Publications by authors named "Mats Nilsson"

373 Publications

Global CO fertilization of Sphagnum peat mosses via suppression of photorespiration during the twentieth century.

Sci Rep 2021 12 31;11(1):24517. Epub 2021 Dec 31.

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.

Natural peatlands contribute significantly to global carbon sequestration and storage of biomass, most of which derives from Sphagnum peat mosses. Atmospheric CO levels have increased dramatically during the twentieth century, from 280 to > 400 ppm, which has affected plant carbon dynamics. Net carbon assimilation is strongly reduced by photorespiration, a process that depends on the CO to O ratio. Here we investigate the response of the photorespiration to photosynthesis ratio in Sphagnum mosses to recent CO increases by comparing deuterium isotopomers of historical and contemporary Sphagnum tissues collected from 36 peat cores from five continents. Rising CO levels generally suppressed photorespiration relative to photosynthesis but the magnitude of suppression depended on the current water table depth. By estimating the changes in water table depth, temperature, and precipitation during the twentieth century, we excluded potential effects of these climate parameters on the observed isotopomer responses. Further, we showed that the photorespiration to photosynthesis ratio varied between Sphagnum subgenera, indicating differences in their photosynthetic capacity. The global suppression of photorespiration in Sphagnum suggests an increased net primary production potential in response to the ongoing rise in atmospheric CO, in particular for mire structures with intermediate water table depths.
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http://dx.doi.org/10.1038/s41598-021-02953-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720097PMC
December 2021

Global maps of soil temperature.

Glob Chang Biol 2021 Dec 29. Epub 2021 Dec 29.

Department of Physical Geography and Ecosystem Science, Lund University, Sölvegatan 12, 223 62 Lund, Sweden.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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http://dx.doi.org/10.1111/gcb.16060DOI Listing
December 2021

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects.

Am J Physiol Regul Integr Comp Physiol 2022 Feb 15;322(2):R112-R122. Epub 2021 Dec 15.

Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.
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http://dx.doi.org/10.1152/ajpregu.00220.2021DOI Listing
February 2022

A Novel Multi-Ingredient Supplement Activates a Browning Program in White Adipose Tissue and Mitigates Weight Gain in High-Fat Diet-Fed Mice.

Nutrients 2021 Oct 22;13(11). Epub 2021 Oct 22.

Department of Pediatrics, Faculty of Health Sciences, McMaster University Medical Centre (MUMC), 1200 Main St. W, Hamilton, ON L8N 3Z5, Canada.

We investigated the effects of a novel multi-ingredient supplement comprised of polyphenol antioxidants and compounds known to facilitate mitochondrial function and metabolic enhancement (ME) in a mouse model of obesity. In this study, 6-week-old male C57/BL6J mice were placed on a high-fat diet (HFD; ~60% fat) for 6 weeks, with subsequent allocation into experimentalgroups for 4 weeks: HFD control, HFD + ME10 (10 components), HFD + ME7 (7 components), HFD + ME10 + EX, HFD + EX (where '+EX' animals exercised 3 days/week), and chow-fed control. After the intervention, HFD control animals had significantly greater body weight and fat mass. Despite the continuation of HFD, animals supplemented with multi-ingredient ME or who performed exercise training showed an attenuation of fat mass and preservation of lean body mass, which was further enhanced when combined (ME+EX). ME supplementation stimulated the upregulation of white and brown adipose tissue mRNA transcripts associated with mitochondrial biogenesis, browning, fatty acid transport, and fat metabolism. In WAT depots, this was mirrored by mitochodrial oxidative phosphorylation (OXPHOS) protein expression, and increased in vivo fat oxidation measured via CLAMS. ME supplementation also decreased systemic and local inflammation markers. Herein, we demonstrated that novel multi-ingredient nutritional supplements induced significant fat loss independent of physical activity while preserving muscle mass in obese mice. Mechanistically, these MEs appear to act by inducing a browning program in white adipose tissue and decreasing other pathophysiological impairments associated with obesity, including mitochondrial respiration alterations induced by HFD.
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http://dx.doi.org/10.3390/nu13113726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623014PMC
October 2021

Rolling Circle Amplification in Integrated Microsystems: An Uncut Gem toward Massively Multiplexed Pathogen Diagnostics and Genotyping.

Acc Chem Res 2021 11 12;54(21):3979-3990. Epub 2021 Oct 12.

Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, 17165 Solna, Sweden.

The development of robust methods allowing the precise detection of specific nucleic acid sequences is of major societal relevance, paving the way for significant advances in biotechnology and biomedical engineering. These range from a better understanding of human disease at a molecular level, allowing the discovery and development of novel biopharmaceuticals and vaccines, to the improvement of biotechnological processes providing improved food quality and safety, efficient green fuels, and smart textiles. Among these applications, the significance of pathogen diagnostics as the main focus of this Account has become particularly clear during the recent SARS-CoV-2 pandemic. In this context, while RT-PCR is the gold standard method for unambiguous detection of genetic material from pathogens, other isothermal amplification alternatives circumventing rapid heating-cooling cycles up to ∼95 °C are appealing to facilitate the translation of the assay into point-of-care (PoC) analytical platforms. Furthermore, the possibility of routinely multiplexing the detection of tens to hundreds of target sequences with single base pair specificity, currently not met by state-of-the-art methods available in clinical laboratories, would be instrumental along the path to tackle emergent viral variants and antimicrobial resistance genes. Here, we advocate that padlock probes (PLPs), first reported by Nilsson et al. in 1994, coupled with rolling circle amplification (RCA), termed here as PLP-RCA, is an underexploited technology in current arena of isothermal nucleic acid amplification tests (NAATs) providing an unprecedented degree of multiplexing, specificity, versatility, and amenability to integration in miniaturized PoC platforms. Furthermore, the intrinsically digital amplification of PLP-RCA retains spatial information and opens new avenues in the exploration of pathogenesis with spatial multiomics analysis of infected cells and tissue.The Account starts by introducing PLP-RCA in a nutshell focusing individually on the three main assay steps, namely, (1) PLP design and ligation mechanism, (2) RCA after probe ligation, and (3) detection of the RCA products. Each subject is touched upon succinctly but with sufficient detail for the reader to appreciate some assay intricacies and degree of versatility depending on the analytical challenge at hand. After familiarizing the reader with the method, we discuss specific examples of research in our group and others using PLP-RCA for viral, bacterial, and fungal diagnostics in a variety of clinical contexts, including the genotyping of antibiotic resistance genes and viral subtyping. Then, we dissect key developments in the miniaturization and integration of PLP-RCA to minimize user input, maximize analysis throughput, and expedite the time to results, ultimately aiming at PoC applications. These developments include molecular enrichment for maximum sensitivity, spatial arrays to maximize analytical throughput, automation of liquid handling to streamline the analytical workflow in miniaturized devices, and seamless integration of signal transduction to translate RCA product titers (and ideally spatial information) into a readable output. Finally, we position PLP-RCA in the current landscape of NAATs and furnish a systematic Strengths, Weaknesses, Opportunities and Threats analysis to shine light upon unpolished edges to uncover the gem with potential for ubiquitous, precise, and unbiased pathogen diagnostics.
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http://dx.doi.org/10.1021/acs.accounts.1c00438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567418PMC
November 2021

A novel belowground in-situ gas labeling approach: CH oxidation in deep peat using passive diffusion chambers and C excess.

Sci Total Environ 2022 Feb 20;806(Pt 1):150457. Epub 2021 Sep 20.

Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, Umeå, Sweden.

In-vitro incubation of environmental samples is a common approach to estimate CH oxidation potential. Here we developed and verified an in-situ method utilizing passive diffusion chambers (PDC, silicone tubes) to deliver C-labeled CH into peat for the determination of the CH oxidation potential based on C excess of CO. To target CH oxidation under semi-aerobic and anaerobic conditions, we installed 20 PDCs (30 ml volume) below the water table in profiles from 35-cm to 2-m depths of a peatland in north-eastern Sweden in July 2017 using a peat auger. C-labeled CH was injected into PDCs through tubing twice during 12 days (day 0 and 6) and samples were collected at days 1, 3, 6, 8 and 11. Background (non-labeled) δC of CO ranged from -7.3 (35 cm) to +5.7‰ (200 cm) with depth. These δC values rose to +110 and + 204‰ after the CH injection. The estimated CH-derived C in CO was the lowest at the bottom of the profile (0.3 μmol L), whereas the maximum was at 100 cm (6.1 μmol L) at five days after the second labeling. This corresponded to 1.5-7.2% of the total CH pool to be oxidized, depending on depth. This novel approach with belowground in-situ C labeling of gases demonstrated the suitability of tracing the transformations of these gases in soil depth by PDCs and for the first time verified the in-situ occurrence of a deep-peat CH oxidation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150457DOI Listing
February 2022

Survival Time among Young and Old Breast Cancer Patients in Relation to Circulating Blood-Based Biomarkers, Acute Radiation Skin Reactions, and Tumour Recurrence.

Oncology 2021 3;99(11):740-746. Epub 2021 Sep 3.

Department of Oncology, Ryhov Hospital, Jönköping, Sweden.

Introduction: It has been suggested that age could influence the treatment-induced side effects and survival time of cancer patients. The influence of age on blood-based biomarkers, acute radiation skin reactions (ARSRs), and survival time of breast cancer patients was analysed.

Materials And Methods: Two hundred ninety-three individuals, 119 breast cancer patients, and 174 healthy blood donors were included.

Results: Before radiotherapy (RT), decreased levels of lymphocytes, interleukin 2, platelet-derived growth factors, and tumour necrosis factor but increased levels of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, C-reactive protein, and macrophage inflammatory protein 1b (MIP1b) were detected in the patient group. All of the patients developed ARSRs and intensity of ARSRs was inversely related to the MIP1b level before RT. Fifteen out of 119 (13%) patients deceased during follow-up time. No influence of age (≤50 compared to >50 years) on survival time was detected (p = 0.442). Tumour recurrence, found in 11 out of 119 (9%) patients, had impact on survival time of these patients (p < 0.001).

Conclusions: The level of circulating MIP1b before RT was associated with intensity of ARSRs. Tumour recurrence, but not age, was associated with poor survival time. Analysis of circulating MIP1b was low cost, rapid, and could be done in routine laboratory facility. Since RT almost always induces ARSRs, the possibility of using MIP1b as a prognostic biomarker for ARSRs is of interests for further investigation.
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http://dx.doi.org/10.1159/000518184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686701PMC
November 2021

A roadmap for the Human Developmental Cell Atlas.

Nature 2021 09 8;597(7875):196-205. Epub 2021 Sep 8.

Wellcome Sanger Institute, Hinxton, UK.

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development.
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http://dx.doi.org/10.1038/s41586-021-03620-1DOI Listing
September 2021

Comprehensive in situ mapping of human cortical transcriptomic cell types.

Commun Biol 2021 08 24;4(1):998. Epub 2021 Aug 24.

Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Solna, Sweden.

The ability to spatially resolve the cellular architecture of human cortical cell types over informative areas is essential to understanding brain function. We combined in situ sequencing gene expression data and single-nucleus RNA-sequencing cell type definitions to spatially map cells in sections of the human cortex via probabilistic cell typing. We mapped and classified a total of 59,816 cells into all 75 previously defined subtypes to create a first spatial atlas of human cortical cells in their native position, their abundances and genetic signatures. We also examined the precise within- and across-layer distributions of all the cell types and provide a resource for the cell atlas community. The abundances and locations presented here could serve as a reference for further studies, that include human brain tissues and disease applications at the cell type level.
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http://dx.doi.org/10.1038/s42003-021-02517-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384853PMC
August 2021

Mortality in Edentulous Patients: A Registry-Based Cohort Study in Sweden Comparing 8463 Patients Treated with Removable Dentures or Implant-Supported Dental Prostheses.

Int J Dent 2021 30;2021:9919732. Epub 2021 Jul 30.

Brånemark Clinic, Public Dental Health Care Service, Region of Västra Götaland, Gothenburg, Sweden.

Objectives: The purpose of this study was to investigate if edentulism is associated with all-cause mortality. The aims were to analyze the association between age, socioeconomic factors, and mortality in edentulous patients treated with either removable dentures or implant-supported prostheses.

Methods: All patients who became edentulous according to the Swedish Social Insurance Agency (SSIA) between 2009 and 2013 (  = 8463) were analyzed regarding prosthetic treatment, age, gender, and socioeconomic status. The patients were divided into two groups, depending on whether they were treated with dental implants (implant group; IG) or with conventional removable dentures (denture group; DG). Data on mortality for all included individuals were obtained from the Swedish National Cause of Death Register and compared to a reference population. Cumulative survival rates were calculated, and a multivariable regression analysis for the included variables was performed.

Results: Between 2009 and 2018, 2192 of the patients (25.9%) were treated with implant-supported dental prostheses (IG) and 6271 patients (74.1%) were treated with removable dentures without support of dental implants (DG). Altogether 2526 patients (30%) died until December 31, 2019, and the overall mortality was significantly higher for the DG compared to the IG during follow-up ( < 0.001). Younger edentulous patients (≤59 years) presented a higher mortality than the reference population, while implant patients over 79 years of age demonstrated a lower mortality. The final results from the multivariable logistic analysis showed that lower equalized disposable income (EDI) and the choice of conventional removable dentures are the most important factors for increased patient mortality ( < 0.001).

Conclusions: Edentulous patients have an overall higher mortality compared to a reference population. Low socioeconomic status increases all-cause mortality. Individuals treated with dental implants show statistically significant lower 10-year mortality compared to patients treated with conventional removable dentures, regardless of socioeconomic status.
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http://dx.doi.org/10.1155/2021/9919732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349274PMC
July 2021

Food intake in children and adolescents: a cross-sectional study from 2009/2010 to 2015/2016.

J Nutr Sci 2021 15;10:e51. Epub 2021 Jul 15.

Futurum, Region Jönköping County, and Department of Health, Medicine and Caring Sciences, Linköping University, Jönköping, Sweden.

The aim was to describe food intake over time in children and adolescents, with respect to age and gender. The present study was a repeated cross-sectional study using self-reported data from a health questionnaire. Data were collected from the School Health Services in south-east Sweden from 44 297 students, 10, 13-14 and 16 years of age, 48 % girls and 52 % boys from 2009/2010 to 2015/2016. Reported intakes for eight foods were analysed in relation to the Nordic Nutrition Recommendations. Seventeen per cent of the students reported an intake in line with the recommendations for at least six of the eight foods fish, vegetables, fruit, mealtime beverages, juice/chocolate drinks, sugar-sweetened beverages, sweets/snacks and pastries. Intake of at least two fruits a day was the recommendation that was followed by the lowest proportion of students (30 %), and this result was stable over the study period. There was a gradual increase over time in the proportion of students who reported an intake in line with the recommendations. Younger students compared to older students, as well as girls compared to boys, reported intakes in line with the recommendations to a statistically significant larger extent. Few students reported intakes in line with the recommendations, although the quality of food intake seems to improve over time. The present results indicate a deterioration in reported food intake in the early years of adolescence. Finding methods to support all children and especially older adolescents to eat healthier, including eating more fruit, is of great importance to public health.
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http://dx.doi.org/10.1017/jns.2021.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327392PMC
July 2021

Matisse: a MATLAB-based analysis toolbox for in situ sequencing expression maps.

BMC Bioinformatics 2021 Jul 31;22(1):391. Epub 2021 Jul 31.

Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, 171 65, Solna, Sweden.

Background: A range of spatially resolved transcriptomic methods has recently emerged as a way to spatially characterize the molecular and cellular diversity of a tissue. As a consequence, an increasing number of computational techniques are developed to facilitate data analysis. There is also a need for versatile user friendly tools that can be used for a de novo exploration of datasets.

Results: Here we present MATLAB-based Analysis toolbox for in situ sequencing (ISS) expression maps (Matisse). We demonstrate Matisse by characterizing the 2-dimensional spatial expression of 119 genes profiled in a mouse coronal section, exploring different levels of complexity. Additionally, in a comprehensive analysis, we further analyzed expression maps from a second technology, osmFISH, targeting a similar mouse brain region.

Conclusion: Matisse proves to be a valuable tool for initial exploration of in situ sequencing datasets. The wide set of tools integrated allows for simple analysis, using the position of individual reads, up to more complex clustering and dimensional reduction approaches, taking cellular content into account. The toolbox can be used to analyze one or several samples at a time, even from different spatial technologies, and it includes different segmentation approaches that can be useful in the analysis of spatially resolved transcriptomic datasets.
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http://dx.doi.org/10.1186/s12859-021-04302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325818PMC
July 2021

Molecular architecture of the developing mouse brain.

Nature 2021 08 28;596(7870):92-96. Epub 2021 Jul 28.

Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

The mammalian brain develops through a complex interplay of spatial cues generated by diffusible morphogens, cell-cell interactions and intrinsic genetic programs that result in probably more than a thousand distinct cell types. A complete understanding of this process requires a systematic characterization of cell states over the entire spatiotemporal range of brain development. The ability of single-cell RNA sequencing and spatial transcriptomics to reveal the molecular heterogeneity of complex tissues has therefore been particularly powerful in the nervous system. Previous studies have explored development in specific brain regions, the whole adult brain and even entire embryos. Here we report a comprehensive single-cell transcriptomic atlas of the embryonic mouse brain between gastrulation and birth. We identified almost eight hundred cellular states that describe a developmental program for the functional elements of the brain and its enclosing membranes, including the early neuroepithelium, region-specific secondary organizers, and both neurogenic and gliogenic progenitors. We also used in situ mRNA sequencing to map the spatial expression patterns of key developmental genes. Integrating the in situ data with our single-cell clusters revealed the precise spatial organization of neural progenitors during the patterning of the nervous system.
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http://dx.doi.org/10.1038/s41586-021-03775-xDOI Listing
August 2021

Child health professionals' experiences of the introduction and successful implementation of rotavirus vaccination in Sweden.

Acta Paediatr 2021 Oct 28;110(10):2833-2841. Epub 2021 Jul 28.

Public Health Agency of Sweden, Solna, Sweden.

Aim: To explore child health professionals' experiences of the early implementation of the rotavirus vaccination in the two regions that first introduced this vaccination in Sweden.

Methods: A descriptive and repeated cross-sectional study based on a digital study-specific questionnaire with a baseline in 2014 and with a 2-year follow-up in 2016. The study population consisted of nurses and doctors working in child health centres in the health care regions of Stockholm and Jönköping.

Results: In Stockholm, a larger proportion of the respondents (n = 355) had concerns in 2014, in comparison with the respondents in Jönköping (n = 101), mostly about the vaccination being a new and time-consuming task (60% versus 23%). In 2016, the overall attitude to vaccination was more positive in both regions and the levels of concern about increased workload were reduced (Stockholm, n = 519, 39%, versus Jönköping, n = 96, 10%). Challenges before and after the introduction in both regions were particularly related to how to give information about the vaccine's potential increased risk of intussusception.

Conclusion: The gap between respondents' knowledge, attitudes and concerns pre- and post-vaccination introduction was larger in Stockholm compared to Jönköping. In both regions, overall, the implementation of the rotavirus vaccination was perceived as being easier than expected.
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http://dx.doi.org/10.1111/apa.16038DOI Listing
October 2021

Individual differences in the ability to access spatial information in lag-clicks.

J Acoust Soc Am 2021 05;149(5):2963

Gösta Ekman Laboratory, Department of Psychology, Stockholm University, Stockholm, Sweden.

It may be difficult to determine whether a dichotic lag-click points to the left or right when preceded by a diotic lead-click. Previous research suggests that this loss of spatial information is most prominent at inter-click intervals (ICIs) <10 ms. However, a study by Nilsson, Tirado, and Szychowska [(2019). J. Acoust. Soc. Am. 145, 512-524] found support for loss of spatial information in lag-clicks at much longer ICIs using a stimulus setup differing from those in previous research. The present study used a setup similar to that of the Nilsson, Tirado, and Szychowska study [(2019). J. Acoust. Soc. Am. 145, 512-524] to measure 13 listeners' ability to lateralize (left versus right) and detect (present versus absent) the lag-click in lead-lag click pairs with ICIs of 6-48 ms. The main finding was distinct individual differences in performance. Some listeners could lateralize lag-clicks all the way down to their detection threshold, whereas others had lateralization thresholds substantially higher than their detection thresholds, i.e., they could not lateralize lag-clicks that they could easily detect. Two such listeners trained for 30 days and managed to improve their lateralization thresholds to reach their detection thresholds, but only at longer ICIs (>20 ms), suggesting different mechanisms underlying lag-click lateralization at short versus long ICIs.
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http://dx.doi.org/10.1121/10.0004821DOI Listing
May 2021

Identifying dominant environmental predictors of freshwater wetland methane fluxes across diurnal to seasonal time scales.

Glob Chang Biol 2021 08 29;27(15):3582-3604. Epub 2021 May 29.

Department of Earth System Science, Stanford University, Stanford, CA, USA.

While wetlands are the largest natural source of methane (CH ) to the atmosphere, they represent a large source of uncertainty in the global CH budget due to the complex biogeochemical controls on CH dynamics. Here we present, to our knowledge, the first multi-site synthesis of how predictors of CH fluxes (FCH4) in freshwater wetlands vary across wetland types at diel, multiday (synoptic), and seasonal time scales. We used several statistical approaches (correlation analysis, generalized additive modeling, mutual information, and random forests) in a wavelet-based multi-resolution framework to assess the importance of environmental predictors, nonlinearities and lags on FCH4 across 23 eddy covariance sites. Seasonally, soil and air temperature were dominant predictors of FCH4 at sites with smaller seasonal variation in water table depth (WTD). In contrast, WTD was the dominant predictor for wetlands with smaller variations in temperature (e.g., seasonal tropical/subtropical wetlands). Changes in seasonal FCH4 lagged fluctuations in WTD by ~17 ± 11 days, and lagged air and soil temperature by median values of 8 ± 16 and 5 ± 15 days, respectively. Temperature and WTD were also dominant predictors at the multiday scale. Atmospheric pressure (PA) was another important multiday scale predictor for peat-dominated sites, with drops in PA coinciding with synchronous releases of CH . At the diel scale, synchronous relationships with latent heat flux and vapor pressure deficit suggest that physical processes controlling evaporation and boundary layer mixing exert similar controls on CH volatilization, and suggest the influence of pressurized ventilation in aerenchymatous vegetation. In addition, 1- to 4-h lagged relationships with ecosystem photosynthesis indicate recent carbon substrates, such as root exudates, may also control FCH4. By addressing issues of scale, asynchrony, and nonlinearity, this work improves understanding of the predictors and timing of wetland FCH4 that can inform future studies and models, and help constrain wetland CH emissions.
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http://dx.doi.org/10.1111/gcb.15661DOI Listing
August 2021

Statistical upscaling of ecosystem CO fluxes across the terrestrial tundra and boreal domain: Regional patterns and uncertainties.

Glob Chang Biol 2021 Sep 10;27(17):4040-4059. Epub 2021 Jun 10.

Agronomy Department, University of Florida, Gainesville, FL, USA.

The regional variability in tundra and boreal carbon dioxide (CO ) fluxes can be high, complicating efforts to quantify sink-source patterns across the entire region. Statistical models are increasingly used to predict (i.e., upscale) CO fluxes across large spatial domains, but the reliability of different modeling techniques, each with different specifications and assumptions, has not been assessed in detail. Here, we compile eddy covariance and chamber measurements of annual and growing season CO fluxes of gross primary productivity (GPP), ecosystem respiration (ER), and net ecosystem exchange (NEE) during 1990-2015 from 148 terrestrial high-latitude (i.e., tundra and boreal) sites to analyze the spatial patterns and drivers of CO fluxes and test the accuracy and uncertainty of different statistical models. CO fluxes were upscaled at relatively high spatial resolution (1 km ) across the high-latitude region using five commonly used statistical models and their ensemble, that is, the median of all five models, using climatic, vegetation, and soil predictors. We found the performance of machine learning and ensemble predictions to outperform traditional regression methods. We also found the predictive performance of NEE-focused models to be low, relative to models predicting GPP and ER. Our data compilation and ensemble predictions showed that CO sink strength was larger in the boreal biome (observed and predicted average annual NEE -46 and -29 g C m  yr , respectively) compared to tundra (average annual NEE +10 and -2 g C m  yr ). This pattern was associated with large spatial variability, reflecting local heterogeneity in soil organic carbon stocks, climate, and vegetation productivity. The terrestrial ecosystem CO budget, estimated using the annual NEE ensemble prediction, suggests the high-latitude region was on average an annual CO sink during 1990-2015, although uncertainty remains high.
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http://dx.doi.org/10.1111/gcb.15659DOI Listing
September 2021

Substantial hysteresis in emergent temperature sensitivity of global wetland CH emissions.

Nat Commun 2021 04 15;12(1):2266. Epub 2021 Apr 15.

Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, Umeå, Sweden.

Wetland methane (CH) emissions ([Formula: see text]) are important in global carbon budgets and climate change assessments. Currently, [Formula: see text] projections rely on prescribed static temperature sensitivity that varies among biogeochemical models. Meta-analyses have proposed a consistent [Formula: see text] temperature dependence across spatial scales for use in models; however, site-level studies demonstrate that [Formula: see text] are often controlled by factors beyond temperature. Here, we evaluate the relationship between [Formula: see text] and temperature using observations from the FLUXNET-CH database. Measurements collected across the globe show substantial seasonal hysteresis between [Formula: see text] and temperature, suggesting larger [Formula: see text] sensitivity to temperature later in the frost-free season (about 77% of site-years). Results derived from a machine-learning model and several regression models highlight the importance of representing the large spatial and temporal variability within site-years and ecosystem types. Mechanistic advancements in biogeochemical model parameterization and detailed measurements in factors modulating CH production are thus needed to improve global CH budget assessments.
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http://dx.doi.org/10.1038/s41467-021-22452-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050324PMC
April 2021

Evaluation of Immuno-Rolling Circle Amplification for Multiplex Detection and Profiling of Antigen-Specific Antibody Isotypes.

Anal Chem 2021 04 7;93(15):6169-6177. Epub 2021 Apr 7.

Department of Biosystems, Biosensors Group, KU Leuven, Willem De Croylaan 42, Heverlee B-3001, Belgium.

Antibody characterization is essential for understanding the immune system and development of diagnostics and therapeutics. Current technologies are mainly focusing on the detection of antigen-specific immunoglobulin G (IgG) using bulk singleplex measurements, which lack information on other isotypes and specificity of individual antibodies. Digital immunoassays based on nucleic acid amplification have demonstrated superior performance by allowing the detection of single molecules in a multiplex and sensitive manner. In this study, we demonstrate for the first time an immuno-rolling circle amplification (immuno-RCA) assay for the multiplex detection of three antigen-specific antibody isotypes (IgG, IgA, and IgM) and its integration with microengraving. To validate this approach, we used the autoimmune disease immune-mediated thrombotic thrombocytopenic purpura (iTTP) as the model disease with anti-ADAMTS13 autoantibodies as the diagnostic target molecules. To identify the anti-ADAMTS13 autoantibody isotypes, we designed a pool of three unique antibody-oligonucleotide conjugates for identification and subsequent amplification and visualization via RCA. To validate this approach, we first confirmed an assay specificity of >88% and a low limit of detection of 0.3 ng/mL in the spiked buffer. Subsequently, we performed a dilution series of an iTTP plasma sample for the multiplex detection of the three isotypes with higher sensitivity compared to an enzyme-linked immunosorbent assay. Finally, we demonstrated single-cell analysis of human B cells and hybridoma cells for the detection of secreted antibodies using microengraving and achieved a detection of 23.3 pg/mL secreted antibodies per hour. This approach could help to improve the understanding of antibody isotype distributions and their roles in various diseases.
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http://dx.doi.org/10.1021/acs.analchem.1c00172DOI Listing
April 2021

Electrochemical Genosensing of Based on Padlock Probes and Rolling Circle Amplification.

Sensors (Basel) 2021 Mar 3;21(5). Epub 2021 Mar 3.

Grup de Sensors i Biosensors, Departament de Química, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

Isothermal amplification techniques are emerging nowadays for the rapid and accurate detection of pathogenic bacteria in low resource settings, where many infectious diseases are endemic, and the lack of reliable power supply, trained personnel and specialized facilities pose critical barriers for timely diagnosis. This work addresses the detection of based on DNA isothermal amplification performed on magnetic particles (MPs) followed by electrochemical genosensing on disposable electrodes by square-wave voltammetry. In this approach, the bacterial DNA is preconcentrated using a target-specific magnetic probe and then amplified on the MPs by rolling circle amplification (RCA). Two different electrochemical readout methods for the RCA amplicons are tested. The first one relied on the labelling of the magnetic RCA product with a digoxigenin probe followed by the incubation with antiDIG-HRP antibody as electrochemical reporter. In the second case, the direct detection with an HRP-probe was performed. This latter strategy showed an improved analytical performance, while simultaneously avoiding the use of thermocyclers or bulky bench top equipment.
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http://dx.doi.org/10.3390/s21051749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959471PMC
March 2021

CO fertilization of Sphagnum peat mosses is modulated by water table level and other environmental factors.

Plant Cell Environ 2021 06 29;44(6):1756-1768. Epub 2021 Mar 29.

Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.

Sphagnum mosses account for most accumulated dead organic matter in peatlands. Therefore, understanding their responses to increasing atmospheric CO is needed for estimating peatland C balances under climate change. A key process is photorespiration: a major determinant of net photosynthetic C assimilation that depends on the CO to O ratio. We used climate chambers to investigate photorespiratory responses of Sphagnum fuscum hummocks to recent increases in atmospheric CO (from 280 to 400 ppm) under different water table, temperature, and light intensity levels. We tested the photorespiratory variability using a novel method based on deuterium isotopomers (D6 /D6 ratio) of photosynthetic glucose. The effect of elevated CO on photorespiration was highly dependent on water table. At low water table (-20 cm), elevated CO suppressed photorespiration relative to C assimilation, thus substantially increasing the net primary production potential. In contrast, a high water table (~0 cm) favored photorespiration and abolished this CO effect. The response was further tested for Sphagnum majus lawns at typical water table levels (~0 and -7 cm), revealing no effect of CO under those conditions. Our results indicate that hummocks, which typically experience low water table levels, benefit from the 20th century's increase in atmospheric CO .
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http://dx.doi.org/10.1111/pce.14043DOI Listing
June 2021

Comparing Echo-Detection and Echo-Localization in Sighted Individuals.

Perception 2021 Apr 5;50(4):308-327. Epub 2021 Mar 5.

7675Stockholm University, Sweden.

Echolocation is the ability to gather information from sound reflections. Most previous studies have focused on the ability to detect sound reflections, others on the ability to localize sound reflections, but no previous study has compared the two abilities in the same individuals. Our study compared echo-detection (reflecting object present or not?) and echo-localization (reflecting object to the left or right?) in 10 inexperienced sighted participants across 10 distances (1-4.25 m) to the reflecting object, using an automated system for studying human echolocation. There were substantial individual differences, particularly in the performance on the echo-localization task. However, most participants performed better on the detection than the localization task, in particular at the closest distances (1 and 1.7 m), illustrating that it sometimes may be hard to perceive whether an audible reflection came from the left or right.
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http://dx.doi.org/10.1177/03010066211000617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044610PMC
April 2021

Extracellular Vesicles and Exosomes: Insights From Exercise Science.

Front Physiol 2020 1;11:604274. Epub 2021 Feb 1.

Department of Pediatrics, McMaster University Medical Centre (MUMC), Hamilton, ON, Canada.

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or 'exerkines'). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or 'mediators' of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.
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http://dx.doi.org/10.3389/fphys.2020.604274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882633PMC
February 2021

Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer.

PLoS One 2021 28;16(1):e0243084. Epub 2021 Jan 28.

Dept Oncology, Ryhov Hospital, Jönköping, Sweden.

Introduction: Cigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor.

Methods: Three hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed.

Results: Out of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa.

Conclusion: SNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243084PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842923PMC
April 2021

Chronic Atmospheric Reactive Nitrogen Deposition Suppresses Biological Nitrogen Fixation in Peatlands.

Environ Sci Technol 2021 01 4;55(2):1310-1318. Epub 2021 Jan 4.

School of Geography, Earth, and Environmental Sciences, and Birmingham Institute of Forest Research, University of Birmingham, Birmingham B15 2TT, United Kingdom.

Biological nitrogen fixation (BNF) represents the natural pathway by which mosses meet their demands for bioavailable/reactive nitrogen (Nr) in peatlands. However, following intensification of nitrogen fertilizer and fossil fuel use, atmospheric Nr deposition has increased exposing peatlands to Nr loading often above the ecological threshold. As BNF is energy intensive, therefore, it is unclear whether BNF shuts down when Nr availability is no longer a rarity. We studied the response of BNF under a gradient of Nr deposition extending over decades in three peatlands in the U.K., and at a background deposition peatland in Sweden. Experimental nitrogen fertilization plots in the Swedish site were also evaluated for BNF activity. In situ BNF activity of peatlands receiving Nr deposition of 6, 17, and 27 kg N ha yr was not shut down but rather suppressed by 54, 69, and 74%, respectively, compared to the rates under background Nr deposition of ∼2 kg N ha yr. These findings were corroborated by similar BNF suppression at the fertilization plots in Sweden. Therefore, contribution of BNF in peatlands exposed to chronic Nr deposition needs accounting when modeling peatland's nitrogen pools, given that nitrogen availability exerts a key control on the carbon capture of peatlands, globally.
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http://dx.doi.org/10.1021/acs.est.0c04882DOI Listing
January 2021

SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution.

PLoS Biol 2020 11 20;18(11):e3000675. Epub 2020 Nov 20.

Science for Life Laboratory, Solna, Sweden.

Changes in cell identities and positions underlie tissue development and disease progression. Although single-cell mRNA sequencing (scRNA-Seq) methods rapidly generate extensive lists of cell states, spatially resolved single-cell mapping presents a challenging task. We developed SCRINSHOT (Single-Cell Resolution IN Situ Hybridization On Tissues), a sensitive, multiplex RNA mapping approach. Direct hybridization of padlock probes on mRNA is followed by circularization with SplintR ligase and rolling circle amplification (RCA) of the hybridized padlock probes. Sequential detection of RCA-products using fluorophore-labeled oligonucleotides profiles thousands of cells in tissue sections. We evaluated SCRINSHOT specificity and sensitivity on murine and human organs. SCRINSHOT quantification of marker gene expression shows high correlation with published scRNA-Seq data over a broad range of gene expression levels. We demonstrate the utility of SCRINSHOT by mapping the locations of abundant and rare cell types along the murine airways. The amenability, multiplexity, and quantitative qualities of SCRINSHOT facilitate single-cell mRNA profiling of cell-state alterations in tissues under a variety of native and experimental conditions.
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http://dx.doi.org/10.1371/journal.pbio.3000675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717588PMC
November 2020

Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury.

Nat Commun 2020 11 17;11(1):5860. Epub 2020 Nov 17.

Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, 17177, Stockholm, Sweden.

Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.
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http://dx.doi.org/10.1038/s41467-020-19453-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673029PMC
November 2020

Automated identification of the mouse brain's spatial compartments from in situ sequencing data.

BMC Biol 2020 10 19;18(1):144. Epub 2020 Oct 19.

Centre for Image Analysis, Department of Information Technology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.

Background: Neuroanatomical compartments of the mouse brain are identified and outlined mainly based on manual annotations of samples using features related to tissue and cellular morphology, taking advantage of publicly available reference atlases. However, this task is challenging since sliced tissue sections are rarely perfectly parallel or angled with respect to sections in the reference atlas and organs from different individuals may vary in size and shape and requires manual annotation. With the advent of in situ sequencing technologies and automated approaches, it is now possible to profile the gene expression of targeted genes inside preserved tissue samples and thus spatially map biological processes across anatomical compartments.

Results: Here, we show how in situ sequencing data combined with dimensionality reduction and clustering can be used to identify spatial compartments that correspond to known anatomical compartments of the brain. We also visualize gradients in gene expression and sharp as well as smooth transitions between different compartments. We apply our method on mouse brain sections and show that a fully unsupervised approach can computationally define anatomical compartments, which are highly reproducible across individuals, using as few as 18 gene markers. We also show that morphological variation does not always follow gene expression, and different spatial compartments can be defined by various cell types with common morphological features but distinct gene expression profiles.

Conclusion: We show that spatial gene expression data can be used for unsupervised and unbiased annotations of mouse brain spatial compartments based only on molecular markers, without the need of subjective manual annotations based on tissue and cell morphology or matching reference atlases.
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http://dx.doi.org/10.1186/s12915-020-00874-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574211PMC
October 2020
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