| 1. |
|
|
| 2. |
- Namkoong, H, et al.
(author)
-
DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
-
Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
|
|
| 3. |
|
|
| 4. |
- Wang, QBS, et al.
(author)
-
The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
-
Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
|
|
| 5. |
- Adare, A., et al.
(author)
-
Direct photon production in d+Au collisions at root s(NN)=200 GeV
- 2013
-
In: Physical Review C (Nuclear Physics). - 0556-2813. ; 87:5
-
Journal article (peer-reviewed)abstract
- Direct photons have been measured in root s(NN) = 200 GeV d + Au collisions at midrapidity. A wide p(T) range is covered by measurements of nearly real virtual photons (1 < p(T) < 6 GeV/c) and real photons (5 < p(T) < 16 GeV/c). The invariant yield of the direct photons in d + Au collisions over the scaled p + p cross section is consistent with unity. Theoretical calculations assuming standard cold-nuclear-matter effects describe the data well for the entire p(T) range. This indicates that the large enhancement of direct photons observed in Au + Au collisions for 1.0 < p(T) < 2.5 GeV/c is attributable to a source other than the initial-state nuclear effects.
|
|
| 6. |
- Abelev, B., et al.
(author)
-
Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at root s=7 TeV
- 2012
-
In: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 86:11
-
Journal article (peer-reviewed)abstract
- The differential production cross section of electrons from semileptonic heavy-flavor hadron decays has been measured at midrapidity (\y\ < 0.5) in proton-proton collisions at root s = 7 TeV with ALICE at the LHC. Electrons were measured in the transverse momentum range 0.5 < p(t) < 8 GeV/c. Predictions from a fixed-order perturbative QCD calculation with next-to-leading-log resummation agree with the data within the theoretical and experimental uncertainties. DOI: 10.1103/PhysRevD.86.112007
|
|
| 7. |
- Abelev, B., et al.
(author)
-
Net-Charge Fluctuations in Pb-Pb Collisions at root s(NN)=2.76 TeV
- 2013
-
In: Physical Review Letters. - 1079-7114. ; 110:15
-
Journal article (peer-reviewed)abstract
- We report the first measurement of the net-charge fluctuations in Pb-Pb collisions at root s(NN) = 2.76 TeV, measured with the ALICE detector at the CERN Large Hadron Collider. The dynamical fluctuations per unit entropy are observed to decrease when going from peripheral to central collisions. An additional reduction in the amount of fluctuations is seen in comparison to the results from lower energies. We examine the dependence of fluctuations on the pseudorapidity interval, which may account for the dilution of fluctuations during the evolution of the system. We find that the fluctuations at the LHC are smaller compared to the measurements at the BNL Relativistic Heavy Ion Collider, and as such, closer to what has been theoretically predicted for the formation of a quark-gluon plasma. DOI: 10.1103/PhysRevLett.110.152301
|
|
| 8. |
- Aamodt, K., et al.
(author)
-
Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
- 2010
-
In: Journal of Instrumentation. - 1748-0221. ; 5
-
Conference paper (peer-reviewed)abstract
- ALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 mu m in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10(5) charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.
|
|
| 9. |
- Aamodt, K., et al.
(author)
-
Charged-particle multiplicity measurement in proton-proton collisions at root s=0.9 and 2.36 TeV with ALICE at LHC
- 2010
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:1-2, s. 89-108
-
Journal article (peer-reviewed)abstract
- Charged-particle production was studied in proton-proton collisions collected at the LHC with the ALICE detector at centre-of-mass energies 0.9 TeV and 2.36 TeV in the pseudorapidity range vertical bar eta vertical bar < 1.4. In the central region (vertical bar eta vertical bar < 0.5), at 0.9 TeV, we measure charged-particle pseudo-rapidity density dN(ch)/d eta = 3.02 +/- 0.01(stat.)(-0.05)(+0.08)(syst.) for inelastic interactions, and dN(ch)/d eta = 3.58 +/- 0.01 (stat.)(-0.12)(+0.12)(syst.) for non-single-diffractive interactions. At 2.36 TeV, we find dN(ch)/d eta = 3.77 +/- 0.01(stat.)(-0.12)(+0.25)(syst.) for inelastic, and dN(ch)/d eta = 4.43 +/- 0.01(stat.)(-0.12)(+0.17)(syst.) for non-single-diffractive collisions. The relative increase in charged-particle multiplicity from the lower to higher energy is 24.7% +/- 0.5%(stat.)(-2.8)(+5.7)%(syst.) for inelastic and 23.7% +/- 0.5%(stat.)(-1.1)(+4.6)%(syst.) for non-single-diffractive interactions. This increase is consistent with that reported by the CMS collaboration for non-single-diffractive events and larger than that found by a number of commonly used models. The multiplicity distribution was measured in different pseudorapidity intervals and studied in terms of KNO variables at both energies. The results are compared to proton-antiproton data and to model predictions.
|
|
| 10. |
- Aamodt, K., et al.
(author)
-
Charged-particle multiplicity measurement in proton-proton collisions at root s=7 TeV with ALICE at LHC
- 2010
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:3-4, s. 345-354
-
Journal article (peer-reviewed)abstract
- The pseudorapidity density and multiplicity distribution of charged particles produced in proton-proton collisions at the LHC, at a centre-of-mass energy root s = 7 TeV, were measured in the central pseudorapidity region vertical bar eta vertical bar < 1. Comparisons are made with previous measurements at root s = 0.9 TeV and 2.36 TeV. At root s = 7 TeV, for events with at least one charged particle in |eta vertical bar| < 1, we obtain dN(ch)/d eta = 6.01 +/- 0.01(stat.)(-0.12)(+0.20) (syst.). This corresponds to an increase of 57.6%+/-0.4%(stat.)(-1.8%)(+3.6) (syst.) relative to collisions at 0.9 TeV, significantly higher than calculations from commonly used models. The multiplicity distribution at 7 TeV is described fairly well by the negative binomial distribution.
|
|
