Many eukaryotic proteins regulating phosphate (Pi) homeostasis contain SPX domains that are receptors for inositol pyrophosphates (PP-InsP), suggesting that PP-InsPs may regulate Pi homeostasis. Here ...we report that deletion of two diphosphoinositol pentakisphosphate kinases VIH1/2 impairs plant growth and leads to constitutive Pi starvation responses. Deletion of phosphate starvation response transcription factors partially rescues vih1 vih2 mutant phenotypes, placing diphosphoinositol pentakisphosphate kinases in plant Pi signal transduction cascades. VIH1/2 are bifunctional enzymes able to generate and break-down PP-InsPs. Mutations in the kinase active site lead to increased Pi levels and constitutive Pi starvation responses. ATP levels change significantly in different Pi growth conditions. ATP-Mg2+ concentrations shift the relative kinase and phosphatase activities of diphosphoinositol pentakisphosphate kinases in vitro. Pi inhibits the phosphatase activity of the enzyme. Thus, VIH1 and VIH2 relay changes in cellular ATP and Pi concentrations to changes in PP-InsP levels, allowing plants to maintain sufficient Pi levels.
The impact of solution pH has been investigated for the electrooxidation of formic acid on Au(111), taking the mole fraction of formate in solution as the relevant parameter. The electrocatalytic ...current density is increasing with rising pH and reaches a plateau for pH > 4. The pH-dependence of characteristic potentials shows systematic trends for the onset of the reaction, the peak maximum, and the phase transition within the formate adlayer. After the addition of phosphate buffer, a substantial deactivation by specific adsorption of phosphates and a bell-shaped curve for the maximum current density as a function of pH is found. The general behavior of co-adsorbing anions is addressed at low pH using various oxyanions to get more insight into the role of adsorbed formate. While non-carboxylate anions are displaced by formate at high potentials, mixed phases are observed for formate and other carboxylates.
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Recently it was recommended to avoid significance tests, in particular dichotomization into significant/non-significant on the basis of a p-value and a fixed 5% significance level (i.e. false ...positive rate). As an alternative, the interpretation of a suitable effect size and its compatibility interval is recommended, i.e. confidence intervals whose compatibility with the data, the assumptions, and the models is shown. This concept is used for the evaluation of assays in regulatory toxicology with special emphasis on the proof of hazard and proof of safety. Three case studies for multiple endpoints, multiple models and the consideration of historical controls illustrate the applicability of this concept. The corresponding software code for the open-source R project for statistical computing (www.r-project.org) is provided.
Purpose
Psychosocial health (PH) and quality of life (QoL) are important health outcomes. We compared PH and QoL of adolescents conceived with intrazytoplasmatic sperm injection (ICSI) and of ...naturally conceived controls. The impact of disclosure of ICSI-conception on QoL and PH was quantified.
Methods
The cross-sectional sample consisted of 545 ICSI-conceived adolescents and 427 unmatched singleton controls aged 14–18 years. Adolescents reported PH with the ‘Strengths and Difficulties Questionnaire’ (low values indicating high PH), and QoL with the KINDL questionnaire (high values indicating high QoL). Because of clustering of multiples within families, adjusted linear regressions with generalized estimating equations were used to compare ICSI- and naturally conceived adolescents. Missing values were treated by multiple imputation. Minimal importance was defined as half a standard deviation.
Results
Both ICSI and control adolescents had high PH (low mean ‘total difficulties’ score: 9 of 40) and high QoL (mean ‘total KINDL’ score: 75 of 100). Differences were generally in favour of the ICSI group. Significant differences occurred for ‘impact of behavioural problems’ (
p
= 0.033), the ‘total KINDL’ score (
p
= 0.021) and the dimensions ‘physical wellbeing’ (
p
= 0.031) and ‘school’ (
p
= 0.005), but all differences were far below minimal importance. About 80% of ICSI adolescents were informed about their mode of conception. PH and QoL were slightly higher in informed adolescents; behavioural difficulties (‘total behavioural problems’ and ‘conduct problems’) were significantly lower (
p
= 0.013 and
p
= 0.003), behavioural strengths (‘prosocial behaviour’) and ‘physical QoL’ significantly higher (
p
= 0.004 and
p
= 0.018), but differences remained clearly below minimal importance.
Conclusions
Our results are reassuring for parents using ICSI and their children. Speaking openly about an ICSI conception in the family may be beneficial.
To study the effect of statin exposure on the progression from non-exudative to exudative age-related macular degeneration (AMD).
Retrospective cohort study of commercially insured patients diagnosed ...with non-exudative AMD (n = 231,888) from 2007 to 2015. Time-to-event analysis of the association between exposure to lipid-lowering medications and time from non-exudative AMD to exudative AMD diagnosis was conducted. Outcome measures included progression to exudative AMD, indicated by diagnosis codes for exudative AMD or procedural codes for intravitreal injections.
In the year before and after first AMD diagnosis, 11,330 patients were continuously prescribed lipid-lowering medications and 31,627 patients did not take any lipid-lowering medication. Of those taking statins, 21 (1.6%) patients were on very-high-dose lipophilic statins, 644 (47.6%) on high-dose lipophilic statins, and 689 (50.9%) on low-dose lipophilic statins. We found no statistically significant relationship between exposure to low (HR 0.89, 95% CI 0.83 to 1.38) or high-dose lipophilic statins (HR 1.12, 95% CI 0.86 to 1.45) and progression to exudative AMD. No patients taking very-high-dose lipophilic statins converted from non-exudative to exudative AMD, though this difference was not statistically significant due to the subgroup size (p = .23, log-rank test).
No statistically significant relationship was found between statin exposure and risk of AMD progression. Interestingly, no patients taking very-high-dose lipophilic statins progressed to exudative AMD, a finding that warrants further exploration.
We report the breakdown of the electric dipole approximation in the long-wavelength limit in strong-field ionization with linearly polarized few-cycle mid-infrared laser pulses at intensities on the ...order of 10¹³ W/cm². Photoelectron momentum distributions were recorded by velocity map imaging and projected onto the beam propagation axis. We observe an increasing shift of the peak of this projection opposite to the beam propagation direction with increasing laser intensities. From a comparison with semiclassical simulations, we identify the combined action of the magnetic field of the laser pulse and the Coulomb potential as the origin of our observations.
We investigate experimentally the validity of proposed theories extending the tunneling approximation towards the multiphoton regime in strong-field ionization of helium. We employ elliptically ...polarized laser pulses and demonstrate how the influence of the ion potential on the released electron encoded in the measured observable provides the desired sensitivity to detect nonadiabatic effects in tunnel ionization. Our results show that for a large intensity range the proposed nonadiabatic theories contradict the experimental trends of the data, while adiabatic assumptions are confirmed.
We demonstrate a new attosecond pulse reconstruction modality which uses an algorithm that is derived from ptychography. In contrast to other methods, energy and delay sampling are not correlated, ...and as a result, the number of electron spectra to record is considerably smaller. Together with the robust algorithm, this leads to a more precise and fast convergence of the reconstruction.
Mask ventilation is an essential element of airway management that has rarely been studied as the primary outcome. The authors sought to determine the incidence and predictors of difficult and ...impossible mask ventilation.
A four-point scale to grade difficulty in performing mask ventilation (MV) is used at the authors' institution. They used a prospective, observational study to identify cases of grade 3 MV (inadequate, unstable, or requiring two providers), grade 4 MV (impossible to ventilate), and difficult intubation. Univariate and multivariate analyses of a variety of patient history and physical examination characteristics were used to establish risk factors for grade 3 and 4 MV.
During a 24-month period, 22,660 attempts at MV were recorded. 313 cases (1.4%) of grade 3 MV, 37 cases (0.16%) of grade 4 MV, and 84 cases (0.37%) of grade 3 or 4 MV and difficult intubation were observed. Body mass index of 30 kg/m or greater, a beard, Mallampati classification III or IV, age of 57 yr or older, severely limited jaw protrusion, and snoring were identified as independent predictors for grade 3 MV. Snoring and thyromental distance of less than 6 cm were independent predictors for grade 4 MV. Limited or severely limited mandibular protrusion, abnormal neck anatomy, sleep apnea, snoring, and body mass index of 30 kg/m or greater were independent predictors of grade 3 or 4 MV and difficult intubation.
The authors observed the incidence of grade 3 MV to be 1.4%, similar to studies with the same definition of difficult MV. Presence of a beard is the only easily modifiable independent risk factor for difficult MV. The mandibular protrusion test may be an essential element of the airway examination.