Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Forearc carbon sink reduces long-term volatile recycling into the mantle.

Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.

Forearc carbon sink reduces long-term volatile recycling into the mantle.

Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.

Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1.

Diet has a significant impact on colorectal cancer and both dietary fiber and plant-derived compounds have been independently shown to be inversely related to colon cancer risk. Butyrate (NaB), one of the principal products of dietary fiber fermentation, induces differentiation of colon cancer cell lines by inhibiting histone deacetylases (HDACs). On the other hand, (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG), two abundant phenolic compounds of green tea, have been shown to exhibit antitumoral properties. In this study we used colon cancer cell lines to study the cellular and molecular events that take place during co-treatment with NaB, EC and EGCG. We found that (i) polyphenols EC and EGCG fail to induce differentiation of colon adenocarcinoma cell lines; (ii) polyphenols EC and EGCG reduce NaB-induced differentiation; (iii) the effect of the polyphenols is specific for NaB, since differentiation induced by other agents, such as trichostatin A (TSA), was unaltered upon EC and EGCG treatment, and (iv) is independent of the HDAC inhibitory activity of NaB. Also, (v) polyphenols partially reduce cellular NaB; and (vi) on a molecular level, reduction of cellular NaB uptake by polyphenols is achieved by impairing the capacity of NaB to relocalize its own transporter (monocarboxylate transporter 1, MCT1) in the plasma membrane. Our findings suggest that beneficial effects of NaB on colorectal cancer may be reduced by green tea phenolic supplementation. This valuable information should be of assistance in choosing a rational design for more effective diet-driven therapeutic interventions in the prevention or treatment of colorectal cancer.

Metabolic profile in endothelial cells of chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.

[Perioperative anesthetic management of 300 morbidly obese patients undergoing laparoscopic bariatric surgery and a brief review of relevant pathophysiology]. / Tratamiento anestésico perioperatorio de 300 pacientes con obesidad mórbida sometidos a cirugía bariátrica laparoscópica y breve revisión fisiopatológica.

OBJECTIVES: Laparoscopic bariatric surgery is a challenge for anesthesiologists because morbidly obese patients are at high risk and laparoscopy may complicate respiratory and hemodynamic management. The aim of this study was to analyze the perioperative anesthetic management of morbidly obese patents undergoing laparoscopic bariatric surgery. MATERIAL AND METHODS: Prospective study of 300 consecutive patients diagnosed with morbid obesity and scheduled for laparoscopic bariatric surgery. Patients were positioned with a wedge cushion under the head and shoulders. A rapid sequence induction of anesthesia was carried out. A short-handled, articulated-blade McCoy laryngoscope was used for intubation; an intubation laryngeal mask airway (Fastrach) was on hand as a rescue device. Propofol and remifentanil were used for maintenance of anesthesia and morphine was administered at the end of surgery. Incentive spirometry was initiated in the postanesthetic recovery unit. RESULTS: Eighty percent of the patients were women with a mean (SD) body mass index (kg/m2) of 46 (5). The first choice of direct laryngoscopic intubation was successful in 98.6% of cases. All patients were successfully intubated. Only 5 patients required intensive care. Postoperative complications (mainly respiratory problems, bleeding, and infections) were observed in 17%. No patient died. CONCLUSIONS: Perianesthetic management of morbidly obese patients who undergo laparoscopic surgery is safe. To minimize pulmonary complications, preoxygenation and rapid sequence induction should be performed correctly and incentive spirometry should be initiated in the immediate postoperative period. The McCoy laryngoscope ensures intubation in most cases.

[Laughter therapy for chronic skeletal muscular pain]. / Terapia de la risa en el dolor crónico músculo-esquelético.

The authors explain the effects introducing workshops for laughter therapy and relaxation to a unit dedicated to therapeutic education and functional rehabilitation; the authors test to see if the application of this therapy helps to decrease pain, to improve mobility and to reduce an altered emotional state, such as anxiety-depression, common among chronic pain patients.

[Tuberculosis pathology attended in emergency through the analysis of the hospital discharges MBDS in the West Valladolid Area, Spain (2002-2006)]. / Patología tuberculosa atendida en urgencias a través del análisis del CMBD de hospitalización en el área de Valladolid Oeste (2002-2006).

BACKGROUND: Tuberculosis (TB) continues to be an important health problem, in many cases the Hospital Emergency Services (HES) are the first contact of the patients with the sanitary system, there is not known the impact of this disease in the above mentioned services. The objectives of this study are to know the importance of TB in HES and to describe hospital discharges (MBDS) with TB diagnosis and if they had already been diagnosed in the HES. METHODS: A retrospective descriptive study of discharges with TB diagnosis in the hospital ward and in the HES of a tertiary care university hospital from 2002 to 2006. The Diagnostic concordance study and analysis of variables according to two groups: Coincidents (discharge with TB diagnosis in the HES and in the MBDS) and Only in the MBDS. Calculate statisticals of central tendency and dispersal for the quantitative variables and proportions and tables of contingency with application of the test chi(2) for the qualitative ones. RESULTS: Of the 172 (0.26%) emergencies admitted which were hospital discharges with Tb diagnosis, 61(35.5%) came in HES. The diagnostic concordance was 0.43(43.66%). The hospital discharges with Tb diagnosis (coincidents) changed from 47 (17) in 2002 to 21(5) in 2006. The 65.1% (68.9% in coincidents) were males. As regards age groups (coincidents%): 0-14: 6 (33.3%), 15-45: 81(47%), 46-65: 46(28.7%), 65: 39(19.7%); excluding group 0-14, p=0.009. Respiratory location (coincidents): 110 (50) and positive direct examination of smears for acid-fast bacilli (coincidents): 87 (43). Between well-known risk factors immigration stands out (p=0.001). CONCLUSIONS: The discharges with TB diagnosis declined during the period studied. The diagnostic concordance in the HES was moderate. We would have to insist more on seniors, and in people with well-known risk factors. In the HES the respiratory TB is also the most frequent being the direct examination of smears for acid-fast bacilli the principal diagnostic method.

The changes in the energy metabolism of human muscle induced by training.

The biochemical effects of training programmes have been studied with a kinetic model of central metabolism, using enzyme activities and metabolite concentrations measured at rest and after 30 s maximum-intensity exercise, collected before and after long and short periods of training, which differed only by the duration of the rest intervals. After short periods of training the glycolytic flux at rest was three times higher than it had been before training, whereas during exercise the flux and energy consumption remained the same as before training. Long periods of training had less effect on the glycolytic flux at rest, but increased it in response to exercise, increasing the contribution of oxidative phosphorylation.

The importance of polymerization and galloylation for the antiproliferative properties of procyanidin-rich natural extracts.

Grape (Vitis vinifera) and pine (Pinus pinaster) bark extracts are widely used as nutritional supplements. Procyanidin-rich fractions from grape and pine bark extract showing different mean degrees of polymerization, percentage of galloylation (percentage of gallate esters) and reactive oxygen species-scavenging capacity were tested on HT29 human colon cancer cells. We observed that the most efficient fractions in inhibiting cell proliferation, arresting the cell cycle in G(2) phase and inducing apoptosis were the grape fractions with the highest percentage of galloylation and mean degree of polymerization. Additionally, the antiproliferative effects of grape fractions were consistent with their oxygen radical-scavenging capacity and their ability to trigger DNA condensation-fragmentation.

Anticancer effect of a new benzophenanthridine isolated from Zanthoxylum madagascariense (Rutaceline).

Fractionation of the cyclohexane extract from the stem bark powder of Zanthoxylum madagascariense led to the isolation of a new benzophenanthridine-type alkaloid, hydrochloride of 2,3-methylendioxy-8-hydroxy- 7-methoxy-benzo[C]phenanthridine (Rutaceline), characterized on the basis of its spectral data. Rutaceline was evaluated for its antiproliferative capacity on the human colorectal adenocarcinoma (Caco-2) and the African green monkey kidney (Vero) cell lines. The 50% inhibition of cell growth (IC50) obtained after 24 h incubation was similar for both cells lines (110-115 microg/ml, i.e. 269-281 microM), but at 48 h the IC50 value for the Caco-2 cells was lower than for the Vero cells (20 microg/lml, i.e. 49 microM versus 90 microg/ml, i.e. 220 microM) indicating a higher cell growth inhibitory effect on the colon adenocarcinoma cells. At the respective IC50 concentrations, Rutaceline did not significantly induce apoptosis but induced cell cycle arrest in the GO/G1 phase, as well as a decrease of cells in S phase. Rutaceline also induced DNA fragmentation in both cell lines, as revealed by agarose gel electrophoresis, and a dose-dependent clastogenic effect in both cell lines as revealed by the Comet assay.

Functional fatty fish supplemented with grape procyanidins. Antioxidant and proapoptotic properties on colon cell lines.

This work shows the properties of grape procyanidins with additional anticarcinogenic properties for increasing the shelf life of functional seafood preparations. Galloylated procyanidins (100 ppm, 2.7 mean degree of polymerization, 25% galloylation) extended the shelf life of minced horse mackerel muscle stored at 4 degrees C more than 8 days compared to controls without addition of polyphenols. The levels of endogenous alpha-tocopherol, EPA, and DHA of fish muscle were also preserved after 10 days at 4 degrees C. Therefore, the presence of procyanidins increased the stability of a product based on minced fish muscle during cold storage and maintained its functionality associated with the presence of polyunsaturated fatty acids and alpha-tocopherol. In addition, grape procyanidins showed a significant capacity to induce apoptosis in colon cancer cells (HT29 cell line) while being inactive in noncancer control cells (IEC-6). Thus, the product based on fatty fish muscle supplemented with grape procyanidins appears to be a stable functional food offering the combined action of omega-3 fatty acids and natural polyphenols.

Transforming growth factor beta2 promotes glucose carbon incorporation into nucleic acid ribose through the nonoxidative pentose cycle in lung epithelial carcinoma cells.

The invasive transformation of A-459 lung epithelial carcinoma cells has been linked to the autocrine regulation of malignant phenotypic changes by transforming growth factor beta (TGF-beta). Here we demonstrate, using stable 13C glucose isotopes, that the transformed phenotype is characterized by decreased CO2 production via direct glucose oxidation but increased nucleic acid ribose synthesis through the nonoxidative reactions of the pentose cycle. Increased nucleic acid synthesis through the nonoxidative pentose cycle imparts the metabolic adaptation of nontransformed cells to the invasive phenotype that potentially explains the fundamental metabolic disturbance in tumor cells: highly increased nucleic acid synthesis despite hypoxia and decreased glucose oxidation.

Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation.

This study investigates the significance of the glucose-6-phosphate dehydrogenase (G6PD) catalyzed oxidative and the transketolase (TK) catalyzed nonoxidative pentose cycle (PC) reactions in the tumor proliferation process by characterizing tumor growth patterns and synthesis of the RNA ribose moiety in the presence of respective inhibitors of G6PD and TK. Mass spectra analysis of 13C-labeled carbons revealed that these PC reactions contribute to over 85% of de novo ribose synthesis in RNA from [1,2-(13)C]glucose in cultured Mia pancreatic adenocarcinoma cells, with the fraction synthesized through the TK pathway predominating (85%). Five days of treatment with the TK inhibitor oxythiamine (OT) and the G6PD inhibitor dehydroepiandrosterone-sulfate (0.5 microM each) exerted a 39 and a 23% maximum inhibitory effect on cell proliferation in culture, which was increased to 60% when the two drugs were administered in combination. In vivo testing of 400 mg/kg OT or dehydroepiandrosterone-sulfate in C57BL/6 mice hosting Ehrlich's ascitic tumor cells revealed a 90.4 and a 46% decrease in the final tumor mass after 3 days of treatment. RNA ribose fractional synthesis through the TK reaction using metabolites directly from glycolysis declined by 9.1 and 23.9% after OT or the combined treatment, respectively. Nonoxidative PC reactions play a central regulating role in the carbon-recruiting process toward de novo nucleic acid ribose synthesis and cell proliferation in vitro and in vivo. Therefore, enzymes or substrates regulating the nonoxidative synthesis of ribose could also be the sites to preferentially target tumor cell proliferation by new anticancer drugs.

Control analysis of metabolic systems involving quasi-equilibrium reactions.

Reactions for which the rates are extremely sensitive to changes in the concentrations of variable metabolite concentrations contribute little to the control of biochemical reaction networks. Yet they do interfere with the calculation of the system's behaviour, both in terms of numerical integration of the rate equations and in terms of the analysis of metabolic control. We here present a way to solve this problem systematically for systems with time hierarchies. We identify the fast reactions and fast metabolites, group them apart from the other ("slow") reactions and metabolites, and then apply the appropriate quasi-equilibrium condition for the fast subsystem. This then makes it possible to eliminate the fast reactions and their elasticity coefficients from the calculations, allowing the calculation of the control coefficients of the slow reactions in terms of the elasticity coefficients of the slow reactions. As expected, the elasticity coefficients of the fast reactions drop out of the calculations, and they are irrelevant for control at the time resolution of the steady state of the slow reactions. The analysis, when applied iteratively, is expected to be particularly valuable for the control analysis of living cells, where a time hierarchy exists, the fastest being at the level of enzyme kinetics and the slowest at gene expression.

Quantitative characterization of homo- and heteroassociations of muscle phosphofructokinase with aldolase.

Dissociation of purified phosphofructokinase accompanied with inactivation was analyzed in the absence and presence of aldolase and the data were compared with those obtained with muscle extract. The kinetics of the decrease in enzymatic activity was highly dependent on the dilution factor in both cases, but the inactivation appeared to be biphasic only with extract. The inactivation of the phosphofructokinase was impeded by addition of excess of aldolase. Time courses of kinase inactivation were fitted by alternative kinetic models to characterize the multiple equilibria of several homo- and hetero-oligomers of phosphofructokinase. The combination of modeling data obtained with purified and extract systems suggests that aldolase binds to an intermediate dimer of phosphofructokinase and within this heterocomplex the kinase is completely active. The intermediate dimer is stabilized by association with microtubules and the kinase activity decreased due to dilution can be recovered by addition of excess aldolase. In extract, the phosphofructokinase is of sigmoidal character (Hill coefficient of 2.3); the addition of excess exogenous aldolase to phosphofructokinase resulted in heterocomplex formation displaying Michaelian kinetics. The possible physiological relevance of heterocomplex formation of phosphofructokinase in muscle extract is discussed.

Optimization of xanthatin extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties.

The aqueous extraction of the sesquiterpene lactone xanthatin from Xanthium spinosum L. favours the conversion of xanthinin (1) to xanthatin (2) via the loss of acetic acid. The cytotoxic (Hep-G2 and L1210 human cell lines) and antiviral activities of isolated xanthatin are established. This natural compound shows significant cytotoxicity against the Hep-G2 cell line and our experimental results reveal its strong anti-angiogenesis capacity in vitro. The structure of xanthatin is determined by spectroscopic methods and for the first time confirmed by X-ray diffraction.

Melt electrospinning and its technologization in tissue engineering.

Melt electrospinning is an emerging fiber-based manufacturing technique that can be used to design and build scaffolds suitable for many tissue engineering (TE) applications. Contrary to the widely used solution electrospinning, the melt process is solvent-free and therefore volatility and toxicity issues associated with solvents can be avoided. Furthermore, molten polymers are often viscous and nonconductive, making them candidates for generating electrospinning jets without electrical instabilities. This in turn permits a precise and predictable fiber deposition in the combination with moving collectors, termed melt electrospinning writing (MEW), allows the layer-by-layer fabrication of small to large volume scaffolds with specific designs, shapes and thicknesses. In vitro studies have demonstrated that scaffolds designed and fabricated via MEW can support cell attachment, proliferation and extracellular matrix formation, as well as cell infiltration throughout the thickness of the scaffold facilitated by the large pores and pore interconnectivity. Moreover, in vivo studies show that scaffolds designed for specific tissue regeneration strategies performed superbly. This review describes the state-of-the-art and unique perspectives of melt electrospinning and its writing applied to scaffold-based TE.

Dramatic changes in control properties that accompany channelling and metabolite sequestration.

A simple summation theorem describes the control of fluxes in 'ideal' metabolic pathways. This paper shows how this theorem and the control properties of a pathway change when direct transfer of intermediates and/or sequestration of metabolites involved in moiety conservations (by enzymes present at high concentrations) take place. The derived generalized summation theorem quantifies the extent to which metabolite sequestration decreases and direct metabolite transfer can increase the control exerted by enzymes on the flux. The implications of metabolite channelling for the control of fluxes are discussed quantitatively.