bluuebunny/crossref_metadata_2025 huggingface dataset:
Venous vascular closure system vs. figure-of-eight suture following atrial fibrillation ablation: the STYLE-AF Study
Authors: Tilz Roland Richard , Feher Marcel , Vogler Julia , Bode Kerstin , Duta Alexandru Ionut , Ortolan Angela , Lopez Lisbeth Delgado , Küchler Mirco , Mamaev Roman , Lyan Evgeny , Sommer Philipp , Braun Martin , Sciacca Vanessa , Demming Thomas , Maslova Vera , Kuck Karl-Heinz , Heeger Christian-Hendrik , Eitel Charlotte , Popescu Sorin Stefan
Published: April 2024

Aims

Simplified ablation technologies for pulmonary vein isolation (PVI) are increasingly performed worldwide. One of the most common complications following PVI are vascular access-related complications. Lately, venous closure systems (VCSs) were introduced into clinical practice, aiming to reduce the time of bed rest, to increase the patients’ comfort, and to reduce vascular access-related complications. The aim of the present study is to compare the safety and efficacy of using a VCS to achieve haemostasis following single-shot PVI to the actual standard of care [figure-of-eight suture and manual compression (MC)].

Methods and results

This is a prospective, multicentre, randomized, controlled, open-label trial performed at three German centres. Patients were randomized 1:1 to undergo haemostasis either by means of VCS (VCS group) or of a figure-of-eight suture and MC (F8 group). The primary efficacy endpoint was the time to ambulation, while the primary safety endpoint was the incidence of major periprocedural adverse events until hospital discharge. A total of 125 patients were randomized. The baseline characteristics were similar between the groups. The VCS group showed a shorter time to ambulation [109.0 (82.0, 160.0) vs. 269.0 (243.8, 340.5) min; P < 0.001], shorter time to haemostasis [1 (1, 2) vs. 5 (2, 10) min; P < 0.001], and shorter time to discharge eligibility [270 (270, 270) vs. 340 (300, 458) min; P < 0.001]. No major vascular access-related complication was reported in either group. A trend towards a lower incidence of minor vascular access-related complications on the day of procedure was observed in the VCS group [7 (11.1%) vs. 15 (24.2%); P = 0.063] as compared to the control group.

Conclusion

Following AF ablation, the use of a VCS results in a significantly shorter time to ambulation, time to haemostasis, and time to discharge eligibility. No major vascular access-related complications were identified. The use of MC and a figure-of-eight suture showed a trend towards a higher incidence of minor vascular access-related complications.
The gut microbiome of farmed Arctic char (Salvelinus alpinus) is shaped by feeding stage and nutrient presence
Authors: Knobloch Stephen , Skirnisdóttir Sigurlaug , Dubois Marianne , Mayolle Lucie , Kolypczuk Laetitia , Leroi Françoise , Leeper Alexandra , Passerini Delphine , Marteinsson Viggó Þ
Published: April 2024

The gut microbiome plays an important role in maintaining health and productivity of farmed fish. However, the functional role of most gut microorganisms remains unknown. Identifying the stable members of the gut microbiota and understanding their functional roles could aid in the selection of positive traits or act as a proxy for fish health in aquaculture. Here, we analyse the gut microbial community of farmed juvenile Arctic char (Salvelinus alpinus) and reconstruct the metabolic potential of its main symbionts. The gut microbiota of Arctic char undergoes a succession in community composition during the first weeks post-hatch, with a decrease in Shannon diversity and the establishment of three dominant bacterial taxa. The genome of the most abundant bacterium, a Mycoplasma sp., shows adaptation to rapid growth in the nutrient-rich gut environment. The second most abundant taxon, a Brevinema sp., has versatile metabolic potential, including genes involved in host mucin degradation and utilization. However, during periods of absent gut content, a Ruminococcaceae bacterium becomes dominant, possibly outgrowing all other bacteria through the production of secondary metabolites involved in quorum sensing and cross-inhibition while benefiting the host through short-chain fatty acid production. Whereas Mycoplasma is often present as a symbiont in farmed salmonids, we show that the Ruminococcaceae species is also detected in wild Arctic char, suggesting a close evolutionary relationship between the host and this symbiotic bacterium.
Dietary Vitamin C Intake and Changes in Frequency, Severity, and Location of Pain in Older Adults
Authors: Delgado-Velandia Mario , Ortolá Rosario , García-Esquinas Esther , Carballo-Casla Adrián , Sotos-Prieto Mercedes , Rodríguez-Artalejo Fernando
Published: April 2024

Background

Oral vitamin C supplementation has been associated with lower risk of chronic postsurgical pain. However, the effect of dietary vitamin C on pain in a nonsurgical setting is unknown. We aimed to investigate the association between dietary vitamin C intake and changes over time in chronic pain and its characteristics in community-dwelling adults aged 60 + years.

Methods

We pooled data from participants of the Seniors-ENRICA-1 (n = 864) and Seniors-ENRICA-2 (n = 862) cohorts who reported pain at baseline or at follow up. Habitual diet was assessed with a face-to-face diet history and dietary vitamin C intake was estimated using standard food composition tables. Pain changes over time were the difference between scores at baseline and follow up obtained from a pain scale that considered the frequency, severity, and number of pain locations. Multivariable-adjusted relative risk ratios were obtained using multinomial logistic regression.

Results

After a median follow-up of 2.6 years, pain worsened for 696 (40.3%) participants, improved for 734 (42.5%), and did not change for 296 (17.2%). Compared with the lowest tertile of energy-adjusted vitamin C intake, those in the highest tertile had a higher likelihood of overall pain improvement (RRR 1.61 [95% confidence interval 1.07–2.41], p-trend .02). Higher vitamin C intake was also associated with lower pain frequency (1.57 [1.00–2.47], p-trend = .05) and number of pain locations (1.75 [1.13–2.70], p-trend = .01).

Conclusions

Higher dietary vitamin C intake was associated with improvement of pain and with lower pain frequency and number of pain locations in older adults. Nutritional interventions to increase dietary vitamin C intake with the aim of improving pain management require clinical testing.
Network dynamics of civil society: a longitudinal study in Malaysia amidst changing political opportunity structures
Authors: Sommerfeldt Erich J , Pilny Andrew , Saffer Adam J
Published: April 2024

This article explores the role of macro-level factors, specifically political opportunity structures (POS), in shaping interorganizational network tie formation and persistence. Grounded in the POS literature and the multitheoretical multilevel (MTML) framework—specifically using the theories of resource dependency and collective action—we examine how changes in POS are associated with network structures in Malaysian civil society. Data were collected in two phases, reflecting different political contexts. Although the network never evolved into a decentralized or centralized structure, the most central organizations remained consistent and seemed to have been active in bringing others closer to reconfigure toward a more cohesive structure as the POS became more closed. This research contributes to communication network theory by demonstrating how incorporating exogenous environmental factors like POS can advance theory. It offers new insights into operationalizing POS within network analysis and challenges conventional interpretations of centralization in interorganizational relationships.
Health insurance and subjective well-being: evidence from integrating medical insurance across urban and rural areas in China
Authors: Zhou Qin , Eggleston Karen , Liu Gordon G
Published: April 2024

Health insurance coverage and the risk protection it provides may improve enrollees’ subjective well-being (SWB), as demonstrated, e.g. by Oregon Medicaid’s randomized expansion significantly improving enrollees’ mental health and happiness. Yet little evidence from low- and middle-income countries documents the link between insurance coverage and SWB. We analyse individual-level data on a large natural experiment in China: the integration of the rural and urban resident health insurance programmes. This reform, expanded nationally since 2016, is recognized as a vital step towards attaining the goal of providing affordable and equitable basic healthcare in China, because integration raises the level of healthcare coverage for rural residents to that enjoyed by their urban counterparts. This study is the first to investigate the impact of urban–rural health insurance integration on the SWB of the Chinese population. Analysing 2011–18 data from the China Health and Retirement Longitudinal Study in a difference-in-difference framework with variation in the treatment timing, we find that the integration policy significantly improved the life satisfaction of rural residents, especially among low-income and elderly individuals. The positive impact of the integration on SWB appears to stem from the improvement of rural residents’ mental health (decrease in depressive symptoms) and associated increases in some health behaviours, as well as a mild increase in outpatient care utilization and financial risk protection. There was no discernible impact of the integration on SWB among urban residents, suggesting that the reform reduced inequality in healthcare access and health outcomes for poorer rural residents without negative spillovers on their urban counterparts.
Identification of allelic relationship and translocation region among chromosomal translocation lines that leads to less-seed watermelon
Authors: Jiao Di , Zhao Hong , Sun Honghe , Zhang Jie , Zhang Haiying , Gong Guoyi , Anees Muhammad , Zhu Hongju , Liu Wenge , Xu Yong
Published: April 2024

Less-seed and seedless traits are desirable characteristics in watermelon (Citrullus lanatus). Hybridization between watermelon chromosomal translocated lines and wild lines significantly reduced seed counts in the hybrid fruits, approaching even seedless. However, the allelic relationships and the chromosomal translocation breakpoints from different sources are unclear, which limits their utility in breeding practices. This study focused on three groups of chromosomal translocation materials from different sources and conducted inheritance and allelic relationship analysis of translocation points. The results from third-generation genome sequencing and fluorescence in situ hybridization (FISH) revealed that the specific translocations in the naturally mutated material MT-a involved reciprocal translocations between Chr6 and Chr10. The Co60γ radiation-induced mutant material MT-b involved reciprocal translocations between Chr1 and Chr5, Chr4 and Chr8. The Co60γ radiation-induced mutant material MT-c involved complex translocations among Chr1, Chr5, and Chr11. Cytological observation showed that heterozygous translocation hybrids showed chromosomal synapsis abnormalities during meiotic diakinesis. Further, dominant and codominant molecular markers were developed on both sides of the translocation breakpoints, which could facilitate rapid and efficient identification of chromosome translocation lines. This study provides technical guidance for utilizing chromosomal translocation materials in the development of less-seed watermelon varieties.
Cytochemical localization and synthesis mechanism of the glucomannan in pseudobulbs of Bletilla striata Reichb. f
Authors: Huang Junfeng , Ma Shuang , Zhou Ming , Liu Zhihao , Liang Qiong
Published: April 2024

The dried pseudobulbs of Bletilla striata, an important traditional Chinese medicine named BaiJi, have an extraordinary polysaccharide content and excellent prospects for medicinal effects. However, the distribution and molecular mechanism underlying biosynthesis are poorly understood. In this study, chemical and immunologic analyses were performed in representative tissues of B. striata, and the results showed that what are conventionally termed Bletilla striata polysaccharides (BSPs) are water-soluble polysaccharides deposited only in pseudobulbs. The structural component of BSPs is glucomannan, with a mannose:glucose mass ratio of ~3:2. BSPs are present in the parenchyma of the pseudobulbs in cells known as glucomannan idioblasts and distributed in the cytoplasm within cellular membranes, but are not contained in the vacuole. Comparative transcriptomics and bioinformatics analyses mapped the pathway from sucrose to BSP and identified BsGPI, BsmanA, and BsCSLAs as the key genes of BSP biosynthesis, suggesting that the functional differentiation of the cellulose synthase-like family A (CSLA) may be critical for the flow of glucomannan to the BSP or cell wall. Subsequently, virus-mediated gene silencing showed that silencing of two CSLAs (Bs03G11846 and Bs03G11849) led to a decrease in BSP content, and yeast two-hybrid and luciferase complementation experiments confirmed that four CSLAs (Bs03G11846, Bs03G11847, Bs03G11848, and Bs03G11849) can form homo- or heterodimers, suggesting that multiple CSLAs may form a large complex that functions in BSP synthesis. Our results provide cytological evidence of BSP and describe the isolation and characterization of candidate genes involved in BSP synthesis, laying a solid foundation for further research on its regulation mechanisms and the genetic engineering breeding of B. striata.
A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance
Authors: Yang Tianyu , Cai Yifan , Huang Tianping , Yang Danni , Yang Xingyu , Yin Xin , Zhang Chengjun , Yang Yunqiang , Yang Yongping
Published: April 2024

Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.
Quality, Formality and the Evolution of International Labour Law: The New ILO Quality Apprenticeships Standard
Authors: McCann Deirdre , Stewart Andrew
Published: April 2024

In an era of sequential crises and spiralling youth unemployment, the International Labour Organization (ILO) has adopted a historic instrument: the Quality Apprenticeships Recommendation, 2023 (No 208). This article explores the recommendation as both a landmark in the regulation of training and a site of regulatory innovation and contestation at the heart of contemporary labour law. It first traces the history of apprenticeship standards and the discursive processes that generated the new Recommendation. The article then adopts a dual analytical framework to explore key aspects of the Recommendation as driving and illuminating both the regulation of apprenticeships and the broader evolution of labour law. We highlight the Recommendation’s articulation and ascription of ‘quality’, including as crucial to the debates on the personal scope of labour law; the evolving presence of precarious work in the international normative arena; equality, diversity and inclusion as a heightening aspiration of both apprenticeship regimes and international labour norms; the Recommendation’s exclusion of non-apprenticeship training, and traineeships as an urgent site of future international standard-setting; and the significance of the instrument’s notion of informality for the regulation of informal apprenticeships, not least in the Global South, and for the global debates on the concept, transition, and regulation of informal work.
Contestation from Within: Norm Dynamics and the Crisis of the Liberal International Order
Authors: Lesch Max , Zimmermann Lisbeth , Deitelhoff Nicole
Published: April 2024

To what extent is the current “crisis of the liberal international order” a result of features of the order itself? In this article, we focus on the role of formal and informal hierarchies by comparing two cases of contestation of core norms of the liberal international order: The African states and the African Union contesting the duty to prosecute institutionalized in the International Criminal Court and the United States contesting the international prohibition of torture. The African contestation of the duty to prosecute became radicalized and diffused, leading to challenges to the broader international criminal accountability regime. The US contestation of the prohibition of torture did not spread, leaving the broader human rights regime untouched. We argue that the formal and informal hierarchies in both orders shaped their contestation dynamics more than their formal institutionalization. While the duty to prosecute is situated in a highly hierarchical setting that fueled frustration and contestation, the contestation of the prohibition of torture evolved in the less hierarchical setting of the human rights treaty bodies, which helped prevent contestation from spreading.
Secondary messenger signalling influences Pseudomonas aeruginosa adaptation to sinus and lung environments
Authors: Ruhluel Dilem , Fisher Lewis , Barton Thomas E , Leighton Hollie , Kumar Sumit , Amores Morillo Paula , O’Brien Siobhan , Fothergill Joanne L , Neill Daniel R
Published: April 2024

Pseudomonas aeruginosa is a cause of chronic respiratory tract infections in people with cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease. Prolonged infection allows the accumulation of mutations and horizontal gene transfer, increasing the likelihood of adaptive phenotypic traits. Adaptation is proposed to arise first in bacterial populations colonizing upper airway environments. Here, we model this process using an experimental evolution approach. Pseudomonas aeruginosa PAO1, which is not airway adapted, was serially passaged, separately, in media chemically reflective of upper or lower airway environments. To explore whether the CF environment selects for unique traits, we separately passaged PAO1 in airway-mimicking media with or without CF-specific factors. Our findings demonstrated that all airway environments—sinus and lungs, under CF and non-CF conditions—selected for loss of twitching motility, increased resistance to multiple antibiotic classes, and a hyper-biofilm phenotype. These traits conferred increased airway colonization potential in an in vivo model. CF-like conditions exerted stronger selective pressures, leading to emergence of more pronounced phenotypes. Loss of twitching was associated with mutations in type IV pili genes. Type IV pili mediate surface attachment, twitching, and induction of cAMP signalling. We additionally identified multiple evolutionary routes to increased biofilm formation involving regulation of cyclic-di-GMP signalling. These included the loss of function mutations in bifA and dipA phosphodiesterase genes and activating mutations in the siaA phosphatase. These data highlight that airway environments select for traits associated with sessile lifestyles and suggest upper airway niches support emergence of phenotypes that promote establishment of lung infection.
Hypoparathyroidism: changes in brain structure, cognitive impairment, and reduced quality of life
Authors: Sikjaer Tanja , Eskildsen Simon Fristed , Underbjerg Line , Østergaard Leif , Rejnmark Lars , Evald Lars
Published: April 2024

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system—including subjective feelings of confusion, a reduced ability to focus and think clearly (ie, “brain fog”). However, the extent to which these complex symptoms relate to quantifiable changes in patients’ cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires—the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of magnetic resonance imaging images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus—and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients’ cognitive functioning.
β,γ-Methylene-ATP and its metabolite medronic acid affect both arterial media calcification and bone mineralization in non-CKD and CKD rats
Authors: Opdebeeck Britt , Van den Branden Astrid , Adriaensen Saar , Orriss Isabel R , Patel Jessal J , Geryl Hilde , Zwijsen Kathleen , D’Haese Patrick C , Verhulst Anja
Published: April 2024

Arterial media calcification or pathological deposition of calcium-phosphate crystals in the vessel wall contributes significantly to the high mortality rate observed in patients with CKD. Extracellular nucleotides (ie, ATP or UTP) regulate the arterial calcification process by interacting with (1) purinergic receptors and (2) breakdown via ecto-nucleotidases, such as ectonucleotide pyrophosphatase/phosphodiesterase NPP1 or NPP3, affecting the local levels of calcification inhibitor, pyrophosphate, and stimulator inorganic phosphate (PPi/Pi ratio). Also, it has been shown that ATP analogs (ie, β,γ-methylene-ATP [β,γ-meATP]) inhibit vascular smooth muscle cell calcification in vitro. In the first experiment, daily dosing of β,γ-meATP (2 mg/kg) was investigated in rats fed a warfarin diet to trigger the development of non–CKD-related arterial medial calcifications. This study showed that β,γ-meATP significantly lowered the calcium scores in the aorta and peripheral vessels in warfarin-exposed rats. In a second experiment, daily dosing of 4 mg/kg β,γ-meATP and its metabolite medronic acid (MDP) was analyzed in rats fed an adenine diet to promote the development of CKD-related arterial medial calcification. Administration of β,γ-meATP and MDP did not significantly decrease aortic calcification scores in this model. Moreover, both compounds induced deleterious effects on physiological bone mineralization, causing an imminent risk for worsening the already compromised bone status in CKD. Due to this, it was not possible to raise the dosage of both compounds to tackle CKD-related arterial calcification. Again, this points out the difficult task of targeting solely ectopic calcifications without negatively affecting physiological bone mineralization. On the other hand, aortic mRNA expression of Enpp1 and Enpp3 was significantly and positively associated with aortic calcification scores, suggesting that normalizing the aortic NPP1/3 activity to control values might be a possible target to treat (CKD-induced) arterial media calcifications.
Developing semiochemical repellents for protecting Picea from Dendroctonus rufipennis (Coleoptera: Curculionidae) in Alaska and Utah, USA
Authors: Audley Jackson P , Fettig Christopher J , Moan Jason E , Moan Jessie , Swenson Steve , Munson A Steven , Mortenson Leif A , Blackford Darren C , Graham Elizabeth E , Mafra-Neto Agenor
Published: April 2024

Spruce beetle, Dendroctonus rufipennis (Kirby) (Coleoptera: Curculionidae), is the most destructive pest of mature spruce (Picea) in western North America. Recent outbreaks in Alaska and other western US states highlight the need for tools to protect Picea from D. rufipennis. The primary antiaggregation pheromone of D. rufipennis (3-methylcyclohex-2-en-1-one, MCH) and various combinations of potential repellents (1-octen-3-ol, exo-brevicomin, endo-brevicomin, ipsdienol, ipsenol, limonene, and verbenone) were tested for their ability to disrupt the response of D. rufipennis to attractant-baited multiple-funnel traps. Two assays were conducted on the Kenai Peninsula, Alaska, in June and July 2021. All treatments significantly reduced the mean number of D. rufipennis caught compared to the baited control. No other significant differences were observed among treatments. Informed by these and other data, tree protection studies were established in Lutz spruce, Picea × lutzii, on the Kenai Peninsula in 2022 and in Engelmann spruce, Pi. engelmannii, in the Uinta Mountains, Utah, in 2021. All experimental trees were baited with frontalin. Repellent treatments included MCH (SPLAT MCH, ISCA Inc., Riverside, CA, USA) and at least 1 additional repellent combination. In Alaska, all treatments significantly reduced colonization (strip attacks + mass attacks) and mortality of individually treated Pi. × lutzii and all Picea within 11.3-m radius of each treated Pi. × lutzii compared to the control. In Utah, all treatments except for SPLAT MCH + octenol significantly reduced colonization compared to the control. Only SPLAT MCH + Acer kairomone blend (AKB) and SPLAT MCH + octenol reduced Pi. engelmannii mortality compared to the control. SPLAT MCH + AKB and SPLAT MCH + acetophenone and green leaf volatiles (PLUS) were the most effective across both studies. The implications of these and other results to the development of an effective semiochemical repellent for D. rufipennis are discussed.
The university as sanctuary: home and unhomeliness
Authors: Fulford Amanda , Mahon Áine
Published: April 2024

Recent work at the confluence of Philosophy and Higher Education Studies has conceptualized the university as a place for belonging. The university, on this understanding, offers respite and refuge and familiarity; it is a place for insiders and outsiders to come together and to forge meaningful and lasting bonds. One of the interesting aspects about this body of scholarship is that its antithesis also exists. There is an equally compelling body of work in the philosophy of education that conceptualizes the university as singularly alienating, troubling, and disorientating. But are these two ideas of what it means to experience a higher education at odds with each other? We would argue to the contrary, rather maintaining that they are ineluctably related through the idea of sanctuary. We propose the idea of the university as sanctuary to encapsulate both what it means for the university to be a site for safety and familiarity and, paradoxically, a place where such senses are importantly challenged. We are interested in the implications of this idea for scholars' experiences of belonging as well as their encounters with radical otherness.
Changes in repair pathways of radiation-induced DNA double-strand breaks at the midblastula transition in Xenopus embryo
Authors: Morozumi Ryosuke , Shimizu Naoto , Tamura Kouhei , Nakamura Makoto , Suzuki Atsushi , Ishiniwa Hiroko , Ide Hiroshi , Tsuda Masataka
Published: April 2024

Ionizing radiation (IR) causes DNA damage, particularly DNA double-strand breaks (DSBs), which have significant implications for genome stability. The major pathways of repairing DSBs are homologous recombination (HR) and nonhomologous end joining (NHEJ). However, the repair mechanism of IR-induced DSBs in embryos is not well understood, despite extensive research in somatic cells. The externally developing aquatic organism, Xenopus tropicalis, serves as a valuable model for studying embryo development. A significant increase in zygotic transcription occurs at the midblastula transition (MBT), resulting in a longer cell cycle and asynchronous cell divisions. This study examines the impact of X-ray irradiation on Xenopus embryos before and after the MBT. The findings reveal a heightened X-ray sensitivity in embryos prior to the MBT, indicating a distinct shift in the DNA repair pathway during embryo development. Importantly, we show a transition in the dominant DSB repair pathway from NHEJ to HR before and after the MBT. These results suggest that the MBT plays a crucial role in altering DSB repair mechanisms, thereby influencing the IR sensitivity of developing embryos.
A randomized controlled trial of two hepatitis A vaccine doses among adolescents with juvenile idiopathic arthritis and Crohn’s disease on immunosuppressive therapy: a pilot study
Authors: Githumbi Racheal , Kuhn Susan , Osiowy Carla , Day Jacqueline , deBruyn Jennifer C C , Fritzler Marvin J , Johnson Nicole A , Vanderkooi Otto , Schmeling Heinrike
Published: April 2024

This pilot randomized controlled trial assessed the immunogenicity of paediatric vs adult hepatitis A vaccine doses in immunosuppressed adolescents (12–15 years) with juvenile idiopathic arthritis and Crohn’s disease. The study aimed to assess if a single, higher dose provides better immunogenicity, particularly before travel.
The dynamics of colicin E9 release from Escherichia coli in native conditions
Authors: Bano Shaista , Tunio Sarfraz Ali , Penfold Christopher N , James Richard
Published: April 2024

Colicin (Col) plasmid contains colicin encoding genes arranged in an operon controlled by an SOS inducible promoter. Therefore, any external stresses to the host cell can induce the expression of the downstream genes in the Col operon, including a lysis gene. The lysis protein is involved in the extracellular release of colicin through lysis of the producer cells, which causes a decline in culture turbidity. However, it is not yet known that E. coli cells with the native pColE9-J plasmid hold the same level of cell death at the population level following a set of induced conditions. In this study, using a mitomycin C sensitivity assay along with a live dead staining method of detection, we showed that the native pColE9-J plasmid, which unusually carries an extended Col operon (ColE9) containing two lysis genes, did not confer a rapid decline in the culture turbidity following induction with mitomycin C. Interestingly a subset of the cells suffered perturbation of their outer membrane, which was not observed from single lysis mutant (∆celE or ∆celI) cells. This observed heterogeneity in the colicin E9 release leading to differential outer membrane perforation may bring a competitive advantage to these cells in a mixed population.
Epidemiology and management of tinea capitis in France: A 6-year nationwide retrospective survey
Authors: Gangneux Jean-Pierre , Miossec Charline , Machouart Marie , Gits-Muselli Maud , Benderdouche Mazouz , Ranque Stéphane , Botterel Françoise , Brun Sophie ,   for the SFMM Tinea capitis study group, Damiani Céline , Pihet Marc , Benderdouce Mazouz , Botterel Françoise , Brun Sophie , Fekkar Arnaud , Foulet Françoise , Gits-Muselli Maud , Hamane Samia , Moreno-Sabater Alicia , Sitterlé Emilie , Bellanger Anne-Pauline , Gabriel Frédéric , Quinio Dorothée , Nourrisson Céline , Sautour Marc , Cognet Odile , Pelloux Hervé , Nicolas Muriel , Bouteille Bernard , Durieux Marie-Fleur , Deleplancque Anne-Sophie , Persat Florence , Ranque Stéphane , Miossec Charline , Desbois Nicole , Schneider Christine , Machouart Marie , Debourgogne Anne , Lavergne Rose-Anne , Hasseine Lilia , Cremer Geneviève , Cateau Estelle , Huguenin Antoine , Gangneux Jean-Pierre , Guegan Hélène , Belaz Sorya , Lepoutre Xavier , Favennec Loïc , Letscher-Bru Valérie , Camin-Ravenne Anne-Marie , Cassaing Sophie , Desoubeaux Guilllaume , Moreau Farida
Published: April 2024

Tinea capitis (TC) is still a frequent dermatophytosis in France, both autochthonous and imported. A nationwide retrospective survey was performed and a total of 4395 TC cases were recorded within 36 French mycology laboratories during a 6-year period. TC is a disease that occurs in childhood with 85% of the cases occurring before 10 years old and 94% before the age of 15. Anthropophilic origin was predominant with 779 cases of Trichophyton tonsurans (32.6%), 738 cases of Trichophyton soudanense/T. violaceum (31%), and 445 cases of Microsporum audouinii (19.2%). Of note, T. tonsurans represents more than 80% of the cases in the French West Indies (Martinique and Guadeloupe). By contrast, zoophilic species were less prevalent with mainly M. canis (10.3%) confirming the shift from zoophilic to anthropophilic species observed in many centers during the last decades. During this survey, diagnosis methods were also collected. Most labs had a classical process for the diagnosis: microscopic direct examination associated to cultures on Sabouraud and Sabouraud-cycloheximide media (incubated between 25 ± 5°C for at least 3 weeks) in all laboratories. Identification of the causal dermatophyte was performed by microscopic and macroscopic examination of the cultures in 100% of the labs, with various specific culture media available when fructification was insufficient (mainly malt or potato-dextrose agar, or Borelli medium). New techniques were also implemented with the introduction of MALDI-TOF mass spectrometry identification in more than two third of the labs, and molecular identification available if necessary in half of the labs.
Mitigating bias in deep learning: training unbiased models on biased data for the morphological classification of galaxies
Authors: Medina-Rosales Esteban , Cabrera-Vives Guillermo , Miller Christopher J
Published: April 2024

Galaxy morphologies and their relation with physical properties have been a relevant subject of study in the past. Most galaxy morphology catalogues have been labelled by human annotators or by machine learning models trained on human-labelled data. Human-generated labels have been shown to contain biases in terms of the observational properties of the data, such as image resolution. These biases are independent of the annotators, that is, are present even in catalogues labelled by experts. In this work, we demonstrate that training deep learning models on biased galaxy data produces biased models, meaning that the biases in the training data are transferred to the predictions of the new models. We also propose a method to train deep learning models that considers this inherent labelling bias, to obtain a de-biased model even when training on biased data. We show that models trained using our deep de-biasing method are capable of reducing the bias of human-labelled data sets.
smarty: The MILES moderate resolution near-infrared stellar library
Authors: Bertoldo-Coêlho Michele , Riffel Rogério , Trevisan Marina , Dametto Natacha Zanon , Dahmer-Hahn Luis , Coelho Paula , Martins Lucimara , Ruschel-Dutra Daniel , Vazdekis Alexandre , Rodríguez-Ardila Alberto , Chies-Santos Ana L , Riffel Rogemar A , La Barbera Francesco , Martín-Navarro Ignacio , Falcón-Barroso Jesus , Moura Tatiana
Published: April 2024

Most of the observed galaxies cannot be resolved into individual stars and are studied through their integrated spectrum using simple stellar populations (SSPs) models, with stellar libraries being a key ingredient in building them. Spectroscopic observations are increasingly being directed towards the near-infrared (NIR), where much is yet to be explored. SSPs in the NIR are still limited, and there are inconsistencies between different sets of models. One of the ways to minimize this problem is to have reliable NIR stellar libraries. The main goal of this work is to present smarty (mileS Moderate resolution neAr-infRared sTellar librarY) a ∼0.9−2.4 $\mu$m stellar spectral library composed of 31 stars observed with the Gemini Near-IR Spectrograph (GNIRS) at the 8.1 m Gemini North telescope and make it available to the community. The stars were chosen from the miles library, for which the atmospheric parameters are reliable (and well-tested), to populate different regions of the Hertzsprung–Russell (HR) diagram. Furthermore, five of these stars have NIR spectra available that we use to assess the quality of smarty. The remaining 26 stars are presented for the first time in the NIR. We compared the observed smarty spectra with synthetic and interpolated spectra, finding a mean difference of $\sim 20~{{\ \rm per\ cent}}$ in the equivalent widths and ∼1 per cent in the overall continuum shape in both sets of comparisons. We computed the spectrophotometric broad-band magnitudes and colours and compared them with the 2MASS ones, resulting in mean differences up to 0.07 and 0.10 mag in magnitudes and colours, respectively. In general, a small difference was noted between the smarty spectra corrected using the continuum from the interpolated and the theoretical stars.
MAUVE: a 6 kpc bipolar outflow launched from NGC 4383, one of the most H i-rich galaxies in the Virgo cluster
Authors: Watts Adam B , Cortese Luca , Catinella Barbara , Fraser-McKelvie Amelia , Emsellem Eric , Coccato Lodovico , van de Sande Jesse , Brown Toby H , Ascasibar Yago , Battisti Andrew , Boselli Alessandro , Davis Timothy A , Groves Brent , Thater Sabine
Published: April 2024

Stellar feedback-driven outflows are important regulators of the gas–star formation cycle. However, resolving outflow physics requires high-resolution observations that can only be achieved in very nearby galaxies, making suitable targets rare. We present the first results from the new VLT/MUSE large programme MAUVE (MUSE and ALMA Unveiling the Virgo Environment), which aims to understand the gas–star formation cycle within the context of the Virgo cluster environment. Outflows are a key part of this cycle, and we focus on the peculiar galaxy NGC 4383, which hosts a $\sim\!\! 6\,$ kpc bipolar outflow fuelled by one of Virgo’s most H i-rich discs. The spectacular MUSE data reveal the clumpy structure and complex kinematics of the ionized gas in this M82-like outflow at 100 pc resolution. Using the ionized gas geometry and kinematics, we constrain the opening half-angle to θ = 25–35°, while the average outflow velocity is $\sim\!\! 210\ \text{km} \, \text{s}^{-1}$. The emission line ratios reveal an ionization structure where photoionization is the dominant excitation process. The outflowing gas shows a marginally elevated gas-phase oxygen abundance compared to the disc but lower than the central starburst, highlighting the contribution of mixing between the ejected and entrained gas. Making some assumptions about the outflow geometry, we estimate an integrated mass outflow rate of $\sim\!\! 1.8~\mathrm{M}_{\odot } \, \mathrm{yr}^{-1}$ and a corresponding mass-loading factor in the range of 1.7–2.3. NGC 4383 is a useful addition to the few nearby examples of well-resolved outflows, and will provide a useful baseline for quantifying the role of outflows within the Virgo cluster.
Extensive long-range polycomb interactions and weak compartmentalization are hallmarks of human neuronal 3D genome
Authors: Pletenev Ilya A , Bazarevich Maria , Zagirova Diana R , Kononkova Anna D , Cherkasov Alexander V , Efimova Olga I , Tiukacheva Eugenia A , Morozov Kirill V , Ulianov Kirill A , Komkov Dmitriy , Tvorogova Anna V , Golimbet Vera E , Kondratyev Nikolay V , Razin Sergey V , Khaitovich Philipp , Ulianov Sergey V , Khrameeva Ekaterina E
Published: April 2024

Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernicke's area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization. We find that genome segregation into active and inactive compartments is greatly reduced in neurons compared to other brain cells. Furthermore, neuronal Hi-C maps reveal strong long-range interactions, forming a specific network of PcG-mediated contacts in neurons that is nearly absent in other brain cells. These interacting loci contain developmental transcription factors with repressed expression in neurons and other mature brain cells. But only in neurons, they are rich in bivalent promoters occupied by H3K4me3 histone modification together with H3K27me3, which points to a possible functional role of PcG contacts in neurons. Importantly, other layers of chromatin organization also exhibit a distinct structure in neurons, characterized by an increase in short-range interactions and a decrease in long-range ones.
Live-cell imaging reveals the trade-off between target search flexibility and efficiency for Cas9 and Cas12a
Authors: Olivi Lorenzo , Bagchus Cleo , Pool Victor , Bekkering Ezra , Speckner Konstantin , Offerhaus Hidde , Wu Wen Y , Depken Martin , Martens Koen J A , Staals Raymond H J , Hohlbein Johannes
Published: April 2024

CRISPR-Cas systems have widely been adopted as genome editing tools, with two frequently employed Cas nucleases being SpyCas9 and LbCas12a. Although both nucleases use RNA guides to find and cleave target DNA sites, the two enzymes differ in terms of protospacer-adjacent motif (PAM) requirements, guide architecture and cleavage mechanism. In the last years, rational engineering led to the creation of PAM-relaxed variants SpRYCas9 and impLbCas12a to broaden the targetable DNA space. By employing their catalytically inactive variants (dCas9/dCas12a), we quantified how the protein-specific characteristics impact the target search process. To allow quantification, we fused these nucleases to the photoactivatable fluorescent protein PAmCherry2.1 and performed single-particle tracking in cells of Escherichia coli. From our tracking analysis, we derived kinetic parameters for each nuclease with a non-targeting RNA guide, strongly suggesting that interrogation of DNA by LbdCas12a variants proceeds faster than that of SpydCas9. In the presence of a targeting RNA guide, both simulations and imaging of cells confirmed that LbdCas12a variants are faster and more efficient in finding a specific target site. Our work demonstrates the trade-off of relaxing PAM requirements in SpydCas9 and LbdCas12a using a powerful framework, which can be applied to other nucleases to quantify their DNA target search.
Comprehensive genomic features indicative for Notch responsiveness
Authors: Giaimo Benedetto Daniele , Friedrich Tobias , Ferrante Francesca , Bartkuhn Marek , Borggrefe Tilman
Published: April 2024

Transcription factor RBPJ is the central component in Notch signal transduction and directly forms a coactivator complex together with the Notch intracellular domain (NICD). While RBPJ protein levels remain constant in most tissues, dynamic expression of Notch target genes varies depending on the given cell-type and the Notch activity state. To elucidate dynamic RBPJ binding genome-wide, we investigated RBPJ occupancy by ChIP-Seq. Surprisingly, only a small set of the total RBPJ sites show a dynamic binding behavior in response to Notch signaling. Compared to static RBPJ sites, dynamic sites differ in regard to their chromatin state, binding strength and enhancer positioning. Dynamic RBPJ sites are predominantly located distal to transcriptional start sites (TSSs), while most static sites are found in promoter-proximal regions. Importantly, gene responsiveness is preferentially associated with dynamic RBPJ binding sites and this static and dynamic binding behavior is repeatedly observed across different cell types and species. Based on the above findings we used a machine-learning algorithm to predict Notch responsiveness with high confidence in different cellular contexts. Our results strongly support the notion that the combination of binding strength and enhancer positioning are indicative of Notch responsiveness.
admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties
Authors: Gu Yaxin , Yu Zhuohang , Wang Yimeng , Chen Long , Lou Chaofeng , Yang Chen , Li Weihua , Liu Guixia , Tang Yun
Published: April 2024

Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across. In the prediction module, we introduced comprehensive ADMET endpoints and two new sections for environmental and cosmetic risk assessments, empowering admetSAR3.0 to provide prediction for 119 endpoints, more than double numbers compared to the previous version. Furthermore, the advanced multi-task graph neural network framework offered robust and reliable support for ADMET prediction. In particular, a module named ADMETopt was added to automatically optimize the ADMET properties of query molecules through transformation rules or scaffold hopping. Finally, admetSAR3.0 provides user-friendly interfaces for multiple types of input data, such as SMILES string, chemical structure and batch molecule file, and supports various output types, including digital, chart displays and file downloads. In summary, admetSAR3.0 is anticipated to be a valuable and powerful tool in drug discovery and chemical safety assessment at http://lmmd.ecust.edu.cn/admetsar3/.