| 1. |
|
|
| 2. |
- Echelmeier, A., et al.
(författare)
-
Segmented flow generator for serial crystallography at the European X-ray free electron laser
- 2020
-
Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.
|
|
| 3. |
|
|
| 4. |
- Wiedorn, Max O., et al.
(författare)
-
Megahertz serial crystallography
- 2018
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a beta-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.
|
|
| 5. |
- Vazquez, SE, et al.
(författare)
-
Autoantibody discovery across monogenic, acquired, and COVID19-associated autoimmunity with scalable PhIP-Seq
- 2022
-
Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Phage Immunoprecipitation-Sequencing (PhIP-Seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-Seq for autoantigen discovery, including our previous work (Vazquez et al. 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki Disease (KD), Multisystem Inflammatory Syndrome in Children (MIS-C), and finally, mild and severe forms of COVID19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as PDYN in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in 2 patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-Seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID19, including the endosomal protein EEA1. Together, scaled PhIP-Seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
|
|
| 6. |
- Duncanson, Laura, et al.
(författare)
-
Aboveground biomass density models for NASA's Global Ecosystem Dynamics Investigation (GEDI) lidar mission
- 2022
-
Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257 .- 1879-0704. ; 270
-
Tidskriftsartikel (refereegranskat)abstract
- NASA's Global Ecosystem Dynamics Investigation (GEDI) is collecting spaceborne full waveform lidar data with a primary science goal of producing accurate estimates of forest aboveground biomass density (AGBD). This paper presents the development of the models used to create GEDI's footprint-level (~25 m) AGBD (GEDI04_A) product, including a description of the datasets used and the procedure for final model selection. The data used to fit our models are from a compilation of globally distributed spatially and temporally coincident field and airborne lidar datasets, whereby we simulated GEDI-like waveforms from airborne lidar to build a calibration database. We used this database to expand the geographic extent of past waveform lidar studies, and divided the globe into four broad strata by Plant Functional Type (PFT) and six geographic regions. GEDI's waveform-to-biomass models take the form of parametric Ordinary Least Squares (OLS) models with simulated Relative Height (RH) metrics as predictor variables. From an exhaustive set of candidate models, we selected the best input predictor variables, and data transformations for each geographic stratum in the GEDI domain to produce a set of comprehensive predictive footprint-level models. We found that model selection frequently favored combinations of RH metrics at the 98th, 90th, 50th, and 10th height above ground-level percentiles (RH98, RH90, RH50, and RH10, respectively), but that inclusion of lower RH metrics (e.g. RH10) did not markedly improve model performance. Second, forced inclusion of RH98 in all models was important and did not degrade model performance, and the best performing models were parsimonious, typically having only 1-3 predictors. Third, stratification by geographic domain (PFT, geographic region) improved model performance in comparison to global models without stratification. Fourth, for the vast majority of strata, the best performing models were fit using square root transformation of field AGBD and/or height metrics. There was considerable variability in model performance across geographic strata, and areas with sparse training data and/or high AGBD values had the poorest performance. These models are used to produce global predictions of AGBD, but will be improved in the future as more and better training data become available.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Miyake, F., et al.
(författare)
-
A Single-Year Cosmic Ray Event at 5410 BCE Registered in 14C of Tree Rings
- 2021
-
Ingår i: Geophysical Research Letters. - 0094-8276. ; 48:11
-
Tidskriftsartikel (refereegranskat)abstract
- The annual 14C data in tree rings is an outstanding proxy for uncovering extreme solar energetic particle (SEP) events in the past. Signatures of extreme SEP events have been reported in 774/775 CE, 992/993 CE, and ∼660 BCE. Here, we report another rapid increase of 14C concentration in tree rings from California, Switzerland, and Finland around 5410 BCE. These 14C data series show a significant increase of ∼6‰ in 5411–5410 BCE. The signature of 14C variation is very similar to the confirmed three SEP events and points to an extreme short-term flux of cosmic ray radiation into the atmosphere. The rapid 14C increase in 5411/5410 BCE rings occurred during a period of high solar activity and 60 years after a grand 14C excursion during 5481–5471 BCE. The similarity of our 14C data to previous events suggests that the origin of the 5410 BCE event is an extreme SEP event.
|
|
| 10. |
- Rodriguez-Castaneda, Genoveva, et al.
(författare)
-
Tropical forests are not flat : how mountains affect herbivore diversity
- 2010
-
Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 13:11, s. 1348-1357
-
Tidskriftsartikel (refereegranskat)abstract
- Ecologists debate whether tropical insect diversity is better explained by higher plant diversity or by host plant species specialization. However, plant-herbivore studies are primarily based in lowland rainforests (RF) thus excluding topographical effects on biodiversity. We examined turnover in Eois (Geometridae) communities across elevation by studying elevational transects in Costa Rica and Ecuador. We found four distinct Eois communities existing across the elevational gradients. Herbivore diversity was highest in montane forests (MF), whereas host plant diversity was highest in lowland RF. This was correlated with higher specialization and species richness of Eois/host plant species we found in MF. Based on these relationships, Neotropical Eois richness was estimated to range from 313 (only lowland RF considered) to 2034 (considering variation with elevation). We conclude that tropical herbivore diversity and diet breadth covary significantly with elevation and urge the inclusion of montane ecosystems in host specialization and arthropod diversity estimates.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Usoskin, Ilya, et al.
(författare)
-
Extreme Solar Events : Setting up a Paradigm
- 2023
-
Ingår i: Space Science Reviews. - 0038-6308. ; 219:8
-
Forskningsöversikt (refereegranskat)abstract
- The Sun is magnetically active and often produces eruptive events on different energetic and temporal scales. Until recently, the upper limit of such events was unknown and believed to be roughly represented by direct instrumental observations. However, two types of extreme events were discovered recently: extreme solar energetic particle events on the multi-millennial time scale and super-flares on sun-like stars. Both discoveries imply that the Sun might rarely produce events, called extreme solar events (ESE), whose energy could be orders of magnitude greater than anything we have observed during recent decades. During the years following these discoveries, great progress has been achieved in collecting observational evidence, uncovering new events, making statistical analyses, and developing theoretical modelling. The ESE paradigm lives and is being developed. On the other hand, many outstanding questions still remain open and new ones emerge. Here we present an overview of the current state of the art and the forming paradigm of ESE from different points of view: solar physics, stellar–solar projections, cosmogenic-isotope data, modelling, historical data, as well as terrestrial, technological and societal effects of ESEs. Special focus is paid to open questions and further developments. This review is based on the joint work of the International Space Science Institute (ISSI) team #510 (2020–2022).
|
|
| 14. |
- Vazquez, Sara E., et al.
(författare)
-
Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq
- 2022
-
Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls. Here, we develop and validate a high throughput extension of PhIP-seq in various etiologies of autoimmune and inflammatory diseases, including APS1, IPEX, RAG1/2 deficiency, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and finally, mild and severe forms of COVID-19. We demonstrate that these scaled datasets enable machine-learning approaches that result in robust prediction of disease status, as well as the ability to detect both known and novel autoantigens, such as prodynorphin (PDYN) in APS1 patients, and intestinally expressed proteins BEST4 and BTNL8 in IPEX patients. Remarkably, BEST4 antibodies were also found in two patients with RAG1/2 deficiency, one of whom had very early onset IBD. Scaled PhIP-seq examination of both MIS-C and KD demonstrated rare, overlapping antigens, including CGNL1, as well as several strongly enriched putative pneumonia-associated antigens in severe COVID-19, including the endosomal protein EEA1. Together, scaled PhIP-seq provides a valuable tool for broadly assessing both rare and common autoantigen overlap between autoimmune diseases of varying origins and etiologies.
|
|
| 15. |
- Zenker, Mauricio M., et al.
(författare)
-
Systematics and origin of moths in the subfamily Arctiinae (Lepidoptera, Erebidae) in the Neotropical region
- 2017
-
Ingår i: Zoologica Scripta. - : Wiley. - 0300-3256 .- 1463-6409. ; 46:3, s. 348-362
-
Tidskriftsartikel (refereegranskat)abstract
- The availability of standard protocols to obtain DNA sequences has allowed the inference of phylogenetic Hypotheses for many taxa, including moths. We here have inferred a phylogeny using maximum-Likelihood and Bayesian approaches for a species-rich group of moths (Erebidae, Arctiinae), with strong emphasis on Neotropical genera collected in different field campaigns in the Atlantic Forest of Brazil, eastern Amazon and southern Ecuador. A total of 277 species belonging to 246 genera were included in the analysis. Our main objectives were to shed light on the relationships between suprageneric groups, especially subtribes, and hypothesize colonization events in and out of the Neotropics. The monophyly of Arctiinae and its four tribes (Lithosiini, Amerilini, Syntomini and Arctiini) was recovered in the ML and Bayesian trees. Three Lithosiini subtribes previously found and two additional species groups were recovered monophyletic in both phylogenetic estimation methods. In Arctiini, the monophyly of Spilosomina and Arctiina was highly supported in the ML and Bayesian trees, but the monophyly of Ctenuchina and Echromiina was weakly supported in the ML tree and absent in the Bayesian tree; the remaining subtribes were paraphyletic and, in the case of Phageopterina, formed several species groups. The mapping of species occurrence in our ML tree suggests that Arctiinae have an Old World origin and that the Neotropical region was colonized at least six times independently. Our analysis also suggests that a number of species that occur in Neotropical and other zoogeographic regions may have originated in the Neotropics, although further taxon sampling is required to support this hypothesis. To our knowledge, this is the first time that a highly speciose group of tropical moths is well covered in a phylogeny, and it seems plausible that the results reported here may be extendable to other species-rich tropical undersampled moth taxa.
|
|
