Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas

The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture of invasive lung ADC and its precursors by transcriptomic immune profiling, T cell receptor (TCR) sequencing and multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor immunity evolved as a continuum from lung preneoplasia, to preinvasive ADC, minimally-invasive ADC and frankly invasive lung ADC with a gradually less effective and more intensively regulated immune response including down-regulation of immune-activation pathways, up-regulation of immunosuppressive pathways, lower infiltration of cytotoxic T cells (CTLs) and anti-tumor helper T cells (Th), higher infiltration of regulatory T cells (Tregs), decreased T cell clonality, and lower frequencies of top T cell clones in later-stages. Driver mutations, chromosomal copy number aberrations (CNAs) and aberrant DNA methylation may collectively impinge host immune responses and facilitate immune evasion, promoting the outgrowth of fit subclones in preneoplasia into dominant clones in invasive ADC

Global patterns in endemicity and vulnerability of soil fungi

Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms

ϒ production in p–Pb collisions at √sNN=8.16 TeV

ϒ production in p–Pb interactions is studied at the centre-of-mass energy per nucleon–nucleon collision √sNN = 8.16 TeV with the ALICE detector at the CERN LHC. The measurement is performed reconstructing bottomonium resonances via their dimuon decay channel, in the centre-of-mass rapidity intervals 2.03 < ycms < 3.53 and −4.46 < ycms < −2.96, down to zero transverse momentum. In this work, results on the ϒ(1S) production cross section as a function of rapidity and transverse momentum are presented. The corresponding nuclear modification factor shows a suppression of the ϒ(1S) yields with respect to pp collisions, both at forward and backward rapidity. This suppression is stronger in the low transverse momentum region and shows no significant dependence on the centrality of the interactions. Furthermore, the ϒ(2S) nuclear modification factor is evaluated, suggesting a suppression similar to that of the ϒ(1S). A first measurement of the ϒ(3S) has also been performed. Finally, results are compared with previous ALICE measurements in p–Pb collisions at √sNN = 5.02 TeV and with theoretical calculations.publishedVersio

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 &gt; 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

Connecting the multiple dimensions of global soil fungal diversity

15 páginas.- 5 figuras.- 99 referenciasHow the multiple facets of soil fungal diversity vary worldwide remains virtually unknown, hindering the management of this essential species-rich group. By sequencing high-resolution DNA markers in over 4000 topsoil samples from natural and human-altered ecosystems across all continents, we illustrate the distributions and drivers of different levels of taxonomic and phylogenetic diversity of fungi and their ecological groups. We show the impact of precipitation and temperature interactions on local fungal species richness (alpha diversity) across different climates. Our findings reveal how temperature drives fungal compositional turnover (beta diversity) and phylogenetic diversity, linking them with regional species richness (gamma diversity). We integrate fungi into the principles of global biodiversity distribution and present detailed maps for biodiversity conservation and modeling of global ecological processes.This work was supported by the Estonian Science Foundation: PRG632 (to L.T.), Estonian Research Council: PRG1615 (to R.D.), Estonian Research Council: PRG1170 (to U.K. and Ka.Po.), Estonian Science Foundation: MOBTP198 (to St.An.), Novo Nordisk Fonden: NNF20OC0059948 (to L.T.), Norway-Baltic financial mechanism: EMP442 (to L.T., K.-A.B., and M.T.), King Saud University: DFSP-2020-2 (to L.T.), King Saud University: Highly Cited Program (to L.T.), European Regional Development Fund: Centre of Excellence EcolChange TK131 (to M.O., M.Z., Ü.M., U.K., and M.E.), Estonian Research Council: PRG1789 (to M.O. and I.H.), British Ecological Society: LRB17\1019 (MUSGONET) (to M.D.-B.), Spanish Ministry of Science and Innovation: PID2020-115813RA-I00 (to M.D.-B.), Spanish Ministry of Science and Innovation: SOIL4GROWTH (to M.D.-B.), Marie Sklodowska-Curie: 702057 (CLIMIFUN) (to M.D.- B.), European Research Council (ERC): grant 647038 [BIODESERT] (to F.T.M.), Generalitat Valenciana: CIDEGENT/2018/041 (to F.T.M.), Spanish Ministry of Science and Innovation: EUR2022-134048 (to F.T.M.), Estonian Research Council: PRG1065 (to M.M. and M.Z.), Swedish Research Council Formas: 2020-00807 (to Mo.Ba.), Swedish Research Council: 2019-05191 (to Al. An.), Swedish Foundation for Strategic Environmental Research MISTRA: Project BioPath (to Al. An.), Kew Foundation (to Al.An.), EEA Financial Mechanism Baltic Research Programme in Estonia: EMP442 (to Ke.Ar. and Je.An.), Ghent University Special Research Fund (BOF): Metusalem (to N.S.), Estonian Research Council: PSG825 (to K.R.), European Research Council (ERC): 101096403 (MLTOM23415R) (to Ü.M.), European Regional Development Fund (ERDF): 1.1.1.2/VIAA/2/18/298 (to D.K.), Estonian Research Council: PUT1170 (to I.H.), German Federal Ministry of Education and Research (BMBF): 01DG20015FunTrAf (to K.T.I., M.P., and N.Y.), Proyecto SIA: SA77210019 (ANID—Chile) (to C.M.), Fondecyt: 1190642 (ANID—Chile) (to R.G.), European Research Council (ERC): Synergy Grant 856506—LIFEPLAN (to T.R.), Academy of Finland: grant 322266 (to T.R.), U.S. National Science Foundation: DEB-0918591 (to T.H.), U.S. National Science Foundation: DEB-1556338 (to T.H.), U.S. National Science Foundation: DEB 1737898 (to G.B.), UNAM-PAPIIT: IV200223 (to R.G.-O.), Czech Science Foundation: 21-26883S (to J.D.), Estonian Research Council: PRG352 (to M.E.), NERC core funding: the BAS Biodiversity, Evolution and Adaptation Team (to K.K.N.), NERC-CONICYT: NE/P003079/1 (to E.M.B.), Carlsberg Foundation: CF18-0267 (to E.M.B.), Qatar Petroleum: QUEX-CAS-QP-RD-18/19 (to Ju.Al.), Russian Ministry of Science and Higher Education: 075-15-2021-1396 (to V.F. and V.O.), Secretaria de Ciencia y Técnica (SECYT) of Universidad Nacional de Córdoba and CONICET (to E.N.), HighLevel Talent Recruitment Plan of Yunnan Province 2021:“High-End Foreign Experts” (to Pe.Mo.), AUA grant from research council of UAE University: G00003654 (to S.M.), Ghent University: Bijzonder Onderzoeksfonds (to A.V.), Ghent University: Bijzonder Onderzoeksfonds (BOF-PDO2017-001201) (to E.D.C.), Ghent University: The Faculty Committee Scientific Research, FCWO (to E.D.C. and A.V.), The King Leopold III Fund for Nature Exploration and Conservation (to A.V. and E.D.C.), The Research Foundation—Flanders (FWO) (to E.D.C. and A.V.), The High-Level Talent Recruitment Plan of Yunnan Provinces: “Young Talents” Program (to D.-Q.D.), The HighLevel Talent Recruitment Plan of Yunnan Provinces: “High-End Foreign Experts" Program (to N. N.W.), IRIS scholarship for progressive and ambitious women (to L.H.), Estonian University of Life Sciences: P190250PKKH (to Kr.Pa.), Hungarian Academy of Sciences: Lendület Programme (96049) (to J.G.), Eötvös Loránd Research Network (to J.G.), Botswana International University of Science and Technology (to C.N.), and Higher Education Commision (HEC, Islamabad, Pakistan): Indigenous and International research support initiative program (IRSIP) scholarship (to M.S.)Peer reviewe

Centrality evolution of the charged-particle pseudorapidity density over a broad pseudorapidity range in Pb-Pb collisions at root s(NN)=2.76TeV

Peer reviewe

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects