Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Effect of Zinc Supplementation on Growth of Low Birth Weight Infants Aged 1–6 Mo in Ardabil, Iran

Objective To assess the effect of zinc supplementation on growth of low birth weight (LBW) infants aged 1–6 mo. Methods LBW infants were enrolled at birth and randomly assigned to receive 5 mg elemental Zn per day (n=45) or placebo (n=45) until 6 mo of age. They were followed monthly for information on compliance; anthropometric measurements were performed monthly. Results After randomization, 5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age, significantly greater weight gains were observed in the zinc than in the placebo group (4995±741g in zinc group vs. 3896±865 g in placebo group, p = 0.036). Length gain during the study period improved in zinc group (16.9±8.2 cm vs. 15.1±4.1 cm, p = 0.039); after zinc supplementation head circumference were increased (8.7±1.4 cm vs.7.4± 1.5 cm p<0.001). In male infants, total weight gain and height and head circumference gain were higher in the zinc than in the placebo group. However, only head circumference change was statistically significant. A similar trend was observed among female infants, but these differences were not statistically significant. There was no significant relation between breast-feeding status and the main outcome variables. Conclusions Infants in the present study showed improve¬ments in growth rate, but more studies are required in this field to confirm this fact

Malaysia and the end of the Bretton Woods system 1965-72: disentangling from Sterling

This article examines the tense and complex monetary relationship between Britain, Singapore and Malaysia in the period from 1965 to 1972. It questions the assumption that Malaysia's economic significance to Britain was 'on the wane' by the 1960s. As the second largest government holder of sterling assets in the world, Malaysia should have been able to exert considerable leverage in London over the disposition of these assets. Ultimately, however, the very scale of these assets limited Malaysia's room for manoeuvre, as it could not sell off a significant proportion of them without undermining international confidence in the exchange rate of the pound and thereby precipitating the devaluation of its remaining sterling assets. The devaluation of sterling in 1967 emerges as a watershed in relations between London and Kuala Lumpur, with the Malaysians thereafter seeking to forge a more independent monetary policy. It is clear, however, that they did not actually succeed in doing so until 1972

Mechanisms of translational regulation by a human eIF5-mimic protein

The translation factor eIF5 is an important partner of eIF2, directly modulating its function in several critical steps. First, eIF5 binds eIF2/GTP/Met-tRNAiMet ternary complex (TC), promoting its recruitment to 40S ribosomal subunits. Secondly, its GTPase activating function promotes eIF2 dissociation for ribosomal subunit joining. Finally, eIF5 GDP dissociation inhibition (GDI) activity can antagonize eIF2 reactivation by competing with the eIF2 guanine exchange factor (GEF), eIF2B. The C-terminal domain (CTD) of eIF5, a W2-type HEAT domain, mediates its interaction with eIF2. Here, we characterize a related human protein containing MA3- and W2-type HEAT domains, previously termed BZW2 and renamed here as eIF5-mimic protein 1 (5MP1). Human 5MP1 interacts with eIF2 and eIF3 and inhibits general and gene-specific translation in mammalian systems. We further test whether 5MP1 is a mimic or competitor of the GEF catalytic subunit eIF2Bε or eIF5, using yeast as a model. Our results suggest that 5MP1 interacts with yeast eIF2 and promotes TC formation, but inhibits TC binding to the ribosome. Moreover, 5MP1 is not a GEF but a weak GDI for yeast eIF2. We propose that 5MP1 is a partial mimic and competitor of eIF5, interfering with the key steps by which eIF5 regulates eIF2 function

Stamp transferred suspended graphene mechanical resonators for radio-frequency electrical readout

We present a simple micromanipulation technique to transfer suspended graphene flakes onto any substrate and to assemble them with small localized gates into mechanical resonators. The mechanical motion of the graphene is detected using an electrical, radio-frequency (RF) reflection readout scheme where the time-varying graphene capacitor reflects a RF carrier at f=5-6 GHz producing modulation sidebands at f +/- fm. A mechanical resonance frequency up to fm=178 MHz is demonstrated. We find both hardening/softening Duffing effects on different samples, and obtain a critical amplitude of ~40 pm for the onset of nonlinearity in graphene mechanical resonators. Measurements of the quality factor of the mechanical resonance as a function of DC bias voltage Vdc indicate that dissipation due to motion-induced displacement currents in graphene electrode is important at high frequencies and large Vdc

Emission of intermediate mass fragments from hot 116^{116}Ba∗^* formed in low-energy 58^{58}Ni+58^{58}Ni reaction

The complex fragments (or intermediate mass fragments) observed in the low-energy $^{58}$Ni+$^{58}$Ni$\to ^{116}$Ba$^*$ reaction, are studied within the dynamical cluster decay model for s-wave with the use of the temperature-dependent liquid drop, Coulomb and proximity energies. The important result is that, due to the temperature effects in liquid drop energy, the explicit preference for $\alpha$-like fragments is washed out, though the $^{12}$C (or the complementary $^{104}$Sn) decay is still predicted to be one of the most probable $\alpha$-nucleus decay for this reaction. The production rates for non-$\alpha$ like intermediate mass fragments (IMFs) are now higher and the light particle production is shown to accompany the IMFs at all incident energies, without involving any statistical evaporation process in the model. The comparisons between the experimental data and the (s-wave) calculations for IMFs production cross sections are rather satisfactory and the contributions from other $\ell$-waves need to be added for a further improvement of these comparisons and for calculations of the total kinetic energies of fragments.Comment: 22 pages, 15 figure

Glycine-rich RNA binding protein of Oryza sativa inhibits growth of M15 E. coli cells

<p>Abstract</p> <p>Background</p> <p>Plant glycine-rich RNA binding proteins have been implicated to have roles in diverse abiotic stresses.</p> <p>Findings</p> <p><it>E. coli </it>M15 cells transformed with full-length rice glycine-rich RNA binding protein4 (OsGR-RBP4), truncated rice glycine-rich RNA binding protein4 (OsGR-RBP4ΔC) and rice FK506 binding protein (OsFKBP20) were analyzed for growth profiles using both broth and solid media. Expression of OsGR-RBP4 and OsGR-RBP4ΔC proteins caused specific, inhibitory effect on growth of recombinant M15 <it>E. coli </it>cells. The bacterial inhibition was shown to be time and incubation temperature dependent. Removal of the inducer, IPTG, resulted in re-growth of the cells, indicating that effect of the foreign proteins was of reversible nature. Although noted at different levels of dilution factors, addition of purified Os-GR-RBP4 and OsGR-RBP4ΔC showed a similar inhibitory effect as seen with expression inside the bacterial cells.</p> <p>Conclusions</p> <p>Expression of eukaryotic, stress-associated OsGR-RBP4 protein in prokaryotic <it>E. coli </it>M15 cells proves injurious to the growth of the bacterial cells. <it>E. coli </it>genome does not appear to encode for any protein that has significant homology to OsGR-RBP4 protein. Therefore, the mechanism of inhibition appears to be due to some illegitimate interactions of the OsGR-RBP4 with possibly the RNA species of the trans-host bacterial cells. The detailed mechanism underlying this inhibition remains to be worked out.</p

Robotic-assisted ultrasound for fetal imaging: Evolution from single-arm to dual-arm system

© Springer Nature Switzerland AG 2019. The development of robotic-assisted extracorporeal ultrasound systems has a long history and a number of projects have been proposed since the 1990s focusing on different technical aspects. These aim to resolve the deficiencies of on-site manual manipulation of hand-held ultrasound probes. This paper presents the recent ongoing developments of a series of bespoke robotic systems, including both single-arm and dual-arm versions, for a project known as intelligent Fetal Imaging and Diagnosis (iFIND). After a brief review of the development history of the extracorporeal ultrasound robotic system used for fetal and abdominal examinations, the specific aim of the iFIND robots, the design evolution, the implementation details of each version, and the initial clinical feedback of the iFIND robot series are presented. Based on the preliminary testing of these newly-proposed robots on 42 volunteers, the successful and reliable working of the mechatronic systems were validated. Analysis of a participant questionnaire indicates a comfortable scanning experience for the volunteers and a good acceptance rate to being scanned by the robots