bluuebunny/crossref_metadata_2025 huggingface dataset:
Ursodeoxycholic acid in the management of symptomatic gallstone disease: systematic review and clinician survey
Authors: Hall Lewis , Halle-Smith James , Evans Richard , Toogood Giles , Wiggins Tom , Markar Sheraz R , Kapoulas Spyros , Super Paul , Tucker Olga , McKay Siobhan C
Published: March 2023

Background

Symptomatic gallstones are common. Ursodeoxycholic acid (UDCA) is a bile acid that dissolves gallstones. There is increasing interest in UDCA for symptomatic gallstones, particularly in those unfit for surgery.

Method

A UK clinician survey of use and opinions about UDCA in symptomatic gallstones was performed, assessing clinicians’ beliefs and perceptions of UDCA effectiveness. A systematic review was performed in accordance with the PRISMA guidelines. PubMed, MEDLINE, and Embase databases were searched for studies of UDCA for symptomatic gallstones (key terms included ‘ursodeoxycholic acid’; ‘UDCA’; ‘biliary pain’; and ‘biliary colic’). Information was assessed by two authors, including bias assessment, with independent review of conflicts.

Results

Overall, 102 clinicians completed the survey, and 42 per cent had previous experience of using UDCA. Survey responses demonstrated clinical equipoise surrounding the benefit of UDCA for the management of symptomatic gallstones, with no clear consensus for benefit or non-benefit; however, 95 per cent would start using UDCA if there was a randomized clinical trial (RCT) demonstrating a benefit. Eight studies were included in the review: four RCTs, three prospective studies, and one retrospective study. Seven of eight studies were favourable of UDCA for biliary pain. Outcomes and follow-up times were heterogenous, as well as comparator type, with only four of eight studies comparing with placebo.

Conclusion

Evidence for UDCA in symptomatic gallstones is scarce and heterogenous. Clinicians currently managing symptomatic gallstone disease are largely unaware of the benefit of UDCA, and there is clinical equipoise surrounding the benefit of UDCA. Level 1 evidence is required by clinicians to support UDCA use in the future.
Biliary drainage surgery before or after 3 months of life versus primary liver transplantation in children with biliary atresia: comparative cohort study
Authors: Fuchs Juri , Mrad Chaima , Gonzales Emmanuel , Ndiaye Dior , Fouquet Virginie , Héry Géraldine , Baujard Catherine , Guérin Florent , Branchereau Sophie
Published: March 2023

Background

Early biliary drainage surgery (BDS; Kasai) is associated with longer transplant-free survival in biliary atresia. However, evidence is lacking on whether an age limit can be established at which liver transplantation should be performed as first-line treatment for children with a delayed diagnosis of biliary atresia. The aim of the current study was to compare the outcome of a large cohort of children with biliary atresia who underwent BDS after 90 days of life with those who underwent early BDS (before 90 days) and those who did not receive BDS and were directly referred for primary liver transplantation.

Methods

All patients with biliary atresia treated at Bicêtre, Paris-Saclay University Hospital between 1995 and 2017 were analysed in this STROBE-compliant study. Three groups were defined: BDS before 90 days of life (early BDS); BDS after 90 days of life (late BDS); and patients without BDS who were referred for primary liver transplantation (no BDS). Patient characteristics, overall survival, and native liver survival were compared.

Results

Of 424 children with biliary atresia, 69 patients (16 per cent) were older than 90 days when they underwent BDS. Twenty-five patients had no BDS and were referred for primary liver transplantation (6 per cent). The main reason for not performing BDS was manifest portal hypertension (18/25). Two- and 5-year transplant-free survival were significantly higher in patients with late BDS compared with no BDS (53.5 versus 12.0 per cent respectively for 2-year data and 30.4 versus 4.0 per cent respectively for 5-year data, P < 0.001). Five- and 10-year overall survival did not differ between early BDS (92 and 91 per cent respectively), late BDS (88 and 83 per cent respectively) and no BDS (80 and 80 per cent respectively, P = 0.061).

Conclusion

Age alone should not routinely be considered a contraindication to BDS in patients older than 90 days. Liver transplantation in infancy (less than 12 months) could be avoided in 88 per cent of cases with late diagnosis of biliary atresia and is delayed significantly even when BDS is performed after 3 months. Overall survival is at least equal to patients who are referred for primary liver transplantation.
Thermo-economic analysis of the performance of the combined system with evacuated tube collectors
Authors: Fadhil Smaisim Ghassan , Hadrawi Salema K , Abed Azher M , Majdi Hasan Sh. , Shamel Ali
Published: March 2023

Using combined cooling, heat and power systems can be an appropriate substitute for preventing emissions of pollutants and excessive consumption of fossil fuels. Utilizing renewable energy in these systems as a source of power generation can be an appropriate substitute for fossil-fuel-based systems. Therefore, in this paper, cogeneration cooling, heat and power systems based on gas-fired internal combustion engines with a solar-thermal system with evacuated tube collectors have been modelled and thermo-economic analysis has been done to compare fossil-fuel-based systems. The required rate of heat to supply the hot water is 50 kW. In the studied system, the internal combustion engine produces electrical energy. Then, the solar-thermal system with evacuated tube collectors and the gas-burning generator provide the thermal energy required by the studied building and the primary stimulus of the absorption chiller for cooling. In this study, two different scenarios are conducted in states considering simultaneous production systems and regardless of this environmental and thermo-economic analysis system. The results showed that the efficiency of the studied system was 60% in summer and 56% in winter.
Origin of hydrogen in aromatic and olefin products derived from (Al-) MCM-41 catalysed co-pyrolysis of glucose and polypropylene via isotopic labelling
Authors: Xue Junjie , Zhuo Jiankun , Wu Yifan , Jin Mingnuo , Sun Mufei , Yao Qiang
Published: March 2023

Catalytic co-pyrolysis of biomass and plastic is an effective method to improve bio-oil produced by biomass pyrolysis. To further exploit the synergistic mechanism between biomass and plastic, co-pyrolysis of polypropylene (PP) and deuterated glucose (G) (1:1 wt%) over mesoporous catalysts MCM-41 (M) and Al-MCM-41(Al) was studied using a thermal gravimetric analyser (TGA) and pyrolysis–gas chromatography–mass spectrometry. The findings show that M and Al overlap the decomposition of PP and G, making synergy possible. With catalysts M and Al, the yield of olefins increases sharply to 36.75% and 13.66% more than the calculated value. Additionally, hydrogen transfers from G to 4C–13C olefins and aromatic products are influenced by the catalysts. Without a catalyst, there is no deuterium in all the co-pyrolytic products. However, catalysts M and Al can help transfer one to four deuterium atoms from G to the products. M and Al provide the pool for the intermediates of PP and G to form synergetic products. Additionally, Al helps break the carbon chain and transfer more deuterium into the products by reducing carbon atoms.
Multiple direct fetal amiodarone administration for supraventricular tachycardia with hydrops fetalis: a case report
Authors: Adenin Irvan , Kapnosa Hasani Rachmat Dediat
Published: March 2023

Background

Fetal supraventricular tachycardia (SVT) is the most common fetal tachyarrhythmia and can cause fetal heart failure and intrauterine death. The management varies within institution and usually based on published case series, institutional experience.

Case summary

Fetal SVT with hydrops (ascites and subcutaneous edema) was diagnosed at 26 weeks of gestational age. The first direct injection of fetal amiodarone into the umbilical vein resulted in temporary cardioversion to the sinus rhythm and mild transient maternal adverse event. The second direct fetal amiodarone to the fetal peritoneal cavity resulted in conversion to sinus rhythm, resolution of fetal hydrops, and normal fetal growth until delivery at 39 weeks gestational age.

Discussion

Treatment of fetal SVT often requires prolonged maternal antiarrhythmic treatment and carries a significant risk of maternal adverse events. Direct fetal antiarrhythmic treatment often requires achieving adequate therapeutic drugs, especially in hydropic fetus. Amiodarone is one of drugs options for fetal SVT with hydrops because it has been shown to be highly effective with low fetal mortality. Continuous vital sign and ECG monitoring should be performed during direct fetal antiarrhythmic administration.
Impact of the antiplatelet strategy following patent foramen ovale percutaneous closure
Authors: Guedeney Paul , Farjat-Pasos Julio I , Asslo Gabriel , Roule Vincent , Beygui Farzin , Hermida Alexis , Gabrion Paul , Leborgne Laurent , Houde Christine , Huang Florent , Lattuca Benoit , Leclercq Florence , Mesnier Jules , Abtan Jérémie , Rouanet Stéphanie , Hammoudi Nadjib , Collet Jean-Philippe , Zeitouni Michel , Silvain Johanne , Montalescot Gilles , Rodés-Cabau Josep ,   for the AIR-FORCE Task Force
Published: March 2023

Aims

Temporary dual antiplatelet therapy (DAPT) is recommended following patent foramen ovale (PFO) percutaneous closure although its benefit, compared to single antiplatelet therapy (SAPT), has not been demonstrated in this setting. We aimed at assessing outcomes following PFO closure according to the antiplatelet strategy at discharge.

Methods and results

The ambispective AIR-FORCE cohort included consecutive patients from seven centres in France and Canada undergoing PFO closure and discharged without anticoagulation. Patients treated in French and Canadian centres were mostly discharged with DAPT and SAPT, respectively. The primary endpoint was the composite of death, stroke, transient ischaemic attack, peripheral embolism, myocardial infarction, or BARC type ≥2 bleeding with up to 5 years of follow-up. The impact of the antiplatelet strategy on outcomes was evaluated with a marginal Cox model (cluster analyses per country) with inverse probability weighting according to propensity score. A total of 1532 patients (42.2% female, median age: 49 [40–57] years) were included from 2001 to 2022, of whom 599 (39.1%) were discharged with SAPT and 933 (60.9%) with DAPT, for ≤3 months in 894/923 (96.9%) cases. After a median follow-up of 2.4 [1.1–4.4] years, a total of 58 events were observed. In the weighted analysis, the rate of the primary endpoint up to 5 years was 7.8% in the SAPT strategy and 7.3% in the DAPT strategy (weighted hazard ratio 1.04, 95% confidence interval 0.59–1.83).

Conclusion

The antiplatelet strategy following PFO closure did not seem to impact clinical outcomes, thus challenging the current recommendations of temporary DAPT.
Avoiding misleading estimates using mtDNA heteroplasmy statistics to study bottleneck size and selection
Authors: Giannakis Konstantinos , Broz Amanda K , Sloan Daniel B , Johnston Iain G
Published: March 2023

Mitochondrial DNA heteroplasmy samples can shed light on vital developmental and genetic processes shaping mitochondrial DNA populations. The sample means and sample variance of a set of heteroplasmy observations are typically used both to estimate bottleneck sizes and to perform fits to the theoretical “Kimura” distribution in seeking evidence for mitochondrial DNA selection. However, each of these applications raises problems. Sample statistics do not generally provide optimal fits to the Kimura distribution and so can give misleading results in hypothesis testing, including false positive signals of selection. Using sample variance can give misleading results for bottleneck size estimates, particularly for small samples. These issues can and do lead to false positive results for mitochondrial DNA mechanisms—all published experimental datasets we re-analyzed, reported as displaying departures from the Kimura model, do not in fact give evidence for such departures. Here we outline a maximum likelihood approach that is simple to implement computationally and addresses all of these issues. We advocate the use of maximum likelihood fits and explicit hypothesis tests, not fits and Kolmogorov–Smirnov tests via summary statistics, for ongoing work with mitochondrial DNA heteroplasmy.
Aminoacyl-tRNA Synthetase Evolution within the Dynamic Tripartite Translation System of Plant Cells
Authors: Sloan Daniel B , DeTar Rachael A , Warren Jessica M
Published: March 2023

Eukaryotes maintain separate protein translation systems for nuclear and organellar genes, including distinct sets of tRNAs and aminoacyl-tRNA synthetases (aaRSs). In animals, mitochondrial-targeted aaRSs are expressed at lower levels and are less conserved in sequence than cytosolic aaRSs involved in translation of nuclear mRNAs, likely reflecting lower translational demands in mitochondria. In plants, translation is further complicated by the presence of plastids, which share most aaRSs with mitochondria. In addition, plant mitochondrial tRNA pools have a dynamic history of gene loss and functional replacement by tRNAs from other compartments. To investigate the consequences of these distinctive features of translation in plants, we analyzed sequence evolution in angiosperm aaRSs. In contrast to previously studied eukaryotic systems, we found that plant organellar and cytosolic aaRSs exhibit only a small difference in expression levels, and organellar aaRSs are slightly more conserved than cytosolic aaRSs. We hypothesize that these patterns result from high translational demands associated with photosynthesis in mature chloroplasts. We also investigated aaRS evolution in Sileneae, an angiosperm lineage with extensive mitochondrial tRNA replacement and aaRS retargeting. We predicted positive selection for changes in aaRS sequence resulting from these recent changes in subcellular localization and tRNA substrates but found little evidence for accelerated sequence divergence. Overall, the complex tripartite translation system in plant cells appears to have imposed more constraints on the long-term evolutionary rates of organellar aaRSs compared with other eukaryotic lineages, and plant aaRS protein sequences appear largely robust to more recent perturbations in subcellular localization and tRNA interactions.
Coseismic and post-seismic characteristics of the 2021 Ganaveh earthquake along the Zagros foredeep fault based on InSAR data
Authors: Jafari Mahin , Aflaki Mahtab , Mousavi Zahra , Walpersdorf Andrea , Motaghi Khalil
Published: March 2023

The Ganaveh earthquake on 2021 April 18 (Mw 5.8) occurred in the southwest of the Dezful embayment of the Zagros Mountain belt, Iran, as a mainly compressive event. The InSAR coseismic displacement maps reveal a maximum of 17 cm of surface displacement in the satellite line of sight direction. InSAR inversion indicates a low-angle NE-dipping causative fault plane with a maximum slip of 95 cm at ∼6 km depth. It highlights the occurrence of the Ganaveh earthquake within the competent layers of the Zagros sedimentary cover, beneath the Gachsaran formation. A slight sinistral slip component (2.9 cm) is retrieved which is compatible with the USGS focal mechanism. Time-series analysis of SAR images after the main shock until the end of 2021 indicates a maximum of 7 cm of post-seismic surface displacement with a similar strike and pattern as the coseismic phase. This similarity and the distribution of aftershocks suggest an afterslip mechanism for the post-seismic phase. The inversion of post-seismic cumulative displacement evaluates a maximum of 30 cm slip at a depth of ∼5 km along the coseismic causative fault. A regional compressional stress regime (N041°E for the direction of the σ1 stress axis) is constrained by using the focal mechanisms of 39 earthquakes occurring between 1968 and 2021, including the Ganaveh main shock and its five larger aftershocks. Applying this direction of compression on the Ganaveh fault plane also results in a minor sinistral movement, consistent with the geodetic results. The relocated main shock and aftershocks as well as our InSAR coseismic displacement situations on the hanging wall of the Zagros Foredeep fault highlight it as the causative fault of the Ganaveh earthquake. To fit the geometry of the Ganaveh rupture plane with the Zagros Foredeep fault, we modelled a listric fault plane and its slip distribution using the available geological data. The retrieved slip variation on the listric plane is in close agreement with the slip pattern on the modelled planar geometry. The low dip angle of the rupture plane combined with a listric geometry highlights the thin-skin characteristics of the Zagros Foredeep fault as the causative fault of the Ganaveh earthquake. The occurrence of this moderate magnitude earthquake on the Zagros Foredeep fault underlines its role as the western structural boundary for the recurrence of Mb > 5 events in the Dezful embayment.
The Holy Cross Mountains (Poland) terranes palaeoposition and depositional environment in Silurian—new insights from rock magnetic studies
Authors: Niezabitowska D K , Szaniawski R
Published: March 2023

The Holy Cross Mountains (HCM) in Poland, is an isolated natural outcrop of Palaeozoic rocks located within the Trans-European Suture Zone, a tectonic collage of continental terranes adjacent to the Tornquist margin of the Baltica. This uniqueness made the HCM a target for palaeogeographic research. Based on the facies differences, the HCM had been divided into two major units, the southern (the Kielce Unit) and northern (the Łysogóry Unit) part (SHCM and NHCM, respectively). Their position in relation to each other and the Baltica continent during Silurian times is still a matter of discussion, whether both parts of the HCM were separated terranes located along the Baltica margin or they shared in common palaeogeographic history. Here, we present the results of comprehensive rock magnetic measurements applied as a tool to interpret palaeoenvironmental conditions during deposition and burial and therefore allow discussion about the terranes’ relative position. To recognize the magnetic mineral composition and texture of studied Silurian graptolitic shales several rock magnetic measurements were conducted including low-temperature Saturated Isothermal Remanent Magnetization, thermal demagnetization of three-component IRM and hysteresis measurements, as well as anisotropy of magnetic susceptibility (AMS). The sampled rocks come from both units of the HCM. In all analysed samples we found single domain (SD) stoichiometric magnetite of mostly diagenetic (i.e. post-depositional) origin and goethite resulting likely from weathering. In turn, detrital magnetite, even if observed in previously investigated Silurian rocks from the Baltica margin, was not identified in this study, what we attribute to dissolution during diagenesis in the deep-water environment. Solely in the NHCM, SD hematite and maghemite grains were observed, which we interpret as detrital in origin. These grains have been preserved in the suboxic environment of the NHCM sub-basin bottom waters due to their resistance to dissolution in marine waters. Considering the deposition conditions (oxygenation of the near-bottom zone) rather similar for both HCM parts, we associate the presence of aeolian hematite grains solely in the NHCM rocks with a more proximal position of the NHCM than the SHCM in relation to the Baltica continent during late Llandovery (Silurian). This conclusion agrees with some existing palaeogeographic models. In addition to petromagnetic studies focused on the analysis of ferromagnets, AMS measurements were also carried out. The results indicate that the magnetic susceptibility is mainly governed by paramagnetic minerals, mostly phyllosilicates with small ferromagnetic contributions. Oblate AMS ellipsoid and distinct bedding parallel foliation indicate prevailing sedimentary-compactional alignment. Observed magnetic lineation of tectonic origin resulting from weak strain is related presumably to Variscian deformations.
The nursing home as a hub: boundary work as a key to community health promotion
Authors: Wegener Charlotte , Storm Marianne , Willumsen Elisabeth
Published: March 2023

This article considers ways in which a nursing home can come to serve as a hub for community health promotion. Inspired by the term ‘boundary crossing’ (Akkerman and Bakker. Boundary crossing and boundary objects. Rev Educ Res 2011;81:132–69), we suggest the notion of ‘boundary work’ to illustrate how a nursing home arranges community activities and includes a wide range of participants. In health research, a ‘hub’ refers to a space in which activities and expertise are ‘bound together’ over time. The concept of the hub indicates that health organizations have the power to become centres for health promotion by initiating new collaborations and opening up initiatives in two-way processes with the local community. The term ‘boundary work’ supports a perspective that dissolves organizational, professional and conceptual boundaries and directs attention towards social inclusion as a key to community health promotion in and beyond institutionalized elderly care. The article is based on a 4-year-long practice-based study of social innovation in elderly care in Norway and Denmark. Empirical illustrations show boundary work in which a nursing home comes to serve as a hub. We discuss a flexible framework for understanding, mapping and planning participatory approaches for health and wellbeing (South et al. An evidence-based framework on community-centred approaches for health: England, UK. Health Promot Int 2019;34:356–66) and briefly connect these approaches to the concept of social innovation as a possible future research path.
Life course effects of genetic susceptibility to higher body size on body fat and lean mass: prospective cohort study
Authors: Waterfield Scott , Richardson Tom G , Davey Smith George , O’Keeffe Linda M , Bell Joshua A
Published: March 2023

Background/objectives

Different genetic variants are associated with larger body size in childhood vs adulthood. Whether and when these variants predominantly influence adiposity are unknown. We examined how genetic variants influence total body fat and total lean mass trajectories.

Methods

Data were from the Avon Longitudinal Study of Parents and Children birth cohort (N = 6926). Sex-specific genetic risk scores (GRS) for childhood and adulthood body size were generated, and dual-energy X-ray absorptiometry scans measured body fat and lean mass six times between the ages of 9 and 25 years. Multilevel linear spline models examined associations of GRS with fat and lean mass trajectories.

Results

In males, the sex-specific childhood and adulthood GRS were associated with similar differences in fat mass from 9 to 18 years; 8.3% [95% confidence interval (CI) 5.1, 11.6] and 7.5% (95% CI 4.3, 10.8) higher fat mass at 18 years per standard deviation (SD) higher childhood and adulthood GRS, respectively. In males, the sex-combined childhood GRS had stronger effects at ages 9 to 15 than the sex-combined adulthood GRS. In females, associations for the sex-specific childhood GRS were almost 2-fold stronger than the adulthood GRS from 9 to 18 years: 10.5% (95% CI 8.5, 12.4) higher fat mass at 9 years per SD higher childhood GRS compared with 5.1% (95% CI 3.2, 6.9) per-SD higher adulthood GRS. In females, the sex-combined GRS had similar effects, with slightly larger effect estimates. Lean mass effect sizes were much smaller.

Conclusions

Genetic variants for body size are more strongly associated with adiposity than with lean mass. Sex-combined childhood variants are more strongly associated with increased adiposity until early adulthood. This may inform future studies that use genetics to investigate the causes and impact of adiposity at different life stages.
IGF-1 Microinjection in the Prefrontal Cortex Attenuates Fentanyl-Seeking Behavior in Mice
Authors: Li Guohui , Yue Shuwen , Wang Yunwanbin , Singh Archana , Wang Zi-Jun
Published: March 2023

Background

Opioid use disorder (OUD) is a chronic relapsing psychiatric disorder with an enormous socioeconomic burden. Opioid overdose deaths have reached an epidemic level, especially for fentanyl. One of the biggest challenges to treat OUD is the relapse to drug seeking after prolonged abstinence. Abnormalities in insulin-like growth factor-1 (IGF-1) have been reported in various neurological and psychiatric disorders, including OUD. However, whether IGF-1 and its downstream signaling pathways are associated with relapse to fentanyl seeking remains unclear.

Methods

Mice were subjected to daily 2-hour fentanyl (10 μg/mL, 27 μL/infusion) oral self-administration training for 14 days, followed by 14-day fentanyl cessation. Expression levels of IGF-1/IGF-1 receptor and downstream signaling pathways in the dorsomedial prefrontal cortex (dmPFC) were detected. Then, IGF-1 was bilaterally microinjected into the dmPFC from fentanyl cessation day 9 to day 13. Fentanyl-seeking behavior and excitatory synaptic transmission of pyramidal neurons in PFC were evaluated.

Results

We found that 14-day cessation from fentanyl oral self-administration caused significant downregulation of IGF-1 and IGF-1 receptor phosphorylation in the dmPFC. These changes were accompanied by inhibition of the downstream Akt and S6 signaling pathway. In addition, local administration of IGF-1 in the dmPFC attenuated context-induced fentanyl-seeking behavior. Furthermore, electrophysiology and immunohistochemistry analyses showed that IGF-1 blocked fentanyl-induced reduction of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptors-mediated excitatory synaptic transmission as well as synaptic expression of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor and N-methyl-D-aspartate receptor subunits.

Conclusions

These results suggest that IGF-1 in the PFC plays a pivotal role in regulating fentanyl seeking after prolonged cessation from fentanyl oral self-administration.
On the Image of Hitchin Morphism for Algebraic Surfaces: The Case GLn
Authors: Song Lei , Sun Hao
Published: March 2023

The Hitchin morphism is a map from the moduli space of Higgs bundles $\mathscr {M}_{X}$ to the Hitchin base $\mathscr {B}_{X}$, where $X$ is a smooth projective variety. When $X$ has dimension at least two, this morphism is not surjective in general. Recently, Chen-Ngô introduced a closed subscheme $\mathscr {A}_{X}$ of $\mathscr {B}_{X}$, which is called the space of spectral data. They proved that the Hitchin morphism factors through $\mathscr {A}_{X}$ and conjectured that $\mathscr {A}_{X}$ is the image of the Hitchin morphism. We prove that when $X$ is a smooth projective surface, this conjecture is true for vector bundles. Moreover, we show that $\mathscr {A}_{X}$, for any dimension, is invariant under any proper birational morphism and apply the result to study $\mathscr {A}_{X}$ for ruled surfaces.
Ypel5 regulates liver development and function in zebrafish
Authors: Deng Yun , Han Xiao , Chen Huiqiao , Zhao Chaoxian , Chen Yi , Zhou Jun , de The Hugues , Zhu Jun , Yuan Hao
Published: March 2023

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5−/− mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5−/− mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.
Development and applications of ultrafast transmission electron microscopy
Authors: Shimojima T , Nakamura A , Ishizaka K
Published: March 2023

We present a review on the development and applications of ultrafast transmission electron microscopy (UTEM) at Institute of Physical and Chemical Research (RIKEN). We introduce the UTEM system for the pump-probe transmission electron microscopy (TEM) observation in a wide temporal range. By combining the UTEM and pixelated detector, we further develop five-dimensional scanning TEM (5D STEM), which provides the ultrafast nanoscale movie of physical quantities in nanomaterials, such as crystal lattice information and electromagnetic field, by convergent-beam electron diffraction (CBED) and differential phase contrast imaging technique. We show our recent results on the nanosecond-to-microsecond magnetic skyrmion dynamics observed by Lorentz TEM (LTEM) and photoinduced acoustic wave generation in the picosecond regime by bright-field TEM and electron diffraction measurements by UTEM. We also show the demonstration of the 5D STEM on the quantitative time (t)–dependent strain mapping by CBED with an accuracy of 4 ps and 8 nm and the ultrafast demagnetization under a zero magnetic field observed by differential phase contrast with 10 ns and 400 nm resolution.
Transmission Kikuchi Diffraction Mapping Induces Structural Damage in Atom Probe Specimens
Authors: Gault Baptiste , Khanchandani Heena , Prithiv Thoudden Sukumar , Antonov Stoichko , Britton T Ben
Published: March 2023

Measuring local chemistry of specific crystallographic features by atom probe tomography (APT) is facilitated by using transmission Kikuchi diffraction (TKD) to help position them sufficiently close to the apex of the needle-shaped specimen. However, possible structural damage associated to the energetic electrons used to perform TKD is rarely considered and is hence not well-understood. Here, in two case studies, we evidence damage in APT specimens from TKD mapping. First, we analyze a solid solution, metastable β-Ti-12Mo alloy, in which the Mo is expected to be homogenously distributed. Following TKD, APT reveals a planar segregation of Mo among other elements. Second, specimens were prepared near Σ3 twin boundaries in a high manganese twinning-induced plasticity steel, and subsequently charged with deuterium gas. Beyond a similar planar segregation, voids containing a high concentration of deuterium, i.e., bubbles, are detected in the specimen on which TKD was performed. Both examples showcase damage from TKD mapping leading to artefacts in the distribution of solutes. We propose that the structural damage is created by surface species, including H and C, subjected to recoil from incoming energetic electrons during mapping, thereby getting implanted and causing cascades of structural damage in the sample.
Cosmological Fisher forecasts for next-generation spectroscopic surveys
Authors: d’Assignies D William , Zhao Cheng , Yu Jiaxi , Kneib Jean-Paul
Published: March 2023

Next-generation spectroscopic surveys such as the MegaMapper, MUltiplexed Survey Telescope (MUST), MaunaKea Spectroscopic Explorer (MSE), and WideField Spectroscopic Telescope (WST) are foreseen to increase the number of galaxy/quasar redshifts by an order of magnitude, with hundred millions of spectra that will be measured at z > 2. We perform a Fisher matrix analysis for these surveys on the baryonic acoustic oscillation (BAO), the redshift-space distortion (RSD) measurement, the non-Gaussianity (NG) amplitude fNL, and the total neutrino mass Mν. For BAO and RSD parameters, these surveys may achieve precision at sub-per cent level (<0.5 per cent), representing an improvement of factor 10 w.r.t. the latest data base. For NG, these surveys may reach an accuracy of σ(fNL) ∼ 1. They can also put a tight constraint on Mν with $\sigma (M_\nu) \sim 0.02\, \rm eV$ if we do joint analysis with Planck and even $0.01\, \rm eV$ if combined with other data. In addition, we introduce a general survey model to derive the cosmic volume and number density of tracers, given instrumental facilities and survey strategy. Using our Fisher formalism, we can explore (continuously) a wide range of survey observational parameters and propose different survey strategies that optimize the cosmological constraints. Fixing the fibre number and survey duration, we show that the best strategy for fNL and Mν measurement is to observe large volumes, despite the noise increase. However, the strategy differs for the apparent magnitude limit. Finally, we prove that increasing the fibre number improves Mν measurement but not significantly fNL.
Identification of tidal features in deep optical galaxy images with convolutional neural networks
Authors: Sánchez H Domínguez , Martin G , Damjanov I , Buitrago F , Huertas-Company M , Bottrell C , Bernardi M , Knapen J H , Vega-Ferrero J , Hausen R , Kado-Fong E , Población-Criado D , Souchereau H , Leste O K , Robertson B , Sahelices B , Johnston K V
Published: March 2023

Interactions between galaxies leave distinguishable imprints in the form of tidal features, which hold important clues about their mass assembly. Unfortunately, these structures are difficult to detect because they are low surface brightness features, so deep observations are needed. Upcoming surveys promise several orders of magnitude increase in depth and sky coverage, for which automated methods for tidal feature detection will become mandatory. We test the ability of a convolutional neural network to reproduce human visual classifications for tidal detections. We use as training ∼6000 simulated images classified by professional astronomers. The mock Hyper Suprime Cam Subaru (HSC) images include variations with redshift, projection angle, and surface brightness (μlim = 26–35 mag arcsec−2). We obtain satisfactory results with accuracy, precision, and recall values of Acc = 0.84, P = 0.72, and R  = 0.85 for the test sample. While the accuracy and precision values are roughly constant for all surface brightness, the recall (completeness) is significantly affected by image depth. The recovery rate shows strong dependence on the type of tidal features: we recover all the images showing shell features and 87 per cent of the tidal streams; these fractions are below 75 per cent for mergers, tidal tails, and bridges. When applied to real HSC images, the performance of the model worsens significantly. We speculate that this is due to the lack of realism of the simulations, and take it as a warning on applying deep learning models to different data domains without prior testing on the actual data.
Shock shaping? Nebular spectroscopy of nova V906 Carinae
Authors: Harvey É J , Aydi E , Izzo L , Morisset C , Darnley M J , Fitzgerald K , Molaro P , Murphy-Glaysher F , Redman M P , Shrestha M
Published: March 2023

V906 Carinae was one of the best observed novae of recent times. It was a prolific dust producer and harboured shocks in the early evolving ejecta outflow. Here, we take a close look at the consequences of these early interactions through study of high-resolution Ultraviolet and Visual Echelle spectrograph spectroscopy of the nebular stage and extrapolate backwards to investigate how the final structure may have formed. A study of ejecta geometry and shaping history of the structure of the shell is undertaken following a spectral line $\rm {\small SHAPE}$ model fit. A search for spectral tracers of shocks in the nova ejecta is undertaken and an analysis of the ionized environment. Temperature, density, and abundance analyses of the evolving nova shell are presented.
What sets the splashback radius of dark matter haloes: accretion history or other properties?
Authors: Shin Tae-hyeon , Diemer Benedikt
Published: March 2023

The density profiles of dark matter haloes contain rich information about their growth history and physical properties. One particularly interesting region is the splashback radius, Rsp, which marks the transition between particles orbiting in the halo and particles undergoing first infall. While the dependence of Rsp on the recent accretion rate is well-established and theoretically expected, it is not clear exactly what parts of the accretion history Rsp responds to, and what other halo properties might additionally influence its position. We comprehensively investigate these questions by correlating the dynamically measured splashback radii of a large set of simulated haloes with their individual growth histories as well as their structural, dynamical, and environmental properties. We find that Rsp is sensitive to the accretion over one crossing time but largely insensitive to the prior history (in contrast to concentration, which probes earlier epochs). All secondary correlations are much weaker, but we discern a relatively higher Rsp in less massive, older, more elliptical, and more tidally deformed haloes. Despite these minor influences, we conclude that the splashback radius is a clean indicator of a halo’s growth over the past dynamical time. We predict that the magnitude gap should be a promising observable indicator of a halo’s accretion rate and splashback radius.
Optical counterparts of two candidate ultraluminous X-ray sources in NGC 4536
Authors: Avdan H , Sonbas E , Dhuga K S , Vinokurov A , Göğüş E , Avdan S , Solovyeva Y N , Kostenkov A E , Shablovinskaya E S , Goktas D
Published: March 2023

Archival XMM–Newton, Chandra, and Hubble Space Telescope(HST) data have been used to study the X-ray and optical properties of two candidate ultraluminous X-ray sources in NGC 4536. In order to search for potential optical counterparts, relative astrometry between Chandra and HST was improved, and as a result, optical counterparts were detected for both X-ray sources. To complement our findings (based on the archival data), ground-based optical spectra of the counterparts were obtained with the 6-m BTA (Big Telescope Alt-azimuth) Telescope located at the Special Astrophysical Observatory. The calculated redshift (z = 0.4391 ± 0.0010) for one of the sources (X-3) indicates that the source is, in fact, a background active galactic nucleus. Two possible optical counterparts (s1 and s2) were found for X-2. Whether s1 is point-like or an extended source is unclear: If it is point-like and the emission is dominated by the donor, its spectral type indicates O–B star. The second source (s2) is point-like and is consistent with the colours and absolute magnitudes of a red supergiant.
The Local Group’s mass: probably no more than the sum of its parts
Authors: Sawala Till , Teeriaho Meri , Johansson Peter H
Published: March 2023

The total mass of the Local Group and the masses of its primary constituents, the Milky Way (MW) and M31, are important anchors for several cosmological questions. Recent independent measurements have consistently yielded halo masses close to 1012M⊙ for the MW, and 1–2 × 1012M⊙ for M31, while estimates derived from the pair’s kinematics via the ‘timing argument’ have yielded a combined mass of around 5 × 1012M⊙. We analyse the extremely large Uchuu simulation to constrain the mass of the Local Group and its two most massive members. First, we demonstrate the importance of selecting pairs whose kinematics reflect their mutual interactions. Adopting the observed separation and radial velocity, we obtain a weighted posterior of $75_{-40}^{+65}$ km s−1 for the uncertain transverse velocity. Via Gaussian process regression, we infer a total mass of $3.2^{+1.2}_{-0.9} \times 10^{12} \mathrm{M}_\odot$, significantly below the timing argument value. Importantly, the remaining uncertainty is not rooted in the analysis or observational errors, but in the irreducible scatter in the kinematics–mass relation. We further find a mass for the less massive halo of $0.9_{-0.3}^{+0.6} \times 10^{12} \mathrm{M}_\odot$ and for the more massive halo of $2.3_{-0.9}^{+1.0} \times 10^{12} \mathrm{M}_\odot$, consistent with independent measurements of the masses of MW and M31, respectively. Incorporating the MW mass as an additional prior let us constrain all measurements further and determine that the MW is very likely less massive than M31.
Minimal lensing solutions in the singular perturbative approach
Authors: Alard C
Published: March 2023

This paper analyses the properties of minimal solutions for the reconstruction of the lens potential in the singular perturbative approach. These minimal solutions corresponds to an expansion with a minimal degree in Fourier expansion of the perturbative fields. Using these minimal solutions prevent spurious physically meaningless terms in the reconstruction of the fields. In effect, a perturbative analysis indicates that a small change in the source model will corresponds to the higher order terms in the expansion of the fields. The results of the perturbative analysis are valid not only for slightly non-circular sources but also for more distorted sources to order two. It is, thus, of crucial importance to minimize the number of terms used in the modelling of the lens. Another important asset of the minimal solutions is that they offer a de-coupling between the source and lens model, and thus help to break the source lens degeneracy issue. The possible drawback of minimal solutions is to underestimate the higher order terms in the solution. However, this bias has its merit since the detection of higher order terms using this method will ensure that these terms are real. This type of analysis using minimal solutions will be of particular interest when considering the statistical analysis of a large number of lenses, especially in light of the incoming satellite surveys.
Genome-encoded ABCF factors implicated in intrinsic antibiotic resistance in Gram-positive bacteria: VmlR2, Ard1 and CplR
Authors: Obana Nozomu , Takada Hiraku , Crowe-McAuliffe Caillan , Iwamoto Mizuki , Egorov Artyom A , Wu Kelvin J Y , Chiba Shinobu , Murina Victoriia , Paternoga Helge , Tresco Ben I C , Nomura Nobuhiko , Myers Andrew G , Atkinson Gemma C , Wilson Daniel N , Hauryliuk Vasili
Published: March 2023

Genome-encoded antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F subfamily (ARE-ABCFs) mediate intrinsic resistance in diverse Gram-positive bacteria. The diversity of chromosomally-encoded ARE-ABCFs is far from being fully experimentally explored. Here we characterise phylogenetically diverse genome-encoded ABCFs from Actinomycetia (Ard1 from Streptomyces capreolus, producer of the nucleoside antibiotic A201A), Bacilli (VmlR2 from soil bacterium Neobacillus vireti) and Clostridia (CplR from Clostridium perfringens, Clostridium sporogenes and Clostridioides difficile). We demonstrate that Ard1 is a narrow spectrum ARE-ABCF that specifically mediates self-resistance against nucleoside antibiotics. The single-particle cryo-EM structure of a VmlR2-ribosome complex allows us to rationalise the resistance spectrum of this ARE-ABCF that is equipped with an unusually long antibiotic resistance determinant (ARD) subdomain. We show that CplR contributes to intrinsic pleuromutilin, lincosamide and streptogramin A resistance in Clostridioides, and demonstrate that C. difficile CplR (CDIF630_02847) synergises with the transposon-encoded 23S ribosomal RNA methyltransferase Erm to grant high levels of antibiotic resistance to the C. difficile 630 clinical isolate. Finally, assisted by uORF4u, our novel tool for detection of upstream open reading frames, we dissect the translational attenuation mechanism that controls the induction of cplR expression upon an antibiotic challenge.
Cryo-EM reconstruction of the human 40S ribosomal subunit at 2.15 Å resolution
Authors: Pellegrino Simone , Dent Kyle C , Spikes Tobias , Warren Alan J
Published: March 2023

The chemical modification of ribosomal RNA and proteins is critical for ribosome assembly, for protein synthesis and may drive ribosome specialisation in development and disease. However, the inability to accurately visualise these modifications has limited mechanistic understanding of the role of these modifications in ribosome function. Here we report the 2.15 Å resolution cryo-EM reconstruction of the human 40S ribosomal subunit. We directly visualise post-transcriptional modifications within the 18S rRNA and four post-translational modifications of ribosomal proteins. Additionally, we interpret the solvation shells in the core regions of the 40S ribosomal subunit and reveal how potassium and magnesium ions establish both universally conserved and eukaryote-specific coordination to promote the stabilisation and folding of key ribosomal elements. This work provides unprecedented structural details for the human 40S ribosomal subunit that will serve as an important reference for unravelling the functional role of ribosomal RNA modifications.
Fission yeast Swi2 designates cell-type specific donor and stimulates Rad51-driven strand exchange for mating-type switching
Authors: Maki Takahisa , Thon Geneviève , Iwasaki Hiroshi
Published: March 2023

A haploid of the fission yeast Schizosaccharomyces pombe expresses either the P or M mating-type, determined by the active, euchromatic, mat1 cassette. Mating-type is switched by Rad51-driven gene conversion of mat1 using a heterochromatic donor cassette, mat2-P or mat3-M. The Swi2-Swi5 complex, a mating-type switching factor, is central to this process by designating a preferred donor in a cell-type-specific manner. Swi2-Swi5 selectively enables one of two cis-acting recombination enhancers, SRE2 adjacent to mat2-P or SRE3 adjacent to mat3-M. Here, we identified two functionally important motifs in Swi2, a Swi6 (HP1 homolog)-binding site and two DNA-binding AT-hooks. Genetic analysis demonstrated that the AT-hooks were required for Swi2 localization at SRE3 to select the mat3-M donor in P cells, while the Swi6-binding site was required for Swi2 localization at SRE2 to select mat2-P in M cells. In addition, the Swi2-Swi5 complex promoted Rad51-driven strand exchange in vitro. Taken together, our results show how the Swi2-Swi5 complex would localize to recombination enhancers through a cell-type specific binding mechanism and stimulate Rad51-driven gene conversion at the localization site.
DiSiR: fast and robust method to identify ligand–receptor interactions at subunit level from single-cell RNA-sequencing data
Authors: Vahid Milad R , Kurlovs Andre H , Andreani Tommaso , Augé Franck , Olfati-Saber Reza , de Rinaldis Emanuele , Rapaport Franck , Savova Virginia
Published: March 2023

Most cell–cell interactions and crosstalks are mediated by ligand–receptor interactions. The advent of single-cell RNA-sequencing (scRNA-seq) techniques has enabled characterizing tissue heterogeneity at single-cell level. In the past few years, several methods have been developed to study ligand–receptor interactions at cell type level using scRNA-seq data. However, there is still no easy way to query the activity of a specific user-defined signaling pathway in a targeted way or to map the interactions of the same subunit with different ligands as part of different receptor complexes. Here, we present DiSiR, a fast and easy-to-use permutation-based software framework to investigate how individual cells are interacting with each other by analyzing signaling pathways of multi-subunit ligand-activated receptors from scRNA-seq data, not only for available curated databases of ligand–receptor interactions, but also for interactions that are not listed in these databases. We show that, when utilized to infer ligand–receptor interactions from both simulated and real datasets, DiSiR outperforms other well-known permutation-based methods, e.g. CellPhoneDB and ICELLNET. Finally, to demonstrate DiSiR’s utility in exploring data and generating biologically relevant hypotheses, we apply it to COVID lung and rheumatoid arthritis (RA) synovium scRNA-seq datasets and highlight potential differences between inflammatory pathways at cell type level for control versus disease samples.