Genome-wide association study of classical Hodgkin lymphoma identifies key regulators of disease susceptibility

Several susceptibility loci for classical Hodgkin lymphoma (cHL) have been reported, however much of the heritable risk is unknown. Here, we perform a meta-analysis of two existing genome-wide association studies (GWAS), a new GWAS, and replication totalling 5,314 cases and 16,749 controls. We identify risk loci for all cHL at 6q22.33 (rs9482849, P=1.52 × 10-8) and for nodular sclerosis HL (NSHL) at 3q28 (rs4459895, P=9.43 × 10-17), 6q23.3 (rs6928977, P=4.62 × 10-55 11), 10p14 (rs3781093, P=9.49 × 10-13), 13q34 (rs112998813, P=4.58 × 10-8) and 16p13.13 (rs34972832, P=2.12 × 10-8). Additionally, independent loci within the HLA region are observed for NSHL (rs9269081, HLA-DPB1*03:01, Val86 in HLA-DRB1) and mixed cellularity HL (rs1633096, rs13196329, Val86 in HLA-DRB1). The new and established risk loci localise to areas of active chromatin and show an over-representation of transcription factor binding for determinants of B-cell development and immune response.In the United Kingdom, Bloodwise (LLR; 10021) provided principal funding for the study. Support from Cancer Research UK (C1298/A8362 supported by the Bobby Moore Fund) and the Lymphoma Research Trust is also acknowledged. A.S. is supported by a clinical fellowship from Cancer Research UK. For the UK-GWAS, sample and data acquisition were supported by Breast Cancer Now, the European Union and the Lymphoma Research Trust. The UK-GWAS made use of control genotyping data generated by the WTCCC. For further information, please visit the publishr's website

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Combination of searches for Higgs boson decays into a photon and a massless dark photon using pp collisions at √s = 13 TeV with the ATLAS detector

A combination of searches for Higgs boson decays into a visible photon and a massless dark photon (H → γγd) is presented using 139 fb−1 of proton-proton collision data at a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector at the Large Hadron Collider. The observed (expected) 95% confidence level upper limit on the Standard Model Higgs boson decay branching ratio is determined to be B(H → γγd) < 1.3% (1.5)%. The search is also sensitive to higher-mass Higgs bosons decaying into the same final state. The observed (expected) 95% confidence level limit on the cross-section times branching ratio ranges from 16 fb (20 fb) for mH = 400 GeV to 1.0 fb (1.5 fb) for mH = 3 TeV. Results are also interpreted in the context of a minimal simplified model

Microbial transformation of some triterpenoids of Guayule resin by Chaetomium sp.

Microbial biotransformation of argentatin A (1), isoargentatin A (2) and argentatin C (3), the triterpenoid constituents of guayule (Parthenium argentatum) resin was conducted with Chaetomium sp. PA001, an endophytic fungus of the same plant. The experiments yielded six new products (4–9) formed by: (i) nucleophilic oxygenation of the 3-ketone moiety resulting in Baeyer-Villiger oxidation; (ii) lactone ring opening of these oxidation products; (iii) rearrangement of the 9(10)-cyclopropane ring; and (iv) reduction of the 3-ketone moiety. The structures of all new biotransformation products were established by detailed analysis of their spectroscopic data. None of the products exhibited any antimicrobial activity. However, the hydroxy-carboxylic acid derivative 5 of argentatin A showed weak cytotoxic activity, but improved selectivity against human breast cancer cell line MCF-7 compared to the parent compound. This constitutes the first report of microbial biotransformation of isoargentatin A and argentatin C.This project was supported by the USDA-NIFA (grant # 2017- 68005–26867; Dr. Kimberly Ogden, PI) and Hatch Projects 1005072 and 1020652 to A.A.L.G and I.M. Any opinions, findings, conclusions, or recommendations expressed in this publication/work are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture. We thank Dr. Lijiang Xuan, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, P. R. China for HRMS data.24 month embargo; first published 16 May 2023This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Mobilidade e persistência de herbicidas aplicados em pré-emergência em diferentes solos Mobility and persistence of herbicides applied in pre-emergence on different soils

O objetivo deste ensaio foi verificar a mobilidade e persistência de herbicidas aplicados em pré-emergência em diferentes solos e quantidades de palha de cana-de-açúcar. Os herbicidas ametryn + clomazone (1.500 + 1.000 g i.a. ha-1), isoxaflutole (187,5 g i.a. ha-1) e diuron + hexazinone (1.170 + 330 g i.a. ha-1) foram aplicados em solo com textura argilosa e média nas seguintes condições: aplicação sobre 10 e 15 t ha-1 de palha com posterior simulação de chuva; simulação de chuva sobre o solo seguida da aplicação dos herbicidas, sendo coberto posteriormente com palha seca (10 t ha-1); aplicação dos herbicidas no solo sem palha; e testemunha. Aos 10, 20, 40 e 60 dias após aplicação dos herbicidas (DAA), foram semeados como bioindicadores sorgo e pepino, que foram avaliados com relação à fitotoxicidade aos 21 dias após emergência. A mistura ametryn + clomazone aplicada diretamente no solo controlou o bioindicador até 40 DAA, entretanto, após esse período, o efeito residual foi menor. A palha de cana-de-açúcar afetou negativamente o desempenho deste produto. O herbicida isoxaflutole aplicado diretamente no solo apresentou efeito residual até 60 DAA, com 82,5 e 77,5% de controle do bioindicador, em solos com textura argilosa e média, respectivamente; a presença de 10 e 15 t ha-1 de palha não alterou sua eficácia até 20 DAA. Para diuron + hexazinone aplicados no solo sem a presença de palha, verificou-se persistência até 60 DAA, principalmente em solo com textura argilosa; a deposição de 15 t ha-1 de palha reduziu a eficácia desta mistura.<br>The objective of this work was to verify the mobility and persistence of herbicides applied in pre-emergence on different soils and amounts of sugarcane straw. The herbicides ametryn + clomazone (1,500 + 1,000 g i.a. ha-1), isoxaflutole (187,5 g.i.a. ha-1) and diuron + hexazinone (1,170 + 330 g i.a. ha-1) were applied in soil with clayey and medium texture under the following conditions:on 10 and 15 t ha-1 of sugarcane straw followed by rain simulation ; on the ground and covered with 10 t ha-1 of sugarcane straw; on the ground without straw; and control without herbicide. At 10, 20, 40 and 60 days after herbicide application (DAA), species bioindicators such as sorghum and cucumber were sown. Percentage of phytotoxicity was observed at 21 days after emergence. The mixture ametryn + clomazone applied directly on the soil affected the bioindicator up to 40 DAA; however, after this period, the residual effect was smaller. The sugarcane straw affected the performance of this product negatively. The herbicide isoxaflutole applied directly in the soil presented residual effect up to 60 DAA, with 82.5 and 77.5% of bioindicator control, in soils with clayey and medium texture, respectively, and the presence of 10 and 15 t ha-1 of straw did not alter efficiency up to 20 DAA. The herbicide diuron + hexazinone applied on the soil without straw presented residual effect up to 60 DAA, mainly in soil with clayey texture. With 15 t ha-1 of straw, significant reduction was observed in the effectiveness of this mixture