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  • 1.
    Aalberg Haugen, Inger M.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Berger, David
    Stockholm University, Faculty of Science, Department of Zoology. Uppsala University, Sweden.
    Gotthard, Karl
    Stockholm University, Faculty of Science, Department of Zoology.
    The evolution of alternative developmental pathways: footprints of selection on life-history traits in a butterfly2012In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 25, no 7, p. 1377-1388Article in journal (Refereed)
    Abstract [en]

    Developmental pathways may evolve to optimize alternative phenotypes across environments. However, the maintenance of such adaptive plasticity under relaxed selection has received little study. We compare the expression of life-history traits across two developmental pathways in two populations of the butterfly Pararge aegeria where both populations express a diapause pathway but one never expresses direct development in nature. In the population with ongoing selection on both pathways, the difference between pathways in development time and growth rate was larger, whereas the difference in body size was smaller compared with the population experiencing relaxed selection on one pathway. This indicates that relaxed selection on the direct pathway has allowed life-history traits to drift towards values associated with lower fitness when following this pathway. Relaxed selection on direct development was also associated with a higher degree of genetic variation for protandry expressed as within-family sexual dimorphism in growth rate. Genetic correlations for larval growth rate across sexes and pathways were generally positive, with the notable exception of correlation estimates that involved directly developing males of the population that experienced relaxed selection on this pathway. We conclude that relaxed selection on one developmental pathway appears to have partly disrupted the developmental regulation of life-history trait expression. This in turn suggests that ongoing selection may be responsible for maintaining adaptive developmental regulation along alternative developmental pathways in these populations.

  • 2.
    Aalberg Haugen, Inger M.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Gotthard, Karl
    Stockholm University, Faculty of Science, Department of Zoology.
    Diapause induction and relaxed selection on alternative developmental pathways in a butterfly2015In: Journal of Animal Ecology, ISSN 0021-8790, E-ISSN 1365-2656, Vol. 84, no 2, p. 464-472Article in journal (Refereed)
    Abstract [en]

    Seasonal phenotypic plasticity entails differential trait expression depending on the time of season. The facultative induction of winter diapause in temperate insects is a developmental switch mechanism often leading to differential expression in life-history traits. However, when there is a latitudinal shift from a bivoltine to univoltine life cycle, selection for pathway-specific expression is disrupted, which may allow drift towards less optimal trait values within the non-selected pathway. We use field- and experimental data from five Swedish populations of Pararge aegeria to investigate latitudinal variation in voltinism, local adaptation in the diapause switch and footprints of selection on pathway-specific regulation of life-history traits and sexual dimorphism in larval development. Field data clearly illustrated how natural populations gradually shift from bivoltinism to univoltinism as latitude increases. This was supported experimentally as the decrease in direct development at higher latitudes was accompanied by increasing critical daylengths, suggesting local adaptation in the diapause switch. The differential expression among developmental pathways in development time and growth rate was significantly less pronounced in univoltine populations. Univoltine populations showed no significant signs of protandry during larval development, suggesting that erosion of the direct development pathway under relaxed selection has led to the loss of its sex-specific modifications.

  • 3.
    Aalberg Haugen, Inger M.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Gotthard, Karl
    Stockholm University, Faculty of Science, Department of Zoology.
    Latitudinal phenological adaptation: diapause induction and differentiation between alternative developmental pathways in a butterflyManuscript (preprint) (Other academic)
    Abstract [en]

    1. Seasonal phenotypic plasticity entails differential trait expression depending on the time of season. The facultative induction of winter diapause in temperate insects is a developmental switch mechanism often leading to differential expression in life history traits. However, when there is a latitudinal shift from a bivoltine to univoltine life cycle, selection for pathway-specific expression is disrupted, which may allow drift towards less optimal trait values within the non-selected pathway.

    2. We use field- and experimental data from five Swedish populations of Pararge aegeria to investigate latitudinal variation in voltinism, local adaptation in the diapause switch, and footprints of selection on pathway-specific regulation of life history traits and sexual dimorphism in larval development.

    3. Field data clearly illustrated how natural populations gradually shift from bivoltinism to univoltinism as latitude increases. This was supported experimentally as the decrease in direct development at higher latitudes was accompanied by increasing critical daylengths, suggesting local adaptation in the diapause switch.

    4. The differential expression among developmental pathways in development time and growth rate was significantly less pronounced in univoltine populations. Univoltine populations showed no significant signs of protandry during larval development, suggesting that erosion of the direct development pathway under relaxed selection has led to the loss of its sex-specific modifications.

  • 4.
    Aalberg Haugen, Inger M.
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Gotthard, Karl
    The development and expression of seasonal polyphenism in life-history traits in the butterfly Pararge aegeriaManuscript (preprint) (Other academic)
  • 5.
    Aalberg Haugen, Inger Marie
    Stockholm University, Faculty of Science, Department of Zoology.
    The diapause switch: Evolution of alternative developmental pathways in a butterfly2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diapause decision is a classic example of a threshold switch mechanism with cascading effects on morphology, behaviour and life-history traits. This thesis addresses the downstream effects of the insect diapause switch, with the main focus on pathway-specific regulation of life-history traits, using the speckled wood butterfly (Pararge aegeria) as a study species. The ultimate pathway decision is made towards the end of larval development and allows the larvae to take into account up-to-date information from the environment about future conditions (Paper I, IV). However, already from an early point in development the larvae are sensitive to environmental cues and continuously adjust their growth trajectory in accordance to current information about the environmental conditions to be expected in future (Paper IV). An asymmetry in the ability to change from one developmental pathway to another at a late point in larval development suggests that the diapause and the direct pathway require different physiological preparations (Paper IV). Pathway-specific regulation of traits downstream of the diapause switch is maintained by ongoing selection. When the direct pathway is not regularly expressed, as with a shift from bivoltinism to univoltinism, relaxed selection on the unexpressed pathway leads to genetic drift and loss of protandry (Paper II, III). Natural populations display local adaptations in the diapause switch with an increase in critical daylengths as there is a gradual shift from bivoltinism to univoltinism (Paper III). This thesis highlights two aspects of the diapause decision, the determination of how and when this decision is made as well as the way the resulting pathways are moulded by selection in order to produce adaptive seasonal polyphenism in life-history traits.

  • 6. Abalde, Samuel
    et al.
    Tellgren-Roth, Christian
    Heintz, Julia
    Pettersson, Olga Vinnere
    Jondelius, Ulf
    Stockholm University, Faculty of Science, Department of Zoology, Systematic Zoology.
    The draft genome of the microscopic Nemertoderma westbladi sheds light on the evolution of Acoelomorpha genomes2023In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, article id 1244493Article in journal (Refereed)
    Abstract [en]

    Background: Xenacoelomorpha is a marine clade of microscopic worms that is an important model system for understanding the evolution of key bilaterian novelties, such as the excretory system. Nevertheless, Xenacoelomorpha genomics has been restricted to a few species that either can be cultured in the lab or are centimetres long. Thus far, no genomes are available for Nemertodermatida, one of the group's main clades and whose origin has been dated more than 400 million years ago.Methods: DNA was extracted from a single specimen and sequenced with HiFi following the PacBio Ultra-Low DNA Input protocol. After genome assembly, decontamination, and annotation, the genome quality was benchmarked using two acoel genomes and one Illumina genome as reference. The gene content of three cnidarians, three acoelomorphs, four deuterostomes, and eight protostomes was clustered in orthogroups to make inferences of gene content evolution. Finally, we focused on the genes related to the ultrafiltration excretory system to compare patterns of presence/absence and gene architecture among these clades.Results: We present the first nemertodermatid genome sequenced from a single specimen of Nemertoderma westbladi. Although genome contiguity remains challenging (N50: 60 kb), it is very complete (BUSCO: 80.2%, Metazoa; 88.6%, Eukaryota) and the quality of the annotation allows fine-detail analyses of genome evolution. Acoelomorph genomes seem to be relatively conserved in terms of the percentage of repeats, number of genes, number of exons per gene and intron size. In addition, a high fraction of genes present in both protostomes and deuterostomes are absent in Acoelomorpha. Interestingly, we show that all genes related to the excretory system are present in Xenacoelomorpha except Osr, a key element in the development of these organs and whose acquisition seems to be interconnected with the origin of the specialised excretory system.Conclusion: Overall, these analyses highlight the potential of the Ultra-Low Input DNA protocol and HiFi to generate high-quality genomes from single animals, even for relatively large genomes, making it a feasible option for sequencing challenging taxa, which will be an exciting resource for comparative genomics analyses.

  • 7. Abbas, Muhammad Ghazanfar
    et al.
    Haris, Abdullah
    Binyameen, Muhammad
    Nazir, Abdul
    Mozūratis, Raimondas
    Stockholm University, Faculty of Science, Department of Zoology. Nature Research Centre, Lithuania.
    Azeem, Muhammad
    Chemical Composition, Larvicidal and Repellent Activities of Wild Plant Essential Oils against Aedes aegypti2023In: Biology, E-ISSN 2079-7737, Vol. 12, no 1, article id 8Article in journal (Refereed)
    Abstract [en]

    Bio-degradable and eco-friendly essential oils (EOs) extracted from Mentha longifolia, Salsola imbricata, Erigeron bonariensis, E. canadensis, Ailanthus altissima, and Zanthoxylum armatum were investigated for their repellent and larvicidal potential against Aedes aegypti mosquitoes. The EOs of M. longifolia, S. imbricata, E. bonariensis, E. canadensis, A. altissima, and Z. armatum exhibited 99.0%, 96.8%, 40.2%, 41.7%, 29.1%, and 13.2% repellency against mosquitoes at a tested dose of 33.3 μg/cm2, respectively. In time span bioassays, the EOs of M. longifolia, S. imbricata, E. bonariensis, and E. canadensis showed more than 40% repellency for 60 min at a tested dose of 330 μg/cm2. Larvicidal bioassays revealed that larvae of Ae. aegypti were the most susceptible to M. longifolia (LC50, 39.3 mg/L), E. bonariensis (LC50, 26.0 mg/L), E. canadensis (LC50, 35.7 mg/L), and Z. armatum (LC50, 35.9 mg/L) EOs upon 48 h exposure. The most abundant constituents in the EOs of M. longifolia, S. imbricata, E. bonariensis, E. canadensis and A. altissima were piperitone oxide (45.5%), carvone (39.9%), matricaria ester (43.1%), (31.7%) and eugenol (24.4%), respectively. Our study demonstrates that EOs of M. longifolia, S. imbricata, E. bonariensis, and E. canadensis might be used to control Ae. aegypti mosquitoes without harming humans or the environment.

  • 8.
    Abbasi, Saeed
    et al.
    KTH Royal Inst Technol, Dept Machine Design, Stockholm, Sweden.
    Jansson, Anders
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Sellgren, Ulf
    KTH Royal Inst Technol, Dept Machine Design, Stockholm, Sweden.
    Olofsson, Ulf
    KTH Royal Inst Technol, Dept Machine Design, Stockholm, Sweden.
    Particle Emissions From Rail Traffic: A Literature Review2013In: Critical reviews in environmental science and technology, ISSN 1064-3389, E-ISSN 1547-6537, Vol. 43, no 23, p. 2511-2544Article, review/survey (Refereed)
    Abstract [en]

    Particle emissions are a drawback of rail transport. This work is a comprehensive presentation of recent research into particle emissions from rail vehicles. Both exhaust and nonexhaust particle emissions are considered when examining particle characteristics such as PM10, and PM2.5 concentration levels, size, morphology, composition, and adverse health effects, current legislation, and available and proposed solutions for reducing such emissions. High concentration levels in enclosed rail traffic environments are reported and some toxic effects of the particles. The authors find that only a few limited studies have examined the adverse health effects of nonexhaust particle emissions and that no relevant legislation exists. Thus further research in this area is warranted.

  • 9. Abbey-Lee, Robin N.
    et al.
    Uhrig, Emily J.
    Zidar, Josefina
    Favati, Anna
    Stockholm University, Faculty of Science, Department of Zoology.
    Almberg, Johan
    Dahlbom, Josefin
    Winberg, Svante
    Løvlie, Hanne
    The Influence of Rearing on Behavior, Brain Monoamines, and Gene Expression in Three-Spined Sticklebacks2018In: Brain, behavior, and evolution, ISSN 0006-8977, E-ISSN 1421-9743, Vol. 91, no 4, p. 201-213Article in journal (Refereed)
    Abstract [en]

    The causes of individual variation in behavior are often not well understood, and potential underlying mechanisms include both intrinsic and extrinsic factors, such as early environmental, physiological, and genetic differences. In an exploratory laboratory study, we raised three-spined sticklebacks (Gasterosteus aculeatus) under 4 different environmental conditions (simulated predator environment, complex environment, variable social environment, and control). We investigated how these manipulations related to behavior, brain physiology, and gene expression later in life, with focus on brain dopamine and serotonin levels, turnover rates, and gene expression. The different rearing environments influenced behavior and gene expression, but did not alter monoamine levels or metabolites. Specifically, compared to control fish, fish exposed to a simulated predator environment tended to be less aggressive, more exploratory, and more neophobic; and fish raised in both complex and variable social environments tended to be less neophobic. Exposure to a simulated predator environment tended to lower expression of dopamine receptor DRD4A, a complex environment increased expression of dopamine receptor DRD1B, while a variable social environment tended to increase serotonin receptor 5-HTR2B and serotonin transporter SLC6A4A expression. Despite both behavior and gene expression varying with early environment, there was no evidence that gene expression mediated the relationship between early environment and behavior. Our results confirm that environmental conditions early in life can affect phenotypic variation. However, the mechanistic pathway of the monoaminergic systems translating early environmental variation into observed behavioral responses was not detected.

  • 10. Abd El-Wahed, Aida
    et al.
    Yosri, Nermeen
    Sakr, Hanem H.
    Du, Ming
    Algethami, Ahmed F. M.
    Zhao, Chao
    Abdelazeem, Ahmed H.
    Tahir, Haroon Elrasheid
    Masry, Saad H. D.
    Abdel-Daim, Mohamed M.
    Musharraf, Syed Ghulam
    El-Garawani, Islam
    Kai, Guoyin
    Al Naggar, Yahya
    Khalifa, Shaden A. M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    El-Seedi, Hesham R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Menoufia University, Egypt; Jiangsu University, China; Uppsala University, Sweden.
    Wasp Venom Biochemical Components and Their Potential in Biological Applications and Nanotechnological Interventions2021In: Toxins, E-ISSN 2072-6651, Vol. 13, no 3, article id 206Article, review/survey (Refereed)
    Abstract [en]

    Wasps, members of the order Hymenoptera, are distributed in different parts of the world, including Brazil, Thailand, Japan, Korea, and Argentina. The lifestyles of the wasps are solitary and social. Social wasps use venom as a defensive measure to protect their colonies, whereas solitary wasps use their venom to capture prey. Chemically, wasp venom possesses a wide variety of enzymes, proteins, peptides, volatile compounds, and bioactive constituents, which include phospholipase A2, antigen 5, mastoparan, and decoralin. The bioactive constituents have anticancer, antimicrobial, and anti-inflammatory effects. However, the limited quantities of wasp venom and the scarcity of advanced strategies for the synthesis of wasp venom’s bioactive compounds remain a challenge facing the effective usage of wasp venom. Solid-phase peptide synthesis is currently used to prepare wasp venom peptides and their analogs such as mastoparan, anoplin, decoralin, polybia-CP, and polydim-I. The goal of the current review is to highlight the medicinal value of the wasp venom compounds, as well as limitations and possibilities. Wasp venom could be a potential and novel natural source to develop innovative pharmaceuticals and new agents for drug discovery.

  • 11. Abd-El Azeem, Hoda H.
    et al.
    Osman, Gamalat Y.
    El-Seedi, Hesham R.
    Fallatah, Ahmed M.
    Khalifa, Shaden A. M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Gharib, Mohamed M.
    Antifungal Activity of Soft Tissue Extract from the Garden Snail Helix aspersa (Gastropoda, Mollusca)2022In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 27, no 10, article id 3170Article in journal (Refereed)
    Abstract [en]

    Gastropods comprise approximately 80% of molluscans, of which land snails are used variably as food and traditional medicines due to their high protein content. Moreover, different components from land snails exhibit antimicrobial activities. In this study, we evaluated the antifungal activity of soft tissue extracts from Helix aspersa against Candida albicans, Aspergillus flavus, and Aspergillus brasiliensis by identifying extract components using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Two concentrations of three extracts (methanol, acetone, and acetic acid) showed antifungal activity. Both acetone (1 g/3 mL) and acetic acid extracts (1 g/mL) significantly inhibited C. albicans growth (p = 0.0001, 5.2 +/- 0.2 mm and p = 0.02, 69.7 +/- 0.6 mm, respectively). A. flavus and A. brasiliensis growth were inhibited by all extracts at 1 g/mL, while inhibition was observed for acetic acid extracts against A. brasiliensis (p = 0.02, 50.3 +/- 3.5 mm). The highest growth inhibition was observed for A. flavus using acetic acid and acetone extracts (inhibition zones = 38 +/- 1.7 mm and 3.1 +/- 0.7 mm, respectively). LC-MS-MS studies on methanol and acetone extracts identified 11-α-acetoxyprogesterone with a parent mass of 372.50800 m/z and 287.43500 m/z for luteolin. Methanol extracts contained hesperidin with a parent mass of 611.25400 m/z, whereas linoleic acid and genistein (parent mass = 280.4 and 271.48900 m/z, respectively) were the main metabolites.

  • 12.
    Abdel Rehim, Abbi
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Abdel Rehim, Mohamed
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Screening and determination of drugs in human saliva utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry2013In: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 27, no 9, p. 1188-1191Article in journal (Refereed)
    Abstract [en]

    This study presents a new method for collecting and handling saliva samples using an automated analytical microsyringe and microextraction by packed syringe (MEPS). The screening and determination of lidocaine in human saliva samples utilizing MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. An exact volume of saliva could be collected. The MEPS C-8-cartridge could be used for 50 extractions before it was discarded. The extraction recovery was about 60%. The pharmacokinetic curve of lidocaine in saliva using MEPS-LC-MS/MS is reported.

  • 13.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Graz University of Technology, Austria.
    Freilich, Shiri
    Bartuv, Rotem
    Zhimo, V. Yeka
    Kumar, Ajay
    Biasi, Antonio
    Salim, Shoshana
    Feygenberg, Oleg
    Burchard, Erik
    Dardick, Christopher
    Liu, Jia
    Khan, Awais
    Ellouze, Walid
    Ali, Shawkat
    Spadaro, Davide
    Torres, Rosario
    Teixido, Neus
    Ozkaya, Okan
    Buehlmann, Andreas
    Vero, Silvana
    Mondino, Pedro
    Berg, Gabriele
    Wisniewski, Michael
    Droby, Samir
    Global analysis of the apple fruit microbiome: are all apples the same?2021In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 23, no 10, p. 6038-6055Article in journal (Refereed)
    Abstract [en]

    We present the first worldwide study on the apple (Malus x domestica) fruit microbiome that examines questions regarding the composition and the assembly of microbial communities on and in apple fruit. Results revealed that the composition and structure of the fungal and bacterial communities associated with apple fruit vary and are highly dependent on geographical location. The study also confirmed that the spatial variation in the fungal and bacterial composition of different fruit tissues exists at a global level. Fungal diversity varied significantly in fruit harvested in different geographical locations and suggests a potential link between location and the type and rate of postharvest diseases that develop in each country. The global core microbiome of apple fruit was represented by several beneficial microbial taxa and accounted for a large fraction of the fruit microbial community. The study provides foundational information about the apple fruit microbiome that can be utilized for the development of novel approaches for the management of fruit quality and safety, as well as for reducing losses due to the establishment and proliferation of postharvest pathogens. It also lays the groundwork for studying the complex microbial interactions that occur on apple fruit surfaces.

  • 14.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Università Mediterranea di Reggio Calabria, Italy.
    Ruano-Rosa, David
    Cacciola, Santa Olga
    Nicosia, Maria G. Li Destri
    Schena, Leonardo
    Impact of Bactrocera oleae on the fungal microbiota of ripe olive drupes2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 11, article id e0199403Article in journal (Refereed)
    Abstract [en]

    The olive fruit fly (OFF), Bactrocera oleae is the most devastating pest affecting olive fruit worldwide. Previous investigations have addressed the fungal microbiome associated with olive drupes or B. oleae, but the impact of the insect on fungal communities of olive fruit remains undescribed. In the present work, the fungal microbiome of olive drupes, infested and non-infested by the OFF, was investigated in four different localities and cultivars. Olive fruit fly infestations caused a general reduction of the fungal diversity, a higher quantity of the total DNA and an increase in taxa that remained unidentified or had unknown roles. The infestations led to imbalanced fungal communities with the growth of taxa that are usually outcompeted. While it was difficult to establish a cause-effect link between fly infestation and specific fungi, it is clear that the fly alters the natural microbial balance, especially the low abundant taxa. On the other hand, the most abundant ones, were not significantly influenced by the insect. In fact, despite the slight variation between the sampling locations, Aureobasidium, Cladosporium, and Alternaria, were the dominant genera, suggesting the existence of a typical olive fungal microbiome.

  • 15.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Università Mediterranea di Reggio Calabria, Italy.
    Sanzani, Simona M.
    Wisniewski, Michael
    Berg, Gabriele
    Cacciola, Santa O.
    Schena, Leonardo
    Revealing Cues for Fungal Interplay in the Plant-Air Interface in Vineyards2019In: Frontiers in Plant Science, E-ISSN 1664-462X, Vol. 10, article id 922Article in journal (Refereed)
    Abstract [en]

    Plant-associated microorganisms play a crucial role in plant health and productivity. Belowground microbial diversity is widely reported as a major factor in determining the composition of the plant microbiome. In contrast, much less is known about the role of the atmosphere in relation to the plant microbiome. The current study examined the hypothesis that the atmospheric microbiome influences the composition of fungal communities of the aboveground organs flowers, fruit, and leaves) of table grape and vice versa. The atmosphere surrounding grape plantings exhibited a significantly higher level of fungal diversity relative to the nearby plant organs and shared a higher number of phylotypes 5,536 OTUs, 40.3%) with the plant than between organs of the same plant. Using a Bayesian source tracking approach, plant organs were determined to be the major source of the atmospheric fungal community 92%). In contrast, airborne microbiota had only a minor contribution to the grape microbiome, representing the source of 15, 4, and 35% of the fungal communities of leaves, flowers, and fruits, respectively. Moreover, data indicate that plant organs and the surrounding atmosphere shared a fraction of each other's fungal communities, and this shared pool of fungal taxa serves as a two-way reservoir of microorganisms. Microbial association analysis highlighted more positive than negative interactions between fungal phylotypes. Positive interactions were more common within the same environment, while negative interactions appeared to occur more frequently between different environments, i. e., atmosphere, leaf, flower, and fruit. The current study revealed the interplay between the fungal communities of the grape phyllosphere with the surrounding air. Plants were identified as a major source of recruitment for the atmospheric microbiome, while the surrounding atmosphere contributed only a small fraction of the plant fungal community. The results of the study suggested that the plant-air interface modulates the plant recruitment of atmospheric fungi, taking a step forward in understanding the plant holobiont assembly and how the atmosphere surrounding plants plays a role in this process. The impact of plants on the atmospheric microbiota has several biological and epidemiological implications for plants and humans.

  • 16.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), Germany; Graz University of Technology, Austria .
    Tack, Ayco J. M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Lobato, Carolina
    Wassermann, Birgit
    Berg, Gabriele
    From seed to seed: the role of microbial inheritance in the assembly of the plant microbiome2023In: Trends in Microbiology, ISSN 0966-842X, E-ISSN 1878-4380, Vol. 31, no 4, p. 346-355Article, review/survey (Refereed)
    Abstract [en]

    Despite evidence that the microbiome extends host genetic and phenotypic traits, information on how the microbiome is transmitted and maintained across generations remains fragmented. For seed-bearing plants, seeds harbor a distinct microbiome and play a unique role by linking one generation to the next. Studies on microbial inheritance, a process we suggest including both vertical transmission and the subsequent migration of seed microorganisms to the new plant, thus become essential for our understanding of host evolutionary potential and host–microbiome coevolution. We propose dividing the inheritance process into three stages: (i) plant to seed, (ii) seed dormancy, and (iii) seed to seedling. We discuss the factors affecting the assembly of the microbiome during the three stages, highlight future research directions, and emphasize the implications of microbial inheritance for fundamental science and society.

  • 17. Abdelfattah, Ahmed
    et al.
    Tack, Ayco J. M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Wasserman, Birgit
    Liu, Jia
    Berg, Gabriele
    Norelli, John
    Droby, Samir
    Wisniewski, Michael
    Evidence for host-microbiome co-evolution in apple2022In: New Phytologist, ISSN 0028-646X, E-ISSN 1469-8137, Vol. 234, no 6, p. 2088-2100Article in journal (Refereed)
    Abstract [en]
    • Plants evolved in association with a diverse community of microorganisms. The effect of plant phylogeny and domestication on host–microbiome co-evolutionary dynamics are poorly understood.
    • Here we examined the effect of domestication and plant lineage on the composition of the endophytic microbiome of 11 Malus species, representing three major groups: domesticated apple (M. domestica), wild apple progenitors, and wild Malus species.
    • The endophytic community of M. domestica and its wild progenitors showed higher microbial diversity and abundance than wild Malus species. Heirloom and modern cultivars harbored a distinct community composition, though the difference was not significant. A community-wide Bayesian model revealed that the endophytic microbiome of domesticated apple is an admixture of its wild progenitors, with clear evidence for microbiome introgression, especially for the bacterial community. We observed a significant correlation between the evolutionary distance of Malus species and their microbiome.
    • This study supports co-evolution between Malus species and their microbiome during domestication. This finding has major implications for future breeding programs and our understanding of the evolution of plants and their microbiomes.
  • 18.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Graz University of Technology, Austria.
    Whitehead, Susan R.
    Macarisin, Dumitru
    Liu, Jia
    Burchard, Erik
    Freilich, Shiri
    Dardick, Christopher
    Droby, Samir
    Wisniewski, Michael
    Effect of Washing, Waxing and Low-Temperature Storage on the Postharvest Microbiome of Apple2020In: Microorganisms, E-ISSN 2076-2607, Vol. 8, no 6, article id 944Article in journal (Refereed)
    Abstract [en]

    There is growing recognition of the role that the microbiome plays in the health and physiology of many plant species. However, considerably less research has been conducted on the postharvest microbiome of produce and the impact that postharvest processing may have on its composition. Here, amplicon sequencing was used to study the effect of washing, waxing, and low-temperature storage at 2 degrees C for six months on the bacterial and fungal communities of apple calyx-end, stem-end, and peel tissues. The results of the present work reveal that tissue-type is the main factor defining fungal and bacterial diversity and community composition on apple fruit. Both postharvest treatments and low temperature storage had a strong impact on the fungal and bacterial diversity and community composition of these tissue types. Distinct spatial and temporal changes in the composition and diversity of the microbiota were observed in response to various postharvest management practices. The greatest impact was attributed to sanitation practices with major differences among unwashed, washed and washed-waxed apples. The magnitude of the differences, however, was tissue-specific, with the greatest impact occurring on peel tissues. Temporally, the largest shift occurred during the first two months of low-temperature storage, although fungi were more affected by storage time than bacteria. In general, fungi and bacteria were impacted equally by sanitation practices, especially the epiphytic microflora of peel tissues. This research provides a foundation for understanding the impact of postharvest management practices on the microbiome of apple and its potential subsequent effects on postharvest disease management and food safety.

  • 19.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Graz University of Technology, Austria.
    Wisniewski, Michael
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS), USA.
    Schena, Leonardo
    Tack, Ayco J. M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Experimental evidence of microbial inheritance in plants and transmission routes from seed to phyllosphere and root2021In: Environmental Microbiology, ISSN 1462-2912, E-ISSN 1462-2920, Vol. 23, no 4, p. 2199-2214Article in journal (Refereed)
    Abstract [en]

    While the environment is considered the primary origin of the plant microbiome, the potential role of seeds as a source of transmitting microorganisms has not received much attention. Here we tested the hypothesis that the plant microbiome is partially inherited through vertical transmission. An experimental culturing device was constructed to grow oak seedlings in a microbe-free environment while keeping belowground and aboveground tissues separated. The microbial communities associated with the acorn's embryo and pericarp and the developing seeding's phyllosphere and root systems were analysed using amplicon sequencing of fungal ITS and bacterial 16S rDNA. Results showed that the seed microbiome is diverse and non-randomly distributed within an acorn. The microbial composition of the phyllosphere was diverse and strongly resembled the composition found in the embryo, whereas the roots and pericarp each had a less diverse and distinct microbial community. Our findings demonstrate a high level of microbial diversity and spatial partitioning of the fungal and bacterial community within both seed and seedling, indicating inheritance, niche differentiation and divergent transmission routes for the establishment of root and phyllosphere communities. 

  • 20.
    Abdel-Fattah, Dina
    et al.
    UiT – The Arctic University of Norway, Norway; University of Alaska Fairbanks, USA.
    Danielson, Mats
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences. International Institute for Applied Systems Analysis, Austria.
    Ekenberg, Love
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences. International Institute for Applied Systems Analysis, Austria.
    Hock, Regine
    University of Alaska Fairbanks, USA; University of Oslo, Norway.
    Trainor, Sarah
    University of Alaska Fairbanks, USA.
    Application of a structured decision-making process in cryospheric hazard planning: Case study of Bering Glacier surges on local state planning in Alaska2024In: Journal of Multi-Criteria Decision Analysis, ISSN 1057-9214, E-ISSN 1099-1360, Vol. 31, no 1-2, article id e1825Article in journal (Refereed)
    Abstract [en]

    Surging glaciers are glaciers that experience rapidly accelerated glacier flow over a comparatively short period of time. Though relatively rare worldwide, Alaska is home to the largest number of surge-type glaciers globally. However, their impact on the broader socioecological system in the state is both poorly understood and under-researched, which poses a challenge in developing appropriate sustainability decisions in Alaska. We investigated how the surge patterns of the Bering Glacier in Alaska have potentially devastating effects on the local ecological biodiversity of its watershed via a structured decision-making analysis of the different possible consequences. Specifically, this analysis was conducted to explore the various outcomes of a Bering Glacier surge particularly if humans have an increased presence near the glacier due to the area potentially becoming a state park. This work explored the benefits of applying a risk and decision analytical framework in a cryosphere context, to better understand the socioeconomic impact of glacier surges. This is a novel approach in which a decision analysis tool was used to better understand an environmental sustainability challenge, offering an innovative method to support the achievement of the United Nations Sustainability Development Goals in Alaska. We therefore emphasise the need for integrated biophysical and socioeconomic analyses when it comes to understanding glacier hazards. Our research highlights the importance of understanding and researching biophysical changes as well as using a structured decision-making process for complicated hazard planning scenarios, exemplified via glaciated regions in Alaska, in order to create adaptation strategies that are sustainable and encompass the range of possible outcomes.

  • 21.
    Abdelhamid, Hani Nasser
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Assiut University, Egypt.
    Dowaidar, Moataz
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hällbrink, Mattias
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gene delivery using cell penetrating peptides-zeolitic imidazolate frameworks2020In: Microporous and Mesoporous Materials, ISSN 1387-1811, E-ISSN 1873-3093, Vol. 300, article id 110173Article in journal (Refereed)
    Abstract [en]

    Cell-penetrating peptides (CPPs), and metal-organic frameworks (MOFs) are promising as next-generation for the delivery of gene-based therapeutic agents. Oligonucleotide (ON)-mediated assembly of nanostructures composed of hierarchical porous zeolitic imidazolate framework (ZIF-8), and nanoparticles such as graphene oxide (GO), and magnetic nanoparticles (MNPs) for gene therapy are reported. Five different types of non-viral vectors (ZIF-8, RhB@ZIF-8, BSA@ZIF-8, MNPs@ZIF-8, and GO@ZIF-8), and three gene therapeutic agents (plasmid, splice correction oligonucleotides (SCO), and small interfering RNA (siRNA)) were investigated. The polyplexes were characterized and applied for gene transfection. The materials show very low toxicity with high efficiency for luciferase transfection. ZIF-8 enhances the transfection of plasmid, SCO, siRNA of CPPs by 2-8 folds. The mechanism of the cell uptakes was also highlighted. Data reveal cell internalization via scavenger class A (SCARA).

  • 22.
    Abdelhamid, Hani Nasser
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Assiut University, Egypt.
    Dowaidar, Moataz
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Carbonized chitosan encapsulated hierarchical porous zeolitic imidazolate frameworks nanoparticles for gene delivery2020In: Microporous and Mesoporous Materials, ISSN 1387-1811, E-ISSN 1873-3093, Vol. 302, article id 110200Article in journal (Refereed)
    Abstract [en]

    Hierarchical mesoporous carbon (MPC) nanomaterials derived from the carbonized chitosan (CTS) encapsulated zeolitic imidazolate frameworks (ZIF-8) is synthesized and applied for gene delivery. The synthesis of ZIF-8 is achieved at room temperature using water as a solvent in the presence of CTS within 60 min. The synthesis method offered a hierarchical porous structure of ZIF-8. The carbonization of the prepared materials leads to the formation of MPC nanomaterials. MPC materials were applied as a non-viral vectors for gene delivery using two oligonucleotides (ONs) called Luciferase-expressing plasmid (pGL3), and splice correction oligonucleotides (SCO). The materials are biocompatible and showed insignificant toxicity. The transfection using MPC with and without cell-penetrating peptides (CPPs) was reported. MPC improved the transfection efficiency of CPPs (PepFect 14 (PF-14), and PF-221) by 10 fold due to the synergistic effect of MCP and CPPs. The reasonable mechanism for the cell transfection using these new vectors was also highlighted.

  • 23.
    Abdelhamid, Hani Nasser
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Assiut University, Egypt.
    Mathew, Aji P.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Cellulose-Based Nanomaterials Advance Biomedicine: A Review2022In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 10, article id 5405Article, review/survey (Refereed)
    Abstract [en]

    There are various biomaterials, but none fulfills all requirements. Cellulose biopolymers have advanced biomedicine to satisfy high market demand and circumvent many ecological concerns. This review aims to present an overview of cellulose knowledge and technical biomedical applications such as antibacterial agents, antifouling, wound healing, drug delivery, tissue engineering, and bone regeneration. It includes an extensive bibliography of recent research findings from fundamental and applied investigations. Cellulose-based materials are tailorable to obtain suitable chemical, mechanical, and physical properties required for biomedical applications. The chemical structure of cellulose allows modifications and simple conjugation with several materials, including nanoparticles, without tedious efforts. They render the applications cheap, biocompatible, biodegradable, and easy to shape and process.

  • 24.
    Abdel-Rehim, Abbi
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Abdel-Rehim, Mohamed
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Evaluation of microextraction by packed sorbent and micro-liquid chromatography-tandem mass spectrometry as a green approach in bioanalysis2013In: BMC Biomedical chromotography, ISSN 0269-3879, E-ISSN 1099-0801, Vol. 27, no 10, p. 1225-1233Article in journal (Refereed)
    Abstract [en]

    In this study the use of micro-liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was investigated in routine bioanalysis application for separation and quantification of pro-drug AZD6319 (developed for aldezheimer treatment). Microextraction by packed sorbent (MEPS) was used as sample clean-up method. The focus of this study was put on the evaluation of the usability of smaller column diameters such as 1.0 and 0.3mm instead of 2.1mm in bioanalysis application to reduce solvent consumption and sample volumes. Solvent consumption was reduced by 80% when a 1.0mm column was used compared with 2.1mm column. Robustness of the micro-columns in terms of accuracy and precision was investigated. The application of LC-MS/MS for the quantitative analysis of AZD6319 in plasma samples showed good selectivity, accuracy and precision. The coefficients of determination (R-2) were >0.998 for all runs using plasma samples on the studied micro-columns. The inter-day accuracy values for quality control samples ranged from 99 to 103% and from 96 to 105% for 0.3x50mm and 1.0x50mm columns, respectively. The inter-day precision values ranged from 4.0 to 9.0% and from 4.0 to 8.0% for 0.3x50 and 1.0x50mm columns, respectively. In addition the sensitivity was increased by three times using a 1.0mm column compared with 2.1mm. Furthermore, robustness of the micro-columns from different manufacturers was investigated.

  • 25.
    Abedi-Valugerdi, Manuchehr
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mercury and silver induce B cell activation and anti-nucleolar autoantibody production in outbred mouse stocks: are environmental factors more important than the susceptibility genes in connection with autoimmunity?2009In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 155, no 1, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Environmental and predisposing genetic factors are known to play a crucial role in the development of systemic autoimmune diseases. With respect to the role of environmental factors, it is not known how and to what extent they contribute to the initiation and exacerbation of systemic autoimmunity. In the present study, I considered this issue and asked if environmental factors can induce autoimmunity in the absence of specific susceptible genes. The development of genetically controlled mercury- and silver-induced B cell activation and anti-nucleolar autoantibodies (ANolA) production in genetically heterozygous outbred Institute of Cancer Research (ICR), Naval Medical Research Institute (NMRI) and Black Swiss mouse stocks were analysed. Four weeks of treatment with both mercury and silver induced a strong B cell activation characterized by increased numbers of splenic antibody-secreting cells of at least one or more immunoglobulin (Ig) isotype(s) in all treated stocks. The three stocks also exhibited a marked increase in the serum IgE levels in response to mercury, but not silver. More importantly, in response to mercury a large numbers of ICR (88%), NMRI (96%) and Black Swiss (100%) mice produced different levels of IgG1 and IgG2a ANolA (a characteristic which is linked strictly to the H-2 genes). Similarly, but at lower magnitudes, treatment with silver also induced the production of IgG1 and IgG2a ANolA in 60% of ICR, 75% of NMRI and 100% of Black Swiss mice. Thus, the findings of this study suggest that long-term exposure to certain environmental factors can activate the immune system to produce autoimmunity per se, without requiring specific susceptible genes.

  • 26.
    Abelein, Axel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Modulation of Alzheimer's amyloid β peptide self-assembly: Insights into molecular mechanisms of peptide aggregation associated with Alzheimer's disease2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Misfolding of proteins and peptides is closely linked to several neurodegenerative disorders, among them Alzheimer's disease (AD), the most prominent example of brain diseases. The self-assembly of the amyloid β peptide (Aβ) into amyloid fibrils is one histologic hallmark of AD. A detailed knowledge about the underlying mechanism(s) of Aβ aggregation is crucial for advances toward a fundamental understanding of the disease, which may promote the search for and design of efficient therapeutics. The work presented in this thesis deals with modulation of the aggregation process by various compounds, i.e. small organic molecules (e.g. lacmoid and Congo red), surfactants and metal ions. These results provide insight into the molecular mechanism of modulator interactions and interference with Aβ and its aggregation pathways. Applying a combination of kinetic and dynamic studies as well as structural investigations we characterized the molecular interactions between Aβ and aggregation modulators in terms of microscopic rate constants, conformational preferences and thermodynamics. An important conclusion is that these modulators form highly dynamic complexes with Aβ, with life-times on the timescale of milliseconds. Despite the similar exchange dynamics, the effect on peptide aggregation is modulator-specific and fibril formation can be accelerated, retarded or inhibited by their interactions. In summary, Aβ self-assembly is governed by microscopic kinetic and dynamic processes that can be altered by aggregation modulators. Further elucidation of these mechanisms is beneficial for the understanding and therapeutic intervention of amyloid diseases.

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  • 27.
    Abelein, Axel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Modulation of amyloid β peptide self-assembly: Aggregation mechanisms associated with Alzheimer's disease2013Licentiate thesis, comprehensive summary (Other academic)
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  • 28.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Abrahams, Jan Pieter
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Jarvet, Juri
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. National Institute of Chemical Physics and Biophysics, Estonia.
    Luo, Jinghui
    Tiiman, Ann
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wärmländer, Sebastian K. T. S.
    The hairpin conformation of the amyloid beta peptide is an important structural motif along the aggregation pathway2014In: Journal of Biological Inorganic Chemistry, ISSN 0949-8257, E-ISSN 1432-1327, Vol. 19, no 4-5, p. 623-634Article, review/survey (Refereed)
    Abstract [en]

    The amyloid beta (A beta) peptides are 39-42 residue-long peptides found in the senile plaques in the brains of Alzheimer's disease (AD) patients. These peptides self-aggregate in aqueous solution, going from soluble and mainly unstructured monomers to insoluble ordered fibrils. The aggregation process(es) are strongly influenced by environmental conditions. Several lines of evidence indicate that the neurotoxic species are the intermediate oligomeric states appearing along the aggregation pathways. This minireview summarizes recent findings, mainly based on solution and solid-state NMR experiments and electron microscopy, which investigate the molecular structures and characteristics of the A beta peptides at different stages along the aggregation pathways. We conclude that a hairpin-like conformation constitutes a common motif for the A beta peptides in most of the described structures. There are certain variations in different hairpin conformations, for example regarding H-bonding partners, which could be one reason for the molecular heterogeneity observed in the aggregated systems. Interacting hairpins are the building blocks of the insoluble fibrils, again with variations in how hairpins are organized in the cross-section of the fibril, perpendicular to the fibril axis. The secondary structure propensities can be seen already in peptide monomers in solution. Unfortunately, detailed structural information about the intermediate oligomeric states is presently not available. In the review, special attention is given to metal ion interactions, particularly the binding constants and ligand structures of A beta complexes with Cu(II) and Zn(II), since these ions affect the aggregation process(es) and are considered to be involved in the molecular mechanisms underlying AD pathology.

  • 29.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bolognesi, Benedetta
    Dobson, Christopher M.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lendel, Christofer
    Hydrophobicity and conformational change as mechanistic determinants for nonspecific modulators of amyloid β self-assembly2012In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 51, no 1, p. 126-137Article in journal (Refereed)
    Abstract [en]

    The link between many neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, and the aberrant folding and aggregation of proteins has prompted a comprehensive search for small organic molecules that have the potential to inhibit such processes. Although many compounds have been reported to affect the formation of amyloid fibrils and/or other types of protein aggregates, the mechanisms by which they act are not well understood. A large number of compounds appear to act in a nonspecific way affecting several different amyloidogenic proteins. We describe here a detailed study of the mechanism of action of one representative compound, lacmoid, in the context of the inhibition of the aggregation of the amyloid β-peptide (Aβ) associated with Alzheimer's disease. We show that lacmoid binds Aβ(1-40) in a surfactant-like manner and counteracts the formation of all types of Aβ(1-40) and Aβ(1-42) aggregates. On the basis of these and previous findings, we are able to rationalize the molecular mechanisms of action of nonspecific modulators of protein self-assembly in terms of hydrophobic attraction and the conformational preferences of the polypeptide.

  • 30. Abelein, Axel
    et al.
    Ciofi-Baffoni, Simone
    Mörman, Cecilia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Kumar, Rakesh
    Giachetti, Andrea
    Piccioli, Mario
    Biverstål, Henrik
    Molecular Structure of Cu(II)-Bound Amyloid-β Monomer Implicated in Inhibition of Peptide Self-Assembly in Alzheimer’s Disease2022In: JACS Au, E-ISSN 2691-3704, Vol. 2, no 11, p. 2571-2584Article in journal (Refereed)
    Abstract [en]

    Metal ions, such as copper and zinc ions, have been shown to strongly modulate the self-assembly of the amyloid-β (Aβ) peptide into insoluble fibrils, and elevated concentrations of metal ions have been found in amyloid plaques of Alzheimer’s patients. Among the physiological transition metal ions, Cu(II) ions play an outstanding role since they can trigger production of neurotoxic reactive oxygen species. In contrast, structural insights into Cu(II) coordination of Aβ have been challenging due to the paramagnetic nature of Cu(II). Here, we employed specifically tailored paramagnetic NMR experiments to determine NMR structures of Cu(II) bound to monomeric Aβ. We found that monomeric Aβ binds Cu(II) in the N-terminus and combined with molecular dynamics simulations, we could identify two prevalent coordination modes of Cu(II). For these, we report here the NMR structures of the Cu(II)–bound Aβ complex, exhibiting heavy backbone RMSD values of 1.9 and 2.1 Å, respectively. Further, applying aggregation kinetics assays, we identified the specific effect of Cu(II) binding on the Aβ nucleation process. Our results show that Cu(II) efficiently retards Aβ fibrillization by predominately reducing the rate of fibril-end elongation at substoichiometric ratios. A detailed kinetic analysis suggests that this specific effect results in enhanced Aβ oligomer generation promoted by Cu(II). These results can quantitatively be understood by Cu(II) interaction with the Aβ monomer, forming an aggregation inert complex. In fact, this mechanism is strikingly similar to other transition metal ions, suggesting a common mechanism of action of retarding Aβ self-assembly, where the metal ion binding to monomeric Aβ is a key determinant. 

  • 31.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    The zinc ion – a minimal chaperone mimicking agent forretardation of amyloid β peptide fibril formationManuscript (preprint) (Other academic)
  • 32.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Zinc as chaperone-mimicking agent for retardation of amyloid beta peptide fibril formation2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 17, p. 5407-5412Article in journal (Refereed)
    Abstract [en]

    Metal ions have emerged to play a key role in the aggregation process of amyloid beta (A beta) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic A beta-Zn2+ binding features as well as how Zn2+ modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn2+ effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc A beta(40) aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn2+, the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn2+ transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn2+ ion, forming a marginally stable, short-lived folded A beta(40) species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded A beta(40)-Zn2+ complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for A beta(40).

  • 33.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kaspersen, Jørn Døvling
    Nielsen, Søren Bang
    Jensen, Grethe Vestergaard
    Christiansen, Gunna
    Pedersen, Jan Skov
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Otzen, Daniel E.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates2013In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 32, p. 23518-23528Article in journal (Refereed)
    Abstract [en]

    Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.

  • 34.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lendel, Christofer
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Corrigendum to “Transient small molecule interactions kinetically modulate amyloid β peptide self-assembly” [FEBS Lett. 586 (2012) 3991–3995]2013In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 587, no 9, p. 1452-1452Article in journal (Other academic)
  • 35.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lendel, Christofer
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Transient small molecule interactions kinetically modulate amyloid beta peptide self-assembly2012In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 586, no 22, p. 3991-3995Article in journal (Refereed)
    Abstract [en]

    Small organic molecules, like Congo red and lacmoid, have been shown to modulate the self-assembly of the amyloid beta peptide (A beta). Here, we show that A beta forms NMR invisible non-toxic co-aggregates together with lacmoid as well as Congo red. We find that the interaction involves two distinct kinetic processes and at every given time point only a small fraction of A beta is in the co-aggregate. These weak transient interactions kinetically redirect the aggregation prone A beta from self-assembling into amyloid fibrils. These findings suggest that even such weak binders might be effective as therapeutics against pathogenic protein aggregation.

  • 36.
    Abens, Jānis
    Stockholm University.
    On the neurohormonal peptides NPY and VIP and their receptors1988Doctoral thesis, comprehensive summary (Other academic)
  • 37. Abihudi, Siri A.
    et al.
    de Boer, Hugo J.
    Treydte, Anna C.
    Stockholm University, Faculty of Science, Department of Physical Geography. Nelson Mandela African Institution for Science and Technology (NM-AIST), Tanzania.
    Conservation status revision and communities' perceptions of 22 Aloe species in Tanzania2021In: Plant Ecology and Evolution, ISSN 2032-3913, E-ISSN 2032-3921, Vol. 154, no 3, p. 391-404Article in journal (Refereed)
    Abstract [en]

    Background and aims – Many Aloe species are globally threatened due to overharvesting for trade and habitat destruction. CITES regulates their international trade. In Tanzania, 50% of all existing Aloe species had previously been assessed, though some of these assessments were Data Deficient. For those with sufficient data, an update is required as the rate of decline has rapidly increased over the last years.

    Material and methods – We estimated Area of Occupancy (AOO), Extent of Occurrence (EOO), and number of locations for 22 Tanzanian Aloe species using the Geospatial Conservation Assessment software (GeoCAT). We assessed the reasons leading to their decline based on direct field observations and community perceptions.

    Key results – We revised the conservation status of 22 Aloe species; two were assessed as Critically Endangered, ten as Endangered, five as Vulnerable, and five as Least Concern. We re-discovered the Critically Endangered Aloe boscawenii, which had not been seen in Tanzania for more than six decades. We propose to downgrade the endemic Aloe dorotheaeAloe leptosiphon, and Aloe flexilifolia from Critically Endangered to a lower threat level. The community perception on Aloe species availability did not accurately reflect their categorisation based on the IUCN criteria B. We identified agricultural activities and climate change effects as the two main threats to Tanzanian Aloe species.

    Conclusion – We conclude that overall numbers are declining for 22 Aloe species in Tanzania, mainly due to human activities. We recommend the implementation of laws and policies to protect their natural habitats.

  • 38. Abildgaard, Amanda B.
    et al.
    Voutsinos, Vasileios
    Petersen, Søren D.
    Larsen, Fia B.
    Kampmeyer, Caroline
    Johansson, Kristoffer E.
    Stein, Amelie
    Ravid, Tommer
    Andréasson, Claes
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Jensen, Michael K.
    Lindorff-Larsen, Kresten
    Hartmann-Petersen, Rasmus
    HSP70-binding motifs function as protein quality control degrons2023In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 80, no 1, article id 32Article in journal (Refereed)
    Abstract [en]

    Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding. 

  • 39. Abiven, Samuel
    et al.
    Hund, Andreas
    Martinsen, Vegard
    Cornelissen, Gerard
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM). Norwegian University of Life Sciences (NMBU), Norway; Norwegian Geotechnical Institute (NGI), Norway .
    Biochar amendment increases maize root surface areas and branching: a shovelomics study in Zambia2015In: Plant and Soil, ISSN 0032-079X, E-ISSN 1573-5036, Vol. 395, no 1-2, p. 45-55Article in journal (Refereed)
    Abstract [en]

    Positive crop yield effects from biochar are likely explained by chemical, physical and/or biological factors. However, studies describing plant allometric changes are scarcer, but may be crucial to understand the biochar effect. The main aim of the present study is to investigate the effect of biochar on root architecture under field conditions in a tropical setting. The presented work describes a shovelomics (i.e., description of root traits in the field) study on the effect of biochar on maize root architecture. Four field experiments we carried out at two different locations in Zambia, exhibiting non-fertile to relatively fertile soils. Roots of maize crop (Zea mays L.) were sampled from treatments with fertilizer (control) and with a combination of fertilizer and 4 t.ha(-1) maize biochar application incorporated in the soil. For the four sites, the average grain yield increase upon biochar addition was 45 +/- 14 % relative to the fertilized control (from 2.1-6.0 to 3.1-9.1 ton ha(-1)). The root biomass was approximately twice as large for biochar-amended plots. More extensive root systems (especially characterized by a larger root opening angle (+14 +/- 11 %) and wider root systems (+20 +/- 15 %)) were observed at all biochar-amended sites. Root systems exhibited significantly higher specific surface areas (+54 +/- 14 %), branching and fine roots: +70 +/- 56 %) in the presence of biochar. Biochar amendment resulted in more developed root systems and larger yields. The more extensive root systems may have contributed to the observed yield increases, e.g., by improving immobile nutrients uptake in soils that are unfertile or in areas with prolonged dry spells.

  • 40. Abou-Hamdan, Abbas
    et al.
    Mahler, Roman
    Grossenbacher, Philipp
    Biner, Olivier
    Sjöstrand, Dan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lochner, Martin
    Högbom, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Ballmoos, Christoph
    Functional design of bacterial superoxide: quinone oxidoreductase2022In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1863, no 7, article id 148583Article in journal (Refereed)
    Abstract [en]

    The superoxide anion - molecular oxygen reduced by a single electron - is produced in large amounts by enzymatic and adventitious reactions. It can perform a range of cellular functions, including bacterial warfare and iron uptake, signalling and host immune response in eukaryotes. However, it also serves as precursor for more deleterious species such as the hydroxyl anion or peroxynitrite and defense mechanisms to neutralize superoxide are important for cellular health. In addition to the soluble proteins superoxide dismutase and superoxide reductase, recently the membrane embedded diheme cytochrome b561 (CybB) from E. coli has been proposed to act as a superoxide:quinone oxidoreductase. Here, we confirm superoxide and cellular ubiquinones or menaquinones as natural substrates and show that quinone binding to the enzyme accelerates the reaction with superoxide. The reactivity of the substrates is in accordance with the here determined midpoint potentials of the two b hemes (+48 and -23 mV / NHE). Our data suggest that the enzyme can work near the diffusion limit in the forward direction and can also catalyse the reverse reaction efficiently under physiological conditions. The data is discussed in the context of described cytochrome b561 proteins and potential physiological roles of CybB.

  • 41. Abraham, Mark
    et al.
    Apostolov, Rossen
    Barnoud, Jonathan
    Bauer, Paul
    Blau, Christian
    Bonvin, Alexandre M. J. J.
    Chavent, Matthieu
    Chodera, John
    Condic-Jurkic, Karmen
    Delemotte, Lucie
    Grubmueller, Helmut
    Howard, Rebecca J.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Jordan, E. Joseph
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lindahl, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). KTH Royal Institute of Technology, Sweden.
    Ollila, O. H. Samuli
    Selent, Jana
    Smith, Daniel G. A.
    Stansfeld, Phillip J.
    Tiemann, Johanna K. S.
    Trellet, Mikael
    Woods, Christopher
    Zhmurov, Artem
    Sharing Data from Molecular Simulations2019In: Journal of Chemical Information and Modeling, ISSN 1549-9596, E-ISSN 1549-960X, Vol. 59, no 10, p. 4093-4099Article in journal (Refereed)
    Abstract [en]

    Given the need for modern researchers to produce open, reproducible scientific output, the lack of standards and best practices for sharing data and workflows used to produce and analyze molecular dynamics (MD) simulations has become an important issue in the field. There are now multiple well-established packages to perform molecular dynamics simulations, often highly tuned for exploiting specific classes of hardware, each with strong communities surrounding them, but with very limited interoperability/transferability options. Thus, the choice of the software package often dictates the workflow for both simulation production and analysis. The level of detail in documenting the workflows and analysis code varies greatly in published work, hindering reproducibility of the reported results and the ability for other researchers to build on these studies. An increasing number of researchers are motivated to make their data available, but many challenges remain in order to effectively share and reuse simulation data. To discuss these and other issues related to best practices in the field in general, we organized a workshop in November 2018 (https://bioexcel.eu/events/workshop-on-sharing-data-from-molecular-simulations/). Here, we present a brief overview of this workshop and topics discussed. We hope this effort will spark further conversation in the MD community to pave the way toward more open, interoperable, and reproducible outputs coming from research studies using MD simulations.

  • 42. Abrahamczyk, S.
    et al.
    Kessler, M.
    Hanley, D.
    Karger, D. N.
    Mueller, M. P. J.
    Knauer, A. C.
    Keller, F.
    Schwerdtfeger, M.
    Humphreys, Aelys M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Imperial College London, UK.
    Pollinator adaptation and the evolution of floral nectar sugar composition2017In: Journal of Evolutionary Biology, ISSN 1010-061X, E-ISSN 1420-9101, Vol. 30, no 1, p. 112-127Article in journal (Refereed)
    Abstract [en]

    A long-standing debate concerns whether nectar sugar composition evolves as an adaptation to pollinator dietary requirements or whether it is 'phylogenetically constrained'. Here, we use a modelling approach to evaluate the hypothesis that nectar sucrose proportion (NSP) is an adaptation to pollinators. We analyse similar to 2100 species of asterids, spanning several plant families and pollinator groups (PGs), and show that the hypothesis of adaptation cannot be rejected: NSP evolves towards two optimal values, high NSP for specialist-pollinated and low NSP for generalist-pollinated plants. However, the inferred adaptive process is weak, suggesting that adaptation to PG only provides a partial explanation for how nectar evolves. Additional factors are therefore needed to fully explain nectar evolution, and we suggest that future studies might incorporate floral shape and size and the abiotic environment into the analytical framework. Further, we show that NSP and PG evolution are correlated - in a manner dictated by pollinator behaviour. This contrasts with the view that a plant necessarily has to adapt its nectar composition to ensure pollination but rather suggests that pollinators adapt their foraging behaviour or dietary requirements to the nectar sugar composition presented by the plants. Finally, we document unexpectedly sucrose-poor nectar in some specialized nectarivorous bird-pollinated plants from the Old World, which might represent an overlooked form of pollinator deception. Thus, our broad study provides several new insights into how nectar evolves and we conclude by discussing why maintaining the conceptual dichotomy between adaptation and constraint might be unhelpful for advancing this field.

  • 43. Abrahamczyk, Stefan
    et al.
    Humphreys, Aelys M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Trabert, Felix
    Droppelmann, Fabian
    Gleichmann, Maria
    Krieger, Vera
    Linnartz, Marius
    Lozada-Gobilard, Sissi
    Rahelivololona, Marie Elisette
    Schubert, Marian
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Janssens, Steven B.
    Weigend, Maximilian
    Fischer, Eberhard
    Evolution of brood-site mimicry in Madagascan Impatiens (Balsaminaceae)2021In: Perspectives in plant ecology, evolution and systematics, ISSN 1433-8319, E-ISSN 1618-0437, Vol. 49, article id 125590Article in journal (Refereed)
    Abstract [en]

    The species-rich flora of Madagascar is well known for a range of unusual floral ecologies. One example is Impatiens section Trimorphopetalum with its unique combination of floral traits: small, spur-less, cup-or lip shaped, greenish or brownish flowers. So far no hypotheses on floral function or pollination of this peculiar group have been proposed. We analysed six reproductive traits in relation to pollination syndromes for 34 Madagascan Impatiens species, including 18 species of section Trimorphopetalum plus six outgroup species, in a phylogenetic framework. Further, we present pollinator observations for one additional species of Trimophopetalum. All pollination syndromes occurring in the African species are also present in Madagascan Impatiens. In addition, species of Trimorphopetalum represent two unique floral types, possibly corresponding to two different types of fly pollination. The evolution of these flower types corresponds to a strong decrease in nectar production, flower display size, pollen grain and ovule number. Autogamy is found in one derived sub-clade of the otherwise largely pollinator-dependent Trimorphopetalum. We find evidence consistent with the evolution of brood-site deception and fungus mimicry in combination with fly pollination in one clade of Trimorphopetalum and the stepwise evolution of autogamy in the second clade. The evolution of these very different reproductive strategies may have been triggered by pollinator limitation in the dense, humid forest undergrowth of Madagascar.

  • 44. Abramsson, Mia L.
    et al.
    Sahin, Cagla
    Hopper, Jonathan T. S.
    Branca, Rui M. M.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Xu, Mingming
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Chandler, Shane A.
    Österlund, Nicklas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Leppert, Axel
    Costeira-Paulo, Joana
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Teilum, Kaare
    Laganowsky, Arthur
    Benesch, Justin L. P.
    Oliveberg, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Robinson, Carol V.
    Marklund, Erik G.
    Allison, Timothy M.
    Winther, Jakob R.
    Landreh, Michael
    Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry2021In: JACS Au, E-ISSN 2691-3704, Vol. 1, no 12, p. 2385-2393Article in journal (Refereed)
    Abstract [en]

    In solution, the charge of a protein is intricately linked to its stability, but electrospray ionization distorts this connection, potentially limiting the ability of native mass spectrometry to inform about protein structure and dynamics. How the behavior of intact proteins in the gas phase depends on the presence and distribution of ionizable surface residues has been difficult to answer because multiple chargeable sites are present in virtually all proteins. Turning to protein engineering, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, while coexisting conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. In fact, moving a single ionizable group can dramatically alter the gas-phase conformation of a protein ion. We conclude that although the sum of the charges is governed solely by Coulombic terms, their locations affect the stability of the protein in the gas phase.

  • 45. Abrego, Nerea
    et al.
    Huotari, Tea
    Tack, Ayco J. M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Lindahl, Björn D.
    Tikhonov, Gleb
    Somervuo, Panu
    Schmidt, Niels Martin
    Ovaskainen, Otso
    Roslin, Tomas
    Higher host plant specialization of root-associated endophytes than mycorrhizal fungi along an arctic elevational gradient2020In: Ecology and Evolution, E-ISSN 2045-7758, Vol. 10, no 16, p. 8989-9002Article in journal (Refereed)
    Abstract [en]

    How community-level specialization differs among groups of organisms, and changes along environmental gradients, is fundamental to understanding the mechanisms influencing ecological communities. In this paper, we investigate the specialization of root-associated fungi for plant species, asking whether the level of specialization varies with elevation. For this, we applied DNA barcoding based on the ITS region to root samples of five plant species equivalently sampled along an elevational gradient at a high arctic site. To assess whether the level of specialization changed with elevation and whether the observed patterns varied between mycorrhizal and endophytic fungi, we applied a joint species distribution modeling approach. Our results show that host plant specialization is not environmentally constrained in arctic root-associated fungal communities, since there was no evidence for changing specialization with elevation, even if the composition of root-associated fungal communities changed substantially. However, the level of specialization for particular plant species differed among fungal groups, root-associated endophytic fungal communities being highly specialized on particular host species, and mycorrhizal fungi showing almost no signs of specialization. Our results suggest that plant identity affects associated mycorrhizal and endophytic fungi differently, highlighting the need of considering both endophytic and mycorrhizal fungi when studying specialization in root-associated fungal communities.

  • 46. Abrego, Nerea
    et al.
    Roslin, Tomas
    Huotari, Tea
    Tack, Ayco J. M.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Lindahl, Björn D.
    Tikhonov, Gleb
    Somervuo, Panu
    Schmidt, Niels Martin
    Ovaskainen, Otso
    Accounting for environmental variation in co-occurrence modelling reveals the importance of positive interactions in root-associated fungal communities2020In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 29, no 14, p. 2736-2746Article in journal (Refereed)
    Abstract [en]

    Understanding the role of interspecific interactions in shaping ecological communities is one of the central goals in community ecology. In fungal communities, measuring interspecific interactions directly is challenging because these communities are composed of large numbers of species, many of which are unculturable. An indirect way of assessing the role of interspecific interactions in determining community structure is to identify the species co-occurrences that are not constrained by environmental conditions. In this study, we investigated co-occurrences among root-associated fungi, asking whether fungi co-occur more or less strongly than expected based on the environmental conditions and the host plant species examined. We generated molecular data on root-associated fungi of five plant species evenly sampled along an elevational gradient at a high arctic site. We analysed the data using a joint species distribution modelling approach that allowed us to identify those co-occurrences that could be explained by the environmental conditions and the host plant species, as well as those co-occurrences that remained unexplained and thus more probably reflect interactive associations. Our results indicate that not only negative but also positive interactions play an important role in shaping microbial communities in arctic plant roots. In particular, we found that mycorrhizal fungi are especially prone to positively co-occur with other fungal species. Our results bring new understanding to the structure of arctic interaction networks by suggesting that interactions among root-associated fungi are predominantly positive.

  • 47.
    Abreu-Vieira, Gustavo
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Regulation and measurement of brown adipose tissue blood flow2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Brown adipose tissue (BAT) is an organ specialized in macromolecule combustion in order to produce heat. Because of its high capacity to dissipate energy, it is currently among the best hopes for future treatments of obesity and diabetes. BAT is permeated by a vast capillary network that delivers blood rich in oxygen and nutrients to supply the high metabolic needs of the tissue. At the same time, metabolites, carbon dioxide and warm blood are drained back into systemic circulation. Blood flow is in fact a limiting factor for thermogenesis. Therefore, understanding BAT blood flow regulation is a crucial step for describing the tissue function. This thesis aims to summarize anatomical descriptions, to discuss the methodological evolution of the field, and to synthetize what we have learned about mechanistic regulation of BAT blood flow during the last half century. Manuscript I introduces a new method (high-resolution laser-doppler imaging) for the measurement of BAT blood flow, and gives mechanistic insights about its physiological regulation. Manuscript II focuses on the influence of bombesin receptor subtype-3 on the neurological control of body temperature and thermogenesis.

  • 48.
    Abreu-Vieira, Gustavo
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bengtsson, Tore
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Petrovic, Natasa
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    On adequate procedures for glucose tolerance tests in obese animals: Measurement of glucose tolerance in obesityManuscript (preprint) (Other academic)
    Abstract [en]

    Routine procedures for glucose tolerance test in rodents utilize an amount of injected glucose that is proportional to total body weight (normally 2 mg per g body weight). Obese mice consist of much more chemically inert lipid than lean mice but have only marginal increases in lean body mass (the only compartment where glucose is distributed). Present procedures thus inevitably lead to a diagnosis of impaired glucose tolerance and enhanced insulin levels in obesity. Routine procedures should use fixed glucose amounts per lean body mass (or per mouse).

  • 49.
    Abreu-Vieira, Gustavo
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Fischer, Alexander W.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Hamburg, Germany.
    Mattsson, Charlotte
    de Jong, Jasper M. A.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Shabalina, Irina G.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Ryden, Mikael
    Laurencikiene, Jurga
    Arner, Peter
    Cannon, Barbara
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Petrovic, Natasa
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cidea improves the metabolic profile through expansion of adipose tissue2015In: Nature Communications, E-ISSN 2041-1723, Vol. 6, article id 7433Article in journal (Refereed)
    Abstract [en]

    In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

  • 50.
    Abreu-Vieira, Gustavo
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Hagberg, Carolina E.
    Spalding, Kirsty L.
    Cannon, Barbara
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nedergaard, Jan
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis: Regulation of brown adipose tissue blood flow2015In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 308, no 9, p. E822-E829Article in journal (Refereed)
    Abstract [en]

    Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen, and for the distribution of the generated heat to the rest of the body. It is therefore fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive, in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner, and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine, despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycaemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel non-invasive method to detect BAT perfusion, we demonstrate that adrenergically-stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and is therefore not a reliable parameter for the estimation of BAT activation and heat generation.

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