| 1. |
- Doublet, Vincent, et al.
(författare)
-
Unity in defence : honeybee workers exhibit conserved molecular responses to diverse pathogens
- 2017
-
Ingår i: BMC Genomics. - : BIOMED CENTRAL LTD. - 1471-2164. ; 18
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Organisms typically face infection by diverse pathogens, and hosts are thought to have developed specific responses to each type of pathogen they encounter. The advent of transcriptomics now makes it possible to test this hypothesis and compare host gene expression responses to multiple pathogens at a genome-wide scale. Here, we performed a meta-analysis of multiple published and new transcriptomes using a newly developed bioinformatics approach that filters genes based on their expression profile across datasets. Thereby, we identified common and unique molecular responses of a model host species, the honey bee (Apis mellifera), to its major pathogens and parasites: the Microsporidia Nosema apis and Nosema ceranae, RNA viruses, and the ectoparasitic mite Varroa destructor, which transmits viruses.Results: We identified a common suite of genes and conserved molecular pathways that respond to all investigated pathogens, a result that suggests a commonality in response mechanisms to diverse pathogens. We found that genes differentially expressed after infection exhibit a higher evolutionary rate than non-differentially expressed genes. Using our new bioinformatics approach, we unveiled additional pathogen-specific responses of honey bees; we found that apoptosis appeared to be an important response following microsporidian infection, while genes from the immune signalling pathways, Toll and Imd, were differentially expressed after Varroa/virus infection. Finally, we applied our bioinformatics approach and generated a gene co-expression network to identify highly connected (hub) genes that may represent important mediators and regulators of anti-pathogen responses.Conclusions: Our meta-analysis generated a comprehensive overview of the host metabolic and other biological processes that mediate interactions between insects and their pathogens. We identified key host genes and pathways that respond to phylogenetically diverse pathogens, representing an important source for future functional studies as well as offering new routes to identify or generate pathogen resilient honey bee stocks. The statistical and bioinformatics approaches that were developed for this study are broadly applicable to synthesize information across transcriptomic datasets. These approaches will likely have utility in addressing a variety of biological questions.
|
|
| 2. |
- Engel, Philipp, et al.
(författare)
-
The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions
- 2016
-
Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 7:2
-
Forskningsöversikt (refereegranskat)abstract
- As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the micro biome. The bee micro biome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee micro biome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.
|
|
| 3. |
- Haas, David W., et al.
(författare)
-
Pharmacogenetics of Between-Individual Variability in Plasma Clearance of Bedaquiline and Clofazimine in South Africa
- 2022
-
Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 226:1, s. 147-156
-
Tidskriftsartikel (refereegranskat)abstract
- In a cohort of patients treated for drug-resistant tuberculosis in South Africa, CYP3A5*3was associated with slower plasma bedaquiline clearance. Different CYP3A5*3minor allele frequencies among populations may help explain the more rapid bedaquiline clearance previously reported with African ancestry.Background Plasma bedaquiline clearance is reportedly more rapid with African ancestry. Our objective was to determine whether genetic polymorphisms explained between-individual variability in plasma clearance of bedaquiline, its M2 metabolite, and clofazimine in a cohort of patients treated for drug-resistant tuberculosis in South Africa.Methods Plasma clearance was estimated with nonlinear mixed-effects modeling. Associations between pharmacogenetic polymorphisms, genome-wide polymorphisms, and variability in clearance were examined using linear regression models.Results Of 195 cohort participants, 140 were evaluable for genetic associations. Among 21 polymorphisms selected based on prior genome-wide significant associations with any drug, rs776746 (CYP3A5*3) was associated with slower clearance of bedaquiline (P = .0017) but not M2 (P = .25). CYP3A5*3 heterozygosity and homozygosity were associated with 15% and 30% slower bedaquiline clearance, respectively. The lowest P value for clofazimine clearance was with VKORC1 rs9923231 (P = .13). In genome-wide analyses, the lowest P values for clearance of bedaquiline and clofazimine were with RFX4 rs76345012 (P = 6.4 x 10(-7)) and CNTN5 rs75285763 (P = 2.9 x 10(-8)), respectively.Conclusions Among South Africans treated for drug-resistant tuberculosis, CYP3A5*3 was associated with slower bedaquiline clearance. Different CYP3A5*3 frequencies among populations may help explain the more rapid bedaquiline clearance reported in Africans. Associations with RFX4 and CNTN5 are likely by chance alone.
|
|
| 4. |
- Lauque, Dominique, et al.
(författare)
-
Length-of-Stay in the Emergency Department and In-Hospital Mortality : A Systematic Review and Meta-Analysis
- 2022
-
Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
-
Forskningsöversikt (refereegranskat)abstract
- The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14-15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.
|
|
| 5. |
- Leta, Tesfaye H., et al.
(författare)
-
The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania
- 2023
-
Ingår i: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 416-425
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Den-mark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results — ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion — The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.
|
|
| 6. |
- Mlynczak, Martin G., et al.
(författare)
-
Energy transport in the thermosphere during the solar storms of April 2002
- 2005
-
Ingår i: Journal of Geophysical Research - Space Physics. - 2169-9380 .- 2169-9402. ; 110:A12
-
Tidskriftsartikel (refereegranskat)abstract
- The dramatic solar storm events of April 2002 deposited a large amount of energy into the Earth's upper atmosphere, substantially altering the thermal structure, the chemical composition, the dynamics, and the radiative environment. We examine the flow of energy within the thermosphere during this storm period from the perspective of infrared radiation transport and heat conduction. Observations from the SABER instrument on the TIMED satellite are coupled with computations based on the ASPEN thermospheric general circulation model to assess the energy flow. The dominant radiative response is associated with dramatically enhanced infrared emission from nitric oxide at 5.3 μm from which a total of ∼7.7 × 1023 ergs of energy are radiated during the storm. Energy loss rates due to NO emission exceed 2200 Kelvin per day. In contrast, energy loss from carbon dioxide emission at 15 μm is only ∼2.3% that of nitric oxide. Atomic oxygen emission at 63 μm is essentially constant during the storm. Energy loss from molecular heat conduction may be as large as 3.8% of the NO emission. These results confirm the “natural thermostat” effect of nitric oxide emission as the primary mechanism by which storm energy is lost from the thermosphere below 210 km.
|
|
| 7. |
- Mlynczak, Marty, et al.
(författare)
-
The natural thermostat of nitric oxide emission at 5.3 μm in the thermosphere observed during the solar storms of April 2002
- 2003
-
Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 30:21
-
Tidskriftsartikel (refereegranskat)abstract
- The Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) experiment on the Thermosphere-Ionosphere Mesosphere Energetics and Dynamics (TIMED) satellite observed the infrared radiative response of the thermosphere to the solar storm events of April 2002. Large radiance enhancements were observed at 5.3 μm, which are due to emission from the vibration-rotation bands of nitric oxide (NO). The emission by NO is indicative of the conversion of solar energy to infrared radiation within the atmosphere and represents a "natural thermostat" by which heat and energy are efficiently lost from the thermosphere to space and to the lower atmosphere. We describe the SABER observations at 5.3 μm and their interpretation in terms of energy loss. The infrared enhancements remain only for a few days, indicating that such perturbations to the thermospheric state, while dramatic, are short-lived. Copyright 2003 by the American Geophysical Union.
|
|
| 8. |
- Wu, Lijuan, et al.
(författare)
-
The Association between Emergency Department Length of Stay and In-Hospital Mortality in Older Patients Using Machine Learning : An Observational Cohort Study
- 2023
-
Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:14
-
Tidskriftsartikel (refereegranskat)abstract
- The association between emergency department (ED) length of stay (EDLOS) with in-hospital mortality (IHM) in older patients remains unclear. This retrospective study aims to delineate the relationship between EDLOS and IHM in elderly patients. From the ED patients (n = 383,586) who visited an urban academic tertiary care medical center from January 2010 to December 2016, 78,478 older patients (age ≥60 years) were identified and stratified into three age subgroups: 60-74 (early elderly), 75-89 (late elderly), and ≥90 years (longevous elderly). We applied multiple machine learning approaches to identify the risk correlation trends between EDLOS and IHM, as well as boarding time (BT) and IHM. The incidence of IHM increased with age: 60-74 (2.7%), 75-89 (4.5%), and ≥90 years (6.3%). The best area under the receiver operating characteristic curve was obtained by Light Gradient Boosting Machine model for age groups 60-74, 75-89, and ≥90 years, which were 0.892 (95% CI, 0.870-0.916), 0.886 (95% CI, 0.861-0.911), and 0.838 (95% CI, 0.782-0.887), respectively. Our study showed that EDLOS and BT were statistically correlated with IHM (p < 0.001), and a significantly higher risk of IHM was found in low EDLOS and high BT. The flagged rate of quality assurance issues was higher in lower EDLOS ≤1 h (9.96%) vs. higher EDLOS 7 h
|
|
