Nitrous oxide net exchange in a beech dominated mixed forest in Switzerland measured with a quantum cascade laser spectrometer

International audienceNitrous oxide fluxes were measured at the Lägeren CarboEurope IP flux site over the multi-species mixed forest dominated by European beech and Norway spruce. Measurements were carried out during a four-week period in October?November 2005 during leaf senescence. Fluxes were measured with a standard ultrasonic anemometer in combination with a quantum cascade laser absorption spectrometer that measured N2O, CO2, and H2O mixing ratios simultaneously at 5 Hz time resolution. To distinguish insignificant fluxes from significant ones it is proposed to use a new approach based on the significance of the correlation coefficient between vertical wind speed and mixing ratio fluctuations. This procedure eliminated roughly 56% of our half-hourly fluxes. Based on the remaining, quality checked N2O fluxes we quantified the mean efflux at 0.8 ± 0.4 ?mol m?2 h?1 (mean ± standard error). Most of the contribution to the N2O flux occurred during a 6.5-h period starting 4.5 h before each precipitation event. No relation with precipitation amount could be found. Visibility data representing fog density and duration at the site indicate that wetting of the canopy may have as strong an effect on N2O effluxes as does below-ground microbial activity. It is speculated that above-ground N2O production from the senescing leaves at high moisture (fog, drizzle, onset of precipitation event) may be responsible for part of the measured flux. In comparison with the annual CO2 budget of ?342 g C m?2 yr?1 it is estimated that concurrent N2O fluxes offset at least 5% of the greenhouse forcing reduction via net CO2 uptake

Identifying clinically useful biomarkers in neurodegenerative disease through a collaborative approach: the NeuroToolKit

BACKGROUND: Alzheimer’s disease (AD) is a complex and heterogeneous disease, which requires reliable biomarkers for diagnosis and monitoring disease activity. Preanalytical protocol and technical variability associated with biomarker immunoassays makes comparability of biomarker data across multiple cohorts difficult. This study aimed to compare cerebrospinal fluid (CSF) biomarker results across independent cohorts, including participants spanning the AD continuum. METHODS: Measured on the NeuroToolKit (NTK) prototype panel of immunoassays, 12 CSF biomarkers were evaluated from three cohorts (ALFA+, Wisconsin, and Abby/Blaze). A correction factor was applied to biomarkers found to be affected by preanalytical procedures (amyloid-β1–42, amyloid-β1–40, and alpha-synuclein), and results between cohorts for each disease stage were compared. The relationship between CSF biomarker concentration and cognitive scores was evaluated. RESULTS: Biomarker distributions were comparable across cohorts following correction. Correlations of biomarker values were consistent across cohorts, regardless of disease stage. Disease stage differentiation was highest for neurofilament light (NfL), phosphorylated tau, and total tau, regardless of the cohort. Correlation between biomarker concentration and cognitive scores was comparable across cohorts, and strongest for NfL, chitinase-3-like protein-1 (YKL40), and glial fibrillary acidic protein. DISCUSSION: The precision of the NTK enables merging of biomarker datasets, after correction for preanalytical confounders. Assessment of multiple cohorts is crucial to increase power in future studies into AD pathogenesis

AKT activity orchestrates marginal zone B cell development in mice and humans.

The signals controlling marginal zone (MZ) and follicular (FO) B cell development remain incompletely understood. Here, we show that AKT orchestrates MZ B cell formation in mice and humans. Genetic models that increase AKT signaling in B cells or abolish its impact on FoxO transcription factors highlight the AKT-FoxO axis as an on-off switch for MZ B cell formation in mice. In humans, splenic immunoglobulin (Ig) D <sup>+</sup> CD27 <sup>+</sup> B cells, proposed as an MZ B cell equivalent, display higher AKT signaling than naive IgD <sup>+</sup> CD27 <sup>-</sup> and memory IgD <sup>-</sup> CD27 <sup>+</sup> B cells and develop in an AKT-dependent manner from their precursors in vitro, underlining the conservation of this developmental pathway. Consistently, CD148 is identified as a receptor indicative of the level of AKT signaling in B cells, expressed at a higher level in MZ B cells than FO B cells in mice as well as humans

Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

Because minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive (14)C-DPPC with a treatment dose of surfactant on d 8. After 14 d, lung pool sizes of saturated phosphatidylcholine were measured. Half-life of (2)H-DPPC (d 5) in tracheal aspirates was 28 +/- 4 h (mean +/- SEM). Half-life of radioactive DPPC (d 8) was 35 +/- 4 h. Saturated phosphatidylcholine pool size measured with stable isotopes on d 5 was 129 +/- 14 micro mol/kg, and 123 +/- 11 micro mol/kg on d 14 at autopsy. Half-lives were comparable to those obtained at d 0 and d 6 in our previous baboon studies. We conclude that surfactant metabolism does not change during the early development of bronchopulmonary dysplasia, more specifically, the metabolism of exogenous surfactant on d 8 is similar to that on the day of birth. Surfactant pool size is low at birth, increases after surfactant therapy, and is kept constant during the first 2 wk of life by endogenous surfactant synthesis. Measurements with stable isotopes are comparable to measurements with radioactive tracers and measurements at autopsy

Inhibitors of inflammation and endogenous surfactant pool size as modulators of lung injury with initiation of ventilation in preterm sheep

<p>Abstract</p> <p>Background</p> <p>Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation.</p> <p>Objective</p> <p>We tested the hypothesis that selective inhibitors of pro-inflammatory signaling would decrease lung inflammation induced by ventilation in preterm newborn lambs. We also examined if the variability in injury response was explained by variations in the endogenous surfactant pool size.</p> <p>Methods</p> <p>Date-mated preterm lambs (n = 28) were operatively delivered and mechanically ventilated to cause lung injury (tidal volume escalation to 15 mL/kg by 15 min at age). The lambs then were ventilated with 8 mL/kg tidal volume for 1 h 45 min. Groups of animals randomly received specific inhibitors for IL-8, IL-1, or NF-κB. Unventilated lambs (n = 7) were the controls. Bronchoalveolar lavage fluid (BALF) and lung samples were used to quantify inflammation. Saturated phosphatidylcholine (Sat PC) was measured in BALF fluid and the data were stratified based on a level of 5 μmol/kg (~8 mg/kg surfactant).</p> <p>Results</p> <p>The inhibitors did not decrease the cytokine levels or inflammatory response. The inflammation increased as Sat PC pool size in BALF decreased. Ventilated lambs with a Sat PC level > 5 μmol/kg had significantly decreased markers of injury and lung inflammation compared with those lambs with < 5 μmol/kg.</p> <p>Conclusion</p> <p>Lung injury caused by high tidal volumes at birth were decreased when endogenous surfactant pool sizes were larger. Attempts to decrease inflammation by blocking IL-8, IL-1 or NF-κB were unsuccessful.</p

Interaction of Bestrophin-1 and Ca2+ Channel β-Subunits: Identification of New Binding Domains on the Bestrophin-1 C-Terminus

Bestrophin-1 modulates currents through voltage-dependent L-type Ca2+ channels by physically interacting with the β-subunits of Ca2+ channels. The main function of β-subunits is to regulate the number of pore-forming CaV-subunits in the cell membrane and modulate Ca2+ channel currents. To understand the influence of full-length bestrophin-1 on β-subunit function, we studied binding and localization of bestrophin-1 and Ca2+ channel subunits, together with modulation of CaV1.3 Ca2+ channels currents. In heterologeous expression, bestrophin-1 showed co-immunoprecipitation with either, β3-, or β4-subunits. We identified a new highly conserved cluster of proline-rich motifs on the bestrophin-1 C-terminus between amino acid position 468 and 486, which enables possible binding to SH3-domains of β-subunits. A bestrophin-1 that lacks these proline-rich motifs (ΔCT-PxxP bestrophin-1) showed reduced efficiency to co-immunoprecipitate with β3 and β4-subunits. In the presence of ΔCT-PxxP bestrophin-1, β4-subunits and CaV1.3 subunits partly lost membrane localization. Currents from CaV1.3 subunits were modified in the presence of β4-subunit and wild-type bestrophin-1: accelerated time-dependent activation and reduced current density. With ΔCTPxxP bestrophin-1, currents showed the same time-dependent activation as with wild-type bestrophin-1, but the current density was further reduced due to decreased number of Ca2+ channels proteins in the cell membrane. In summary, we described new proline-rich motifs on bestrophin-1 C-terminus, which help to maintain the ability of β-subunits to regulate surface expression of pore-forming CaV Ca2+-channel subunits

More resistant tendons obtained from the association of Heteropterys aphrodisiaca and endurance training

<p>Abstract</p> <p>Background</p> <p>Popular Brazilian medicine uses <it>Heteropterys aphrodisiaca </it>infusion as a tonic or stimulant, for the treatment of nervous debility and breakdown and for muscle and bone weakness. This study investigated the effects of <it>Heteropterys aphrodisiaca </it>infusion on the tendon properties and extracellular matrix of rats under endurance training.</p> <p>Methods</p> <p>Wistar rats were grouped as follows: CS- control sedentary, HS- <it>H. aphrodisiaca </it>sedentary, CT-control trained, HT- <it>H. aphrodisiaca </it>trained. The training protocol consisted in running on a motorized treadmill, five times a week, with weekly increase in treadmill speed and duration. Control groups received water while the HS and HT groups received <it>H. aphrodisiaca </it>infusion, daily, by gavage for the 8 weeks of training. Achilles tendons were frozen for biochemical and biomechanical analysis or preserved in Karnovsky's fixative, then processed for histomorphological analysis with light microscopy.</p> <p>Results</p> <p>Biomechanical analysis showed significant increase in maximum load, maximum stress, modulus of elasticity and stiffness of the HT animals' tendons. The metalloproteinase-2 activity was reduced in the HT group. The compression region of HT animals' tendons had a stronger and more intense metachromasy, which suggests an increase in glycosaminoglycan concentration in this region of the tendon. The most intense birefringence was observed in both compression and tension regions of HT animals' tendons, which may indicate a higher organizational level of collagen bundles. The hydroxyproline content increased in the HT group.</p> <p>Conclusions</p> <p>The association of endurance training with <it>H. aphrodisiaca </it>resulted in more organized collagen bundles and more resistant tendons to support higher loads from intense muscle contraction. Despite the clear anabolic effects of <it>Heteropterys aphrodisiaca </it>and the endurance exercise association, no side effects were observed, such as those found for synthetic anabolic androgenic steroids.</p

An Overview of the Management of Flexor Tendon Injuries

Flexor tendon injuries still remain a challenging condition to manage to ensure optimal outcome for the patient. Since the first flexor tendon repair was described by Kirchmayr in 1917, several approaches to flexor tendon injury have enabled successful repairs rates of 70-90%. Primary surgical repair results in better functional outcome compared to secondary repair or tendon graft surgery. Flexor tendon injury repair has been extensively researched and the literature demonstrates successful repair requires minimal gapping at the repair site or interference with tendon vascularity, secure suture knots, smooth junction of tendon end and having sufficient strength for healing. However, the exact surgical approach to achieve success being currently used among surgeons is still controversial. Therefore, this review aims to discuss the results of studies demonstrating the current knowledge regarding the optimal approach for flexor tendon repair. Post-operative rehabilitation for flexor tendon surgery is another area, which has caused extensive debate in hand surgery. The trend to more active mobilisation protocols seems to be favoured but further study in this area is needed to find the protocol, which achieves function and gliding but avoids rupture of the tendons. Lastly despite success following surgery complications commonly still occur post surgery, including adhesion formation, tendon rupture and stiffness of the joints. Therefore, this review aims to discuss the appropriate management of these difficulties post surgery. New techniques in management of flexor tendon will also be discussed including external laser devices, addition of growth factors and cytokines