| 1. |
- Saegerman, Claude, et al.
(författare)
-
First Expert Elicitation of Knowledge on Possible Drivers of Observed Increasing Human Cases of Tick-Borne Encephalitis in Europe
- 2023
-
Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 15:3
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence.
|
|
| 2. |
- Sesink, Anouk, et al.
(författare)
-
The AsiDNA™ decoy mimicking DSBs protects the normal tissue from radiation toxicity through a DNA-PK/p53/p21-dependent G1/S arrest
- 2024
-
Ingår i: NAR Cancer. - 2632-8674. ; 6:1
-
Tidskriftsartikel (refereegranskat)abstract
- AsiDNA™, a cholesterol-coupled oligonucleotide mimicking double-stranded DNA breaks, was developed to sensitize tumour cells to radio- and chemotherapy. This drug acts as a decoy hijacking the DNA damage response. Previous studies have demonstrated that standalone AsiDNA™ administration is well tolerated with no additional adverse effects when combined with chemo- and/or radiotherapy. The lack of normal tissue complication encouraged further examination into the role of AsiDNA™ in normal cells. This research demonstrates the radioprotective properties of AsiDNA™. In vitro, AsiDNA™ induces a DNA-PK/p53/p21-dependent G1/S arrest in normal epithelial cells and fibroblasts that is absent in p53 deficient and proficient tumour cells. This cell cycle arrest improved survival after irradiation only in p53 proficient normal cells. Combined administration of AsiDNA™ with conventional radiotherapy in mouse models of late and early radiation toxicity resulted in decreased onset of lung fibrosis and increased intestinal crypt survival. Similar results were observed following FLASH radiotherapy in standalone or combined with AsiDNA™. Mechanisms comparable to those identified in vitro were detected both in vivo, in the intestine and ex vivo, in precision cut lung slices. Collectively, the results suggest that AsiDNA™ can partially protect healthy tissues from radiation toxicity by triggering a G1/S arrest in normal cells.
|
|
| 3. |
- van Meel, Evelien R., et al.
(författare)
-
Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children
- 2022
-
Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.
|
|
| 4. |
- Woodhead, Anna J., et al.
(författare)
-
Fishers perceptions of ecosystem service change associated with climate-disturbed coral reefs
- 2021
-
Ingår i: People and Nature. - : Wiley. - 2575-8314. ; 3:3, s. 639-657
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding ecosystem service change necessitates an understanding of the social and ecological dimensions of ecosystem services and how they contribute to the well-being of different people. These empirical research gaps persist across the tropics and in coastal environments, posing a challenge for small island states that depend on ecosystem services associated with near-shore ecosystems like coral reefs. Perception-based approaches allow for a rapid appraisal of what constitutes ecosystem service change, providing insights into why these changes matter, and how experiences of change differ between individuals. To capture perceptions of change in four ecosystem services associated with coral reefs (habitat, fishery, coastal protection and recreation services), we conducted 41 semi-structured interviews with coral reef fishers from Seychelles, where reef ecosystems have been severely impacted by climate disturbance. We gathered quantitative and qualitative data to understand (a) if and what changes in reef-associated ecosystem services have been perceived; (b) if fishers' characteristics are associated with differences in perceived changes and (c) which changes matter most in fishers' lives. Using a three-dimensional approach to well-being, we sought to identify whether reasons behind the importance of change connect to fishers' well-being. There have been noticeable changes across all four ecosystem services investigated. Changes include social, ecological and behavioural dynamics. Every fisher perceived at least one ecosystem service change but fishers who dive/snorkel or work from larger boats perceived a higher number of ecosystem services to have changed. Education, age and participation in snorkelling/diving were associated with fishers who identified changing habitat services as most important, whereas fishers from families with fewer livelihood alternatives and from smaller islands identified changing fishery services as most important. Different aspects of the subjective, relational and material dimensions of well-being were implicated in why changing services matter. Despite known ecological shifts in reef condition, this research is one of few studies to empirically show how changes across multiple ecosystem services are being perceived. These perceived changes are complex, engage both the social and ecological dimensions of services, and connect in multiple ways to how fishers feel about their lives, their relationships and material well-being. A free Plain Language Summary can be found within the Supporting Information of this article.
|
|
| 5. |
- Altincekic, Nadide, et al.
(författare)
-
Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies
- 2024
-
Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 19:2, s. 563-574
-
Tidskriftsartikel (refereegranskat)abstract
- The main protease Mpro, nsp5, of SARS-CoV-2 (SCoV2) is one of its most attractive drug targets. Here, we report primary screening data using nuclear magnetic resonance spectroscopy (NMR) of four different libraries and detailed follow-up synthesis on the promising uracil-containing fragment Z604 derived from these libraries. Z604 shows time-dependent binding. Its inhibitory effect is sensitive to reducing conditions. Starting with Z604, we synthesized and characterized 13 compounds designed by fragment growth strategies. Each compound was characterized by NMR and/or activity assays to investigate their interaction with Mpro. These investigations resulted in the four-armed compound 35b that binds directly to Mpro. 35b could be cocrystallized with Mpro revealing its noncovalent binding mode, which fills all four active site subpockets. Herein, we describe the NMR-derived fragment-to-hit pipeline and its application for the development of promising starting points for inhibitors of the main protease of SCoV2.
|
|
| 6. |
- Bastard, Paul, et al.
(författare)
-
Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
-
Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
|
|
| 7. |
- Berio, Fidji, et al.
(författare)
-
Husbandry conditions of spotted ratfish (Hydrolagus colliei, Chimaeriformes) in aquaria for successful embryonic development and long-term survival of juveniles
- 2024
-
Ingår i: Zoo Biology. - 0733-3188 .- 1098-2361. ; 43:2, s. 188-198
-
Tidskriftsartikel (refereegranskat)abstract
- The spotted ratfish Hydrolagus colliei is the most common holocephalan species exhibited in aquaria worldwide for introducing deep-sea environments and raising awareness of their conservation. However, little is known about the biology of H. colliei. Current practices in aquaria allow long-term survival of sexually mature H. colliei specimens; however, this species struggles to complete a reproductive cycle in captivity mostly because embryos do not reach the hatchling stage. The aquarists of Planet Ocean Montpellier (POM, France) have bred H. colliei for 15 years and recorded parameters suitable for this species' successful embryonic and post-embryonic development. POM aquarists now regularly record egg-laying events of H. colliei and use four tanks to incubate eggs and raise neonates, late hatchlings, early and intermediate juveniles, subadults, and sexually mature specimens. In this work we provide the first long-term biometric data on H. colliei from the hatchling to the subadult stage. We also report the biotic and abiotic parameters sufficient to breed H. colliei in aquaria. We finally describe the methods used to facilitate individual monitoring of specimens along the ontogeny and several pathologies identified in this species, their putative causes, and the corresponding treatments. This work highlights the importance of ex situ research and points to the valuable outcomes of collaborative efforts between aquaria and academia in deciphering the biology of species whose study in the wild remains challenging.
|
|
| 8. |
- Berne, Olivier, et al.
(författare)
-
PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
- 2022
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
-
Tidskriftsartikel (refereegranskat)abstract
- Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
|
|
| 9. |
- Capogna, Elettra, et al.
(författare)
-
Subtypes of brain change in aging and their associations with cognition and Alzheimer's disease biomarkers.
- 2024
-
Ingår i: bioRxiv : the preprint server for biology.
-
Tidskriftsartikel (refereegranskat)abstract
- Structural brain changes underly cognitive changes in older age and contribute to inter-individual variability in cognition. Here, we assessed how changes in cortical thickness, surface area, and subcortical volume, are related to cognitive change in cognitively unimpaired older adults using structural magnetic resonance imaging (MRI) data-driven clustering. Specifically, we tested (1) which brain structural changes over time predict cognitive change in older age (2) whether these are associated with core cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers phosphorylated tau (p-tau) and amyloid-β (Aβ42), and (3) the degree of overlap between clusters derived from different structural features. In total 1899 cognitively healthy older adults (50 - 93 years) were followed up to 16 years with neuropsychological and structural MRI assessments, a subsample of which (n = 612) had CSF p-tau and Aβ42 measurements. We applied Monte-Carlo Reference-based Consensus clustering to identify subgroups of older adults based on structural brain change patterns over time. Four clusters for each brain feature were identified, representing the degree of longitudinal brain decline. Each brain feature provided a unique contribution to brain aging as clusters were largely independent across modalities. Cognitive change and baseline cognition were best predicted by cortical area change, whereas higher levels of p-tau and Aβ42 were associated with changes in subcortical volume. These results provide insights into the link between changes in brain morphology and cognition, which may translate to a better understanding of different aging trajectories.
|
|
| 10. |
- Cavadino, Alana, et al.
(författare)
-
Signal Detection in EUROmediCAT : Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference
- 2021
-
Ingår i: Drug Safety. - : ADIS INT LTD. - 0114-5916 .- 1179-1942. ; 44:7, s. 765-785
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. Aims This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. Methods Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. Results EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. Conclusion EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.
|
|
