Summary
Current treatment for chronic hepatitis B infection (CHB) consists of interferon‐based therapy. However, for unknown reasons, a large proportion of patients with CHB do not respond to this ...treatment. Hence, there is a pressing need to establish response markers to select patients who will benefit from therapy and to spare potential nonresponders from unnecessary side effects of antiviral therapy. Here, we assessed whether HLA‐C and KIR genotypes were associated with treatment outcome for CHB. Twelve SNPs in or near the HLA‐C gene were genotyped in 86 CHB patients (41 HBeAg positive; 45 HBeAg negative) treated with peginterferon alfa‐2a + adefovir. Genotyping of killer immunoglobin‐like receptors (KIRs) was performed by SSP‐PCR. One SNP in HLA‐C (rs2308557) was significantly associated with combined response in HBeAg‐positive CHB patients (P = 0.003). This SNP is linked to the HLA‐C group C1 or C2 classification, which controls KIR binding. The combination of KIR2DL1 with its ligand HLA‐C2 was observed significantly more often in HBeAg‐positive patients with a combined response (13/14) than in nonresponders (11/27, P = 0.001). Patients with the KIR2DL1/C2 genotype had significantly higher baseline ALT levels (136 vs 50 U/L, P = 0.002) than patients without this combination. Furthermore, KIR2DL1‐C2 predicted response independent of HBV genotype and ALT at baseline. HLA‐C and KIR genotype is strongly associated with response in HBeAg‐positive CHB patients treated with interferon‐based therapy. In combination with other known response markers, HLA‐C/KIR genotype could enable the selection of patients more likely to respond to interferon‐based therapy.
Saproxylic organisms are among the most threatened species in Europe and constitute a major conservation problem because they depend on the most important forestry product – dead wood. Diversity of ...fungal and bryophyte communities occurring on dead beech trees was analyzed in five European countries (Slovenia, Hungary, The Netherlands, Belgium and Denmark) considering tree level species richness (TLSR), country level species richness (CLSR), frequency distributions of species, occurrence of threatened species and relations between TLSR and decay stage, tree size and countries. Altogether 1009 trees were inventoried in 19 beech dominated forest reserves.
The number of fungi in the full dataset was approximately three times larger (456 versus 161 species) and the proportion of low frequent species was higher than among bryophytes. The species richness of bryophytes and fungi was significantly different among countries considering both TLSR and CLSR. In addition the diversity patterns deviated considerably between the two groups of organisms. Slovenian sites appeared to be biodiversity hotspots for bryophytes characterized by high TLSR and CLSR and a high fraction of threatened species. Hungarian sites had somewhat lower bryophyte diversity, while the Atlantic region had deteriorated assemblages. Fungal species richness was very high in Denmark, but the Hungarian and Slovenian sites were richer in threatened and low frequency species. Tree size was better able to explain variation in TLSR in both organism groups than decay stage. TLSR was found to vary significantly between countries but the difference was most considerable in the case of bryophytes.
The diversity patterns of both organism groups along the investigated geographical gradient appear to be influenced by both climatic and management related factors (forest history, dead wood availability and continuity, habitat fragmentation). There is no doubt that an increase in the abundance of dead wood in European beech forests will benefit diversity of saproxylic fungi and bryophytes, especially if a continuous presence of large diameter logs are secured within individual stands.
The CLIC Tracker Detector (CLICTD) is a monolithic pixel sensor. It is fabricated in a 180 nm CMOS imaging process, modified with an additional deep low-dose n-type implant to obtain full lateral ...depletion. The sensor features a small collection diode, which is essential for achieving a low input capacitance. The CLICTD sensor was designed as a technology demonstrator in the context of the tracking detector studies for the Compact Linear Collider (CLIC). Its design characteristics are of broad interest beyond CLIC, for HL-LHC tracking detector upgrades. It is produced in two different pixel flavours: one with a continuous deep n-type implant, and one with a segmented n-type implant to ensure fast charge collection. The pixel matrix consists of 16 × 128 detection channels measuring 300μm×30μm. Each detection channel is segmented into eight sub-pixels to reduce the amount of digital circuity while maintaining a small collection electrode pitch. This paper presents the characterisation results of the CLICTD sensor in a particle beam. The different pixel flavours are compared in detail by using the simultaneous time-over-threshold and time-of-arrival measurement functionalities. Most notably, a spatial resolution down to (4.6±0.2)μm is measured. A time resolution down to (5.8±0.1)ns is observed, after applying an offline time-walk correction using the pixel-charge information. The hit detection efficiency is found to be well above 99.7% for thresholds of the order of several hundred electrons.
To study the pH preference of epiphytic lichens, the bark pH of
Fraxinus, Tilia, Quercus and Ulmus trees in an urban environment was measured using a flat surface electrode. The total number of trees ...was 253. A survey was made of the lichens in a 40 × 40 cm quadrat surrounding the pH measurement point. Our data analysis using multivariate and univariate statistical techniques indicates that the tree species is the most important factor influencing lichen colonisation, and that bark pH alone is of less importance. We hypothesize that the changed pollution climate, with strong decreases in both sulphur dioxide and ammonia concentrations over the past two decades and a concomitant general increase in bark pH, has made epiphytes less sensitive to pH.
Tree species, rather than bark pH determines the occurrence of acidophytes and nitrophytes on trees.
•BNT162b2 or mRNA-1273 induced antibodies are not affected by 25(OH)D concentration.•BNT162b2 induced T cell responses are not associated with 25(OH)D concentration.•Our findings do not support ...vitamin D optimization preceding SARS-CoV-2 vaccination.
To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25OHD) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination.
In this prospective cohort study, blood samples were collected from 98 SARS-CoV-2 naive health care workers (HCW) receiving the first two doses of either BNT162b2 or mRNA-1273 in 2021. Wild-type spike (S) protein binding and neutralizing antibodies were determined approximately three weeks after the first dose and four to five weeks after the second dose. Antigen specific T-cells and functionality (proliferative response and interferon gamma IFN-γ release) were determined in 18 participants four weeks after the second dose of BNT162b2. We studied the association between 25(OH)D concentrations, which were determined prior to vaccination, and humoral and cellular immune responses following vaccination.
We found no association between 25(OH)D concentrations (median 55.9 nmol/L IQR 40.5–69.8) and binding or neutralizing antibody titers after complete vaccination (fold change of antibody titers per 10 nmol/L 25(OH)D increase: 0.98 95% CI 0.93–1.04 and 1.03 95% CI: 0.96–1.11, respectively), adjusted for age, sex and type of mRNA vaccine. Subsequently, continuous 25(OH)D concentrations were divided into commonly used clinical categories (<25 nmol/L n = 6, 6%, 25–49 nmol/L n = 33, 34%, 50–75 nmol/L n = 37, 38% and ≥75 nmol/L n = 22, 22%), but no association with the humoral immune response following vaccination was found. Also, 25(OH)D concentrations were not associated with the SARS-CoV-2 specific T cell response.
No association was found between 25(OH)D concentrations and the humoral or cellular immune response following mRNA vaccination against SARS-CoV-2. Based on our findings there is no rationale to advise vitamin D optimization preceding SARS-CoV-2 vaccination in HCW with moderate vitamin D status.
Healthy individuals carry a constant number of Epstein-Barr virus-infected B cells in the peripheral blood over time. Here, we show that interindividual differences in Epstein-Barr virus DNA levels ...are maintained after HIV infection, providing evidence for the existence of an individual Epstein-Barr virus setpoint. Immune activation may contribute to the increase in this setpoint after human immunodeficiency virus seroconversion.
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