A phloroglucinol derivative from the brown alga Zonaria tournefortii

The major lipid component of the brown seaweed Zonaria tournefortii was identified as the acylphlorogluconol (all Z)-2′-icosa-5,8,11,14,17-pentae     

Synthesis and Cytostatic Activity of Halomethylthiazole C-Nucleosides and Analogues1

Abstract

The synthesis of 2-(β-D-ribofuranosyl)-and 2-(tetrahydropyran-2-yl)-4-halomethylthiazoles from 2, 5-anhydro-D-allonthioamide and tetrahydropyran-2-thiocarboxamide is described. Bromination of 2-(β-D-ribofuranosyl)- and 2-tetrahydropyran-2-yl)-4-methylthiazole with NBS is studied. Cytostatic activity against HeLa cells of all the compounds is reported.     

Microbial Volatile Organic Compounds Produced by Bacillus amyloliquefaciens GB03 Ameliorate the Effects of Salt Stress in Mentha piperita Principally Through Acetoin Emission

Journal of Plant Growth Regulation - We investigated the effects of microbial volatile organic compounds (mVOC) emitted by Bacillus amyloliquefaciens GB03 on Mentha piperita growing under different...     

Scribble is required for normal epithelial cell–cell contacts and lumen morphogenesis in the mammalian lung

During lung development, proper epithelial cell arrangements are critical for the formation of an arborized network of tubes. Each tube requires a lumen, the diameter of which must be tightly regulated to enable optimal lung function. Lung branching and lumen morphogenesis require close epithelial cell–cell contacts that are maintained as a result of adherens junctions, tight junctions and by intact apical–basal (A/B) polarity. However, the molecular mechanisms that maintain epithelial cohesion and lumen diameter in the mammalian lung are unknown. Here we show that Scribble, a protein implicated in planar cell polarity (PCP) signalling, is necessary for normal lung morphogenesis. Lungs of the Scrib mouse mutant Circletail (Crc) are abnormally shaped with fewer airways, and these airways often lack a visible, ‘open’ lumen. Mechanistically we show that Scrib genetically interacts with the core PCP gene Vangl2 in the developing lung and that the distribution of PCP pathway proteins and Rho mediated cytoskeletal modification is perturbed in Scrib^Crc/Crc lungs. However A/B polarity, which is disrupted in Drosophila Scrib mutants, is largely unaffected. Notably, we find that Scrib mediates functions not attributed to other PCP proteins in the lung. Specifically, Scrib localises to both adherens and tight junctions of lung epithelia and knockdown of Scrib in lung explants and organotypic cultures leads to reduced cohesion of lung epithelial cells. Live imaging of Scrib knockdown lungs shows that Scrib does not affect bud bifurcation, as previously shown for the PCP protein Celsr1, but is required to maintain epithelial cohesion. To understand the mechanism leading to reduced cell–cell association, we show that Scrib associates with β-catenin in embryonic lung and the sub-cellular distribution of adherens and tight junction proteins is perturbed in mutant lung epithelia. Our data reveal that Scrib is required for normal lung epithelial organisation and lumen morphogenesis by maintaining cell–cell contacts. Thus we reveal novel and important roles for Scrib in lung development operating via the PCP pathway, and in regulating junctional complexes and cell cohesion.     

Timemresolved fluorescence of S-100a protein: effect of Ca, Mg and unilamellar vesicles of egg phosphatidylcholine

Phase-modulation fluorescence lifetime measurements were used to study the single Trp residue of the Ca²⁺-binding protein S-100a both in the absence and in the presence of Ca²⁺ and/or Mg²⁺. Trp fluorescence decay for the protein was satisfactorily described by Lorentzian lifetime distributions centered around two components (approximately 4 ns and 0.5 ns). Lifetime values were unchanged by 2 mM Ca²⁺, but the fractional intensity associated with longer lifetime increased up to 75%. In the presence of Mg²⁺, the Ca²⁺ induced increase of the fractional intensity associated with longer lifetime was only 57%. For the protein in buffer, about the 85% of the recovered anisotropy was associated to a rotational correlation time of 6.7 ns. After the addition of Ca²⁺, this value was increased to 16.08 ns. In the presence of Mg²⁺, Ca⁺² increased the rotational correlation time to 33.75 ns. Similar studies were performed with S-100a interacting with egg phosphatidylcholine vesicles (SUV). Our data suggest that the conformation of the protein may be influenced by structural features of the lipidic membrane. Moreover, data obtained in the presence of Mg²⁺ indicate some interaction between lipids and S-100, likely mediated by this ion.     

The utilization of ethanolamine and serine for ethanolamine phosphoglyceride synthesis by human Y79 retinoblastoma cells

Phospholipid synthesis was investigated in human Y79 retinoblastoma cells, a cultured cell line of retinal origin that retains many neural characteristics. Ethanolamine is taken up by Y79 cells through a high-affinity transport system and is utilized to synthesize ethanolamine and choline phosphoglycerides. High-affinity ethanolamine uptake has a K'm of 40.6 microM and a V'max of 1.06 nmol/min/mg protein, and the process is Na+ dependent. Choline is the only compound tested that reduced ethanolamine uptake, and very high choline concentrations were required to produce this effect. The cells incorporate ethanolamine into phosphatidylethanolamine and ethanolamine plasmalogen at equivalent rates, and the rates of catabolism of these phospholipids are similar. Only a small quantity of ethanolamine is incorporated into phosphatidylcholine, but the amount is not reduced by the addition of choline. Serine is incorporated into phosphatidylserine, which then is converted to phosphatidylethanolamine. Ethanolamine reduces but does not abolish this conversion. Unlike ethanolamine, only a small amount of serine is incorporated into ethanolamine plasmalogen. It is possible that the ethanolamine high-affinity uptake system is necessary to provide a neural cell with enough free ethanolamine for ethanolamine plasmalogen synthesis.     

Work ability of health care shift workers: What matters?

This paper aims at identifying variables associated with inadequate work ability among nursing personnel at a public hospital, considering factors related to socio-demographic, lifestyles, working conditions, and health outcomes. A cross-sectional study was conducted in a university hospital in S?o Paulo, Brazil, as part of a larger research study on tolerance to 12 h night work. Nursing staff included registered nurses, nurse technicians, and nurse aides; in total, there were 996 healthcare workers (878 female; 118 male) at the time of the study. Some 696 workers (69.9%) of the population agreed to participate. Data collection (October 2004-July 2005) was based on a comprehensive questionnaire about living and working conditions (including incivility at work, work demands, work control, and support), mental and physical health symptoms (fatigue and sleep problems), and work ability. This report presents analyses of the adapted Brazilian version of the Work Ability Index (WAI) and associated variables. The study population worked one of the following shift schedules at this hospital: 12 h nights followed by 36 h off or 9 h or 6 h day (morning or afternoon) shifts. The mean age of the respondents was 34.9 (S.D.+/-10.4) years of age; 31.5% of the participants held two jobs. Statistical analyses using a hierarchical multiple logistic regression model were performed to evaluate the factors associated with inadequate (moderate and low scores) of the WAI. The significantly associated factors were socio-demographic (income responsibility, sole breadwinner, raising kids, age group), working conditions (thermal discomfort, organization of the workplace, and verbal abuse), and health outcomes (high body mass index, obesity, sleep problems, and fatigue). In spite of limitations of the study design, results indicate that the nursing profession is associated with stressful working conditions, contributing to inadequate WAI. This is in addition to bad living conditions and precarious work. Intervention measures, either at the workplace or at individual levels, are necessary to prevent a decrease in work ability, even in this quite young working population.     

Safety and Immunomodulatory Effects of Three Probiotic Strains Isolated from the Feces of Breast-Fed Infants in Healthy Adults: SETOPROB Study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.

Trial Registration

ClinicalTrials.gov NCT01479543     

Disulfiram irreversibly aggregates betaine aldehyde dehydrogenase--a potential target for antimicrobial agents against Pseudomonas aeruginosa

In the human pathogen Pseudomonas aeruginosa, betaine aldehyde dehydrogenase (PaBADH) may play the dual role of assimilating carbon and nitrogen from choline or choline precursors--abundant at infection sites--and producing glycine betaine, which protects the bacterium against the high-osmolality stress prevalent in the infected tissues. This tetrameric enzyme contains four cysteine residues per subunit and is a potential drug target. In our search for specific inhibitors, we mutated the catalytic Cys286 to alanine and chemically modified the recombinant wild-type and the four Cys-->Ala single mutants with thiol reagents. The small methyl-methanethiosulfonate inactivated the enzymes without affecting their stability while the bulkier dithionitrobenzoic acid (DTNB) and bis[diethylthiocarbamyl] disulfide (disulfiram) induced enzyme dissociation--at 23 degrees C--and irreversible aggregation--at 37 degrees C. Of the four Cys-->Ala mutants only C286A retained its tetrameric structure after DTNB or disulfiram treatments, suggesting that steric constraints arising upon the covalent attachment of a bulky group to C286 resulted in distortion of the backbone configuration in the active site region followed by a severe decrease in enzyme stability. Since neither NAD(P)H nor betaine aldehyde prevented disulfiram-induced PaBADH inactivation or aggregation, and reduced glutathione was unable to restore the activity of the modified enzyme, we propose that disulfiram could be a useful drug to combat infection by P. aeruginosa.