| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Hait, A. S., et al.
(författare)
-
Defects in LC3B2 and ATG4A underlie HSV2 meningitis and reveal a critical role for autophagy in antiviral defense in humans
- 2020
-
Ingår i: Science Immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 5:54
-
Tidskriftsartikel (refereegranskat)abstract
- Recurrent herpesvirus infections can manifest in different forms of disease, including cold sores, genital herpes, and encephalitis. There is an incomplete understanding of the genetic and immunological factors conferring susceptibility to recurrent herpes simplex virus 2 (HSV2) infection in the central nervous system (CNS). Here, we describe two adult patients with recurrent HSV2 lymphocytic Mollaret's meningitis that each carry a rare monoallelic variant in the autophagy proteins ATG4A or LC3B2. HSV2-activated autophagy was abrogated in patient primary fibroblasts, which also exhibited significantly increased viral replication and enhanced cell death. HSV2 antigen was captured in autophagosomes of infected cells, and genetic inhibition of autophagy by disruption of autophagy genes, including ATG4A and LC3B2, led to enhanced viral replication and cell death in primary fibroblasts and a neuroblastoma cell line. Activation of autophagy by HSV2 was sensitive to ultraviolet (UV) irradiation of the virus and inhibited in the presence of acyclovir, but HSV2-induced autophagy was independent of the DNA-activated STING pathway. Reconstitution of wild-type ATG4A and LC3B2 expression using lentiviral gene delivery or electroporation of in vitro transcribed mRNA into patient cells restored virus-induced autophagy and the ability to control HSV2 replication. This study describes a previously unknown link between defective autophagy and an inborn error of immunity that can lead to increased susceptibility to HSV2 infection, suggesting an important role for autophagy in antiviral immunity in the CNS.
|
|
| 6. |
|
|
| 7. |
- Bilde, M., et al.
(författare)
-
Saturation Vapor Pressures and Transition Enthalpies of Low-Volatility Organic Molecules of Atmospheric Relevance: From Dicarboxylic Acids to Complex Mixtures
- 2015
-
Ingår i: Chemical Reviews. - : American Chemical Society (ACS). - 0009-2665 .- 1520-6890. ; 115:10, s. 4115-4156
-
Forskningsöversikt (refereegranskat)abstract
- There are a number of techniques that can be used that differ in terms of whether they fundamentally probe the equilibrium and the temperature range over which they can be applied. The series of homologous, straight-chain dicarboxylic acids have received much attention over the past decade given their atmospheric relevance, commercial availability, and low saturation vapor pressures, thus making them ideal test compounds. Uncertainties in the solid-state saturation vapor pressures obtained from individual methodologies are typically on the order of 50-100%, but the differences between saturation vapor pressures obtained with different methods are approximately 1-4 orders of magnitude, with the spread tending to increase as the saturation vapor pressure decreases. Some of the dicarboxylic acids can exist with multiple solid-state structures that have distinct saturation vapor pressures. Furthermore, the samples on which measurements are performed may actually exist as amorphous subcooled liquids rather than solid crystalline compounds, again with consequences for the measured saturation vapor pressures, since the subcooled liquid phase will have a higher saturation vapor pressure than the crystalline solid phase. Compounds with equilibrium vapor pressures in this range will exhibit the greatest sensitivities in terms of their gas to particle partitioning to uncertainties in their saturation vapor pressures, with consequent impacts on the ability of explicit and semiexplicit chemical models to simulate secondary organic aerosol formation.
|
|
| 8. |
|
|
| 9. |
- Matuozzo, D, et al.
(författare)
-
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
-
Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
|
|
| 10. |
- Cederholm, Tommy, et al.
(författare)
-
Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition : A modified Delphi approach
- 2023
-
Ingår i: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 43:5, s. 10
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND : The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS : A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS : The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. Thepresence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION : Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.
|
|
