A study of cis-regulatory elements in Xenopus and planarians

Multicellular organisms have the ability to produce and maintain several cell types despite the DNA molecule being the same in all cells. For that, a complex network of cis-regulatory elements (CRE) and transcription factors is involved in controlling cellular fate. Among the different approaches that allow the identification of CREs, the novel ATAC-sequencing is becoming an increasingly used tool due to its easy-to-perform protocol. In this study, this technique has been optimized to beused in two species (Xenopus laevis and Schmidtea mediterranea) to elucidate (1) the epigenetic mechanism behind Xenopus neural crest (NC) specification and differentiation, and (2) the establishment of anteroposterior identity during planarian regeneration.ATAC-sequencing has been carried out on Xenopus animal caps induced to give rise to NC or neural tissue. Comparison of this data along with non-injected ectodermal animal caps has led to the characterization of the epigenome involved in Xenopus neural crest formation. Results show that 4,528 NC open regions or potential enhancers are present during specification whereas 852 NC potential enhancers are specific for differentiation. In these NC open regions, the transcription factors Zic, Meis and Sox10 play an important role. Five enhancers driving expression of key neural crest genes (cmyc, foxd3, id3, snai2 and sox10) have been identified. ATAC-sequencing has also been successfully validated on dissected blastemas from 48h regenerating planarians. The analysis has revealed nervous system-related transcription factor motifs such as Prep or NeuroD-1 present in anterior specific open regions whereas posterior polarity-related transcription factor binding sites such as Islet or HoxD3 are present in posterior open regions. Key words: ATAC-sequencing, enhancer, transcription factor, Xenopus neural crest, planarian, anteroposterior polarity

The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification

Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a ‘gate-keeper’ for the correct temporal and spatial development of the neural crest

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers

Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06–3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02–1.05) and higher % of sleep time with O2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00–1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01–1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01–1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01–1.07). Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence

Nocturnal Hypoxemia and CT Determined Pulmonary Artery Enlargement in Smokers

Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio &gt; 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06–3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02–1.05) and higher % of sleep time with O2 saturation &lt; 90% (T90) (OR 1.02; 95%CI 1.00–1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01–1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01–1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01–1.07). Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence

Impact of applying the global lung initiative criteria for airway obstruction in GOLD defined COPD cohorts: the BODE and CHAIN experience

Introduction: The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. Methods: COPD patients from the BODE (n=360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n=722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. Results: In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE≥3: 9% and 20%; mMRC≥2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD<350m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality - 33% and 22% respectively. Conclusions: An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice

Impact of Applying the Global Lung Initiative Criteria for Airway Obstruction in GOLD Defined COPD Cohorts: The BODE and CHAIN Experience

Introduction The Global Lung Function Initiative (GLI) has proposed new criteria for airflow limitation (AL) and recommends using these to interpret spirometry. The objective of this study was to explore the impact of the application of the AL GLI criteria in two well characterized GOLD-defined COPD cohorts. Methods COPD patients from the BODE (n = 360) and the COPD History Assessment In SpaiN (CHAIN) cohorts (n = 722) were enrolled and followed. Age, gender, pack-years history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, history of exacerbations and survival were recorded. CT-detected comorbidities were registered in the BODE cohort. The proportion of subjects without AL by GLI criteria was determined in each cohort. The clinical, CT-detected comorbidity, and overall survival of these patients were evaluated. Results In total, 18% of the BODE and 15% of the CHAIN cohort did not meet GLI AL criteria. In the BODE and CHAIN cohorts respectively, these patients had a high clinical burden (BODE ≥ 3: 9% and 20%; mMRC ≥ 2: 16% and 45%; exacerbations in the previous year: 31% and 9%; 6MWD < 350 m: 15% and 19%, respectively), and a similar prevalence of CT-diagnosed comorbidities compared with those with GLI AL. They also had a higher rate of long-term mortality – 33% and 22% respectively. Conclusions An important proportion of patients from 2 GOLD-defined COPD cohorts did not meet GLI AL criteria at enrolment, although they had a significant burden of disease. Caution must be taken when applying the GLI AL criteria in clinical practice

Manufacturing Guidelines for W-Band Full-Metal Waveguide Devices: Selecting the Most Appropriate Technology.

International audienc

Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub

The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.Peer reviewe