On ammonia futile cycling in a marine unicellular alga

AbstractFutile cycling of ammonia, involving passive release of NH3 and active transport of NH4+, is potentially a major energetic cost to a unicellular organism. Nitrogen-starved cells of the marine diatom Phaeodactylum tricornutum possess a sodium-dependent transport system for the ammonium (NH4+) analogue methylammonium (CH3NH3+). In nitrogen-replete cells and nitrogen-starved cells incubated in the absence of sodium the rate of methylamine uptake was low and increased as a linear function of increasing methylamine concentration. Cells incubated with 21 μM ammonia or 500 μM methylamine (which give the same concentration of uncharged base), had similar rates of uptake in both nitrogen-replete and nitrogen-starved cells. In nitrogen-replete cells there was no inhibition of ammonia or methylamine uptake in the absence of sodium, but there was a marked inhibition for both with nitrogen-starved cells. However, despite the abolition of active CH3NH3+ and NH4+ uptake by nitrogen-starved cells in the absence of sodium, these cells did not release ammonia. Moreover, neither urea or low pH (which decreased the rate of ammonia uptake) induced release of ammonia in the absence of sodium. In contrast, nitrogen-replete cells released ammonia in darkness, with greater release occurring in the absence of sodium. Absence of sodium was as effective as the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) in inhibiting methylamine uptake by nitrogen-starved cells. However, release of preaccumulated methylamine by nitrogen-starved cells only occurred in the presence of CCCP; there was little release in the absence of sodium. These results suggest that futile cycling of ammonia across the plasma membrane of P. tricornutum is not quantitatively significant

Transgressive body in Chimamanda Ngozi Adichie’s Americanah

In a society where colour is a major reason for social stratification, the black identity is burdened with the perceived negativities generated by its colour. This reality becomes conspicuous in a space defined by racial superiority and migrant status. In Americanah, unlike her other novels, Adichie migration concerns are more profound to reflect the perception and intense consequences of racial identity for African migrants and black people in the West. Through a close reading of this text from a postcolonial view, this article contends that the migrant status and blackness of African subjects, represented in physical attributes, expose their bearer to racial prejudice. This article further argues that to be integrated and access racial privileges, African migrants must suppress or eliminate the racial burdens attached to blackness by transforming or modifying their identity. Such modification evoked by a transgression is accompanied by a loss of identity. Contribution: The most outstanding feature of this article is the exploration of the interface between transgression, body and space in Chimamanda Ngozi Adichie’s (2013) Americanah. This article contributes to the growing discourse on transgression, racism and African migrants’ realities and examine the concerns of black people regarding colour politics through intercontinental migration. This article further seeks to address significant questions about the way race influences the cultural attitude of minority groups and how black immigrants react to racial Othering

The Measurement of Territorial Differences in the Information Society

Glutamine synthetase (GS, EC 6.3.1.2; also known as γ-glutamyl:ammonia ligase) catalyzes the ATP-dependent condensation of glutamate and ammonia to form glutamine. The enzyme has essential roles in different tissues and species, which have led to its consideration as a drug or an herbicide target. In this article, we describe studies aimed at the discovery of new antimicrobial agents targeting Mycobacterium tuberculosis, the causative pathogen of tuberculosis. A number of distinct classes of GS inhibitors with an IC50 of micromolar value or better were identified via high-throughput screening. A commercially available purine analogue similar to one of the clusters identified (the diketopurines), 1-[(3,4-dichlorophenyl)methyl]-3,7-dimethyl-8-morpholin-4-yl-purine-2,6-dione, was also shown to inhibit the enzyme, with a measured IC50 of 2.5 ± 0.4 μM. Two X-ray structures are presented: one is a complex of the enzyme with the purine analogue alone (2.55-Å resolution), and the other includes the compound together with methionine sulfoximine phosphate, magnesium and phosphate (2.2-Å resolution). The former represents a relaxed, inactive conformation of the enzyme, while the latter is a taut, active one. These structures show that the compound binds at the same position in the nucleotide site, regardless of the conformational state. The ATP-binding site of the human enzyme differs substantially, explaining why it has an ∼ 60-fold lower affinity for this compound than the bacterial GS. As part of this work, we devised a new synthetic procedure for generating l-(SR)-methionine sulfoximine phosphate from l-(SR)-methionine sulfoximine, which will facilitate future investigations of novel GS inhibitors

Synthesis and evaluation of β-substituted fosmidomycin analogues as inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase

Blocking the MEP pathway for isoprenoid biosynthesis offers interesting prospects for inhibiting Plasmodia growth. Fosmidomycin (1) and its homologue FR900098 (2) potently inhibit 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr), a key enzyme in this pathway. Although fosmidomycin is a remarkably safe antimalarial agent, low oral absorption, short serum half-life and malaria recrudescence preclude its use in monotherapy. The development of more lipophilic Dxr inhibitors able to passively permeate into cells with improved pharmacokinetic properties could lead to more efficacious agents. Previously, we discovered that analogue 4, featuring a 3,4-dichlorophenyl substituent in α-position of the phosphonate, surpasses fosmidomycin’s potency in inhibiting P. falciparum growth. Here we explored the introduction of aryl or aralkyl substituents at the β-position of the known hydroxamate analogue 3. We studied the effect of introducing substituents in β-position of the hydroxamate analogue 3. While direct addition of a β-aryl moiety resulted in poor P. falciparum Dxr inhibition, longer linkers between the carbon backbone and the phenyl ring were generally associated with better binding to the enzyme. X-ray structures of the parasite Dxr-inhibitor complexes show that the “longer” compounds generate a substantially different flap structure, in which a key tryptophan residue is displaced, and the aromatic group of the ligand lies between the tryptophan and the hydroxamate’s methyl group. Several analogues emerged as highly potent inhibitors of Plasmodium falciparum in vitro growth. In some cases (e.g. for compounds 7b and 7f) good Dxr inhibitory activity failed to translate in good in vitro activity against the parasite, which may be due to inefficient uptake. Compounds 5a-e likewise failed to inhibit EcDxr and MtbDxr while 6c was optimal for inhibition of these enzymes

Tailored approach to sleep health education (TASHE): study protocol for a web-based randomized controlled trial

Background: Obstructive sleep apnea (OSA) is a sleep disorder that disproportionately affects African Americans (hereafter referred to as blacks). Moreover, blacks may underutilize sleep services including overnight polysomnography. Thus, OSA among blacks may go undiagnosed and untreated, which has significant health consequences, including hypertension, diabetes, cognitive impairment, and daytime sleepiness. Design and Methods: This two-arm randomized controlled trial will assign 200 participants to a culturally and linguistically tailored web-based sleep educational platform. The website will be developed to ensure that the content is user friendly and that it is readable and acceptable by the target community. Participants will receive login information to a password-protected website and will have access to the website for 2 months. Study assessments will be collected at baseline, 2 months (post-enrollment) and at 6 months (follow-up). We will use qualitative and quantitative methods to develop tailored materials and to ascertain whether tailored materials will increase OSA knowledge and OSA health literacy by comparing blacks exposed to tailored materials versus those exposed to standard sleep health literature. We hypothesize that exposure to tailored OSA information will improve OSA health literacy. Discussion: Few studies have investigated the racial/ethnic disparities in relation to OSA screening and treatment comparing blacks and whites. Moreover, we know of no interventions designed to increase OSA knowledge and health literacy among blacks. Use of the Internet to disseminate health information is growing in this population. Thus, the Internet may be an effective means to increase OSA health literacy, thereby potentially increasing utilization of sleep-related services in this population

Метод проектів у процесі музично-виконавської підготовки майбутнього вчителя музики

(uk) У статті визначається сутність інтегрованого методу художньо-творчих проектів, розкривається його специфіка у процесі музично-виконавської підготовки майбутніх учителів музики.(ru) В статье определяется сущность интегрированного метода художественно-творческих проэктов, раскрывается его специфика в процессе музыкально-исполнительской подготовки будущих учителей музыки

Time-Resolved AU-Scale Jets Traced by Masers in the IRAS 4A/B Regions of NGC1333

We present results of VLBI observations of the water masers associated with IRAS 4A and IRAS 4B in the NGC 1333 star-forming region taken in four epochs over a two month period. Both objects have been classified as extremely young sources and each source is known to be a multiple system. Using the Very Long Baseline Array, we detected 35 masers in Epoch I, 40 masers in Epoch II, 35 in Epoch III, and 24 in Epoch IV. Only one identified source in each system associates with these masers. These data are used to calculate proper motions for the masers and trace the jet outflows within 100 AU of IRAS 4A2 and IRAS 4BW. In IRAS 4A2 there are two groups of masers, one near the systemic cloud velocity and one red-shifted. They expand linearly away from each other at velocities of 53 km/s. In IRAS 4BW, masers are observed in two groups that are blue-shifted and red-shifted relative to the cloud velocity. They form complex linear structures with a thickness of 3 mas (1 AU at a distance of 320 pc) that expand linearly away from each other at velocities of 78 km/s. Neither of the jet outflows traced by the maser groups align with the larger scale outflows. We suggest the presence of unresolved companions to both IRAS 4A2 and 4BW.Comment: Accepted by Ap

Developing a Tailored Website for Promoting Awareness about Obstructive Sleep Apnea (OSA) Among Blacks in Community-Based Settings

Blacks are at greater risk for lower sleep quality and higher risk for obstructive sleep apnea (OSA) than other racial groups. In this study, we summarize the development of a tailored website including visuals, key messages, and video narratives, to promote awareness about sleep apnea among community-dwelling blacks. We utilized mixed methods, including in-depth interviews, usability-testing procedures, and brief surveys (n = 9, 55% female, 100% black, average age 38.5 years). Themes from the qualitative analysis illuminated varied knowledge regarding OSA symptoms and prevalent self-reported experience with sleep disturbance and OSA symptoms (e.g., snoring). On a scale from 1 (not at all) to 5 (very high), participants provided favorable ratings of website usefulness (mean = 4.9), user friendliness (mean = 4.9) and attractiveness (mean = 4.3). Our findings suggest although tailored health communication has potential for serving as a tool for advancing health equity, usability-testing of health materials is critical to ensure that culturally and linguistically tailored messages are acceptable and actionable in the intended population

Deuterated Ammonia in Galactic Protostellar Cores

We report on a survey of \nh2d towards protostellar cores in low-mass star formation and quiescent regions in the Galaxy. Twenty-three out of thirty-two observed sources have significant (\gsim 5\sigma) \nh2d emission. Ion-molecule chemistry, which preferentially enhances deuterium in molecules above its cosmological value of \scnot{1.6}{-5} sufficiently explains these abundances. NH2D/NH3 ratios towards Class 0 sources yields information about the ``fossil remnants'' from the era prior to the onset of core collapse and star formation. We compare our observations with predictions of gas-phase chemical networks.Comment: 16 Pages, 7 Figures, Accepted to Ap.J., to appear in the June 20, 2001 editio