The small signaling molecule auxin controls numerous developmental processes in land plants, acting mostly by regulating gene expression. Auxin response proteins are represented by large families of ...diverse functions, but neither their origin nor their evolution is understood. Here, we use a deep phylogenomics approach to reconstruct both the origin and the evolutionary trajectory of all nuclear auxin response protein families. We found that, while all subdomains are ancient, a complete auxin response mechanism is limited to land plants. Functional phylogenomics predicts defined steps in the evolution of response system properties, and comparative transcriptomics across six ancient lineages revealed how these innovations shaped a sophisticated response mechanism. Genetic analysis in a basal land plant revealed unexpected contributions of ancient non-canonical proteins in auxin response as well as auxin-unrelated function of core transcription factors. Our study provides a functional evolutionary framework for understanding diverse functions of the auxin signal.
Recently, Global navigation satellite system (GNSS) positioning has been widely used in various applications (e.g. car navigation system, smartphone map application, autonomous driving). In GNSS ...positioning, coordinates are calculated from observed satellite signals. The observed signals contain various errors, so the calculated coordinates also have some errors. Double-difference is one of the widely used ideas to reduce the errors of the observed signals. Although double-difference can remove many kinds of errors from the observed signals, some errors still remain (e.g. multipath error). In this paper, we define the remaining error as “double-difference-error (DDE)” and propose a method for estimating DDE using machine learning. In addition, we attempt to improve DGNSS positioning by feeding back the estimated DDE. Previous research applying machine learning to GNSS has focused on classifying whether the signal is LOS (Line Of Sight) or NLOS (Non Line Of Sight), and there is no study that attempts to estimate the amount of error itself as far as we know. Furthermore, previous studies had the limitation that their dataset was recorded at only a few locations in the same city. This is because these studies are mainly aimed at improving the positioning accuracy of vehicles, and collecting large amounts of data using vehicles is costly. To avoid this problem, in this research, we use a huge amount of openly available stationary point data for training. Through the experiments, we confirmed that the proposed method can reduce the DGNSS positioning error. Even though the DDE estimator was trained only on stationary point data, the proposed method improved the DGNSS positioning accuracy not only with stationary point but also with mobile rover. In addition, by comparing with the previous (detect and remove) approach, we confirmed the effectiveness of the DDE feedback approach.
The mitochondrial sheath is composed of mitochondria that coil tightly around the midpiece of sperm flagellum. These mitochondria are recruited from the cytoplasm to the flagellum late in ...spermatogenesis. Initially, recruited mitochondria are spherical-shaped but then elongate laterally to become crescent-like in shape. Subsequently, crescent-like mitochondria elongate continuously to coil tightly around the flagellum. Recently, disorganization of the mitochondrial sheath was reported in Glycerol kinase 2 (Gk2) disrupted mice. To analyze the disorganization of the mitochondrial sheath further, we generated Gk2-deficient mice using the CRISPR/Cas9 system and observed sperm mitochondria in testis using a freeze-fracture method with scanning electron microscopy. Gk2-disrupted spermatids show abnormal localization of crescent-like mitochondria, in spite of the initial proper alignment of spherical mitochondria around the flagellum, which causes abnormal mitochondrial sheath formation leading to exposure of the outer dense fibers. These results indicate that GK2 is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis.
To determine whether patient mortality after surgery differs between surgeries performed on surgeons' birthdays compared with other days of the year.
Retrospective observational study.
US acute care ...and critical access hospitals.
100% fee-for-service Medicare beneficiaries aged 65 to 99 years who underwent one of 17 common emergency surgical procedures in 2011-14.
Patient postoperative 30 day mortality, defined as death within 30 days after surgery, with adjustment for patient characteristics and surgeon fixed effects.
980 876 procedures performed by 47 489 surgeons were analyzed. 2064 (0.2%) of the procedures were performed on surgeons' birthdays. Patient characteristics, including severity of illness, were similar between patients who underwent surgery on a surgeon's birthday and those who underwent surgery on other days. The overall unadjusted 30 day mortality on the operating surgeon's birthday was 7.0% (145/2064) and that on other days was 5.6% (54 824/978 812). After adjusting for patient characteristics and surgeon fixed effects (effectively comparing outcomes of patients treated by the same surgeon on different days), patients who underwent surgery on a surgeon's birthday exhibited higher mortality compared with patients who underwent surgery on other days (adjusted mortality rate, 6.9%
5.6%; adjusted difference 1.3%, 95% confidence interval 0.1% to 2.5%; P=0.03). Event study analysis of patient mortality by day of surgery relative to a surgeon's birthday found similar results.
Among Medicare beneficiaries who underwent common emergency surgeries, those who received surgery on the surgeon's birthday experienced higher mortality compared with patients who underwent surgery on other days. These findings suggest that surgeons might be distracted by life events that are not directly related to work.
The plant hormone auxin regulates many aspects of plant growth and development. Recent progress in Arabidopsis provided a scheme that auxin receptors, TIR1/AFBs, target transcriptional co-repressors, ...AUX/IAAs, for degradation, allowing ARFs to regulate transcription of auxin responsive genes. The mechanism of auxin-mediated transcriptional regulation is considered to have evolved around the time plants adapted to land. However, little is known about the role of auxin-mediated transcription in basal land plant lineages. We focused on the liverwort Marchantia polymorpha, which belongs to the earliest diverging lineage of land plants. M. polymorpha has only a single TIR1/AFB (MpTIR1), a single AUX/IAA (MpIAA), and three ARFs (MpARF1, MpARF2, and MpARF3) in the genome. Expression of a dominant allele of MpIAA with mutations in its putative degron sequence conferred an auxin resistant phenotype and repressed auxin-dependent expression of the auxin response reporter proGH3:GUS. We next established a system for DEX-inducible auxin-response repression by expressing the putatively stabilized MpIAA protein fused with the glucocorticoid receptor domain (MpIAA(mDII)-GR). Repression of auxin responses in (pro)MpIAA:MpIAA(mDII)-GR plants caused severe defects in various developmental processes, including gemmaling development, dorsiventrality, organogenesis, and tropic responses. Transient transactivation assays showed that the three MpARFs had different transcriptional activities, each corresponding to their phylogenetic classifications. Moreover, MpIAA and MpARF proteins interacted with each other with different affinities. This study provides evidence that pleiotropic auxin responses can be achieved by a minimal set of auxin signaling factors and suggests that the transcriptional regulation mediated by TIR1/AFB, AUX/IAA, and three types of ARFs might have been a key invention to establish body plans of land plants. We propose that M. polymorpha is a good model to investigate the principles and the evolution of auxin-mediated transcriptional regulation and its roles in land plant morphogenesis.
The basal land plant Marchantia polymorpha efficiently propagates in favourable environments through clonal progeny called gemmae. Gemmae develop in cup-shaped receptacles known as gemma cups, which ...are formed on the gametophyte body. Anatomical studies have described the developmental processes involved over a century ago; however, little is known about the underlying molecular mechanisms. Recent studies have started to unravel the mechanism underlying genetic and hormonal regulation of gemma cup and gemma development, showing that it shares some regulatory mechanisms with several sporophytic organs in angiosperms. Further study of these specialized organs will contribute to our understanding of the core regulatory modules underlying organ development in land plants and how these became so diversified morphologically over the course of evolution.
Objectives
To investigate the impact of no cost sharing on paediatric care on usage and health outcomes, and whether the effect varies by household income levels.
Design
Regression discontinuity ...design.
Setting
Nationwide medical claims database in Japan.
Participants
Children aged younger than 20 years from April 2018 to March 2022.
Exposure
Co-insurance rate that increases sharply from 0% to 30% at a certain age threshold (the threshold age varies between 6 and 20 years depending on region).
Primary outcome measures
The outpatient care usage (outpatient visit days and healthcare spending for outpatient care) and inpatient care (experience of any hospitalisation and healthcare spending for inpatient care).
Results
Of 244 549 children, 49 556 participants were in the bandwidth and thus included in our analyses. Results from the regression discontinuity analysis indicate that no cost sharing was associated with a significant increase in the number of outpatient visit days (+5.26 days; 95% CI, +4.89 to +5.82; p<0.01; estimated arc price elasticity, −0.45) and in outpatient healthcare spending (+US$369; 95% CI, +US$344 to +US$406; p<0.01; arc price elasticity, −0.55). We found no evidence that no cost sharing was associated with changes in inpatient care usage. Notably, the effect of no cost-sharing policy on outpatient healthcare usage was larger among children from high-income households (visit days +5.96 days; 95% CI, +4.88 to +7.64, spending +US$511; 95% CI, +US$440 to +US$627) compared with children from low-income households (visit days +2.64 days; 95% CI, +1.54 to +4.23, spending +US$154; 95% CI, +US$80 to +US$249).
Conclusions
No cost sharing for paediatric care was associated with a greater usage of outpatient care services, but did not affect inpatient care usage. The study found that this effect was more pronounced among children from high-income households, indicating that the no cost sharing disproportionately benefits high-income households and may contribute to larger disparities.
Ultrafine-grained pure Al and Al-based composites with 10 and 20vol% of Al2O3 were produced by cold consolidation of powders using high-pressure torsion (HPT). Ball-on-disc wear resistance of Al was ...improved by HPT when compared to its coarse-grained counterpart processed with H24 treatment (cold rolling followed by low-temperature annealing). Wear width decreased but wear depth and wear volume increased with the addition of Al2O3 to the Al matrix. The wear mechanism was mainly due to adhesion in Al and Al–Al2O3 composites. It was found that the variation of wear width can be represented by a unique function of the ratio of load/hardness in consistency with the Reye's hypothesis and the Holm and Archard relationships. However, the variation of wear depth was inconsistent with the hardness variations.
•Pure Al and Al–Al2O3 composites were consolidated by high-pressure torsion (HPT).•Ball-on-disc wear resistance of Al was improved by consolidation of powders using HPT.•Wear width decreased but wear depth and volume increased with addition of Al2O3 to Al.•Wear mechanism was mainly adhesion in Al and Al–Al2O3 composites.•Variations of wear width and depth were evaluated as a function of load/hardness.
Cell division patterning is important to determine body shape in plants. Nuclear auxin signaling mediated by AUXIN RESPONSE FACTOR (ARF) transcription factors affects plant growth and development ...through regulation of cell division, elongation and differentiation. The evolutionary origin of the ARF-mediated pathway dates back to at least the common ancestor of bryophytes and other land plants. The liverwort Marchantia polymorpha has three phylogenetically distinct ARFs: MpARF1, the sole 'activator' ARF; and MpARF2 and MpARF3, two 'repressor' ARFs. Genetic screens for auxin-resistant mutants revealed that loss of MpARF1 function conferred auxin insensitivity. Mparf1 mutants showed reduced auxin-inducible gene expression and various developmental defects, including thallus twisting and gemma malformation. We further investigated the role of MpARF1 in gemma development, which is traceable at the cellular level. In wild-type plants, a gemma initial first undergoes several transverse divisions to generate a single-celled stalk and a gemma proper, followed by rather synchronous longitudinal divisions in the latter. Mparf1 mutants often contained multicelled stalks and showed defects in the execution and timing of the longitudinal divisions. While wild-type gemmae finally generate two meristem notches, Mparf1 gemmae displayed various numbers of ectopic meristems. These results suggest that MpARF1 regulates formative cell divisions and axis formation through auxin responses. The mechanism for activator ARF regulation of pattern formation may be shared in land plants and therefore important for the general acquisition of three-dimensional body plans.
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