Increasing Hydrophobicity of Residues in an Anti-HIV-1 Env Peptide Synergistically Improves Potency

AbstractT-20/Fuzeon/Enfuvirtide (ENF), a peptide inhibitor of HIV-1 infection, targets the grooves created by heptad repeat 2 (HR2) of Env's coiled-coil, but mutants resistant to ENF emerge. In this study, ENF-resistant mutants—V38A, N43D, N43D/S138A, Q40H/L45M—were combined with modified inhibitory peptides to identify what we believe to be novel ways to improve peptide efficacy. V38A did not substantially reduce infectivity, but was relatively resistant to inhibitory peptides. N43D was more resistant to inhibitory peptides than wild-type, but infectivity was reduced. The additional mutation S138A (N43D/S138A) increased infectivity and further reduced peptide inhibitory potency. It is concluded that S138A increased binding of HR2/ENF into grooves and that S138A compensated for electrostatic repulsion between N43D and HR2. The six-helix bundle structure indicated that E148A should increase hydrophobic interactions between the coiled-coil and peptide. Importantly, the modifications S138A and E148A in the same peptide retained potency against ENF-escape mutants. The double mutant's increase in potency was greater than the increases from the sum of S138A and E148A individually, showing that these two altered residues synergistically contributed to peptide binding. Isothermal titration calorimetry established that hydrophobic substitutions at positions S138 and E148 improved potency of inhibitory peptides against escape mutants by increasing enthalpic release of energy upon peptide binding

The role of family support in work-family balance and subjective well-being of SME owners

Drawing on the conservation of resources (COR) theory, we examine the role of two types of family support—emotional and instrumental support—in work-family balance and subjective well-being of small and medium enterprise (SME) owners. Using a sample of French SME owners, our results show that work-family balance mediates the relationship between family support and subjective well-being of SME owners. Surprisingly, while emotional support has a positive association, instrumental support has a negative association with the subjective well-being of SME owners via work-family balance. We provide a theoretical explanation by integrating COR theory with the threat to self-esteem model

Circulating human leucine-rich a-2-glycoprotein 1 mRNA and protein levels to detect acute appendicitis in patients with acute abdominal pain

Background Elevated levels of circulating plasma and urine leucine-rich-2-glycoprotein-1 (LRG1) protein has been found in patients with acute appendicitis (AA) and may be useful for diagnosis. This study aimed to investigate whether combined tests including circulating LRG1 mRNA levels improve the early diagnosis of AA. Methods Between December 2011 and October 2012, a prospective study was conducted on patients aged 18 years or older presenting to the ED with acute abdominal pain (< 7 days of symptom onset). Levels of whole blood LRG1 mRNA and plasma LRG1 protein taken from these patients within 24 h of arrival (mean 12.4 h) were analyzed. The primary outcome was AA. Results Eighty-four patients (40 (47.6%) with AA and 44 (52.4%) without AA; mean age 35 years; 41.6% males) were recruited. Median whole blood LRG1 mRNA and plasma LRG1 levels were higher in AA patients than in non-AA. Of 40 AA patients, 13 (32.5%) were diagnosed as complicated AA. In ROC analysis of LRG1 mRNA (normalized to GAPDH), LRG1 protein and Alvarado score for discriminating AA and non-AA, the areas under the curve (AUC) were 0.723, 0.742 and 0.805 respectively. The AUC of combination of normalized LRG1 mRNA, LRG1 protein and Alvarado score was 0.845. Conclusion A combination of modified whole blood LRG1 mRNA levels, plasma LRG1 protein and Alvarado score at the ED may be useful to diagnose simple and complicated AA from other causes of abdominal pain

Do neighbourhood characteristics matter in understanding school children’s active lifestyles? a cross-region multi-city comparison of Glasgow, Edinburgh and Hong Kong

Many studies have explored the influence of individual and neighbourhood factors on active school travel (AST), this novel study is the first to examine how AST and formal extracurricular activities are associated with children’s active lifestyles. The aims of this study were to (a) create an active lifestyle variable (ALIFE) measured in terms of total weekly minutes of AST and extracurricular activities, and (b) explore how ALIFE is associated with different attributes at the individual, household and neighbourhood levels, and how these relationships differ for children aged 10 and 11 years old across the three cities: Glasgow, Edinburgh and Hong Kong. We found environmental factors to be important indicators of lower AST, for example greater parking facility density. The most substantial contribution to children’s overall ALIFE was household income, those from the lowest household group having almost 2 h less ALIFE per-week than those from the highest income

Trajectory of functional outcome and health status after moderate-to-major trauma in Hong Kong: A prospective 5 year cohort study

Background Trauma care systems in Asia have been developing in recent years, but there has been little long-term outcome data from injured survivors. This study aims to evaluate the trajectory of functional outcome and health status up to five years after moderate to major trauma in Hong Kong. Methods We report the five year follow up results of a multicentre, prospective cohort from the trauma registries of three regional trauma centres in Hong Kong. The original cohort recruited 400 adult trauma patients with ISS ≥ 9. Telephone follow up was conducted longitudinally at seven time points, and the extended Glasgow Outcome Scale (GOSE) and Short-Form 36 (SF36) were tracked. Results 119 out of 309 surviving patients (39%) completed follow up after 5 years. The trajectory of GOSE, PCS and MCS showed gradual improvements over the seven time points. 56/119 (47.1%) patients reported a GOSE = 8 (upper good recovery), and the mean PCS and MCS was 47.8 (95% CI 45.8, 49.9) and 55.8 (95% CI 54.1, 57.5) respectively at five years. Univariate logistic regression showed change in PCS - baseline to 1 year and 1 year to 2 years, and change in MCS - baseline to 1 year were associated with GOSE = 8 at 5 years. Linear mixed effects model showed differences in PCS and MCS were greatest between 1-month and 6-month follow up. Conclusions After injury, the most rapid improvement in PCS and MCS occurred in the first six to 12 months, but further recovery was still evident for MCS in patients aged under 65 years for up to five years

Narcissism and entrepreneurship: Evidence from six datasets

Widespread attention is being paid to the alleged rise of narcissism in people in general and business leaders in particular. Surprisingly, hardly any studies have focused on the link between narcissism and entrepreneurship. Using self-reported data from 4798 respondents from three countries, we explore the associations between trait narcissism and six different entrepreneurial aspects that represent the entire entrepreneurial process. Overall, our findings suggest that a positive link exists between narcissism and entrepreneurship that is particularly salient in the early stage of the entrepreneurial process (e.g., entrepreneurial intention) and in the individual aspects of entrepreneurship (e.g., entrepreneurial orientation, well-being of the entrepreneur). Our additional analyses reveal that the adaptive aspect of narcissism (i.e., leadership/authority) is most consistently linked to entrepreneurship and that the links between narcissism and entrepreneurship are predominately linear. Finally, our findings are largely robust when different sets of controls are added

Specific Heat of Liquid Helium in Zero Gravity very near the Lambda Point

We report the details and revised analysis of an experiment to measure the specific heat of helium with subnanokelvin temperature resolution near the lambda point. The measurements were made at the vapor pressure spanning the region from 22 mK below the superfluid transition to 4 uK above. The experiment was performed in earth orbit to reduce the rounding of the transition caused by gravitationally induced pressure gradients on earth. Specific heat measurements were made deep in the asymptotic region to within 2 nK of the transition. No evidence of rounding was found to this resolution. The optimum value of the critical exponent describing the specific heat singularity was found to be a = -0.0127+ - 0.0003. This is bracketed by two recent estimates based on renormalization group techniques, but is slightly outside the range of the error of the most recent result. The ratio of the coefficients of the leading order singularity on the two sides of the transition is A+/A- =1.053+ - 0.002, which agrees well with a recent estimate. By combining the specific heat and superfluid density exponents a test of the Josephson scaling relation can be made. Excellent agreement is found based on high precision measurements of the superfluid density made elsewhere. These results represent the most precise tests of theoretical predictions for critical phenomena to date.Comment: 27 Pages, 20 Figure

Survey of Surveys (SoS) ‐ Mapping The Landscape of Survey Papers in Information Visualization

Information visualization as a field is growing rapidly in popularity since the first information visualization conference in 1995.However, as a consequence of its growth, it is increasingly difficult to follow the growing body of literature within the field.Survey papers and literature reviews are valuable tools for managing the great volume of previously published research papers,and the quantity of survey papers in visualization has reached a critical mass. To this end, this survey paper takes a quantumstep forward by surveying and classifying literature survey papers in order to help researchers understand the current landscapeof Information Visualization. It is, to our knowledge, the first survey of survey papers (SoS) in Information Visualization. Thispaper classifies survey papers into natural topic clusters which enables readers to find relevant literature and develops thefirst classification of classifications. The paper also enables researchers to identify both mature and less developed researchdirections as well as identify future directions. It is a valuable resource for both newcomers and experienced researchers in andoutside the field of Information Visualization and Visual Analytic

Radioactivity control strategy for the JUNO detector

602siopenJUNO is a massive liquid scintillator detector with a primary scientific goal of determining the neutrino mass ordering by studying the oscillated anti-neutrino flux coming from two nuclear power plants at 53 km distance. The expected signal anti-neutrino interaction rate is only 60 counts per day (cpd), therefore a careful control of the background sources due to radioactivity is critical. In particular, natural radioactivity present in all materials and in the environment represents a serious issue that could impair the sensitivity of the experiment if appropriate countermeasures were not foreseen. In this paper we discuss the background reduction strategies undertaken by the JUNO collaboration to reduce at minimum the impact of natural radioactivity. We describe our efforts for an optimized experimental design, a careful material screening and accurate detector production handling, and a constant control of the expected results through a meticulous Monte Carlo simulation program. We show that all these actions should allow us to keep the background count rate safely below the target value of 10 Hz (i.e. ∼1 cpd accidental background) in the default fiducial volume, above an energy threshold of 0.7 MeV. [Figure not available: see fulltext.]openAbusleme A.; Adam T.; Ahmad S.; Ahmed R.; Aiello S.; Akram M.; An F.; An Q.; Andronico G.; Anfimov N.; Antonelli V.; Antoshkina T.; Asavapibhop B.; de Andre J.P.A.M.; Auguste D.; Babic A.; Baldini W.; Barresi A.; Basilico D.; Baussan E.; Bellato M.; Bergnoli A.; Birkenfeld T.; Blin S.; Blum D.; Blyth S.; Bolshakova A.; Bongrand M.; Bordereau C.; Breton D.; Brigatti A.; Brugnera R.; Bruno R.; Budano A.; Buscemi M.; Busto J.; Butorov I.; Cabrera A.; Cai H.; Cai X.; Cai Y.; Cai Z.; Cammi A.; Campeny A.; Cao C.; Cao G.; Cao J.; Caruso R.; Cerna C.; Chang J.; Chang Y.; Chen P.; Chen P.-A.; Chen S.; Chen X.; Chen Y.-W.; Chen Y.; Chen Y.; Chen Z.; Cheng J.; Cheng Y.; Chetverikov A.; Chiesa D.; Chimenti P.; Chukanov A.; Claverie G.; Clementi C.; Clerbaux B.; Conforti Di Lorenzo S.; Corti D.; Cremonesi O.; Dal Corso F.; Dalager O.; De La Taille C.; Deng J.; Deng Z.; Deng Z.; Depnering W.; Diaz M.; Ding X.; Ding Y.; Dirgantara B.; Dmitrievsky S.; Dohnal T.; Dolzhikov D.; Donchenko G.; Dong J.; Doroshkevich E.; Dracos M.; Druillole F.; Du S.; Dusini S.; Dvorak M.; Enqvist T.; Enzmann H.; Fabbri A.; Fajt L.; Fan D.; Fan L.; Fang J.; Fang W.; Fargetta M.; Fedoseev D.; Fekete V.; Feng L.-C.; Feng Q.; Ford R.; Formozov A.; Fournier A.; Gan H.; Gao F.; Garfagnini A.; Giammarchi M.; Giaz A.; Giudice N.; Gonchar M.; Gong G.; Gong H.; Gornushkin Y.; Gottel A.; Grassi M.; Grewing C.; Gromov V.; Gu M.; Gu X.; Gu Y.; Guan M.; Guardone N.; Gul M.; Guo C.; Guo J.; Guo W.; Guo X.; Guo Y.; Hackspacher P.; Hagner C.; Han R.; Han Y.; Hassan M.S.; He M.; He W.; Heinz T.; Hellmuth P.; Heng Y.; Herrera R.; Hor Y.K.; Hou S.; Hsiung Y.; Hu B.-Z.; Hu H.; Hu J.; Hu J.; Hu S.; Hu T.; Hu Z.; Huang C.; Huang G.; Huang H.; Huang W.; Huang X.; Huang X.; Huang Y.; Hui J.; Huo L.; Huo W.; Huss C.; Hussain S.; Ioannisian A.; Isocrate R.; Jelmini B.; Jen K.-L.; Jeria I.; Ji X.; Ji X.; Jia H.; Jia J.; Jian S.; Jiang D.; Jiang X.; Jin R.; Jing X.; Jollet C.; Joutsenvaara J.; Jungthawan S.; Kalousis L.; Kampmann P.; Kang L.; Karaparambil R.; Kazarian N.; Khan W.; Khosonthongkee K.; Korablev D.; Kouzakov K.; Krasnoperov A.; Kruth A.; Kutovskiy N.; Kuusiniemi P.; Lachenmaier T.; Landini C.; Leblanc S.; Lebrin V.; Lefevre F.; Lei R.; Leitner R.; Leung J.; Li D.; Li F.; Li F.; Li H.; Li H.; Li J.; Li M.; Li M.; Li N.; Li N.; Li Q.; Li R.; Li S.; Li T.; Li W.; Li W.; Li X.; Li X.; Li X.; Li Y.; Li Y.; Li Z.; Li Z.; Li Z.; Liang H.; Liang H.; Liao J.; Liebau D.; Limphirat A.; Limpijumnong S.; Lin G.-L.; Lin S.; Lin T.; Ling J.; Lippi I.; Liu F.; Liu H.; Liu H.; Liu H.; Liu H.; Liu H.; Liu J.; Liu J.; Liu M.; Liu Q.; Liu Q.; Liu R.; Liu S.; Liu S.; Liu S.; Liu X.; Liu X.; Liu Y.; Liu Y.; Lokhov A.; Lombardi P.; Lombardo C.; Loo K.; Lu C.; Lu H.; Lu J.; Lu J.; Lu S.; Lu X.; Lubsandorzhiev B.; Lubsandorzhiev S.; Ludhova L.; Luo F.; Luo G.; Luo P.; Luo S.; Luo W.; Lyashuk V.; Ma B.; Ma Q.; Ma S.; Ma X.; Ma X.; Maalmi J.; Malyshkin Y.; Mantovani F.; Manzali F.; Mao X.; Mao Y.; Mari S.M.; Marini F.; Marium S.; Martellini C.; Martin-Chassard G.; Martini A.; Mayer M.; Mayilyan D.; Mednieks I.; Meng Y.; Meregaglia A.; Meroni E.; Meyhofer D.; Mezzetto M.; Miller J.; Miramonti L.; Montini P.; Montuschi M.; Muller A.; Nastasi M.; Naumov D.V.; Naumova E.; Navas-Nicolas D.; Nemchenok I.; Nguyen Thi M.T.; Ning F.; Ning Z.; Nunokawa H.; Oberauer L.; Ochoa-Ricoux J.P.; Olshevskiy A.; Orestano D.; Ortica F.; Othegraven R.; Pan H.-R.; Paoloni A.; Parmeggiano S.; Pei Y.; Pelliccia N.; Peng A.; Peng H.; Perrot F.; Petitjean P.-A.; Petrucci F.; Pilarczyk O.; Pineres Rico L.F.; Popov A.; Poussot P.; Pratumwan W.; Previtali E.; Qi F.; Qi M.; Qian S.; Qian X.; Qian Z.; Qiao H.; Qin Z.; Qiu S.; Rajput M.U.; Ranucci G.; Raper N.; Re A.; Rebber H.; Rebii A.; Ren B.; Ren J.; Ricci B.; Robens M.; Roche M.; Rodphai N.; Romani A.; Roskovec B.; Roth C.; Ruan X.; Ruan X.; Rujirawat S.; Rybnikov A.; Sadovsky A.; Saggese P.; Sanfilippo S.; Sangka A.; Sanguansak N.; Sawangwit U.; Sawatzki J.; Sawy F.; Schever M.; Schwab C.; Schweizer K.; Selyunin A.; Serafini A.; Settanta G.; Settimo M.; Shao Z.; Sharov V.; Shaydurova A.; Shi J.; Shi Y.; Shutov V.; Sidorenkov A.; Simkovic F.; Sirignano C.; Siripak J.; Sisti M.; Slupecki M.; Smirnov M.; Smirnov O.; Sogo-Bezerra T.; Sokolov S.; Songwadhana J.; Soonthornthum B.; Sotnikov A.; Sramek O.; Sreethawong W.; Stahl A.; Stanco L.; Stankevich K.; Stefanik D.; Steiger H.; Steinmann J.; Sterr T.; Stock M.R.; Strati V.; Studenikin A.; Sun S.; Sun X.; Sun Y.; Sun Y.; Suwonjandee N.; Szelezniak M.; Tang J.; Tang Q.; Tang Q.; Tang X.; Tietzsch A.; Tkachev I.; Tmej T.; Treskov K.; Triossi A.; Troni G.; Trzaska W.; Tuve C.; Ushakov N.; van den Boom J.; van Waasen S.; Vanroyen G.; Vassilopoulos N.; Vedin V.; Verde G.; Vialkov M.; Viaud B.; Vollbrecht M.C.; Volpe C.; Vorobel V.; Voronin D.; Votano L.; Walker P.; Wang C.; Wang C.-H.; Wang E.; Wang G.; Wang J.; Wang J.; Wang K.; Wang L.; Wang M.; Wang M.; Wang M.; Wang R.; Wang S.; Wang W.; Wang W.; Wang W.; Wang X.; Wang X.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Y.; Wang Z.; Wang Z.; Wang Z.; Wang Z.; Waqas M.; Watcharangkool A.; Wei L.; Wei W.; Wei W.; Wei Y.; Wen L.; Wiebusch C.; Wong S.C.-F.; Wonsak B.; Wu D.; Wu F.; Wu Q.; Wu Z.; Wurm M.; Wurtz J.; Wysotzki C.; Xi Y.; Xia D.; Xie X.; Xie Y.; Xie Z.; Xing Z.; Xu B.; Xu C.; Xu D.; Xu F.; Xu H.; Xu J.; Xu J.; Xu M.; Xu Y.; Xu Y.; Yan B.; Yan T.; Yan W.; Yan X.; Yan Y.; Yang A.; Yang C.; Yang C.; Yang H.; Yang J.; Yang L.; Yang X.; Yang Y.; Yang Y.; Yao H.; Yasin Z.; Ye J.; Ye M.; Ye Z.; Yegin U.; Yermia F.; Yi P.; Yin N.; Yin X.; You Z.; Yu B.; Yu C.; Yu C.; Yu H.; Yu M.; Yu X.; Yu Z.; Yu Z.; Yuan C.; Yuan Y.; Yuan Z.; Yuan Z.; Yue B.; Zafar N.; Zambanini A.; Zavadskyi V.; Zeng S.; Zeng T.; Zeng Y.; Zhan L.; Zhang A.; Zhang F.; Zhang G.; Zhang H.; Zhang H.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang J.; Zhang P.; Zhang Q.; Zhang S.; Zhang S.; Zhang T.; Zhang X.; Zhang X.; Zhang X.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Y.; Zhang Z.; Zhang Z.; Zhao F.; Zhao J.; Zhao R.; Zhao S.; Zhao T.; Zheng D.; Zheng H.; Zheng M.; Zheng Y.; Zhong W.; Zhou J.; Zhou L.; Zhou N.; Zhou S.; Zhou T.; Zhou X.; Zhu J.; Zhu K.; Zhu K.; Zhu Z.; Zhuang B.; Zhuang H.; Zong L.; Zou J.Abusleme, A.; Adam, T.; Ahmad, S.; Ahmed, R.; Aiello, S.; Akram, M.; An, F.; An, Q.; Andronico, G.; Anfimov, N.; Antonelli, V.; Antoshkina, T.; Asavapibhop, B.; de Andre, J. P. A. M.; Auguste, D.; Babic, A.; Baldini, W.; Barresi, A.; Basilico, D.; Baussan, E.; Bellato, M.; Bergnoli, A.; Birkenfeld, T.; Blin, S.; Blum, D.; Blyth, S.; Bolshakova, A.; Bongrand, M.; Bordereau, C.; Breton, D.; Brigatti, A.; Brugnera, R.; Bruno, R.; Budano, A.; Buscemi, M.; Busto, J.; Butorov, I.; Cabrera, A.; Cai, H.; Cai, X.; Cai, Y.; Cai, Z.; Cammi, A.; Campeny, A.; Cao, C.; Cao, G.; Cao, J.; Caruso, R.; Cerna, C.; Chang, J.; Chang, Y.; Chen, P.; Chen, P. -A.; Chen, S.; Chen, X.; Chen, Y. -W.; Chen, Y.; Chen, Y.; Chen, Z.; Cheng, J.; Cheng, Y.; Chetverikov, A.; Chiesa, D.; Chimenti, P.; Chukanov, A.; Claverie, G.; Clementi, C.; Clerbaux, B.; Conforti Di Lorenzo, S.; Corti, D.; Cremonesi, O.; Dal Corso, F.; Dalager, O.; De La Taille, C.; Deng, J.; Deng, Z.; Deng, Z.; Depnering, W.; Diaz, M.; Ding, X.; Ding, Y.; Dirgantara, B.; Dmitrievsky, S.; Dohnal, T.; Dolzhikov, D.; Donchenko, G.; Dong, J.; Doroshkevich, E.; Dracos, M.; Druillole, F.; Du, S.; Dusini, S.; Dvorak, M.; Enqvist, T.; Enzmann, H.; Fabbri, A.; Fajt, L.; Fan, D.; Fan, L.; Fang, J.; Fang, W.; Fargetta, M.; Fedoseev, D.; Fekete, V.; Feng, L. -C.; Feng, Q.; Ford, R.; Formozov, A.; Fournier, A.; Gan, H.; Gao, F.; Garfagnini, A.; Giammarchi, M.; Giaz, A.; Giudice, N.; Gonchar, M.; Gong, G.; Gong, H.; Gornushkin, Y.; Gottel, A.; Grassi, M.; Grewing, C.; Gromov, V.; Gu, M.; Gu, X.; Gu, Y.; Guan, M.; Guardone, N.; Gul, M.; Guo, C.; Guo, J.; Guo, W.; Guo, X.; Guo, Y.; Hackspacher, P.; Hagner, C.; Han, R.; Han, Y.; Hassan, M. S.; He, M.; He, W.; Heinz, T.; Hellmuth, P.; Heng, Y.; Herrera, R.; Hor, Y. K.; Hou, S.; Hsiung, Y.; Hu, B. -Z.; Hu, H.; Hu, J.; Hu, J.; Hu, S.; Hu, T.; Hu, Z.; Huang, C.; Huang, G.; Huang, H.; Huang, W.; Huang, X.; Huang, X.; Huang, Y.; Hui, J.; Huo, L.; Huo, W.; Huss, C.; Hussain, S.; Ioannisian, A.; Isocrate, R.; Jelmini, B.; Jen, K. -L.; Jeria, I.; Ji, X.; Ji, X.; Jia, H.; Jia, J.; Jian, S.; Jiang, D.; Jiang, X.; Jin, R.; Jing, X.; Jollet, C.; Joutsenvaara, J.; Jungthawan, S.; Kalousis, L.; Kampmann, P.; Kang, L.; Karaparambil, R.; Kazarian, N.; Khan, W.; Khosonthongkee, K.; Korablev, D.; Kouzakov, K.; Krasnoperov, A.; Kruth, A.; Kutovskiy, N.; Kuusiniemi, P.; Lachenmaier, T.; Landini, C.; Leblanc, S.; Lebrin, V.; Lefevre, F.; Lei, R.; Leitner, R.; Leung, J.; Li, D.; Li, F.; Li, F.; Li, H.; Li, H.; Li, J.; Li, M.; Li, M.; Li, N.; Li, N.; Li, Q.; Li, R.; Li, S.; Li, T.; Li, W.; Li, W.; Li, X.; Li, X.; Li, X.; Li, Y.; Li, Y.; Li, Z.; Li, Z.; Li, Z.; Liang, H.; Liang, H.; Liao, J.; Liebau, D.; Limphirat, A.; Limpijumnong, S.; Lin, G. -L.; Lin, S.; Lin, T.; Ling, J.; Lippi, I.; Liu, F.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, H.; Liu, J.; Liu, J.; Liu, M.; Liu, Q.; Liu, Q.; Liu, R.; Liu, S.; Liu, S.; Liu, S.; Liu, X.; Liu, X.; Liu, Y.; Liu, Y.; Lokhov, A.; Lombardi, P.; Lombardo, C.; Loo, K.; Lu, C.; Lu, H.; Lu, J.; Lu, J.; Lu, S.; Lu, X.; Lubsandorzhiev, B.; Lubsandorzhiev, S.; Ludhova, L.; Luo, F.; Luo, G.; Luo, P.; Luo, S.; Luo, W.; Lyashuk, V.; Ma, B.; Ma, Q.; Ma, S.; Ma, X.; Ma, X.; Maalmi, J.; Malyshkin, Y.; Mantovani, F.; Manzali, F.; Mao, X.; Mao, Y.; Mari, S. M.; Marini, F.; Marium, S.; Martellini, C.; Martin-Chassard, G.; Martini, A.; Mayer, M.; Mayilyan, D.; Mednieks, I.; Meng, Y.; Meregaglia, A.; Meroni, E.; Meyhofer, D.; Mezzetto, M.; Miller, J.; Miramonti, L.; Montini, P.; Montuschi, M.; Muller, A.; Nastasi, M.; Naumov, D. V.; Naumova, E.; Navas-Nicolas, D.; Nemchenok, I.; Nguyen Thi, M. T.; Ning, F.; Ning, Z.; Nunokawa, H.; Oberauer, L.; Ochoa-Ricoux, J. P.; Olshevskiy, A.; Orestano, D.; Ortica, F.; Othegraven, R.; Pan, H. -R.; Paoloni, A.; Parmeggiano, S.; Pei, Y.; Pelliccia, N.; Peng, A.; Peng, H.; Perrot, F.; Petitjean, P. -A.; Petrucci, F.; Pilarczyk, O.; Pineres Rico, L. F.; Popov, A.; Poussot, P.; Pratumwan, W.; Previtali, E.; Qi, F.; Qi, M.; Qian, S.; Qian, X.; Qian, Z.; Qiao, H.; Qin, Z.; Qiu, S.; Rajput, M. U.; Ranucci, G.; Raper, N.; Re, A.; Rebber, H.; Rebii, A.; Ren, B.; Ren, J.; Ricci, B.; Robens, M.; Roche, M.; Rodphai, N.; Romani, A.; Roskovec, B.; Roth, C.; Ruan, X.; Ruan, X.; Rujirawat, S.; Rybnikov, A.; Sadovsky, A.; Saggese, P.; Sanfilippo, S.; Sangka, A.; Sanguansak, N.; Sawangwit, U.; Sawatzki, J.; Sawy, F.; Schever, M.; Schwab, C.; Schweizer, K.; Selyunin, A.; Serafini, A.; Settanta, G.; Settimo, M.; Shao, Z.; Sharov, V.; Shaydurova, A.; Shi, J.; Shi, Y.; Shutov, V.; Sidorenkov, A.; Simkovic, F.; Sirignano, C.; Siripak, J.; Sisti, M.; Slupecki, M.; Smirnov, M.; Smirnov, O.; Sogo-Bezerra, T.; Sokolov, S.; Songwadhana, J.; Soonthornthum, B.; Sotnikov, A.; Sramek, O.; Sreethawong, W.; Stahl, A.; Stanco, L.; Stankevich, K.; Stefanik, D.; Steiger, H.; Steinmann, J.; Sterr, T.; Stock, M. R.; Strati, V.; Studenikin, A.; Sun, S.; Sun, X.; Sun, Y.; Sun, Y.; Suwonjandee, N.; Szelezniak, M.; Tang, J.; Tang, Q.; Tang, Q.; Tang, X.; Tietzsch, A.; Tkachev, I.; Tmej, T.; Treskov, K.; Triossi, A.; Troni, G.; Trzaska, W.; Tuve, C.; Ushakov, N.; van den Boom, J.; van Waasen, S.; Vanroyen, G.; Vassilopoulos, N.; Vedin, V.; Verde, G.; Vialkov, M.; Viaud, B.; Vollbrecht, M. C.; Volpe, C.; Vorobel, V.; Voronin, D.; Votano, L.; Walker, P.; Wang, C.; Wang, C. -H.; Wang, E.; Wang, G.; Wang, J.; Wang, J.; Wang, K.; Wang, L.; Wang, M.; Wang, M.; Wang, M.; Wang, R.; Wang, S.; Wang, W.; Wang, W.; Wang, W.; Wang, X.; Wang, X.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Y.; Wang, Z.; Wang, Z.; Wang, Z.; Wang, Z.; Waqas, M.; Watcharangkool, A.; Wei, L.; Wei, W.; Wei, W.; Wei, Y.; Wen, L.; Wiebusch, C.; Wong, S. C. -F.; Wonsak, B.; Wu, D.; Wu, F.; Wu, Q.; Wu, Z.; Wurm, M.; Wurtz, J.; Wysotzki, C.; Xi, Y.; Xia, D.; Xie, X.; Xie, Y.; Xie, Z.; Xing, Z.; Xu, B.; Xu, C.; Xu, D.; Xu, F.; Xu, H.; Xu, J.; Xu, J.; Xu, M.; Xu, Y.; Xu, Y.; Yan, B.; Yan, T.; Yan, W.; Yan, X.; Yan, Y.; Yang, A.; Yang, C.; Yang, C.; Yang, H.; Yang, J.; Yang, L.; Yang, X.; Yang, Y.; Yang, Y.; Yao, H.; Yasin, Z.; Ye, J.; Ye, M.; Ye, Z.; Yegin, U.; Yermia, F.; Yi, P.; Yin, N.; Yin, X.; You, Z.; Yu, B.; Yu, C.; Yu, C.; Yu, H.; Yu, M.; Yu, X.; Yu, Z.; Yu, Z.; Yuan, C.; Yuan, Y.; Yuan, Z.; Yuan, Z.; Yue, B.; Zafar, N.; Zambanini, A.; Zavadskyi, V.; Zeng, S.; Zeng, T.; Zeng, Y.; Zhan, L.; Zhang, A.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, H.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, J.; Zhang, P.; Zhang, Q.; Zhang, S.; Zhang, S.; Zhang, T.; Zhang, X.; Zhang, X.; Zhang, X.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Y.; Zhang, Z.; Zhang, Z.; Zhao, F.; Zhao, J.; Zhao, R.; Zhao, S.; Zhao, T.; Zheng, D.; Zheng, H.; Zheng, M.; Zheng, Y.; Zhong, W.; Zhou, J.; Zhou, L.; Zhou, N.; Zhou, S.; Zhou, T.; Zhou, X.; Zhu, J.; Zhu, K.; Zhu, K.; Zhu, Z.; Zhuang, B.; Zhuang, H.; Zong, L.; Zou, J

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men