Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor β (TGF-β)-induced epithelial-mesenchymal transition. In addition to TGF-β receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked α-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-β-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-β-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer

Double-resonant fast particle-wave interaction

In future fusion devices fast particles must be well confined in order to transfer their energy to the background plasma. Magnetohydrodynamic instabilities like Toroidal Alfv\'en Eigenmodes or core-localized modes such as Beta Induced Alfv\'en Eigenmodes and Reversed Shear Alfv\'en Eigenmodes, both driven by fast particles, can lead to significant losses. This is observed in many ASDEX Upgrade discharges. The present study applies the drift-kinetic HAGIS code with the aim of understanding the underlying resonance mechanisms, especially in the presence of multiple modes with different frequencies. Of particular interest is the resonant interaction of particles simultaneously with two different modes, referred to as 'double-resonance'. Various mode overlapping scenarios with different q profiles are considered. It is found that, depending on the radial mode distance, double-resonance is able to enhance growth rates as well as mode amplitudes significantly. Surprisingly, no radial mode overlap is necessary for this effect. Quite the contrary is found: small radial mode distances can lead to strong nonlinear mode stabilization of a linearly dominant mode.Comment: 12 pages, 11 figures; Nuclear Fusion 52 (2012

Aménagement en courbes de niveau et conservation du carbone

Dans la région Mali-sud, au climat semi-aride, la culture sur billons suivant les courbes de niveau permet d'arrêter l'érosion et surtout d'augmenter l'infiltration de l'eau de pluie, ce qui permet l'augmentation de la croissance des plantes cultivées et des arbres associés aux cultures. Il en résulte des effets sur l'ensemble du cycle du carbone. Les teneurs en carbone du sol sableux ferrugineux tropicaux diminuent rapidement sous culture, jusqu'à environ 0,2 à 0,4% dans l'horizon superficiel (0-20 cm). Pendant le même temps, les rendements peuvent rester stables ou augmenter si les modestes apports d'engrais sont suffisants pour corriger les carences en phosphore et fournir un peu de N et K aux cultures. Les rendements moyens, par exemple 10 à 20 q/ha de maïs, sont comparables à ceux qui étaient obtenus en Europe au début du 20ème siècle, quand l'utilisation des engrais a commencé. L'érosion contribue à diminuer encore plus les teneurs en carbone, dans certaines parties de la toposéquence. L'arrêt de l'érosion permet d'éviter ces pertes. Par contre, la production de biomasse par les cultures est augmentée: environ 50% pour le mil, le sorgho et le maïs pendant les années peu pluvieuses. Le carbone est recyclé dans le milieu suivant les voies habituelles: l'alimentation humaine (grains), l'alimentation des animaux (résidus, pailles, adventices), les termites, le fumier, les usages domestiques, le feu. Le parc arboré (karité et autres espèces) profite de l'eau conservée grâce aux courbes de niveau et il s'accroît par la croissance des arbres en place et par la régénération de jeunes arbres. Il en résulte d'une part, un accroissement de la masse ligneuse et d'autre part une augmentation des teneurs en carbone du sol dans les parties du champ couvertes par ces arbres (apports organiques et ombrage). Les courbes de niveau sont marquées par des ados couverts d'une végétation permanente (#Andropogon gayanus#, etc.) qui couvrent 2 à 4% de la surface des champs, avec des teneurs en carbone du sol comparables à celles qu'on trouve sous végétation naturelle. L'effet de l'aménagement sur le stockage du carbone se manifeste donc dans différentes situations (les cultures, des ados enherbés, les arbres, le sol sous les arbres, etc.) et suivant des cycles variables (l'année pour les cultures et les feuilles des arbres, quelques années pour le carbone du sol, quelques dizaines d'années pour le bois). (Résumé d'auteur

Computer programs for saturation properties of hydrogen

Computer programs for saturation properties of liquid and vapor hydroge

Network analysis of the Viking Age in Ireland as portrayed in Cogadh Gaedhel re Gallaibh

Cogadh Gaedhel re Gallaibh (‘The War of the Gaedhil with the Gaill’) is a medieval Irish text, telling how an army under the leadership of Brian Boru challenged Viking invaders and their allies in Ireland, culminating with the Battle of Clontarf in 1014. Brian’s victory is widely remembered for breaking Viking power in Ireland, although much modern scholarship disputes traditional perceptions. Instead of an international conflict between Irish and Viking, interpretations based on revisionist scholarship consider it a domestic feud or civil war. Counterrevisionists challenge this view and a long-standing and lively debate continues. Here, we introduce quantitative measures to the discussions.We present statistical analyses of network data embedded in the text to position its sets of interactions on a spectrum from the domestic to the international. This delivers a picture that lies between antipodal traditional and revisionist extremes; hostilities recorded in the text are mostly between Irish and Viking—but internal conflict forms a significant proportion of the negative interactions too

Genomic Regions Associated With Gestation Length Detected Using Whole-Genome Sequence Data Differ Between Dairy and Beef Cattle

peer-reviewedWhile many association studies exist that have attempted to relate genomic markers to phenotypic performance in cattle, very few have considered gestation length as a phenotype, and of those that did, none used whole genome sequence data from multiple breeds. The objective of the present study was therefore to relate imputed whole genome sequence data to estimated breeding values for gestation length using 22,566 sires (representing 2,262,706 progeny) of multiple breeds [Angus (AA), Charolais (CH), Holstein-Friesian (HF), and Limousin (LM)]. The associations were undertaken within breed using linear mixed models that accounted for genomic relatedness among sires; a separate association analysis was undertaken with all breeds analysed together but with breed included as a fixed effect in the model. Furthermore, the genome was divided into 500 kb segments and whether or not segments harboured a single nucleotide polymorphism (SNP) with a P ≤ 1 × 10-4 common to different combinations of breeds was determined. Putative quantitative trait loci (QTL) regions associated with gestation length were detected in all breeds; significant associations with gestation length were only detected in the HF population and in the across-breed analysis of all 22,566 sires. Twenty-five SNPs were significantly associated (P ≤ 5 × 10-8) with gestation length in the HF population. Of the 25 significant SNPs, 18 were located within three QTLs on Bos taurus autosome number (BTA) 18, six were in two QTL on BTA19, and one was located within a QTL on BTA7. The strongest association was rs381577268, a downstream variant of ZNF613 located within a QTL spanning from 58.06 to 58.19 Mb on BTA18; it accounted for 1.37% of the genetic variance in gestation length. Overall there were 11 HF animals within the edited dataset that were homozygous for the T allele at rs381577268 and these had a 3.3 day longer (P < 0.0001) estimated breeding value (EBV) for gestation length than the heterozygous animals and a 4.7 day longer (P < 0.0001) EBV for gestation length than the homozygous CC animals. The majority of the 500 kb windows harboring a SNP with a P ≤ 1 × 10-4 were unique to a single breed and no window was shared among all four breeds for gestation length, suggesting any QTLs identified are breed-specific associations

Bridging lifelong learning in engineering and healthcare: challenges, opportunities, and best practices

Lifelong learning (LLL) is increasingly recognized as essential for ensuring that engineers remain responsive to technological change, sustainability challenges, and evolving industry needs. While LLL is embedded in engineering, there remains significant potential to strengthen its integration into professional practice, inspired by sectors such as healthcare and industry. This interactive workshop addressed these opportunities by providing cross-sector dialogue and exploring adaptable LLL strategies for engineering. It built on best practices from healthcare and innovative approaches from Asian professional contexts, encouraging participants to analyse transferable models and apply them to engineering settings. The workshop identified simulation-based training, competency frameworks, and interdisciplinary team practices as highly adaptable models. However, these approaches require cultural change and resources, and their scalability varies depending on the type of simulation used. Insights from Asia, particularly Singapore, illustrated how policy-driven initiatives and modular learning pathways can sustain professional growth across career stages. Discussions highlighted that translating such practices into engineering requires technological adaptation, institutional support, stakeholder engagement, and cultural readiness to align diverse needs through flexible and inclusive educational approaches. The workshop concluded with actionable strategies and identified future opportunities for collaboration and knowledge sharing to advance impactful innovations in LLL within engineering education and practice

Genetic parameters of ovarian and uterine reproductive traits in dairy cows

peer-reviewedThe objective of the study was to estimate genetic parameters of detailed reproductive traits derived from ultrasound examination of the reproductive tract as well as their genetic correlations with traditional reproductive traits. A total of 226,141 calving and insemination records as well as 74,134 ultrasound records from Irish dairy cows were used. Traditional reproductive traits included postpartum interval to first service, conception, and next calving, as well as the interval from first to last service; number of inseminations, pregnancy rate to first service, pregnant within 42 d of the herd breeding season, and submission in the first 21 d of the herd breeding season were also available. Detailed reproductive traits included resumed cyclicity at the time of ultrasound examination, incidence of multiple ovulations, incidence of early postpartum ovulation, heat detection, ovarian cystic structures, embryo loss, and uterine score; the latter was a subjectively assessed on a scale of 1 (little fluid with normal uterine tone) to 4 (large quantity of fluid with a flaccid uterine tone). Variance (and covariance) components were estimated using repeatability animal linear mixed models. Heritability for all reproductive traits were generally low (0.001–0.05), with the exception of traits related to cyclicity postpartum, regardless if defined traditionally (0.07; calving to first service) or from ultrasound examination [resumed cyclicity at the time of examination (0.07) or early postpartum ovulation (0.10)]. The genetic correlations among the detailed reproductive traits were generally favorable. The exception was the genetic correlation (0.29) between resumed cyclicity and uterine score; superior genetic merit for cyclicity postpartum was associated with inferior uterine score. Superior genetic merit for most traditional reproductive traits was associated with superior genetic merit for resumed cyclicity (genetic correlations ranged from −0.59 to −0.36 and from 0.56 to 0.70) and uterine score (genetic correlations ranged from −0.47 to 0.32 and from 0.25 to 0.52). Genetic predisposition to an increased incidence of embryo loss was associated with both an inferior uterine score (0.24) and inferior genetic merit for traditional reproductive traits (genetic correlations ranged from −0.52 to −0.42 and from 0.33 to 0.80). The results from the present study indicate that selection based on traditional reproductive traits, such as calving interval or days open, resulted in improved genetic merit of all the detailed reproductive traits evaluated in this study. Additionally, greater accuracy of selection for calving interval is expected for a relatively small progeny group size when detailed reproductive traits are included in a multitrait genetic evaluation