Water status and gas exchange of umbu plants (Spondias tuberosa Arr. Cam.) propagated by seeds and stem cuttings

The experiment was carried out at the Embrapa Semi-Árido, Petrolina-PE, Brazil, in order to study the physiological responses of umbu plants propagated by seeds and by stem cuttings under water stress conditions, based on leaf water potential and gas exchange measurements. Data were collected in one-year plants established in pots containing 30 kg of a sandy soil and submitted to twenty-day progressive soil water deficit. The evaluations were based on leaf water potential and gas exchange data collection using psychrometric chambers and a portable infra-red gas analyzer, respectively. Plants propagated by seeds maintained a significantly higher water potential, stomatal conductance, transpiration and photosynthesis under decreasing soil water availability. However, plants propagated by stem cuttings were unable to maintain a favorable internal water balance, reflecting negatively on stomatal conductance and leaf gas exchange. This fact is probably because umbu plants propagated by stem cuttings are not prone to formation of root tubers which are reservoirs for water and solutes. Thus, the establishing of umbu plants propagated by stem cuttings must be avoided in areas subjected to soil water deficit.

Preparation of alpha-labeled aldehydes by base-catalyzed exchange reactions

A simple, efficient protocol for the preparation of α-labeled aldehydes based on H/D exchange catalyzed by 4-(N,N-dimethylamino)pyridine or Et3N is described. High chemical yields and ratios of isotope incorporation were obtained even when small amounts (1 mmol) of aldehyde were used.

Preparation of alpha-labeled aldehydes by base-catalyzed exchange reactions

A simple, efficient protocol for the preparation of α-labeled aldehydes based on H/D exchange catalyzed by 4-(N,N-dimethylamino)pyridine or Et3N is described. High chemical yields and ratios of isotope incorporation were obtained even when small amounts (1 mmol) of aldehyde were used.

AltitudeOmics : impaired pulmonary gas exchange efficiency and blunted ventilatory acclimatization in humans with patent foramen ovale after 16 days at 5,260 m.

A patent foramen ovale (PFO), present in ∼40% of the general population, is a potential source of right-to-left shunt that can impair pulmonary gas exchange efficiency [i.e., increase the alveolar-to-arterial Po2 difference (A-aDO2)]. Prior studies investigating human acclimatization to high-altitude with A-aDO2 as a key parameter have not investigated differences between subjects with (PFO+) or without a PFO (PFO-). We hypothesized that in PFO+ subjects A-aDO2 would not improve (i.e., decrease) after acclimatization to high altitude compared with PFO- subjects. Twenty-one (11 PFO+) healthy sea-level residents were studied at rest and during cycle ergometer exercise at the highest iso-workload achieved at sea level (SL), after acute transport to 5,260 m (ALT1), and again at 5,260 m after 16 days of high-altitude acclimatization (ALT16). In contrast to PFO- subjects, PFO+ subjects had 1) no improvement in A-aDO2 at rest and during exercise at ALT16 compared with ALT1, 2) no significant increase in resting alveolar ventilation, or alveolar Po2, at ALT16 compared with ALT1, and consequently had 3) an increased arterial Pco2 and decreased arterial Po2 and arterial O2 saturation at rest at ALT16. Furthermore, PFO+ subjects had an increased incidence of acute mountain sickness (AMS) at ALT1 concomitant with significantly lower peripheral O2 saturation (SpO2). These data suggest that PFO+ subjects have increased susceptibility to AMS when not taking prophylactic treatments, that right-to-left shunt through a PFO impairs pulmonary gas exchange efficiency even after acclimatization to high altitude, and that PFO+ subjects have blunted ventilatory acclimatization after 16 days at altitude compared with PFO- subjects.

A simple halide-to-anion exchange method for heteroaromatic salts and ionic liquids

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A− form) in non-aqueous media. The anion loading of the AER (OH− form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A− form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH3OH, CH3CN and the dipolar nonhydroxylic solvent mixture CH3CN:CH2Cl2 (3:7) and the anion exchange was equally successful with both lipophilic cations and anions.

Web Client for Smart Messaging Exchange

TeliaSoneran älykkään viestintäjärjestelmän kehitysluonnoksella (SME) pilotoidaan prototyyppipalveluita, joiden avulla asiakkaat voivat välittää viestejä matkapuhelimilla sekä tietokoneilla. SME:n peruspalveluita voidaan käyttää SIP-standardin mukaisilla asiakasohjelmilla sekä SME:n omilla WAP- ja WWW-käyttöliittymillä. Käyttäjät voivat nähdä toistensa tilatiedon, muuttaa omaa tilatietoaan sekä lähettää SIP-pikaviestejä, sähköpostiviestejä ja tekstiviestejä. Käyttäjät voivat myös ylläpitää listaa yhteyshenkilöistään, vastaanottaa pikaviestejä ja selata vastaanotettuja viestejä. Diplomityössä käsitellään yleisesti SME-järjestelmän rakennetta ja paneudutaan tutkimaan työssä toteutetun SME:n WWW-asiakasohjelman toteutusta. Diplomityössä käydään läpi projektiin liittyviä standardeja, suosituksia, toteustekniikoita sekä palveluita. Lisäksi tarkastellaan työssä hyödynnettyjä ohjelmointirajapintoja, nykyisiä älypuhelimia sekä niiden Internet-selaimia, jotka rajoittavat WWW-asiakaspalvelun toteutuksessa käytettyjä toteutustekniikkavaihtoehtoja. Lopuksi esitellään toteutettujen ohjelmistojen sisäistä rakennetta ja toimintaa.

Differential Dimerization of Variants Linked to Enhanced S-Cone Sensitivity Syndrome (ESCS) Located in the NR2E3 Ligand-Binding Domain.

NR2E3 encodes the photoreceptor-specific nuclear hormone receptor that acts as a repressor of cone-specific gene expression in rod photoreceptors, and as an activator of several rod-specific genes. Recessive variants located in the ligand-binding domain (LBD) of NR2E3 cause enhanced short wavelength sensitive- (S-) cone syndrome (ESCS), a retinal degeneration characterized by an excess of S-cones and non-functional rods. We analyzed the dimerization properties of NR2E3 and the effect of disease-causing LBD missense variants by bioluminescence resonance energy transfer (BRET(2) ) protein interaction assays. Homodimerization was not affected in presence of p.A256V, p.R039G, p.R311Q, and p.R334G variants, but abolished in presence of p.L263P, p.L336P, p.L353V, p.R385P, and p.M407K variants. Homology modeling predicted structural changes induced by NR2E3 LBD variants. NR2E3 LBD variants did not affect interaction with CRX, but with NRL and rev-erbα/NR1D1. CRX and NRL heterodimerized more efficiently together, than did either with NR2E3. NR2E3 did not heterodimerize with TLX/NR2E1 and RXRα/NR2C1. The identification of a new compound heterozygous patient with detectable rod function, who expressed solely the p.A256V variant protein, suggests a correlation between LBD variants able to form functional NR2E3 dimers and atypical mild forms of ESCS with residual rod function.

Gas exchange, phisiological indexes and ionic accumulation in Annona emarginata (Schltdl.) H. Rainer seedlings in nutrients solution

"Araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) has been consider a good alternative in rootstock production for the main commercial Annonaceae species. Although this species develops in different soil and climate conditions, there is no understanding by the physiological responses of this species at different nutritional levels. Thus, the objective of this study was to evaluate the influence of different ionic strengths on development of vegetative species known as "Araticum-de-terra-fria". It was evaluated in seedlings grown in different ionic strengths (25% I, 50% I, 75% I and 100% I) of the complete nutrient solution Hoagland and Arnon (1950) nº 2, for 140 days, the following characteristics: Gas Exchange (CO2 assimilation rate, stomatal conductance, internal CO2 concentration, transpiration rate, water use efficiency, Rubisco carboxylation efficiency); Vegetative growth characteristics (diameter, leaf number, dry matter); Physiological Indexes (leaf area ratio, specific leaf area, relative growth rate, net assimilation rate, leaf weight ratio) and Ionic Accumulation (nutrients leaf analysis). Seedlings grown under 50% I showed the highest values of Leaf CO2 assimilation rate, water use efficiency, carboxylation efficiency, growth, relative growth rate, net assimilation rate and ionic accumulation in the total dry matter. So it is concluded that "Araticum-de-terra-fria" seedlings grown under intermediate nutrient concentrations of complete nutrient solution Hoagland and Arnon (1950) nº 2, explored more adequately their physiological potential that justify their adaptation in different nutritional conditions and allow reducing the amount of mineral nutrition of seedlings production.

Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the peptide-MHC (pMHC) on cells is a key parameter for cell-mediated immunity. Yet a fundamental feature of most tumor antigen-specific CD8(+) T cells is that this avidity is low. In this study, we addressed the need to identify and select tumor-specific CD8(+) T cells of highest avidity, which are of the greatest interest for adoptive cell therapy in patients with cancer. To identify these rare cells, we developed a peptide-MHC multimer technology, which uses reversible Ni(2+)-nitrilotriacetic acid histidine tags (NTAmers). NTAmers are highly stable but upon imidazole addition, they decay rapidly to pMHC monomers, allowing flow-cytometric-based measurements of monomeric TCR-pMHC dissociation rates of living CD8(+) T cells on a wide avidity spectrum. We documented strong correlations between NTAmer kinetic results and those obtained by surface plasmon resonance. Using NTAmers that were deficient for CD8 binding to pMHC, we found that CD8 itself stabilized the TCR-pMHC complex, prolonging the dissociation half-life several fold. Notably, our NTAmer technology accurately predicted the function of large panels of tumor-specific T cells that were isolated prospectively from patients with cancer. Overall, our results demonstrated that NTAmers are effective tools to isolate rare high-avidity cytotoxic T cells from patients for use in adoptive therapies for cancer treatment.

Optimal Exchange Rate Policy in a Growing Semi-Open Economy

This paper considers an alternative perspective to China's exchange rate policy. It studies a semi-open economy where the private sector has no access to international capital markets but the central bank has full access. Moreover, it assumes limited financial development generating a large demand for saving instruments by the private sector. The paper analyzes the optimal exchange rate policy by modeling the central bank as a Ramsey planner. Its main result is that in a growth acceleration episode it is optimal to have an initial real depreciation of the currency combined with an accumulation of reserves, which is consistent with the Chinese experience. This depreciation is followed by an appreciation in the long run. The paper also shows that the optimal exchange rate path is close to the one that would result in an economy with full capital mobility and no central bank intervention.

Ligand binding to heparan sulfate proteoglycans induces their aggregation and distribution along actin cytoskeleton

Cell surface heparan sulfate proteoglycans (HSPGs) participate in molecular events that regulate cell adhesion, migration, and proliferation. The present study demonstrates that soluble heparin-binding proteins or cross-linking antibodies induce the aggregation of cell surface HSPGs and their distribution along underlying actin filaments. Immunofluorescence and confocal microscopy and immunogold and electron microscopy indicate that, in the absence of ligands, HSPGs are irregularly distributed on the fibroblast cell surface, without any apparent codistribution with the actin cytoskeleton. In the presence of ligand (lipoprotein lipase) or antibodies against heparan sulfate, HSPGs aggregate and colocalize with the actin cytoskeleton. Triton X-100 extraction and immunoelectron microscopy have demonstrated that in this condition HSPGs were clustered and associated with the actin filaments. Crosslinking experiments that use biotinylated lipoprotein lipase have revealed three major proteoglycans as binding sites at the fibroblast cell surface. These cross-linked proteoglycans appeared in the Triton X-100 insoluble fraction. Platinum/carbon replicas of the fibroblast surface incubated either with lipoprotein lipase or antiheparan sulfate showed large aggregates of HSPGs regularly distributed along cytoplasmic fibers. Quantification of the spacing between HSPGs by confocal microscopy confirmed that the nonrandom distribution of HSPG aggregates along the actin cytoskeleton was induced by ligand binding. When cells were incubated either with lipoprotein lipase or antibodies against heparan sulfate, the distance between immunofluorescence spots was uniform. In contrast, the spacing between HSPGs on fixed cells not incubated with ligand was more variable. This highly organized spatial relationship between actin and proteoglycans suggests that cortical actin filaments could organize the molecular machinery involved in signal transduction and molecular movements on the cell surface that are triggered by heparin-binding proteins.

Allosteric conversation in the androgen receptor ligand-binding domain surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. We previously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design.

Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma.

BACKGROUND: Immune checkpoint inhibitors targeting programmed cell death 1 (PD1) or its ligand (PD-L1) showed activity in several cancer types. METHODS: We performed immunohistochemistry for CD3, CD8, CD20, HLA-DR, phosphatase and tensin homolog (PTEN), PD-1, and PD-L1 and pyrosequencing for assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status in 135 glioblastoma specimens (117 initial resection, 18 first local recurrence). PD-L1 gene expression was analyzed in 446 cases from The Cancer Genome Atlas. RESULTS: Diffuse/fibrillary PD-L1 expression of variable extent, with or without interspersed epithelioid tumor cells with membranous PD-L1 expression, was observed in 103 of 117 (88.0%) newly diagnosed and 13 of 18 (72.2%) recurrent glioblastoma specimens. Sparse-to-moderate density of tumor-infiltrating lymphocytes (TILs) was found in 85 of 117 (72.6%) specimens (CD3+ 78/117, 66.7%; CD8+ 52/117, 44.4%; CD20+ 27/117, 23.1%; PD1+ 34/117, 29.1%). PD1+ TIL density correlated positively with CD3+ (P < .001), CD8+ (P < .001), CD20+ TIL density (P < .001), and PTEN expression (P = .035). Enrichment of specimens with low PD-L1 gene expression levels was observed in the proneural and G-CIMP glioblastoma subtypes and in specimens with high PD-L1 gene expression in the mesenchymal subtype (P = 5.966e-10). No significant differences in PD-L1 expression or TIL density between initial and recurrent glioblastoma specimens or correlation of PD-L1 expression or TIL density with patient age or outcome were evident. CONCLUSION: TILs and PD-L1 expression are detectable in the majority of glioblastoma samples but are not related to outcome. Because the target is present, a clinical study with specific immune checkpoint inhibitors seems to be warranted in glioblastoma.

Continental faunal exchange and the asymmetrical radiation of carnivores.

Lineages arriving on islands may undergo explosive evolutionary radiations owing to the wealth of ecological opportunities. Although studies on insular taxa have improved our understanding of macroevolutionary phenomena, we know little about the macroevolutionary dynamics of continental exchanges. Here we study the evolution of eight Carnivora families that have migrated across the Northern Hemisphere to investigate if continental invasions also result in explosive diversification dynamics. We used a Bayesian approach to estimate speciation and extinction rates from a substantial dataset of fossil occurrences while accounting for the incompleteness of the fossil record. Our analyses revealed a strongly asymmetrical pattern in which North American lineages invading Eurasia underwent explosive radiations, whereas lineages invading North America maintained uniform diversification dynamics. These invasions into Eurasia were characterized by high rates of speciation and extinction. The radiation of the arriving lineages in Eurasia coincide with the decline of established lineages or phases of climate change, suggesting differences in the ecological settings between the continents may be responsible for the disparity in diversification dynamics. These results reveal long-term outcomes of biological invasions and show that the importance of explosive radiations in shaping diversity extends beyond insular systems and have significant impact at continental scales.