Export of a Toxoplasma gondii Rhoptry Neck Protein Complex at the Host Cell Membrane to Form the Moving Junction during Invasion

One of the most conserved features of the invasion process in Apicomplexa parasites is the formation of a moving junction (MJ) between the apex of the parasite and the host cell membrane that moves along the parasite and serves as support to propel it inside the host cell. The MJ was, up to a recent period, completely unknown at the molecular level. Recently, proteins originated from two distinct post-Golgi specialised secretory organelles, the micronemes (for AMA1) and the neck of the rhoptries (for RON2/RON4/RON5 proteins), have been shown to form a complex. AMA1 and RON4 in particular, have been localised to the MJ during invasion. Using biochemical approaches, we have identified RON8 as an additional member of the complex. We also demonstrated that all RON proteins are present at the MJ during invasion. Using metabolic labelling and immunoprecipitation, we showed that RON2 and AMA1 were able to interact in the absence of the other members. We also discovered that all MJ proteins are subjected to proteolytic maturation during trafficking to their respective organelles and that they could associate as non-mature forms in vitro. Finally, whereas AMA1 has previously been shown to be inserted into the parasite membrane upon secretion, we demonstrated, using differential permeabilization and loading of RON-specific antibodies into the host cell, that the RON complex is targeted to the host cell membrane, where RON4/5/8 remain associated with the cytoplasmic face. Globally, these results point toward a model of MJ organization where the parasite would be secreting and inserting interacting components on either side of the MJ, both at the host and at its own plasma membranes

An Inhibitory Antibody Blocks Interactions between Components of the Malarial Invasion Machinery

Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1 is of widespread interest as a malaria vaccine candidate. Here we report that the AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We demonstrate that the invasion-inhibitory monoclonal antibody (mAb) 4G2, which recognises P. falciparum AMA1 (PfAMA1), cannot bind when PfAMA1 is in a complex with its partner proteins. We further show that a single completely conserved PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1

Enhanced CellClassifier: a multi-class classification tool for microscopy images

BACKGROUND: Light microscopy is of central importance in cell biology. The recent introduction of automated high content screening has expanded this technology towards automation of experiments and performing large scale perturbation assays. Nevertheless, evaluation of microscopy data continues to be a bottleneck in many projects. Currently, among open source software, CellProfiler and its extension Analyst are widely used in automated image processing. Even though revolutionizing image analysis in current biology, some routine and many advanced tasks are either not supported or require programming skills of the researcher. This represents a significant obstacle in many biology laboratories. RESULTS: We have developed a tool, Enhanced CellClassifier, which circumvents this obstacle. Enhanced CellClassifier starts from images analyzed by CellProfiler, and allows multi-class classification using a Support Vector Machine algorithm. Training of objects can be done by clicking directly "on the microscopy image" in several intuitive training modes. Many routine tasks like out-of focus exclusion and well summary are also supported. Classification results can be integrated with other object measurements including inter-object relationships. This makes a detailed interpretation of the image possible, allowing the differentiation of many complex phenotypes. For the generation of the output, image, well and plate data are dynamically extracted and summarized. The output can be generated as graphs, Excel-files, images with projections of the final analysis and exported as variables. CONCLUSION: Here we describe Enhanced CellClassifier which allows multiple class classification, elucidating complex phenotypes. Our tool is designed for the biologist who wants both, simple and flexible analysis of images without requiring programming skills. This should facilitate the implementation of automated high-content screening

Algal MIPs, high diversity and conserved motifs

<p>Abstract</p> <p>Background</p> <p>Major intrinsic proteins (MIPs) also named aquaporins form channels facilitating the passive transport of water and other small polar molecules across membranes. MIPs are particularly abundant and diverse in terrestrial plants but little is known about their evolutionary history. In an attempt to investigate the origin of the plant MIP subfamilies, genomes of chlorophyte algae, the sister group of charophyte algae and land plants, were searched for MIP encoding genes.</p> <p>Results</p> <p>A total of 22 MIPs were identified in the nine analysed genomes and phylogenetic analyses classified them into seven subfamilies. Two of these, Plasma membrane Intrinsic Proteins (PIPs) and GlpF-like Intrinsic Proteins (GIPs), are also present in land plants and divergence dating support a common origin of these algal and land plant MIPs, predating the evolution of terrestrial plants. The subfamilies unique to algae were named MIPA to MIPE to facilitate the use of a common nomenclature for plant MIPs reflecting phylogenetically stable groups. All of the investigated genomes contained at least one <it>MIP </it>gene but only a few species encoded MIPs belonging to more than one subfamily.</p> <p>Conclusions</p> <p>Our results suggest that at least two of the seven subfamilies found in land plants were present already in an algal ancestor. The total variation of MIPs and the number of different subfamilies in chlorophyte algae is likely to be even higher than that found in land plants. Our analyses indicate that genetic exchanges between several of the algal subfamilies have occurred. The PIP1 and PIP2 groups and the Ca²⁺gating appear to be specific to land plants whereas the pH gating is a more ancient characteristic shared by all PIPs. Further studies are needed to discern the function of the algal specific subfamilies MIPA-E and to fully understand the evolutionary relationship of algal and terrestrial plant MIPs.</p

Plasmodium Protease ROM1 Is Important for Proper Formation of the Parasitophorous Vacuole

Apicomplexans are obligate intracellular parasites that invade host cells by an active process leading to the formation of a non-fusogenic parasitophorous vacuole (PV) where the parasite replicates within the host cell. The rhomboid family of proteases cleaves substrates within their transmembrane domains and has been implicated in the invasion process. Although its exact function is unknown, Plasmodium ROM1 is hypothesized to play a role during invasion based on its microneme localization and its ability to cleave essential invasion adhesins. Using the rodent malaria model, Plasmodium yoelii, we carried out detailed quantitative analysis of pyrom1 deficient parasites during the Plasmodium lifecycle. Pyrom1(-) parasites are attenuated during erythrocytic and hepatic stages but progress normally through the mosquito vector with normal counts of oocyst and salivary gland sporozoites. Pyrom1 steady state mRNA levels are upregulated 20-fold in salivary gland sporozoites compared to blood stages. We show that pyrom1(-) sporozoites are capable of gliding motility and traversing host cells normally. Wildtype and pyrom1(-) sporozoites do not differ in the rate of entry into Hepa1–6 hepatocytes. Within the first twelve hours of hepatic development, however, only 50% pyrom1(-) parasites have developed into exoerythrocytic forms. Immunofluorescence microscopy using the PVM marker UIS4 and transmission electron microscopy reveal that the PV of a significant fraction of pyrom1(-) parasites are morphologically aberrant shortly after invasion. We propose a novel function for PyROM1 as a protease that promotes proper PV modification to allow parasite development and replication in a suitable environment within the mammalian host

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

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.; 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.; 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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

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field