic health markers: a novel compositional data analysis approach

<div><p>The associations between time spent in sleep, sedentary behaviors (SB) and physical activity with health are usually studied without taking into account that time is finite during the day, so time spent in each of these behaviors are codependent. Therefore, little is known about the combined effect of time spent in sleep, SB and physical activity, that together constitute a composite whole, on obesity and cardio-metabolic health markers. Cross-sectional analysis of NHANES 2005–6 cycle on N = 1937 adults, was undertaken using a compositional analysis paradigm, which accounts for this intrinsic codependence. Time spent in SB, light intensity (LIPA) and moderate to vigorous activity (MVPA) was determined from accelerometry and combined with self-reported sleep time to obtain the 24 hour time budget composition. The distribution of time spent in sleep, SB, LIPA and MVPA is significantly associated with BMI, waist circumference, triglycerides, plasma glucose, plasma insulin (all p<0.001), and systolic (p<0.001) and diastolic blood pressure (p<0.003), but not HDL or LDL. Within the composition, the strongest positive effect is found for the proportion of time spent in MVPA. Strikingly, the effects of MVPA replacing another behavior and of MVPA being displaced by another behavior are asymmetric. For example, re-allocating 10 minutes of SB to MVPA was associated with a lower waist circumference by 0.001% but if 10 minutes of MVPA is displaced by SB this was associated with a 0.84% higher waist circumference. The proportion of time spent in LIPA and SB were detrimentally associated with obesity and cardiovascular disease markers, but the association with SB was stronger. For diabetes risk markers, replacing SB with LIPA was associated with more favorable outcomes. Time spent in MVPA is an important target for intervention and preventing transfer of time from LIPA to SB might lessen the negative effects of physical inactivity.</p></div

Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3 + 2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e