Search

Abstract Recent advances in methods to culture pluripotent stem cells to model human development have resulted in entities that increasingly have recapitulated advanced stages of early embryo development. These entities, referred to by numerous terms such as embryoids, are becoming more sophisticated and could resemble human embryos ever more closely as research progresses. This paper reports a systematic review of the ethical, legal, regulatory, and policy questions and concerns found in the literature concerning human embryoid research published from 2016 to 2022. We identified 56 papers that use 53 distinct names or terms to refer to embryoids and four broad categories of ethical, legal, regulatory, or policy considerations in the literature: research justifications/benefits, ethical significance or moral status, permissible use, and regulatory and oversight challenges. Analyzing the full range of issues is a critical step toward fostering more robust ethical, legal, and social implications research in this emerging area and toward developing appropriate oversight.

The active vitamin D metabolites, 25-hydroxyvitamin D3 (25D3) and 1,25-dihydroxyvitamin D3 (1,25D3), are produced by successive hydroxylation steps and play key roles in several cellular processes. However, alternative metabolic pathways exist, and among them, the 4-hydroxylation of 25D3 is a major one. This study aims to investigate the structure–activity relationships of 4-hydroxy derivatives of 1,25D3. Structural analysis indicates that 1,4α,25(OH)3D3 and 1,4β,25(OH)3D3 maintain the anchoring hydrogen bonds of 1,25D3 and form additional interactions, stabilizing the active conformation of VDR. In addition, 1,4α,25D3 and 1,4β,25D3 are as potent as 1,25D3 in regulating the expression of VDR target genes in rat intestinal epithelial cells and in the mouse kidney. Moreover, these two 4-hydroxy derivatives promote hypercalcemia in mice at a dose similar to that of the parent compound.

IntroductionMuch of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes.MethodsAPOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.ResultsThe United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.ConclusionThis article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

IntroductionMusculoskeletal problems in professional brass musicians are very common and often involve the muscles of the embouchure. In rare cases, embouchure dystonia (EmD), a task-specific movement disorder with a wide symptomatic and phenotypic variability, occurs. Following trumpeters and horn players, professional tuba players with and without EmD have now been studied using the latest real-time MRI technology to better understand the underlying pathophysiology.Materials and methodsIn the present study, the tongue movement patterns of 11 healthy professional artists and one subject suffering from EmD were compared. The tongue position in the anterior, intermediary and posterior oral cavity were converted into pixel positions based on seven previously generated profile lines, using the established software MATLAB. These data allow a structured comparison of tongue movement patterns between the patient and the healthy subjects, as well as between individual exercises. The main focus of the analysis was on an ascending 7-note harmonic series performed in different playing techniques (slurred, tongued, tenuto and staccato).ResultsPlaying the ascending harmonics, a noticeable ascending tongue movement could be observed in the anterior part of the oral cavity in healthy tubists. In the posterior region, there was a slight decrease in oral cavity space. In the EmD patient, hardly any movement was observed at the tongue apex, but in the middle and posterior regions of the oral cavity there was an increase in size the higher the tone became. These distinct differences are relevant for the characterization and a better understanding of the clinical presentation of EmD. Concerning different playing techniques, it was apparent, that notes played slurred or staccato resulted in a larger oral cavity when compared to notes played tongued or tenuto, respectively.ConclusionBy using real-time MRI videos, the tongue movements of tuba players can be clearly observed and analyzed. The differences between healthy and diseased tuba players demonstrate the great effects of movement disorders in a small area of the tongue. In order to better understand the compensation of this motor control dysfunction, further studies should investigate further parameters of tone production in all brass players with a larger number of EmD patients additional to the observed movement patterns.

COSINE-200 is the next phase experiment of the ongoing COSINE-100 that aims to unambiguously verify the annual modulation signals observed by the DAMA experiment and to reach the world competitive sensitivity on the low-mass dark matter search. To achieve the physics goal of the COSINE-200, the successful production of the low-background NaI(Tl) detectors is crucial and it must begin from the mass production of the ultra-low background NaI powder. A clean facility for mass-producing the pure-NaI powder has been constructed at the Center for Underground Physics (CUP) in Korea. Two years of operation determined efficient parameters of the mass purification and provided a total of 480 kg of the ultra-pure NaI powder in hand. The potassium concentration in the produced powders varied from 5.4 to 11 ppb, and the maximum production capacity of 35 kg per 2 weeks was achieved. Here, we report our operational practice with the mass purification of the NaI powder, which includes raw powder purification, recycling of the mother solution, and recovery of NaI from the residual melt after crystal growth.

The COSINE-100 experiment has been operating with 106 kg of low-background NaI(Tl) detectors to test the results from the DAMA/LIBRA experiment, which claims to have observed dark matter. However, since the background of the NaI(Tl) crystals used in the COSINE-100 experiment is 2–3 times higher than that in the DAMA detectors, no conclusion regarding the claimed observation from the DAMA/LIBRA experiment could be reached. Therefore, we plan to upgrade the current COSINE-100 experiment to the next phase, COSINE-200, by using ultra-low background NaI(Tl) detectors. The basic principle was already proved with the commercially available Astro-grade NaI powder from Sigma-Aldrich (now Merck) company. However, we have developed a mass production process of ultra-pure NaI powder at the Center for Underground Physics (CUP) of the Institute for Basic Science (IBS), Korea, using the direct purification of the raw NaI powder. We plan to produce more than 1,000 kg of ultra-pure powder for the COSINE-200 experiment. With our crystal grower installed at CUP, we have successfully grown a low-background crystal using our purification technique for the NaI powder. We have assembled a low-background NaI(Tl) detector. In this article, we report the performance of this ultra-pure NaI(Tl) crystal detector produced at IBS, Korea.

Insects have evolved diverse strategies to resist extreme high temperatures (EHT). The adaptive value of such strategies has to be evaluated when organisms experience multiple EHT events during their lifetime, as predicted in a changing climate. This is particularly the case for associations with facultative microbial partners involved in insect heat tolerance, the resilience of which to repeated heat stress has never been studied. We compared two artificial lines of the pea aphid (Acyrthosiphon pisum) differing by the absence or presence of the heat-protective facultative bacterium Serratia symbiotica. We exposed insect nymphs to a varying number of EHT events (between 0 and 3), and recorded fitness parameters. Except survival traits, fitness estimates were affected by the interaction between aphid infection status (absence/presence of S. symbiotica) and thermal treatment (number of heat shocks applied). Costs of bacterial infection were detected in the absence of thermal stress: symbiont-hosting aphids incurred longer development, decreased fecundity and body size. However, symbiotic infection turned neutral, and even beneficial for some traits (development and body size), as the number of heat shocks increased, and compared to the aposymbiotic strain. Conversely, symbiotic infection mediated aphid response to heat shock(s): fitness decreased only in the uninfected group. These findings suggest that (i) the facultative symbiont may alternatively act as a pathogen, commensal or mutualist depending on thermal environment, and (ii) the heat protection it delivered to its host persists under frequent EHT. We discuss eco-evolutionary implications and the role of potentially confounding factors (stage-specific effects, genetic polymorphism displayed by the obligate symbiont).

Within the frame of the EMPIrE test, four monolithic mini-plates were irradiated in the ATR reactor. In two of them, the monolithic U(Mo) foil had been PVD-coated with Zr before the plate manufacturing. Extensive microstructural characterizations were performed on a fresh archive mini-plate, using Optical Microscopy (OM), Scanning Electron Microscopy (SEM) combined with Energy Dispersive Spectroscopy (EDS), Electron Backscattered Diffraction (EBSD) and Focused Ion Beam (FIB)/Transmission Electron Microscopy (TEM) with nano EDS. A particular attention was paid to the examination of the U(Mo) foil, the PVD coating, the cladding/Zr and Zr/U(Mo) interfaces.The Zr coating has a thickness around 15 μm. It has a columnar microstructure and appears dense. The cohesion of the cladding/Zr and Zr/U(Mo) interfaces seems to be satisfactory. An almost continuous layer with a thickness of the order of 100–300 nm is present at the cladding/Zr interface and corresponds to an oxidized part of the Zr coating. At the Zr/U(Mo) interface, a thin discontinuous layer is observed. It could correspond to locally oxidized U(Mo).This work provides a basis for interpreting the results of characterizations on EMPIrE irradiated plates.

This article provides an overview of the current status of women in the history of science field. It highlights areas of concern, such as the underrepresentation of women in higher-ranking positions and the lack of visibility and equal opportunities for women. The article presents data on the representation of women in graduate programs, employment status, and their contributions to major journals in the field. It also discusses the challenges faced by women in terms of combining a professional life with marriage and family. The article concludes by recommending the establishment of a committee to address these issues and provide support for women in the field. [Extracted from the article]