The Overlap of Small Molecule and Protein Binding Sites within Families of Protein Structures

Protein–protein interactions are challenging targets for modulation by small molecules. Here, we propose an approach that harnesses the increasing structural coverage of protein complexes to identify small molecules that may target protein interactions. Specifically, we identify ligand and protein binding sites that overlap upon alignment of homologous proteins. Of the 2,619 protein structure families observed to bind proteins, 1,028 also bind small molecules (250–1000 Da), and 197 exhibit a statistically significant (p<0.01) overlap between ligand and protein binding positions. These “bi-functional positions”, which bind both ligands and proteins, are particularly enriched in tyrosine and tryptophan residues, similar to “energetic hotspots” described previously, and are significantly less conserved than mono-functional and solvent exposed positions. Homology transfer identifies ligands whose binding sites overlap at least 20% of the protein interface for 35% of domain–domain and 45% of domain–peptide mediated interactions. The analysis recovered known small-molecule modulators of protein interactions as well as predicted new interaction targets based on the sequence similarity of ligand binding sites. We illustrate the predictive utility of the method by suggesting structural mechanisms for the effects of sanglifehrin A on HIV virion production, bepridil on the cellular entry of anthrax edema factor, and fusicoccin on vertebrate developmental pathways. The results, available at http://pibase.janelia.org, represent a comprehensive collection of structurally characterized modulators of protein interactions, and suggest that homologous structures are a useful resource for the rational design of interaction modulators

Brugia malayi microfilariae adhere to human vascular endothelial cells in a C3-dependent manner

Brugia malayi causes the human tropical disease, lymphatic filariasis. Microfilariae (Mf) of this nematode live in the bloodstream and are ingested by a feeding mosquito vector. Interestingly, in a remarkable co-evolutionary adaptation, Mf appearance in the peripheral blood follows a circadian periodicity and reaches a peak when the mosquito is most likely to feed. For the remaining hours, the majority of Mf sequester in the lung capillaries. This circadian phenomenon has been widely reported and is likely to maximise parasite fitness and optimise transmission potential. However, the mechanism of Mf sequestration in the lungs remains largely unresolved. In this study, we demonstrate that B. malayi Mf can, directly adhere to vascular endothelial cells under static conditions and under flow conditions, they can bind at high (but not low) flow rates. High flow rates are more likely to be experienced diurnally. Furthermore, a non-periodic nematode adheres less efficiently to endothelial cells. Strikingly C3, the central component of complement, plays a crucial role in the adherence interaction. These novel results show that microfilariae have the ability to bind to endothelial cells, which may explain their sequestration in the lungs, and this binding is increased in the presence of inflammatory mediators

WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.This work was supported by the Spanish Ministry of Education and Science [grant BIO2009-13261-CO2], the Spanish Ministry of Economy and Competitivity [grant BIO2012-39922-CO2] including FEDER (European Funds for Regional Development) funds and the Governement of Andalusia [grant CVI-5915]. Marius Sudol was supported by PA Breast Cancer Coalition Grants (#60707 and #920093) plus the Geisinger Clinic

A comparison of four fibrosis indexes in chronic HCV: Development of new fibrosis-cirrhosis index (FCI)

<p>Abstract</p> <p>Background</p> <p>Hepatitis C can lead to liver fibrosis and cirrhosis. We compared readily available non-invasive fibrosis indexes for the fibrosis progression discrimination to find a better combination of existing non-invasive markers.</p> <p>Methods</p> <p>We studied 157 HCV infected patients who underwent liver biopsy. In order to differentiate HCV fibrosis progression, readily available AAR, APRI, FI and FIB-4 serum indexes were tested in the patients. We derived a new fibrosis-cirrhosis index (FCI) comprised of ALP, bilirubin, serum albumin and platelet count. FCI = [(ALP × Bilirubin) / (Albumin × Platelet count)].</p> <p>Results</p> <p>Already established serum indexes AAR, APRI, FI and FIB-4 were able to stage liver fibrosis with correlation coefficient indexes 0.130, 0.444, 0.578 and 0.494, respectively. Our new fibrosis cirrhosis index FCI significantly correlated with the histological fibrosis stages F0-F1, F2-F3 and F4 (r = 0.818, p < 0.05) with AUROCs 0.932 and 0.996, respectively. The sensitivity and PPV of FCI at a cutoff value < 0.130 for predicting fibrosis stage F0-F1 was 81% and 82%, respectively with AUROC 0.932. Corresponding value of FCI at a cutoff value ≥1.25 for the prediction of cirrhosis was 86% and 100%.</p> <p>Conclusions</p> <p>The fibrosis-cirrhosis index (FCI) accurately predicted fibrosis stages in HCV infected patients and seems more efficient than frequently used serum indexes.</p

Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Advanced age represents one of the major risk factors for Parkinson’s Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson’s Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson’s Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson’s Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson’s Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson’s Disease patients, and healthy siblings of Parkinson’s Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson’s Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson’s Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson’s Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson’s Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson’s Disease

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Volume III. DUNE far detector technical coordination

open966siAcknowledgments This document was prepared by the DUNE collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. The DUNE collaboration also acknowledges the international, national, and regional funding agencies supporting the institutions who have contributed to completing this Technical Design Report.The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay-these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- A nd dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module.openAbi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; Back J.J.; Backhouse C.; Baesso P.; Bagby L.; Bajou R.; Balasubramanian S.; Baldi P.; Bambah B.; Barao F.; Barenboim G.; Barker G.; Barkhouse W.; Barnes C.; Barr G.; Monarca J.B.; Barros N.; Barrow J.L.; Bashyal A.; Basque V.; Bay F.; Alba J.B.; Beacom J.F.; Bechetoille E.; Behera B.; Bellantoni L.; Bellettini G.; Bellini V.; Beltramello O.; Belver D.; Benekos N.; Neves F.B.; Berger J.; Berkman S.; Bernardini P.; Berner R.M.; Berns H.; Bertolucci S.; Betancourt M.; Bezawada Y.; Bhattacharjee M.; Bhuyan B.; Biagi S.; Bian J.; Biassoni M.; Biery K.; Bilki B.; Bishai M.; Bitadze A.; Blake A.; Siffert B.B.; Blaszczyk F.; Blazey G.; Blucher E.; Boissevain J.; Bolognesi S.; Bolton T.; Bonesini M.; Bongrand M.; Bonini F.; Booth A.; Booth C.; Bordoni S.; Borkum A.; Boschi T.; Bostan N.; Bour P.; Boyd S.; Boyden D.; Bracinik J.; Braga D.; Brailsford D.; Brandt A.; Bremer J.; Brew C.; Brianne E.; Brice S.J.; Brizzolari C.; Bromberg C.; Brooijmans G.; Brooke J.; Bross A.; Brunetti G.; Buchanan N.; Budd H.; Caiulo D.; Calafiura P.; Calcutt J.; Calin M.; Calvez S.; Calvo E.; Camilleri L.; Caminata A.; Campanelli M.; Caratelli D.; Carini G.; Carlus B.; Carniti P.; Terrazas I.C.; Carranza H.; Castillo A.; Castromonte C.; Cattadori C.; Cavalier F.; Cavanna F.; Centro S.; Cerati G.; Cervelli A.; Villanueva A.C.; Chalifour M.; Chang C.; Chardonnet E.; Chatterjee A.; Chattopadhyay S.; Chaves J.; Chen H.; Chen M.; Chen Y.; Cherdack D.; Chi C.; Childress S.; Chiriacescu A.; Cho K.; Choubey S.; Christensen A.; Christian D.; Christodoulou G.; Church E.; Clarke P.; Coan T.E.; Cocco A.G.; Coelho J.; Conley E.; Conrad J.; Convery M.; Corwin L.; Cotte P.; Cremaldi L.; Cremonesi L.; Crespo-Anadon J.I.; Cristaldo E.; Cross R.; Cuesta C.; Cui Y.; Cussans D.; Dabrowski M.; Motta H.D.; Peres L.D.S.; David Q.; Davies G.S.; Davini S.; Dawson J.; De K.; Almeida R.M.D.; Debbins P.; Bonis I.D.; Decowski M.; Gouvea A.D.; Holanda P.C.D.; Astiz I.L.D.I.; Deisting A.; Jong P.D.; Delbart A.; Delepine D.; Delgado M.; Dell'acqua A.; Lurgio P.D.; Neto J.R.D.M.; Demuth D.M.; Dennis S.; Densham C.; Deptuch G.; Roeck A.D.; Romeri V.D.; Vries J.D.; Dharmapalan R.; Dias M.; Diaz F.; Diaz J.; Domizio S.D.; Giulio L.D.; Ding P.; Noto L.D.; Distefano C.; Diurba R.; Diwan M.; Djurcic Z.; Dokania N.; Dolinski M.; Domine L.; Douglas D.; Drielsma F.; Duchesneau D.; Duffy K.; Dunne P.; Durkin T.; Duyang H.; Dvornikov O.; Dwyer D.; Dyshkant A.; Eads M.; Edmunds D.; Eisch J.; Emery S.; Ereditato A.; Escobar C.; Sanchez L.E.; Evans J.J.; Ewart E.; Ezeribe A.C.; Fahey K.; Falcone A.; Farnese C.; Farzan Y.; Felix J.; Fernandez-Martinez E.; Menendez P.F.; Ferraro F.; Fields L.; Filkins A.; Filthaut F.; Fitzpatrick R.S.; Flanagan W.; Fleming B.; Flight R.; Fowler J.; Fox W.; Franc J.; Francis K.; Franco D.; Freeman J.; Freestone J.; Fried J.; Friedland A.; Fuess S.; Furic I.; Furmanski A.P.; Gago A.; Gallagher H.; Gallego-Ros A.; Gallice N.; Galymov V.; Gamberini E.; Gamble T.; Gandhi R.; Gandrajula R.; Gao S.; Garcia-Gamez D.; Garcia-Peris M.A.; Gardiner S.; Gastler D.; Ge G.; Gelli B.; Gendotti A.; Gent S.; Ghorbani-Moghaddam Z.; Gibin D.; Gil-Botella I.; Girerd C.; Giri A.; Gnani D.; Gogota O.; Gold M.; Gollapinni S.; Gollwitzer K.; Gomes R.A.; Bermeo L.G.; Fajardo L.S.G.; Gonnella F.; Gonzalez-Cuevas J.; Goodman M.C.; Goodwin O.; Goswami S.; Gotti C.; Goudzovski E.; Grace C.; Graham M.; Gramellini E.; Gran R.; Granados E.; Grant A.; Grant C.; Gratieri D.; Green P.; Green S.; Greenler L.; Greenwood M.; Greer J.; Griffith C.; Groh M.; Grudzinski J.; Grzelak K.; Gu W.; Guarino V.; Guenette R.; Guglielmi A.; Guo B.; Guthikonda K.; Gutierrez R.; Guzowski P.; Guzzo M.M.; Gwon S.; Habig A.; Hackenburg A.; Hadavand H.; Haenni R.; Hahn A.; Haigh J.; Haiston J.; Hamernik T.; Hamilton P.; Han J.; Harder K.; Harris D.A.; Hartnell J.; Hasegawa T.; Hatcher R.; Hazen E.; Heavey A.; Heeger K.M.; Hennessy K.; Henry S.; Morquecho M.H.; Herner K.; Hertel L.; Hesam A.S.; Hewes J.; Pichardo A.H.; Hill T.; Hillier S.J.; Himmel A.; Hoff J.; Hohl C.; Holin A.; Hoppe E.; Horton-Smith G.A.; Hostert M.; Hourlier A.; Howard B.; Howell R.; Huang J.; Huang J.; Hugon J.; Iles G.; Iliescu A.M.; Illingworth R.; Ioannisian A.; Itay R.; Izmaylov A.; James E.; Jargowsky B.; Jediny F.; Jesus-Valls C.; Ji X.; Jiang L.; Jimenez S.; Jipa A.; Joglekar A.; Johnson C.; Johnson R.; Jones B.; Jones S.; Jung C.; Junk T.; Jwa Y.; Kabirnezhad M.; Kaboth A.; Kadenko I.; Kamiya F.; Karagiorgi G.; Karcher A.; Karolak M.; Karyotakis Y.; Kasai S.; Kasetti S.P.; Kashur L.; Kazaryan N.; Kearns E.; Keener P.; Kelly K.J.; Kemp E.; Ketchum W.; Kettell S.; Khabibullin M.; Khotjantsev A.; Khvedelidze A.; Kim D.; King B.; Kirby B.; Kirby M.; Klein J.; Koehler K.; Koerner L.W.; Kohn S.; Koller P.P.; Kordosky M.; Kosc T.; Kose U.; Kostelecky V.; Kothekar K.; Krennrich F.; Kreslo I.; Kudenko Y.; Kudryavtsev V.; Kulagin S.; Kumar J.; Kumar R.; Kuruppu C.; Kus V.; Kutter T.; Lambert A.; Lande K.; Lane C.E.; Lang K.; Langford T.; Lasorak P.; Last D.; Lastoria C.; Laundrie A.; Lawrence A.; Lazanu I.; Lazur R.; Le T.; Learned J.; Lebrun P.; Miotto G.L.; Lehnert R.; De Oliveira M.L.; Leitner M.; Leyton M.; Li L.; Li S.; Li S.; Li T.; Li Y.; Liao H.; Lin C.; Lin S.; Lister A.; Littlejohn B.R.; Liu J.; Lockwitz S.; Loew T.; Lokajicek M.; Lomidze I.; Long K.; Loo K.; Lorca D.; Lord T.; Losecco J.; Louis W.C.; Luk K.; Luo X.; Lurkin N.; Lux T.; Luzio V.P.; MacFarland D.; MacHado A.; MacHado P.; MacIas C.; MacIer J.; Maddalena A.; Madigan P.; Magill S.; Mahn K.; Maio A.; Maloney J.A.; Mandrioli G.; Maneira J.C.; Manenti L.; Manly S.; Mann A.; Manolopoulos K.; Plata M.M.; Marchionni A.; Marciano W.; Marfatia D.; Mariani C.; Maricic J.; Marinho F.; Marino A.D.; Marshak M.; Marshall C.; Marshall J.; Marteau J.; Martin-Albo J.; Martinez N.; Caicedo D.A.M.; Martynenko S.; Mason K.; Mastbaum A.; Masud M.; Matsuno S.; Matthews J.; Mauger C.; Mauri N.; Mavrokoridis K.; Mazza R.; Mazzacane A.; Mazzucato E.; McCluskey E.; McConkey N.; McFarland K.S.; McGrew C.; McNab A.; Mefodiev A.; Mehta P.; Melas P.; Mellinato M.; Mena O.; Menary S.; Mendez H.; Menegolli A.; Meng G.; Messier M.; Metcalf W.; Mewes M.; Meyer H.; Miao T.; Michna G.; Miedema T.; Migenda J.; Milincic R.; Miller W.; Mills J.; Milne C.; Mineev O.; Miranda O.G.; Miryala S.; Mishra C.; Mishra S.; Mislivec A.; Mladenov D.; Mocioiu I.; Moffat K.; Moggi N.; Mohanta R.; Mohayai T.A.; Mokhov N.; Molina J.A.; Bueno L.M.; Montanari A.; Montanari C.; Montanari D.; Zetina L.M.M.; Moon J.; Mooney M.; Moor A.; Moreno D.; Morgan B.; Morris C.; Mossey C.; Motuk E.; Moura C.A.; Mousseau J.; Mu W.; Mualem L.; Mueller J.; Muether M.; Mufson S.; Muheim F.; Muir A.; Mulhearn M.; Muramatsu H.; Murphy S.; Musser J.; Nachtman J.; Nagu S.; Nalbandyan M.; Nandakumar R.; Naples D.; Narita S.; Navas-Nicolas D.; Nayak N.; Nebot-Guinot M.; Necib L.; Negishi K.; Nelson J.K.; Nesbit J.; Nessi M.; Newbold D.; Newcomer M.; Newhart D.; Nichol R.; Niner E.; Nishimura K.; Norman A.; Northrop R.; Novella P.; Nowak J.A.; Oberling M.; Campo A.O.D.; Olivier A.; Onel Y.; Onishchuk Y.; Ott J.; Pagani L.; Pakvasa S.; Palamara O.; Palestini S.; Paley J.M.; Pallavicini M.; Palomares C.; Pantic E.; Paolone V.; Papadimitriou V.; Papaleo R.; Papanestis A.; Paramesvaran S.; Parke S.; Parsa Z.; Parvu M.; Pascoli S.; Pasqualini L.; Pasternak J.; Pater J.; Patrick C.; Patrizii L.; Patterson R.B.; Patton S.; Patzak T.; Paudel A.; Paulos B.; Paulucci L.; Pavlovic Z.; Pawloski G.; Payne D.; Pec V.; Peeters S.J.; Penichot Y.; Pennacchio E.; Penzo A.; Peres O.L.; Perry J.; Pershey D.; Pessina G.; Petrillo G.; Petta C.; Petti R.; Piastra F.; Pickering L.; Pietropaolo F.; Pillow J.; Plunkett R.; Poling R.; Pons X.; Poonthottathil N.; Pordes S.; Potekhin M.; Potenza R.; Potukuchi B.V.; Pozimski J.; Pozzato M.; Prakash S.; Prakash T.; Prince S.; Prior G.; Pugnere D.; Qi K.; Qian X.; Raaf J.; Raboanary R.; Radeka V.; Rademacker J.; Radics B.; Rafique A.; Raguzin E.; Rai M.; Rajaoalisoa M.; Rakhno I.; Rakotondramanana H.; Rakotondravohitra L.; Ramachers Y.; Rameika R.; Delgado M.R.; Ramson B.; Rappoldi A.; Raselli G.; Ratoff P.; Ravat S.; Razafinime H.; Real J.; Rebel B.; Redondo D.; Reggiani-Guzzo M.; Rehak T.; Reichenbacher J.; Reitzner S.D.; Renshaw A.; Rescia S.; Resnati F.; Reynolds A.; Riccobene G.; Rice L.C.; Rielage K.; Rigaut Y.; Rivera D.; Rochester L.; Roda M.; Rodrigues P.; Alonso M.R.; Rondon J.R.; Roeth A.; Rogers H.; Rosauro-Alcaraz S.; Rossella M.; Rout J.; Roy S.; Rubbia A.; Rubbia C.; Russell B.; Russell J.; Ruterbories D.; Saakyan R.; Sacerdoti S.; Safford T.; Sahu N.; Sala P.; Samios N.; Sanchez M.; Sanders D.A.; Sankey D.; Santana S.; Santos-Maldonado M.; Saoulidou N.; Sapienza P.; Sarasty C.; Sarcevic I.; Savage G.; Savinov V.; Scaramelli A.; Scarff A.; Scarpelli A.; Schaffer T.; Schellman H.; Schlabach P.; Schmitz D.; Scholberg K.; Schukraft A.; Segreto E.; Sensenig J.; Seong I.; Sergi A.; Sergiampietri F.; Sgalaberna D.; Shaevitz M.; Shafaq S.; Shamma M.; Sharma H.R.; Sharma R.; Shaw T.; Shepherd-Themistocleous C.; Shin S.; Shooltz D.; Shrock R.; Simard L.; Simos N.; Sinclair J.; Sinev G.; Singh J.; Singh V.; Sipos R.; Sippach F.; Sirri G.; Sitraka A.; Siyeon K.; Smargianaki D.; Smith A.; Smith A.; Smith E.; Smith P.; Smolik J.; Smy M.; Snopok P.; Nunes M.S.; Sobel H.; Soderberg M.; Salinas C.J.S.; Soldner-Rembold S.; Solomey N.; Solovov V.; Sondheim W.E.; Sorel M.; Soto-Oton J.; Sousa A.; Soustruznik K.; Spagliardi F.; Spanu M.; Spitz J.; Spooner N.J.; Spurgeon K.; Staley R.; Stancari M.; Stanco L.; Steiner H.; Stewart J.; Stillwell B.; Stock J.; Stocker F.; Stokes T.; Strait M.; Strauss T.; Striganov S.; Stuart A.; Summers D.; Surdo A.; Susic V.; Suter L.; Sutera C.; Svoboda R.; Szczerbinska B.; Szelc A.; Talaga R.; Tanaka H.; Oregui B.T.; Tapper A.; Tariq S.; Tatar E.; Tayloe R.; Teklu A.; Tenti M.; Terao K.; Ternes C.A.; Terranova F.; Testera G.; Thea A.; Thompson J.L.; Thorn C.; Timm S.; Tonazzo A.; Torti M.; Tortola M.; Tortorici F.; Totani D.; Toups M.; Touramanis C.; Trevor J.; Trzaska W.H.; Tsai Y.T.; Tsamalaidze Z.; Tsang K.; Tsverava N.; Tufanli S.; Tull C.; Tyley E.; Tzanov M.; Uchida M.A.; Urheim J.; Usher T.; Vagins M.; Vahle P.; Valdiviesso G.; Valencia E.; Vallari Z.; Valle J.W.; Vallecorsa S.; Berg R.V.; De Water R.G.V.; Forero D.V.; Varanini F.; Vargas D.; Varner G.; Vasel J.; Vasseur G.; Vaziri K.; Ventura S.; Verdugo A.; Vergani S.; Vermeulen M.A.; Verzocchi M.; De Souza H.V.; Vignoli C.; Vilela C.; Viren B.; Vrba T.; Wachala T.; Waldron A.V.; Wallbank M.; Wang H.; Wang J.; Wang Y.; Wang Y.; Warburton K.; Warner D.; Wascko M.; Waters D.; Watson A.; Weatherly P.; Weber A.; Weber M.; Wei H.; Weinstein A.; Wenman D.; Wetstein M.; While M.R.; White A.; Whitehead L.H.; Whittington D.; Wilking M.J.; Wilkinson C.; Williams Z.; Wilson F.; Wilson R.J.; Wolcott J.; Wongjirad T.; Wood K.; Wood L.; Worcester E.; Worcester M.; Wret C.; Wu W.; Wu W.; Xiao Y.; Yang G.; Yang T.; Yershov N.; Yonehara K.; Young T.; Yu B.; Yu J.; Zalesak J.; Zambelli L.; Zamorano B.; Zani A.; Zazueta L.; Zeller G.; Zennamo J.; Zeug K.; Zhang C.; Zhao M.; Zhivun E.; Zhu G.; Zimmerman E.D.; Zito M.; Zucchelli S.; Zuklin J.; Zutshi V.; Zwaska R.Abi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; 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Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties