FEV1 Is a Better Predictor of Mortality than FVC: The PLATINO Cohort Study

Objective

To determine whether the presence of chronic obstructive lung disease (COPD) and reduction of lung function parameters were predictors of mortality in a cohort.

Materials/Patients and Methods

Population based cohorts were followed in Montevideo, Santiago and Sao Paulo during 5, 6 and 9 years, respectively. Outcomes included all-cause, cardiovascular, respiratory and cancer mortality; exposures were COPD, forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC). Cox regression was used for analyses. Sensitivity, specificity, positive and negative predictive values, receiver operator characteristics curves and Youden''s index were calculated.

Results

Main causes of death were cardiovascular, respiratory and cancer. Baseline COPD was associated with overall mortality (HR = 1.43 for FEV₁/FVC<LLN; 2.01 for GOLD 2-4; 1.46 for GOLD 1-4; 1.50 for FEV₁/FEV₆ <LLN). For cardiovascular mortality, significant associations were found with GOLD 2-4 (HR = 2.68) and with GOLD 1-4 (HR = 1.78) for both genders together (not among women). Low FEV₁ was risk for overall and respiratory mortality (both genders combined). FVC was not associated with overall mortality. For most COPD criteria sensitivity was low and specificity high. The area under the curve for FEV₁ was greater than for FVC for overall and cardiovascular mortality.

Answer to the Question

COPD and low FEV₁ are important predictors for overall and cardiovascular mortality in Latin America.     

Capitate glandular trichomes of Helianthus annuus (Asteraceae): ultrastructure and cytological development

Previous studies have shown that capitate glandular trichomes (CGT) of the common sunflower, Helianthus annuus, produce sesquiterpene lactones (STL) and flavonoids, which are sequestered and accumulated between the apical cuticle and the wall of the tip cells. To explore the cellular structures required and putatively involved in the STL biosynthesis and secretion, the present study was focused on the development of CGT and the comparison of the ultrastructure of its different cell types. Gradual maturation of flowers in the capitulum of the sunflower provided the possibility to study the simultaneous differentiation from the primordial to the secretory stage of CGT located by light microscopy (bright field, differential interference contrast and fluorescence) as well as transmission electron microscopy. It was shown that the CGT of sunflower anthers had a biseriate structure with up to 14 cell pairs. In mature trichomes, the apical cells called secretory cells were covered entirely by a large cuticle globe, which enclosed the resinous terpenoids and was specialised in thickness and structure. The secretory cells lacked chloroplasts and contained mainly smooth endoplasmic reticulum (sER). Conspicuous cell wall protuberances and an accumulation of mitochondria nearby occurred in the horizontally oriented cell walls. The cytological differences between stalk cells and secretory cells indicate a different function. The dominance of sER suggests its involvement in STL biosynthesis and cell wall protuberances enlarge the surface of the plasmamembrane of secretory cells and may be involved in the secretion processes of STL into the subcuticular space.     

Design of ant-inspired stochastic control policies for collective transport by robotic swarms

In this paper, we present an approach to designing decentralized robot control policies that mimic certain microscopic and macroscopic behaviors of ants performing collective transport tasks. In prior work, we used a stochastic hybrid system model to characterize the observed team dynamics of ant group retrieval of a rigid load. We have also used macroscopic population dynamic models to design enzyme-inspired stochastic control policies that allocate a robotic swarm around multiple boundaries in a way that is robust to environmental variations. Here, we build on this prior work to synthesize stochastic robot attachment–detachment policies for tasks in which a robotic swarm must achieve non-uniform spatial distributions around multiple loads and transport them at a constant velocity. Three methods are presented for designing robot control policies that replicate the steady-state distributions, transient dynamics, and fluxes between states that we have observed in ant populations during group retrieval. The equilibrium population matching method can be used to achieve a desired transport team composition as quickly as possible; the transient matching method can control the transient population dynamics of the team while driving it to the desired composition; and the rate matching method regulates the rates at which robots join and leave a load during transport. We validate our model predictions in an agent-based simulation, verify that each controller design method produces successful transport of a load at a regulated velocity, and compare the advantages and disadvantages of each method.     

Somatostatin receptor subtype 4 modulates L-type calcium channels via Gβγ and PKC signaling in rat retinal ganglion cells

Somatostatin subtype-4 receptors (sst₄) inhibit L-type calcium channel currents (I_Ca) in retinal ganglion cells (RGCs). Here we identify the signaling pathways involved in sst₄ stimulation leading to suppression of I_Ca in RGCs. Whole cell patch clamp recordings were made on isolated immunopanned RGCs using barium as a charge carrier to isolate I_Ca. Application of the selective sst₄ agonist, L-803 (10 nM), reduced I_Ca by 41.2%. Pretreatment of cells with pertussis toxin (Gi/o inhibitor) did not prevent the action of L-803, which reduced I_Ca by 34.7%. To determine the involvement of Gβγ subunits after sst₄ activation, depolarizing pre-pulse facilitation paradigms were used to remove voltage-dependent inhibition of calcium channels. Pre-pulse facilitation did not reverse the inhibitory effects of L-803 on I_Ca (8.4 vs. 8.8% reductions, ctrl vs. L-803); however, pharmacologic inhibition of Gβγ reduced I_Ca suppression by L-803 (23.0%, P < 0.05). Inhibition of PKC (GF109203X; GFX) showed a concentration-dependent effect in preventing the action of L-803 on I_Ca (1 μM GFX, 34.3%; 5 μM GFX, 14.6%, P < 0.05). When both PKC and Gβγ were inhibited, the effects of L-803 on I_Ca were blocked (1.8%, P < 0.05). These results suggest that sst₄ stimulation modulates RGC calcium channels via Gβγ and PKC activation. Since reducing intracellular Ca²⁺ is known to be neuroprotective in RGCs, modulating these sst₄ signaling pathways may provide insights to the discovery of unique therapeutic targets to reduce intracellular Ca²⁺ levels in RGCs.     

Genome sequence of the exopolysaccharide-producing Salipiger mucosus type strain (DSM 16094T), a moderately halophilic member of the Roseobacter clade

Salipiger mucosus Martínez-Cànovas et al. 2004 is the type species of the genus Salipiger, a moderately halophilic and exopolysaccharide-producing representative of the Roseobacter lineage within the alphaproteobacterial family Rhodobacteraceae. Members of this family were shown to be the most abundant bacteria especially in coastal and polar waters, but were also found in microbial mats and sediments. Here we describe the features of the S. mucosus strain DSM 16094^T together with its genome sequence and annotation. The 5,689,389-bp genome sequence consists of one chromosome and several extrachromosomal elements. It contains 5,650 protein-coding genes and 95 RNA genes. The genome of S. mucosus DSM 16094^T was sequenced as part of the activities of the Transregional Collaborative Research Center 51 (TRR51) funded by the German Research Foundation (DFG).     

Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity

Recent evidence indicates that arrest of mammalian cells at the G(2)/M checkpoint involves inactivation and translocation of Cdc25C, which is mediated by phosphorylation of Cdc25C on serine 216. Data obtained with a phospho-specific antibody against serine 216 suggest that activation of the DNA damage checkpoint is accompanied by an increase in serine 216 phosphorylated Cdc25C in the nucleus after exposure of cells to gamma-radiation. Prior treatment of cells with 2 mM caffeine inhibits such a change and markedly reduces radiation-induced ataxia-telangiectasia-mutated (ATM)-dependent Chk2/Cds1 activation and phosphorylation. Chk2/Cds1 is known to localize in the nucleus and to phosphorylate Cdc25C at serine 216 in vitro. Caffeine does not inhibit Chk2/Cds1 activity directly, but rather, blocks the activation of Chk2/Cds1 by inhibiting ATM kinase activity. In vitro, ATM phosphorylates Chk2/Cds1 at threonine 68 close to the N terminus, and caffeine inhibits this phosphorylation with an IC(50) of approximately 200 microM. Using a phospho-specific antibody against threonine 68, we demonstrate that radiation-induced, ATM-dependent phosphorylation of Chk2/Cds1 at this site is caffeine-sensitive. From these results, we propose a model wherein caffeine abrogates the G(2)/M checkpoint by targeting the ATM-Chk2/Cds1 pathway; by inhibiting ATM, it prevents the serine 216 phosphorylation of Cdc25C in the nucleus. Inhibition of ATM provides a molecular explanation for the increased radiosensitivity of caffeine-treated cells.     

Putative local adaptations modulate the interactions of the carnivorous plant Drosera uniflora Willd (1809) (Droseraceae) with cushion and shrub nurse plants

Cushion and shrub plants are typical high mountain nurse plants. In Magellanic tundras of the Cordillera del Sarao on the coast of Chile, the carnivorous plant Drosera uniflora grows in association with cushions of Donatia fascicularis and the shrubs Chusquea montana var. nigricans and Lepidothamnus fonkii. The different microhabitats for recruitment, in addition to the limited gene flow of D. uniflora, enable us to hypothesise that this plant manifests putative local adaptations, expressed in seed germination and population abundance. Our aim was to evaluate the local adaptation of D. uniflora to cushion and shrub microhabitats by estimating germination and abundance. Local adaptation of seed germination was determined by means of reciprocal transplant experiments. Abundance was determined in small plots located inside, on the edge and outside the nurse plants. Seed origin and growth substrate play a decisive role in D. uniflora germination. Seeds that originate from cushions plant habitat and germinate in the same substrate do so in greater numbers than when those which originate from shrubby habitats. Conversely, seeds that originate from shrubby habitat and germinate in the same substrate do not exhibit significant differences. Abundance was always greater inside than outside of the nurse plants. We concluded that availability and quality of different microhabitats for seed germination and recruitment, together with a limited gene flow, would trigger putative local adaptations in D. uniflora, modulating a long history of interactions with the plants that act as nurse plants.     

Accumulation of the proteolytic marker peptide ubiquitin in the trophoblast of mammalian blastocysts

Ubiquitination is a universal protein degradation pathway in which the molecules of 8.5-kDa proteolytic peptide ubiquitin are covalently attached to the epsilon-amino group of the substrate's lysine residues. Little is known about the importance of this highly conserved mechanism for protein recycling in mammalian gametogenesis and fertilization. The data obtained by the students and faculty of the international training course Window to the Zygote 2000 demonstrate the accumulation of ubiquitin-cross-reactive structures in the trophoblast, but not in the inner cell mass of the expanding bovine and mouse blastocysts. This observation suggests that a major burst of ubiquitin-dependent proteolysis occurs in the trophoblast of mammalian peri-implantation embryos. This event may be important for the success of blastocyst hatching, differentiation of embryonic stem cells into soma and germ line, and/or implantation in both naturally conceived and reconstructed mammalian embryos.     

Annuithrin,a new biologically active germacranolide from Helianthus annuus

Investigations on growth inhibition in Helianthus annuus led to the isolation of a new sesquiterpene lactone, a germacranolide with an α-methylene-γ-lactone moiety. The structure of this new germacranolide, annuithrin, was elucidated by spectroscopic methods. Its biological activity has been proven by growth inhibition in straight growth tests, antibacterial tests and inhibition of DNA-/RNA-synthesis in cells of the ascitic form of Ehrlich carcinoma.