There is intense interest in developing new novel nanostructured photoanodes for water splitting. It is therefore important that methods to analyze the effect of nanostructuring on water splitting ...yields are developed in order to rationalize the relative merits of this approach for different materials. In this study the dependence of charge separation efficiency (η(sep)) on potential during photoelectrochemical water splitting at pH 2 has been quantified in a model electrode system (nanocrystalline, mesoporous TiO2) using two independent methods. These are (i) analysis of incident photon conversion efficiency (IPCE) measurements and (ii) transient absorption (TA) spectroscopy measurements. The techniques provide good agreement with each other and show that a low maximum value of η(sep) (~0.18) is the primary cause of the low IPCE for water oxidation on these nc-TiO2 electrodes.
X-ray free-electron lasers (XFELs) provide very intense X-ray pulses suitable for macromolecular crystallography. Each X-ray pulse typically lasts for tens of femtoseconds and the interval between ...pulses is many orders of magnitude longer. Here we describe two novel acoustic injection systems that use focused sound waves to eject picoliter to nanoliter crystal-containing droplets out of microplates and into the X-ray pulse from which diffraction data are collected. The on-demand droplet delivery is synchronized to the XFEL pulse scheme, resulting in X-ray pulses intersecting up to 88% of the droplets. We tested several types of samples in a range of crystallization conditions, wherein the overall crystal hit ratio (e.g., fraction of images with observable diffraction patterns) is a function of the microcrystal slurry concentration. We report crystal structures from lysozyme, thermolysin, and stachydrine demethylase (Stc2). Additional samples were screened to demonstrate that these methods can be applied to rare samples.
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•Acoustic methods inject crystal-containing droplets directly from microplate wells•On-demand acoustic injection uses crystals efficiently without orifices or clogging•Diffraction patterns from crystals measuring several tens of μm are of high quality•Complete datasets can be obtained from fewer than 50,000 crystals
Acoustic droplet ejection provides an automated tool for efficient use of protein crystals in SFX experiments. Roessler et al. used this method to deliver crystal-containing droplets into the XFEL beam to coincide with each X-ray pulse.
Grasslands cover around 25% of the global ice-free land surface, they are used predominantly for forage and livestock production and are considered to contribute significantly to soil carbon (C) ...sequestration. Recent investigations into using ‘nature-based solutions’ to limit warming to <2 °C suggest up to 25% of GHG mitigation might be achieved through changes to grassland management. In this study we evaluate pasture management interventions at the Rothamsted Research North Wyke Farm Platform, under commercial farming conditions, over two years and consider their impacts on net CO2 exchange. We investigate if our permanent pasture system (PP) is, in the short-term, a net sink for CO2 and whether reseeding this with deep-rooting, high-sugar grass (HS) or a mix of high-sugar grass and clover (HSC) might increase the net removal of atmospheric CO2. In general CO2 fluxes were less variable in 2018 than in 2017 while overall we found that net CO2 fluxes for the PP treatment changed from a sink in 2017 (−5.40 t CO2 ha−1 y−1) to a source in 2018 (6.17 t CO2 ha−1 y−1), resulting in an overall small source of 0.76 t CO2 ha−1 over the two years for this treatment. HS showed a similar trend, changing from a net sink in 2017 (−4.82 t CO2 ha−1 y−1) to a net source in 2018 (3.91 t CO2 ha−1 y−1) whilst the HSC field was a net source in both years (3.92 and 4.10 t CO2 ha−1 y−1, respectively). These results suggested that pasture type has an influence in the atmospheric CO2 balance and our regression modelling supported this conclusion, with pasture type and time of the year (and their interaction) being significant factors in predicting fluxes.
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•Pasture type influenced the atmospheric CO2 balance in a temperate climate.•Permanent (PP) and high sugar grass (HS) pastures had similar yearly net CO2 fluxes.•PP and HS pastures were a sink for atmospheric CO2 in 2017 and a source in 2018.•A pasture of high sugar grass and clover (HSC) acted as a net source of CO2.•Night-time CO2 emissions were influenced by season and pasture type.
Summary
Mucosal‐associated invariant T (MAIT) cells and Vδ2+ γδ T cells are anti‐bacterial innate‐like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control ...of infection. However, the role of ILLs in community‐acquired pneumonia (CAP) is unknown. Using sputum samples from a well‐characterized CAP cohort, MAIT cell and Vδ2+ T cell abundance was determined by quantitative polymerase chain reaction (qPCR). Cytokine and chemokine concentrations in sputum were measured. The capacity of bacteria in sputum to produce activating ligands for MAIT cells and Vδ2+ T cells was inferred by 16S rRNA sequencing. MAIT cell abundance in sputum was higher in patients with less severe pneumonia; duration of hospital admission was inversely correlated with both MAIT and Vδ2+ T cell abundance. The abundance of both ILLs was higher in patients with a confirmed bacterial aetiology; however, there was no correlation with total bacterial load or the predicted capacity of bacteria to produce activating ligands. Sputum MAIT cell abundance was associated with interferon (IFN)‐α, IFN‐γ, and sputum neutrophil abundance, while Vδ2+ T cell abundance was associated with CXCL11 and IFN‐γ. Therefore, MAIT and Vδ2+ T cells can be detected in sputum in CAP, where they may contribute to improved clinical outcome.
Mucosal‐associated invariant T (MAIT) cells and Vδ2+ γδ T cells are innate‐like lymphocytes that are abundant in humans in blood and at mucosal surfaces, including the lungs. They provide rapid effector responses upon activation by specific ligands produced by a broad range of bacteria, including numerous pulmonary pathogens. Here we show that MAIT and Vδ2+ γδ T cells can be detected in sputum in patients with community acquired pneumonia, where they may contribute to improved clinical outcome.
Many models of physics beyond the standard model predict the existence of new Abelian forces with new gauge bosons mediating interactions between "dark sectors" and the standard model. We report a ...search for a dark boson Z' coupling only to the second and third generations of leptons in the reaction e super(+) e super(?)arrowrightmu super(+)mu super(?)Z',Z'arrowrightmu super(+) mu? using 514fb super(?1) of data collected by the BABAR experiment. No significant signal is observed for Z' masses in the range 0.212-10 GeV. Limits on the coupling parameter g' as low as 7x10 super(?4) are derived, leading to improvements in the bounds compared to those previously derived from neutrino experiments.
The amidase from Geobacillus pallidus RAPc8, a moderate thermophile, is a member of the nitrilase superfamily and catalyzes the conversion of amides to the corresponding carboxylic acids and ammonia. ...It shows both amide‐hydrolysis and acyl‐transfer activities and also exhibits stereoselectivity for some enantiomeric substrates, thus making it a potentially important industrial catalyst. The crystal structure of G. pallidus RAPc8 amidase at a resolution of 1.9 Å was solved by molecular replacement from a crystal belonging to the primitive cubic space group P4232. G. pallidus RAPc8 amidase is homohexameric in solution and its monomers have the typical nitrilase‐superfamily α‐β‐β‐α fold. Association in the hexamer preserves the eight‐layered α‐β‐β‐α:α‐β‐β‐α structure across an interface which is conserved in the known members of the superfamily. The extended carboxy‐terminal tail contributes to this conserved interface by interlocking the monomers. Analysis of the small active site of the G. pallidus RAPc8 amidase suggests that access of a water molecule to the catalytic triad (Cys, Glu, Lys) side chains would be impeded by the formation of the acyl intermediate. It is proposed that another active‐site residue, Glu142, the position of which is conserved in the homologues, acts as a general base to catalyse the hydrolysis of this intermediate. The small size of the substrate‐binding pocket also explains the specificity of this enzyme for short aliphatic amides and its asymmetry explains its enantioselectivity.
Parathyroid hormone (PTH) regulates calcium homeostasis via the type I PTH/PTH-related peptide (PTH/PTHrP) receptor (PTH1R). The purpose of the present study was to identify the contributions of ...distinct signaling mechanisms to PTH-stimulated activation of the mitogen-activated protein kinases (MAPK) ERK1/2. In Human embryonic kidney 293 (HEK293) cells transiently transfected with hPTH1R, PTH stimulated a robust increase in ERK activity. The time course of ERK1/2 activation was biphasic with an early peak at 10 min and a later sustained ERK1/2 activation persisting for greater than 60 min. Pretreatment of HEK293 cells with the PKA inhibitor H89 or the PKC inhibitor GF109203X, individually or in combination reduced the early component of PTH-stimulated ERK activity. However, these inhibitors of second messenger dependent kinases had little effect on the later phase of PTH-stimulated ERK1/2 phosphorylation. This later phase of ERK1/2 activation at 30–60 min was blocked by depletion of cellular β-arrestin 2 and β-arrestin 1 by small interfering RNA. Furthermore, stimulation of hPTH1R with PTH analogues, Trp1PTHrp-(1–36) and d-Trp12,Tyr34PTH-(7–34), selectively activated Gs/PKA-mediated ERK1/2 activation or G protein-independent/β-arrestin-dependent ERK1/2 activation, respectively. It is concluded that PTH stimulates ERK1/2 through several distinct signal transduction pathways: an early G protein-dependent pathway meditated by PKA and PKC and a late pathway independent of G proteins mediated through β-arrestins. These findings imply the existence of distinct active conformations of the hPTH1R responsible for the two pathways, which can be stimulated by unique ligands. Such ligands may have distinct and valuable therapeutic properties.
We study the process e + e − → e + e − η ′ in the double-tag mode and measure for the first time the γ * γ * → η ′ transition form factor F η′ ( Q 2 1 , Q 2 2 ) in the momentum-transfer range 2 < Q 2 ...1 , Q 2 2 < 60 GeV 2 . The analysis is based on a data sample corresponding to an integrated luminosity of around 469 fb − 1 collected at the PEP-II e + e − collider with the BABAR detector at center-of-mass energies near 10.6 GeV.
Background.—Pharmaceuticals with calcium‐ or sodium‐channel‐blocking activity have proven useful for migraine prophylaxis, and calcium channel, sodium transporter, and sodium channel gene mutations ...have been found in familial hemiplegic migraine. However, it is not known whether calcium or sodium homeostasis is altered in migraine.
Objective.—To compare levels of sodium, calcium, potassium, and magnesium in cerebrospinal fluid (CSF) and blood plasma between migraineurs and controls.
Methods.—We recruited 20 migraineurs without aura and 11 controls prospectively, and studied migraineurs in sick (MH+) and well (MH−) states. We collected lumbar CSF and venous blood plasma, quantified elements with ion‐selective electrodes or colorimetry, and determined osmolality by depression of freezing point. We compared levels of Na+, Ca2+, K+, and Mg among and also within subjects who were studied in both MH+ and MH− states.
Results.—Mean CSF Na+ levels were increased by 3 mmol/L in MH+ compared with MH− and by 4 mmol/L compared to controls (P < 0.005). In 4 subjects who were sampled in both MH+ and MH− states, mean CSF Na+ concentration increased by 2 mmol/L in the MH+ state compared with the MH− state (P < 0.05). Simultaneous plasma Na+ levels did not differ among the 3 clinical groups, nor did osmolality, total Ca and Ca2+, K+, and total Mg levels in CSF.
Conclusions.—Compared to both controls and the MH− state, CSF Na+ concentration increased in MH+ independently from other clinical or pharmacological fluctuations, CSF concentrations of Ca2+, Mg, and K+, and blood plasma Na+ levels. These results implicate a deviation of Na+ homeostasis in migraine. The modestly elevated extracellular Na+ in MH+ may cause the neural changes that underlie clinical features of migraine.
Mucinous Cystadenoma in Children and Adolescents Cowan, Renee A., MD, MPH; Haber, Erin N., BS; Faucz, Fabio R., PhD ...
Journal of pediatric & adolescent gynecology,
08/2017, Letnik:
30, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract Study Objective Mucinous cystadenomas (MCAs) are benign epithelial ovarian tumors that occur rarely in children and adolescents. Because children and adolescents typically have their ...childbearing years ahead of them, conservative therapy is indicated. However, there is concern that ovarian cystectomy might be associated with significant recurrence risk in patients with MCA. Furthermore, guanine nucleotide binding protein, alpha stimulating ( GNAS ) gene mutations are associated with McCune-Albright syndrome, which is associated with cystic ovaries. We sought to evaluate the outcomes of children and adolescents with MCA treated conservatively. A subset of patients underwent GNAS gene testing. Design, Setting, Participants, and Interventions After institutional board review approval, the pathology database of a large urban children's hospital was queried to identify adolescents with MCA between the years 2008 and 2014. Fourteen patients, aged 8-18 years (median, 14), were identified. A buccal swab for genetic testing was obtained from a subset of consenting patients. Main Outcome Measures MCA recurrence; ovarian return to normal size; GNAS gene variants. Results Two patients underwent oophorectomies, and the remaining 12 underwent cystectomies. Follow-up ultrasound examination revealed slow return of ovary to normal size. Of the 10 patients with available follow-up data, there were no recurrences at a median of 225 days from surgery. Four patients consented to a buccal swab for genetic testing, and the GNAS gene was noted to have rare variants in 2 patients. Conclusion This series supports the use of ovary-sparing surgery in the treatment of MCA. Further research exploring possible genetic variants such as the GNAS gene in children and adolescents diagnosed with MCA is warranted.
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