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1.	Sanli, Kemal, et al. (author) Metagenomic Sequencing of Marine Periphyton: Taxonomic and Functional Insights into Biofilm Communities 2015 In: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6:1192 Journal article (peer-reviewed)abstract Periphyton communities are complex phototrophic, multispecies biofilms that develop on surfaces in aquatic environments. These communities harbor a large diversity of organisms comprising viruses, bacteria, algae, fungi, protozoans and metazoans. However, thus far the total biodiversity of periphyton has not been described. In this study, we use metagenomics to characterize periphyton communities from the marine environment of the Swedish west coast. Although we found approximately ten times more eukaryotic rRNA marker gene sequences compared to prokaryotic, the whole metagenome-based similarity searches showed that bacteria constitute the most abundant phyla in these biofilms. We show that marine periphyton encompass a range of heterotrophic and phototrophic organisms. Heterotrophic bacteria, including the majority of proteobacterial clades and Bacteroidetes, and eukaryotic macro-invertebrates were found to dominate periphyton. The phototrophic groups comprise Cyanobacteria and the alpha-proteobacterial genus Roseobacter, followed by different micro- and macro-algae. We also assess the metabolic pathways that predispose these communities to an attached lifestyle. Functional indicators of the biofilm form of life in periphyton involve genes coding for enzymes that catalyze the production and degradation of extracellular polymeric substances, mainly in the form of complex sugars such as starch and glycogen-like meshes together with chitin. Genes for 278 different transporter proteins were detected in the metagenome, constituting the most abundant protein complexes. Finally, genes encoding enzymes that participate in anaerobic pathways, such as denitrification and methanogenesis, were detected suggesting the presence of anaerobic or low-oxygen micro-zones within the biofilms.
2.	Airaud, M, et al. (author) Biologie - Les manuels visuels pour la Licence 2018 Book (other academic/artistic)abstract En couleurs et très illustré, ce manuel a été conçu pour vous qui débutez un cursus scientifique universitaire. Il vous permettra d’acquérir les connaissances fondamentales en biologie, mais aussi la démarche et la rigueur scientifiques indispensables aux études supérieures. De multiples rubriques vous garantissent un apprentissage progressif et complet : un cours visuel avec de nombreux exemples concrets pour introduire et illustrer les notions et concepts clés ; des encadrés méthodologiques pour vous guider vers les bonnes pratiques et vous faire découvrir les grandes méthodes expérimentales ; des focus sur des applications, sujets de recherche ou thèmes d’actualité ; des repères historiques ; de nombreux QCM et exercices (tous corrigés) pour tester vos acquis et vous entraîner.
3.	Subhash, Santhilal, 1987, et al. (author) Sperm Originated Chromatin Imprints and LincRNAs in Organismal Development and Cancer 2020 In: iScience. - : Elsevier BV. - 2589-0042. ; 23:6 Journal article (peer-reviewed)abstract Importance of sperm-derived transcripts and chromatin imprints in organismal development is poorly investigated. Here using an integrative approach, we show that human sperm transcripts are equally important as oocyte. Sperm-specific and sperm-oocyte common transcripts carry distinct chromatin structures at their promoters correlating with corresponding transcript levels in sperm. Interestingly, sperm-specific H3K4me3 patterns at the lincRNA promoters are not maintained in the germ layers and somatic tissues. However, bivalent chromatin at the sperm-specific protein-coding gene promoters is maintained throughout the development. Sperm-specific transcripts reach their peak expression during zygotic genome activation, whereas sperm-oocyte common transcripts are present during early preimplantation development but decline at the onset of zygotic genome activation. Additionally, there is an inverse correlation between sperm-specific and sperm-oocyte lincRNAs throughout the development. Sperm-lincRNAs also show aberrant activation in tumors. Overall, our observations indicate that sperm transcripts carrying chromatin imprints may play an important role in human development and cancer.
4.	Bienert, Gern, 2008, et al. (author) A subgroup of plant aquaporins facilitate the bi-directional diffusion of As(OH)3 and Sb(OH)3 across membranes 2008 In: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 6:26 Journal article (peer-reviewed)abstract Background Arsenic is a toxic and highly abundant metalloid that endangers human health through drinking water and the food chain. The most common forms of arsenic in the environment are arsenate (As(V)) and arsenite (As(III)). As(V) is a non-functional phosphate analog that enters the food chain via plant phosphate transporters. Inside cells, As(V) becomes reduced to As(III) for subsequent extrusion or compartmentation. Although much is known about As(III) transport and handling in microbes and mammals, the transport systems for As(III) have not yet been characterized in plants. Results Here we show that the Nodulin26-like Intrinsic Proteins (NIPs) AtNIP5;1 and AtNIP6;1 from Arabidopsis thaliana, OsNIP2;1 and OsNIP3;2 from Oryza sativa, and LjNIP5;1 and LjNIP6;1 from Lotus japonicus are bi-directional As(III) channels. Expression of these NIPs sensitized yeast cells to As(III) and antimonite (Sb(III)), and direct transport assays confirmed their ability to facilitate As(III) transport across cell membranes. On medium containing As(V), expression of the same NIPs improved yeast growth, probably due to increased As(III) efflux. Our data furthermore provide evidence that NIPs can discriminate between highly similar substrates and that they may have differential preferences in the direction of transport. A subgroup of As(III) permeable channels that group together in a phylogenetic tree required N-terminal truncation for functional expression in yeast. Conclusion This is the first molecular identification of plant As(III) transport systems and we propose that metalloid transport through NIPs is a conserved and ancient feature. Our observations are potentially of great importance for improved remediation and tolerance of plants, and may provide a key to the development of low arsenic crops for food production.
5.	Green, Leon, et al. (author) Ancestral Sperm Ecotypes Reveal Multiple Invasions of a Non-Native Fish in Northern Europe 2021 In: Cells. - : MDPI AG. - 2073-4409. ; 10:7 Journal article (peer-reviewed)abstract For externally fertilising organisms in the aquatic environment, the abiotic fertilisation medium can be a strong selecting force. Among bony fishes, sperm are adapted to function in a narrow salinity range. A notable exception is the family Gobiidae, where several species reproduce across a wide salinity range. The family also contains several wide-spread invasive species. To better understand how these fishes tolerate such varying conditions, we measured sperm performance in relation to salinity from a freshwater and a brackish population within their ancestral Ponto-Caspian region of the round goby, Neogobius melanostomus. These two ancestral populations were then compared to nine additional invaded sites across northern Europe, both in terms of their sperm traits and by using genomic SNP markers. Our results show clear patterns of ancestral adaptations to freshwater and brackish salinities in their sperm performance. Population genomic analyses show that the ancestral ecotypes have generally established themselves in environments that fit their sperm adaptations. Sites close to ports with intense shipping show that both outbreeding and admixture can affect the sperm performance of a population in a given salinity. Rapid adaptation to local conditions is also supported at some sites. Historical and contemporary evolution in the traits of the round goby sperm cells is tightly linked to the population and seascape genomics as well as biogeographic processes in these invasive fishes. Since the risk of a population establishing in an area is related to the genotype by environment match, port connectivity and the ancestry of the round goby population can likely be useful for predicting the species spread.
6.	Mozzachiodi, S., et al. (author) Aborting meiosis allows recombination in sterile diploid yeast hybrids 2021 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1 Journal article (peer-reviewed)abstract Hybrids are often considered evolutionary dead ends because they do not generate viable offspring. Here, the authors show that sterile yeast hybrids generate genetic diversity through meiotic-like recombination by aborting meiosis and return to asexual growth. Hybrids between diverged lineages contain novel genetic combinations but an impaired meiosis often makes them evolutionary dead ends. Here, we explore to what extent an aborted meiosis followed by a return-to-growth (RTG) promotes recombination across a panel of 20 Saccharomyces cerevisiae and S. paradoxus diploid hybrids with different genomic structures and levels of sterility. Genome analyses of 275 clones reveal that RTG promotes recombination and generates extensive regions of loss-of-heterozygosity in sterile hybrids with either a defective meiosis or a heavily rearranged karyotype, whereas RTG recombination is reduced by high sequence divergence between parental subgenomes. The RTG recombination preferentially arises in regions with low local heterozygosity and near meiotic recombination hotspots. The loss-of-heterozygosity has a profound impact on sexual and asexual fitness, and enables genetic mapping of phenotypic differences in sterile lineages where linkage analysis would fail. We propose that RTG gives sterile yeast hybrids access to a natural route for genome recombination and adaptation.
7.	Sköld, Helen Nilsson, et al. (author) Hormonal regulation of female nuptial coloration in a fish. 2008 In: Hormones and behavior. - : Elsevier BV. - 1095-6867 .- 0018-506X. ; 54:4, s. 549-56 Journal article (peer-reviewed)abstract Physiological color change in camouflage and mating is widespread among fishes, but little is known about the regulation of such temporal changes in nuptial coloration and particularly concerning female coloration. To better understand regulation of nuptial coloration we investigated physiological color change in female two-spotted gobies (Gobiusculus flavescens). Females of this species develop an orange belly that acts as an ornament. The orange color is caused by the color of the gonads combined with the chromathophore based pigmentation and transparency of the skin. Often during courtship and female-female competition, a rapid increase in orange coloration, in combination with lighter sides and back that increases skin and body transparency, gives the belly an intense 'glowing' appearance. To understand how this increased orange coloration can be regulated we analysed chromatic and transparency effects of neurohumoral agents on abdominal skin biopsies in vitro. We found prolactin and alpha-melanocyte stimulating hormone (MSH) to increase orange coloration of the skin. By contrast, melatonin and noradrenaline increased skin transparency, but had a negative effect on orange coloration. However, mixtures of melatonin and MSH, or melatonin and prolactin, increased both orange coloration and transparency. This effect mimics the chromatic 'glow' effect that commonly takes place during courtship and intra sexual aggression. Notably, not only epidermal chromatophores but also internal chromatophores lining the peritoneum responded to hormone treatments. There were no chromatic effects of the sex steroids 17beta-estradiol, testosterone or 11-ketotestosterone. We hypothesize that similar modulation of nuptial coloration by multiple hormones may be widespread in nature.
8.	Stenberg, Simon, et al. (author) Control of mitochondrial superoxide production includes programmed mtDNA deletion and restoration 2020 Journal article (other academic/artistic)abstract Deletion of mitochondrial DNA in eukaryotes is mainly attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that the regulatory circuitry underlying this editing critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. Our results may therefore be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.One-Sentence SummaryGenetically controlled editing of mitochondrial DNA is an integral part of the yeast’s defenses against oxidative damage.
9.	Tapani, Sofia, 1982 (author) Stochastic modelling and analysis of early mouse development 2011 Doctoral thesis (other academic/artistic)abstract The aim of this thesis is to model and describe dynamical events for biological cells using statistical and mathematical tools. The thesis includes five papers that all relate to stochastic modelling of cells. In order to understand the development and patterning of the early mammalian embryo, stochastic modelling has become a more important tool than ever. It allows for studying the processes that mediate the transition from pluripotency of the embryonic cells to their differentiation. It is still unclear whether the positions of cells determine their future fates. One alternative possibility is that cells are pre-specified at random positions and then sort according to a already set fate. Mouse embryonic cells are thought to be equivalent in their developmental properties until approaching the eight-cell stage. Some biological studies show, in comparison, that patterning can be present already at sperm entry and in the pronuclei migration. We investigate in Paper I the dynamics of the pronuclei migration by analysing their trajectories and find that not only do the pronuclei follow a noise corrupted path towards the centre of the egg but they also have some attraction to each other which affects their dynamics. Continuing in Paper II and III, we use these results to model this behaviour with a coupled stochastic differential equation model. This enables us to simulate distributions that describe the meeting plane between pronuclei which in turn can be related to the orientation of the first cleavage of the egg. Our results show that adding randomness in sperm entry point is different from the randomness added through the environment of the egg. We are also able to show that data sets with normal eggs and eggs treated with an actin growth inhibitor give rise to considerably different model dynamics, suggesting that the treatment is affecting the migration in an invasive way. Altering the pronuclei dynamics can alter the polarity of the egg and may transfer into the later axis-formation process. Invasiveness of experimental procedures is a difficult issue to handle. The alternative to invasive procedures is not appealing since it means that important developmental features may not be discovered because of individual variability and noise, leading to guesswork of the underlying mechanisms. The embryonic cells are easily affected by treatments performed to make the measuring, made by hand, easier or by the light exposure of the microscope. Treatments as such are used for example for producing flourescent proteins in membranes or slowing processes down. Paper IV and Paper V serve to analyse how light induced stress affects yeast cells and we employ a method for analysing the noisy non-stationary time series, which are a result of the yeast experiments, using wavelet decomposition.
10.	Wieloch, Thomas, 1979-, et al. (author) Intramolecular carbon isotope signals reflect metabolite allocation in plants 2022 In: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 73:8, s. 2558-2575 Journal article (other academic/artistic)abstract Stable isotopes at natural abundance are key tools to study physiological processes occurring outside the temporal scope of manipulation and monitoring experiments. Whole-molecule carbon isotope ratios (13C/12C) enable assessments of plant carbon uptake yet conceal information about carbon allocation. Here, we identify an intramolecular 13C/12C signal at tree-ring glucose C-5 and C-6 and develop experimentally testable theories on its origin. More specifically, we assess the potential of processes within C3 metabolism for signal introduction based (inter alia) on constraints on signal propagation posed by metabolic networks. We propose that the intramolecular signal reports carbon allocation into major metabolic pathways in actively photosynthesizing leaf cells including the anaplerotic, shikimate, and non-mevalonate pathway. We support our theoretical framework by linking it to previously reported whole-molecule 13C/12C increases in cellulose of ozone-treated Betula pendula and a highly significant relationship between the intramolecular signal and tropospheric ozone concentration. Our theory postulates a pronounced preference for leaf cytosolic triose-phosphate isomerase to catalyse the forward reaction in vivo (dihydroxyacetone phosphate to glyceraldehyde 3-phosphate). In conclusion, intramolecular 13C/12C analysis resolves information about carbon uptake and allocation enabling more comprehensive assessments of carbon metabolism than whole-molecule 13C/12C analysis.
11.	Cheregi, Otilia, et al. (author) Transcriptome analysis reveals insights into adaptive responses of two marine microalgae species to Nordic seasons 2023 In: Algal Research. - 2211-9264. ; 74 Journal article (peer-reviewed)abstract There is an increasing interest in algae-based biomass produced outdoors in natural and industrial settings for biotechnological applications. To predict the yield and biochemical composition of the biomass, it is important to understand how the transcriptome of species and strains of interest is affected by seasonal changes. Here we studied the effects of Nordic winter and summer on the transcriptome of two phytoplankton species, namely the diatom Skeletonema marinoi (Sm) and the eustigmatophyte Nannochloropsis granulata (Ng), recently identified as potentially important for biomass production on the west coast of Sweden. Cultures were grown in photobioreactors in simulated Nordic summer and winter, and the gene expression in two phases was quantified by Illumina RNA-sequencing. Five paired comparisons were made among the four conditions. Sm was overall more responsive to seasons since 70 % of the total transcriptome (14,783 genes) showed differential expression in at least one comparison as compared to 1.6 % (1403 genes) for Ng. For both species, we observed larger differences between the seasons than between the phases of the same season. In summer phase 1, Sm cells focused on photosynthesis and polysaccharide biosynthesis. Nitrate assimilation and recycling of intracellular nitrogen for protein biosynthesis were more active in summer phase 2 and throughout winter. Lipid catabolism was upregulated in winter relative to summer to supply carbon for respiration. Ng favored lipid accumulation in summer, while in winter activated different lipid remodeling pathways as compared to Sm. To cope with winter, Ng upregulated breakdown and transport of carbohydrates for energy production. Taken together, our transcriptome data reveal insights into adaptive seasonal responses of Sm and Ng important for biotechnological applications on the west coast of Sweden, but more work is required to decipher the molecular mechanisms behind these responses.
12.	Dukic Marinkov, Emilija, 1991, et al. (author) Chloroplast magnesium transporters play essential but differential roles in maintaining magnesium homeostasis 2023 In: Frontiers in Plant Science. - 1664-462X. ; 14 Journal article (peer-reviewed)abstract Magnesium (Mg2+ ) is essential for photosynthesis in the chloroplasts of land plants and algae. Being the central ion of chlorophyll, cofactor and activator of many photosynthetic enzymes including RuBisCO, magnesium-deficient plants may suffer from leaf chlorosis symptoms and retarded growth. Therefore, the chloroplast Mg2+ concentration is tightly controlled by magnesium transport proteins. Recently, three different transporters from two distinct families have been identified in the chloroplast inner envelope of the model plant Arabidopsis thaliana: MGT10, MGR8, and MGR9. Here, we assess the individual roles of these three proteins in maintaining chloroplast Mg2+ homeostasis and regulating photosynthesis, and if their role is conserved in the model green alga Chlamydomonas reinhardtii. Phylogenetic analysis and heterologous expression revealed that the CorC-like MGR8 and MGR9 transport Mg2+ by a different mechanism than the CorA-like MGT10. MGR8 and MGT10 genes are highest expressed in leaves, indicating a function in chloroplast Mg2+ transport. MGR9 is important for chloroplast function and plant adaptation in conditions of deficiency or excess of Mg2+ . Transmission electron microscopy indicated that MGT10 plays a differential role in thylakoid stacking than MGR8 and MGR9. Furthermore, we report that MGR8, MGR9, and MGT10 are involved in building up the pH gradient across the thylakoid membrane and activating photoprotection in conditions of excess light, however the mechanism has not been resolved yet. While there are no chloroplast MGR-like transporters in Chlamydomonas, we show that MRS4 is a homolog of MGT10, that is required for photosynthesis and cell growth. Taken together, our findings reveal that the studied Mg2+ transporters play essential but differential roles in maintaining chloroplast Mg2+ homeostasis.
13.	Axäng, Claes, 1977, et al. (author) Developmental genetics of the C. elegans pharyngeal neurons NSML and NSMR. 2008 In: BMC Developmental Biology. - 1471-213X. ; 8 Journal article (peer-reviewed)abstract Background We are interested in understanding how the twenty neurons of the C. elegans pharynx develop in an intricate yet reproducible way within the narrow confines of the embryonic pharyngeal primordium. To complement an earlier study of the pharyngeal M2 motorneurons, we have now examined the effect of almost forty mutations on the morphology of a bilateral pair of pharyngeal neurosecretory-motor neurons, the NSMs. Results A careful description of the NSM morphology led to the discovery of a third, hitherto unreported process originating from the NSM cell body and that is likely to play a proprioceptive function. We found that the three NSM processes are differently sensitive to mutations. The major dorsal branch was most sensitive to mutations that affect growth cone guidance and function (e.g. unc-6, unc-34, unc-73), while the major sub-ventral branch was more sensitive to mutations that affect components of the extracellular matrix (e.g. sdn-1). Of the tested mutations, only unc-101, which affects an adaptin, caused the loss of the newly described thin minor process. The major processes developed synaptic branches post-embryonically, and these exhibited activity-dependent plasticity. Conclusion By studying the effects of nearly forty different mutations we have learned that the different NSM processes require different genes for their proper guidance and use both growth cone dependent and growth cone independent mechanisms for establishing their proper trajectories. The two major NSM processes develop in a growth cone dependent manner, although the sub-ventral process relies more on substrate adhesion. The minor process also uses growth cones but uniquely develops using a mechanism that depends on the clathrin adaptor molecule UNC-101. Together with the guidance of the M2 neuron, this is the second case of a pharyngeal neuron establishing one of its processes using an unexpected mechanism.
14.	Blockhuys, Stephanie, 1983, et al. (author) Defining the human copper proteome and analysis of its expression variation in cancers. 2017 In: Metallomics. - : Oxford University Press (OUP). - 1756-5901 .- 1756-591X. ; 9:2, s. 112-123 Journal article (peer-reviewed)abstract Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.
15.	Gollan, Peter, et al. (author) Photosynthetic and transcriptome responses to fluctuating light in Arabidopsis thylakoid ion transport triple mutant 2023 In: Plant Direct. - 2475-4455. ; 7:10 Journal article (peer-reviewed)abstract Fluctuating light intensity challenges fluent photosynthetic electron transport in plants, inducing photoprotection while diminishing carbon assimilation and growth, and also influencing photosynthetic signaling for regulation of gene expression. Here, we employed in vivo chlorophyll-a fluorescence and P700 difference absorption measurements to demonstrate the enhancement of photoprotective energy dissipation of both photosystems in wild-type Arabidopsis thaliana after 6 h exposure to fluctuating light as compared with constant light conditions. This acclimation response to fluctuating light was hampered in a triple mutant lacking the thylakoid ion transport proteins KEA3, VCCN1, and CLCe, leading to photoinhibition of photosystem I. Transcriptome analysis revealed upregulation of genes involved in biotic stress and defense responses in both genotypes after exposure to fluctuating as compared with constant light, yet these responses were demonstrated to be largely upregulated in triple mutant already under constant light conditions compared with wild type. The current study illustrates the rapid acclimation of plants to fluctuating light, including photosynthetic, transcriptomic, and metabolic adjustments, and highlights the connection among thylakoid ion transport, photosynthetic energy balance, and cell signaling.
16.	Hong, Kuk-ki, 1976 (author) Advancing Metabolic Engineering through Combination of Systems Biology and Adaptive Evolution 2012 Doctoral thesis (other academic/artistic)abstract Understanding evolutionary strategies of microorganisms may provide opportunities foradvanced strain development with the aim to produce valuable bio-products from renewablebiomass resources. Through evolutionary processes, microorganisms can attain new traitsassociated with genetic changes that may be useful for the construction of improved strains.Therefore, the characterization of evolutionary strategies may result in identification of themolecular and genetic changes underlying newly obtained traits, and can hereby become anessential step in strain development. However, so far the depth of analysis has limited the rangeof comprehension. This thesis applied genome-wide analyses such as transcriptome, metabolomeand whole-genome sequencing to investigate the evolutionary strategies of the yeastSaccharomyces cerevisiae. Three evolved mutants were independently generated by adaptiveevolution on galactose minimal media to obtain the trait of improved galactose utilization byyeast. Those strains expressed higher galactose utilization rates than a reference strain in terms ofboth maximum specific growth rate and specific galactose uptake rate. Application of thegenome-scale comparative analyses employing engineered strains as controls elucidated uniquechanges obtained by adaptive evolution. Molecular bases referred from the changes oftranscriptome and metabolome were located around galactose metabolism, while genetic basesfrom whole-genome sequencing showed no mutations in those changes. Common mutationsamong the evolved mutants were identified in the Ras/PKA signaling pathway. Those mutationswere placed on the reference strain background and their effects were evaluated by comparisonwith the evolved mutants. One of the site-directed mutants showed even higher specific galactoseuptake rate than the evolved mutants, and just few number of genetic and molecular changes wereenough to recover complete the adaptive phenotype. These results indicate that identification ofkey mutations provide new strategies for further metabolic engineering of strains. In addition, thepleiotropy of obtained phenotype that is improved galactose availability was tested. When thegalactose-evolved mutants were cultured on glucose that is the most favorite carbon source ofyeast, those mutants showed reduction of glucose utilization. Genome-wide analyses and sitedirectedmutagenesis were applied again to understand underlying molecular and genetic bases ofthis trade-off in carbon utilization. The results indicated that loosening of tight glucose regulationwas likely the reason of increased galactose availability. The implications of evolutionarystrategies and the impact of genome-scale analyses on characterization of evolved mutants arediscussed.
17.	Molin, Mikael, 1973, et al. (author) Protein kinase A controls yeast growth in visible light 2020 In: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 18:1 Journal article (peer-reviewed)abstract Background: A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. While the biology of UV light-induced damage has been well studied, cellular responses to stress from visible light (400–700 nm) remain poorly understood despite being a regular part of the life cycle of many organisms. Here, we developed a high-throughput method for measuring growth under visible light stress and used it to screen for light sensitivity in the yeast gene deletion collection. Results: We found genes involved in HOG pathway signaling, RNA polymerase II transcription, translation, diphthamide modifications of the translational elongation factor eEF2, and the oxidative stress response to be required for light resistance. Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. We therefore used an ectopic fluorescent PKA reporter and mutants with constitutively altered PKA activity to show that repression of PKA is essential for resistance to visible light. Conclusion: We conclude that yeast photobiology is multifaceted and that protein kinase A plays a key role in the ability of cells to grow upon visible light exposure. We propose that visible light impacts on the biology and evolution of many non-photosynthetic organisms and have practical implications for how organisms are studied in the laboratory, with or without illumination.
18.	Mörck, Catarina, 1972, et al. (author) C. elegans ten-1 is synthetic lethal with mutations in cytoskeleton regulators, and enhances many axon guidance defective mutants. 2010 In: BMC developmental biology. - 1471-213X. ; 10 Journal article (peer-reviewed)abstract Teneurins are transmembrane proteins that assist morphogenetic processes in many organisms. ten-1 is the C. elegans teneurin homolog with two transcripts, ten-1a and ten-1b, that respectively encode a long (TEN-1L) and short (TEN-1S) form of the protein. We previously isolated a C. elegans mutant where one pharyngeal neuron was frequently misplaced, and now show that it corresponds to a novel allele of ten-1.
19.	Razaghi, Ali, et al. (author) Effects of nitrogen on growth and carbohydrate formation in Porphyridium cruentum 2014 In: Central European Journal of Biology. - : Walter de Gruyter GmbH. - 1895-104X .- 1644-3632. ; 9:2, s. 156-162 Journal article (peer-reviewed)abstract The microalga Porphyridium cruentum (Rhodophyta) has several industrial and pharmaceutical uses, especially for its polysaccharide production. This study aimed to investigate the influence of nitrogen levels as reflected by altered N:P ratios on the production and content of biomass and carbohydrate. N:P molar ratios were altered in batch cultures to range from 1.6 to 50 using the Redfield ratio of 1:16 as reference. Algal growth (estimated as final cell number, biomass concentration and maximum specific growth rate) was negatively affected at low N:P ratios. The optimal N:P ratio for growth was identified at 35-50, with specific growth rates of 0.19 day(-1) and maximum cell concentrations of 59 center dot 10(8) cells L-1 and 1.2 g dry weight of biomass L-1. In addition, variation in cell size was seen. Cells with larger diameters were at higher N:P ratios and smaller cells at lower ratios. The cellular carbohydrate content increased under reduced nitrogen availability. However, because accumulation was moderate at the lowest N:P ratio, 0.4 g per g dry weight biomass compared to 0.24 at the Redfield ratio of 16:1, conditions for increased total carbohydrate formation were identified at the N:P ratios optimal for growth. Additionally, carbohydrates were largely accumulated in late exponential to stationary phase.
20.	Stamenković, Marija, et al. (author) Fatty acids as chemotaxonomic and ecophysiological traits in green microalgae (desmids, Zygnematophyceae, Streptophyta): A discriminant analysis approach 2020 In: Phytochemistry. - : Elsevier BV. - 0031-9422. ; 170 Journal article (peer-reviewed)abstract © 2019 Elsevier Ltd Desmids (Zygnematophyceae) are a group of poorly studied green microalgae. The aim of the present study was to identify fatty acids (FAs) that could be used as biomarkers in desmids in general, and to determine FAs as traits within different ecophysiological desmid groups. FA profiles of 29 desmid strains were determined and analysed with respect to their geographic origin, trophic preference and age of cultivation. It appeared that merely FAs present in relatively large proportions such as palmitic, linoleic, α-linolenic and hexadecatrienoic acids could be used as biomarkers for reliable categorization of this microalgal group. Linear discriminant analysis applied to three a priori defined groups of desmids, revealed clear strain-specific characteristics regarding FA distribution, influenced by climate and trophic conditions at the source sites as well as by the age of culture and growth phase. Accordingly, when considering FAs for the determination of lower taxonomic ranks we recommend using the term “trait” instead of “biomarker”, as the latter designates unchangeable “fingerprint” of a specific taxon. Furthermore, despite that desmids were regarded as microalgae having stable genomes, long-term cultivation appeared to cause modifications in FA metabolic pathways, evident as a larger proportion of stearidonic acid in desmid strains cultivated over extensive time periods (>35 years).
21.	Purayil, Siju, et al. (author) Neuropeptides in the Antennal Lobe of the Yellow Fever Mosquito, Aedes aegypti. 2014 In: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 522, s. 592-608 Journal article (peer-reviewed)abstract For many insects, including mosquitoes, olfaction is the dominant modality regulating their behavioral repertoire. Many neurochemicals modulate olfactory information in the central nervous system, including the primary olfactory center of insects, the antennal lobe. The most diverse and versatile neurochemicals in the insect nervous system are found in the neuropeptides. In the present study, we analyzed neuropeptides in the antennal lobe of the yellow fever mosquito, Aedes aegypti, a major vector of arboviral diseases. Direct tissue profiling of the antennal lobe by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry indicated the presence of 28 mature products from 10 different neuropeptide genes. In addition, immunocytochemical techniques were used to describe the cellular location of the products of up to seven of these genes within the antennal lobe. Allatostatin A, allatotropin, SIFamide, FMRFamide-related peptides, short neuropeptide F, myoinhibitory peptide, and tachykinin-related peptides were found to be expressed in local interneurons and extrinsic neurons of the antennal lobe. Building on these results, we discuss the possible role of neuropeptide signaling in the antennal lobe of Ae. aegypti. J. Comp. Neurol. 522:592-608, 2014. (c) 2013 Wiley Periodicals, Inc.
22.	Sandström, Olof, et al. (author) Integrated fish monitoring in Sweden 2003 In: Utredningsrapport till Naturvårdsverket. ; , s. 1-32 Reports (other academic/artistic)
23.	Alexandersson, Marina, 1972, et al. (author) Initial sequencing and comparative analysis of the mouse genome 2002 In: Nature. - 0028-0836 .- 1476-4687. ; 420:6915, s. 520-562 Journal article (peer-reviewed)
24.	Fagman, Henrik, 1975, et al. (author) Morphogenetics of early thyroid development. 2010 In: Journal of molecular endocrinology. - 1479-6813. Research review (peer-reviewed)abstract The thyroid develops from the foregut endoderm. Yet uncharacterized inductive signals specify endoderm progenitors to a thyroid cell fate that assemble in the pharyngeal floor from which the primordium buds and migrates to the final position of the gland. The morphogenetic process is regulated by both cell-autonomous (activated by e.g. Nkx2-1, Foxe1, Pax8 and Hhex) and mesoderm-derived (mediated by e.g. Tbx1 and Fgf) mechanisms acting in concert to promote growth and survival of progenitor cells. The developmental role of thyroid-stimulating hormone is limited to thyroid differentiation set to work after the gross anatomy of the gland is already sculptured. This review summarizes recent advances on the molecular genetics of thyroid morphogenesis put into context of endoderm developmental traits and highlights established and potentially novel mechanisms of thyroid dysgenesis of relevance to congenital hypothyroidism in man.
25.	Kradolfer, David, et al. (author) Increased Maternal Genome Dosage Bypasses the Requirement of the FIS Polycomb Repressive Complex 2 in Arabidopsis Seed Development 2013 In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9 Journal article (peer-reviewed)abstract Seed development in flowering plants is initiated after a double fertilization event with two sperm cells fertilizing two female gametes, the egg cell and the central cell, leading to the formation of embryo and endosperm, respectively. In most species the endosperm is a polyploid tissue inheriting two maternal genomes and one paternal genome. As a consequence of this particular genomic configuration the endosperm is a dosage sensitive tissue, and changes in the ratio of maternal to paternal contributions strongly impact on endosperm development. The FERTILIZATION INDEPENDENT SEED (FIS) Polycomb Repressive Complex 2 (PRC2) is essential for endosperm development; however, the underlying forces that led to the evolution of the FIS-PRC2 remained unknown. Here, we show that the functional requirement of the FIS-PRC2 can be bypassed by increasing the ratio of maternal to paternal genomes in the endosperm, suggesting that the main functional requirement of the FIS-PRC2 is to balance parental genome contributions and to reduce genetic conflict. We furthermore reveal that the AGAMOUS LIKE (AGL) gene AGL62 acts as a dosage-sensitive seed size regulator and that reduced expression of AGL62 might be responsible for reduced size of seeds with increased maternal genome dosage.
26.	Nachin, Laurence, 1971, et al. (author) Heterodimer formation within universal stress protein classes revealed by an in silico and experimental approach. 2008 In: Journal of molecular biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 380:2, s. 340-50 Journal article (peer-reviewed)abstract Universal stress proteins (Usps) are found in all kingdoms of life and can be divided into four classes by phylogenic analysis. According to available structures, Usps exist as homodimers, and genetic studies show that their cellular assignments are extensive, including functions relating to stress resistance, carbon metabolism, cellular adhesion, motility, and bacterial virulence. We approached the question of how Usps can achieve such a variety of functions in a cell by using a new procedure for statistical analysis of multiple sequence alignments, based on physicochemically related values for each amino acid residue of Usp dimer interfaces. The results predicted that Usp proteins within a class may, in addition to forming homodimers, be able to form heterodimers. Using Escherichia coli Usps as model proteins, we confirmed the existence of such interactions. We especially focused on class I UspA and UspC and demonstrated that they are able to form homo- and heterodimers in vitro and in vivo. We suggest that this ability to form both homo- and heterodimers may allow for an expansion of the functional repertoire of Usps and explains why organisms usually contain multiple usp paralogues.
27.	Rebernig, Carolin, et al. (author) Non-reciprocal Interspecies Hybridization Barriers in the Capsella Genus Are Established in the Endosperm 2015 In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 11 Journal article (peer-reviewed)abstract The transition to selfing in Capsella rubella accompanies its recent divergence from the ancestral outcrossing C. grandiflora species about 100,000 years ago. Whether the change in mating system was accompanied by the evolution of additional reproductive barriers that enforced species divergence remained unknown. Here, we show that C. rubella and C. grandiflora are reproductively separated by an endosperm-based, non-reciprocal postzygotic hybridization barrier. While hybridizations of C. rubella maternal plants with C. grandiflora pollen donors resulted in complete seed abortion caused by endosperm cellularization failure, the reciprocal hybridization resulted in the formation of small seeds with precociously cellularized endosperm. Strikingly, the transcriptomic response of both hybridizations mimicked respectively the response of paternal and maternal excess hybridizations in Arabidopsis thaliana, suggesting unbalanced genome strength causes hybridization failure in both species. These results provide strong support for the theory that crosses between plants of different mating systems will be unbalanced, with the outcrosser behaving like a plant of increased ploidy, evoking a response that resembles an interploidy-type seed failure. Seed incompatilibity of C. rubella pollinated by C. grandiflora followed the Bateson-Dobzhansky-Muller model, involving negative genetic interaction of multiple paternal C. grandiflora loci with at least one maternal C. rubella locus. Given that both species only recently diverged, our data suggest that a fast evolving mechanism underlies the post-zygotic hybridization barrier(s) separating both species.
28.	Villanova, Valeria, et al. (author) Unveiling the ecological resilience and industrial potential of Skeletonema marinoi through mixotrophic cultivation in Nordic winter condition 2024 In: Physiologia Plantarum : An International Journal for Plant Biology. - 0031-9317. ; 176:3 Journal article (peer-reviewed)abstract Mixotrophy, the concurrent use of inorganic and organic carbon in the presence of light for microalgal growth, holds ecological and industrial significance. However, it is poorly explored in diatoms, especially in ecologically relevant species like Skeletonema marinoi. This study strategically employed mixotrophic metabolism to optimize the growth of a strain of Skeletonema marinoi (Sm142), which was found potentially important for biomass production on the west coast of Sweden in winter conditions. The aim of this study was to discern the most effective organic carbon sources by closely monitoring microalgal growth through the assessment of optical density, chlorophyll a fluorescence, and biomass concentration. The impact of various carbon sources on the physiology of Sm142 was investigated using photosynthetic and respiratory parameters. The findings revealed that glycerol exhibited the highest potential for enhancing the biomass concentration of Sm142 in a multi-cultivator under the specified experimental conditions, thanks to the increase in respiration activity. Furthermore, the stimulatory effect of glycerol was confirmed at a larger scale using environmental photobioreactors simulating the winter conditions on the west coast of Sweden; it was found comparable to the stimulation by CO2-enriched air versus normal air. These results were the first evidence of the ability of Skeletonema marinoi to perform mixotrophic metabolism during the winter and could explain the ecological success of this diatom on the Swedish west coast. These findings also highlight the importance of both organic and inorganic carbon sources for enhancing biomass productivity in harsh winter conditions.
29.	Andersson, Stefanie, 1989, et al. (author) Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity 2021 In: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:11 Journal article (peer-reviewed)abstract The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper.
30.	Ibstedt, Sebastian, 1983, et al. (author) Global analysis of protein aggregation in yeast during physiological conditions and arsenite stress. 2014 In: Biology open. - : The Company of Biologists. - 2046-6390. ; 3:10, s. 913-923 Journal article (peer-reviewed)abstract Protein aggregation is a widespread phenomenon in cells and associated with pathological conditions. Yet, little is known about the rules that govern protein aggregation in living cells. In this study, we biochemically isolated aggregation-prone proteins and used computational analyses to identify characteristics that are linked to physiological and arsenite-induced aggregation in living yeast cells. High protein abundance, extensive physical interactions, and certain structural properties are positively correlated with an increased aggregation propensity. The aggregated proteins have high translation rates and are substrates of ribosome-associated Hsp70 chaperones, indicating that they are susceptible for aggregation primarily during translation/folding. The aggregation-prone proteins are enriched for multiple chaperone interactions, thus high protein abundance is probably counterbalanced by molecular chaperones to allow soluble expression in vivo. Our data support the notion that arsenite interferes with chaperone activity and indicate that arsenite-aggregated proteins might engage in extensive aberrant protein-protein interactions. Expression of aggregation-prone proteins is down-regulated during arsenite stress, possibly to prevent their toxic accumulation. Several aggregation-prone yeast proteins have human homologues that are implicated in misfolding diseases, suggesting that similar mechanisms may apply in disease- and non-disease settings.
31.	Wieloch, Thomas, 1979- (author) Intramolecular isotope analysis reveals plant ecophysiological signals covering multiple timescales 2019 Doctoral thesis (other academic/artistic)abstract Our societies' wellbeing relies on stable and healthy environments. However, our current lifestyles, growth-oriented economic policies and the population explosion are leading to potentially catastrophic degradation of ecosystems and progressive disruption of food chains. Hopefully, more clarity about what the future holds in store will trigger stronger efforts to find, and adopt, problem-focused coping strategies and encourage environmentally friendly lifestyles.Forecasting environmental change/destruction is complicated (inter alia) by lack of complete understanding of plant-environment interactions, particularly those involved in slow processes such as plant acclimatisation and adaptation. This stems from deficiencies in tools to analyse such slow processes. The present work aims at developing tools that can provide retrospective ecophysiological information covering timescales from days to millennia.Natural archives, such as tree-rings, preserve plant metabolites over long timescales. Analyses of intramolecular isotope abundances in plant metabolites have the potential to provide retrospective information about metabolic processes and underlying environmental controls. Thus, my colleagues and I (hereafter we) analysed intramolecular isotope patterns in tree rings to develop analytical tools that can convey information about clearly-defined plant metabolic processes over multiple timescales. Such tools might help (inter alia) to constrain plants' capacities to sequester excess amounts of anthropogenic CO2; the so-called CO2 fertilisation effect. This, in turn, might shed light on plants' sink strength for the greenhouse gas CO2, and future plant performance and growth under climate change.In the first of three studies, reported in appended papers, we analysed intramolecular 13C/12C ratios in tree-ring glucose. In six angiosperm and six gymnosperm species we found pronounced intramolecular 13C/12C differences, exceeding 10‰. These differences are transmitted into major global C pools, such as soil organic matter. Taking intramolecular 13C/12C differences into account might improve isotopic characterisation of soil metabolic processes and soil CO2 effluxes. In addition, we analysed intramolecular 13C/12C ratios in a Pinus nigra tree-ring archive spanning the period 1961 to 1995. These data revealed new ecophysiological 13C/12C signals, which can facilitate climate reconstructions and assessments of plant-environment interactions at higher resolution; thus providing higher quality information. We proposed that 13C/12C signals at glucose C-1 to C-2 derive from carbon injection into the Calvin-Benson cycle via the oxidative pentose phosphate pathway. We concluded that intramolecular 13C/12C measurements provide valuable new information about long-term metabolic dynamics for application in biogeochemistry, plant physiology, plant breeding, and paleoclimatology.In the second study, we developed a comprehensive theory on the metabolic and ecophysiological origins of 13C/12C signals at tree-ring glucose C-5 and C-6. According to this theory and theoretical implications of the first study on signals at C-1 to C-3, analysis of such intramolecular signals can provide information about several metabolic processes. At C-3, a well-known signal reflecting CO2 uptake is preserved. The glucose-6-phosphate shunt around the Calvin-Benson cycle affects 13C/12C compositions at C-1 and C-2, while the 13C/12C signals at C-5 and C-6 reflect carbon fluxes into downstream metabolism. This theoretical framework enables further experimental studies to be conducted in a hypothesis-driven manner. In conclusion, the intramolecular approach provides information about carbon allocation in plant leaves. Thus, it gives access to long-term information on key ecophysiological processes, which could not be acquired by previous approaches.The abundance of the hydrogen isotope deuterium, δD, is important for linking the water cycle with plant ecophysiology. The main factors affecting δD in plant organic matter are commonly assumed to be the δD in source water and leaf-level evaporative enrichment. Current δD models incorporate biochemical D fractionations as constants. In the third study we showed that biochemical D fractionations respond strongly to low ambient CO2 levels and low light intensity. Thus, models of δD values in plant organic matter should incorporate biochemical fractionations as variables. In addition, we found pronounced leaf-level δD differences between α-cellulose and wax n-alkanes. We explained this by metabolite-specific contributions of distinct hydrogen sources during biosynthesis.Overall, this work advances our understanding of isotope distributions and isotope fractionations in plants. It reveals the immense potential of intramolecular isotope analyses for retrospective assessment of plant metabolism and associated environmental controls.
32.	Ohrvik, Helena, et al. (author) Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation? 2015 In: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 16:8, s. 16728-39 Journal article (peer-reviewed)abstract The human copper (Cu) chaperone Atox1 delivers Cu to P1B type ATPases in the Golgi network, for incorporation into essential Cu-dependent enzymes. Atox1 homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein that binds Cu in a conserved surface-exposed Cys-X-X-Cys (CXXC) motif. In addition to its well-documented cytoplasmic chaperone function, in 2008 Atox1 was suggested to have functionality in the nucleus. To identify new interactions partners of Atox1, we performed a yeast two-hybrid screen with a large human placenta library of cDNA fragments using Atox1 as bait. Among 98 million fragments investigated, 25 proteins were found to be confident interaction partners. Nine of these were uncharacterized proteins, and the remaining 16 proteins were analyzed by bioinformatics with respect to cell localization, tissue distribution, function, sequence motifs, three-dimensional structures and interaction networks. Several of the hits were eukaryotic-specific proteins interacting with DNA or RNA implying that Atox1 may act as a modulator of gene regulation. Notably, because many of the identified proteins contain CXXC motifs, similarly to the Cu transport reactions, interactions between these and Atox1 may be mediated by Cu.
33.	Ariöz, Candan, 1983- (author) Exploring the Interplay of Lipids and Membrane Proteins 2014 Doctoral thesis (other academic/artistic)abstract The interplay between lipids and membrane proteins is known to affect membrane protein topology and thus have significant effect (control) on their functions. In this PhD thesis, the influence of lipids on the membrane protein function was studied using three different membrane protein models.A monotopic membrane protein, monoglucosyldiacylglyecerol synthase (MGS) from Acholeplasma laidlawii is known to induce intracellular vesicles when expressed in Escherichia coli. The mechanism leading to this unusual phenomenon was investigated by various biochemical and biophysical techniques. The results indicated a doubling of lipid synthesis in the cell, which was triggered by the selective binding of MGS to anionic lipids. Multivariate data analysis revealed a good correlation with MGS production. Furthermore, preferential anionic lipid sequestering by MGS was shown to induce a different fatty acid modeling of E. coli membranes. The roles of specific lipid binding and the probable mechanism leading to intracellular vesicle formation were also investigated.As a second model, a MGS homolog from Synechocystis sp. PCC6803 was selected. MgdA is an integral membrane protein with multiple transmembrane helices and a unique membrane topology. The influence of different type of lipids on MgdA activity was tested with different membrane fractions of Synechocystis. Results indicated a very distinct profile compared to Acholeplasma laidlawii MGS. SQDG, an anionic lipid was found to be the species of the membrane that increased the MgdA activity 7-fold whereas two other lipids (PG and PE) had only minor effects on MgdA. Additionally, a working model of MgdA for the biosynthesis and flow of sugar lipids between Synechocystis membranes was proposed.The last model system was another integral membrane protein with a distinct structure but also a different function. The envelope stress sensor, CpxA and its interaction with E. coli membranes were studied. CpxA autophosphorylation activity was found to be positively regulated by phosphatidylethanolamine and negatively by anionic lipids. In contrast, phosphorylation of CpxR by CpxA revealed to be increased with PG but inhibited by CL. Non-bilayer lipids had a negative impact on CpxA phosphotransfer activity.Taken together, these studies provide a better understanding of the significance of the interplay of lipids and model membrane proteins discussed here.
34.	Astorga, Jeanette, 1976, et al. (author) Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4 2007 In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 134:20, s. 3753-61 Journal article (peer-reviewed)abstract The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo(-/-)) has no effect on Foxf1 expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1(-/-) phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4 expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo(-/-) yolk sacs can be rescued by exogenous Bmp4, consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
35.	Caballero, Antonio, et al. (author) Absence of mitochondrial translation control proteins extends life span by activating sirtuin-dependent silencing. 2011 In: Molecular cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 42:3, s. 390-400 Journal article (peer-reviewed)abstract Altered mitochondrial functionality can extend organism life span, but the underlying mechanisms are obscure. Here we report that inactivating SOV1, a member of the yeast mitochondrial translation control (MTC) module, causes a robust Sir2-dependent extension of replicative life span in the absence of respiration and without affecting oxidative damage. We found that SOV1 interacts genetically with the cAMP-PKA pathway and the chromatin remodeling apparatus. Consistently, Sov1p-deficient cells displayed reduced cAMP-PKA signaling and an elevated, Sir2p-dependent, genomic silencing. Both increased silencing and life span extension in sov1Δ cells require the PKA/Msn2/4p target Pnc1p, which scavenges nicotinamide, a Sir2p inhibitor. Inactivating other members of the MTC module also resulted in Sir2p-dependent life span extension. The data demonstrate that the nuclear silencing apparatus senses and responds to the absence of MTC proteins and that this response converges with a pathway for life span extension elicited by reducing TOR signaling.
36.	Eme, Laura, et al. (author) Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes 2023 In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 992- Journal article (peer-reviewed)abstract In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes(1). However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved(2-4). Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells.
37.	Guan, Jikui, et al. (author) FAM150A and FAM150B are activating ligands for anaplastic lymphoma kinase 2015 In: eLIFE. - Cambridge : eLife Sciences Publications. - 2050-084X. ; 4 Journal article (peer-reviewed)abstract Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range of human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg and Palmer, 2013). Vertebrate ALK has been considered to be an orphan receptor and the identity of the ALK ligand(s) is a critical issue. Here we show that FAM150A and FAM150B are potent ligands for human ALK that bind to the extracellular domain of ALK and in addition to activation of wild-type ALK are able to drive 'superactivation' of activated ALK mutants from neuroblastoma. In conclusion, our data show that ALK is robustly activated by the FAM150A/B ligands and provide an opportunity to develop ALK-targeted therapies in situations where ALK is overexpressed/activated or mutated in the context of the full length receptor.
38.	Guerra, Lina, et al. (author) The biology of the cytolethal distending toxins 2011 In: Toxins. - : MDPI. - 2072-6651. ; 3:3, s. 172-190 Research review (peer-reviewed)abstract The cytolethal distending toxins (CDTs), produced by a variety of Gram-negative pathogenic bacteria, are the first bacterial genotoxins described, since they cause DNA damage in the target cells. CDT is an A-B(2) toxin, where the CdtA and CdtC subunits are required to mediate the binding on the surface of the target cells, allowing internalization of the active CdtB subunit, which is functionally homologous to the mammalian deoxyribonuclease I. The nature of the surface receptor is still poorly characterized, however binding of CDT requires intact lipid rafts, and its internalization occurs via dynamin-dependent endocytosis. The toxin is retrograde transported through the Golgi complex and the endoplasmic reticulum, and subsequently translocated into the nuclear compartment, where it exerts the toxic activity. Cellular intoxication induces DNA damage and activation of the DNA damage responses, which results in arrest of the target cells in the G1 and/or G2 phases of the cell cycle and activation of DNA repair mechanisms. Cells that fail to repair the damage will senesce or undergo apoptosis. This review will focus on the well-characterized aspects of the CDT biology and discuss the questions that still remain unanswered.
39.	Guidi, Riccardo, et al. (author) Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response 2013 In: Cellular Microbiology. - : John Wiley & Sons. - 1462-5814 .- 1462-5822. ; 15:1, s. 98-113 Journal article (peer-reviewed)abstract Epidemiological evidence links chronic bacterial infections to the increased incidence of certain types of cancer but the molecular mechanisms by which bacteria contribute to tumour initiation and progression are still poorly characterized. Here we show that chronic exposure to the genotoxin cytolethal distending toxin (CDT) of Gram-negative bacteria promotes genomic instability and acquisition of phenotypic properties of malignancy in fibroblasts and colon epithelial cells. Cells grown for more than 30 weeks in the presence of sublethal doses of CDT showed increased mutation frequency, and accumulation of chromatin and chromosomal aberrations in the absence of significant alterations of cell cycle distribution, decreased viability or senescence. Cell survival was dependent on sustained activity of the p38 MAP kinase. The ongoing genomic instability was associated with impaired activation of the DNA damage response and failure to efficiently activate cell cycle checkpoints upon exposure to genotoxic stress. Independently selected sublines showed enhanced anchorage-independent growth as assessed by the formation of colonies in semisolid agarose. These findings support the notion that chronic infection by CDT-producing bacteria may promote malignant transformation, and point to the impairment of cellular control mechanisms associated with the detection and repair of DNA damage as critical events in the process.
40.	Hao, Meng-Shu, et al. (author) The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants Is Controlled by Cytosolic pH 2015 In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9 Journal article (peer-reviewed)abstract NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K-0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O-2 and decylubiquinone as electron acceptors. The K-0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K-0.5(Ca2+) for NADPH oxidation was high (approximate to 100 mu M), yet 20-fold lower K-0.5(Ca2+) values were determined at pH 6.8. Lower K-0.5(Ca2+) values were observed with decylubiquinone than with O-2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene.
41.	Jagers, Peter, 1941 (author) Branching Processes: A Personal Historical Perspective. 2020 In: Statistical Modeling for Biological Systems: In Memory of Andrei Yakovlev. - Cham : Springer International Publishing. Book chapter (other academic/artistic)abstract The chapter, based on an Oberwolfach talk, gives a - personally biased - sketch of the development of branching processes, from the mid 19th Century to recently, emphasizing relations to bioscience and demography, and to society and culture in general.
42.	Jakobsen, J. S., et al. (author) Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network 2007 In: Genes Dev. - : Cold Spring Harbor Laboratory. - 0890-9369. ; 21:19, s. 2448-60 Journal article (peer-reviewed)abstract Smooth muscle plays a prominent role in many fundamental processes and diseases, yet our understanding of the transcriptional network regulating its development is very limited. The FoxF transcription factors are essential for visceral smooth muscle development in diverse species, although their direct regulatory role remains elusive. We present a transcriptional map of Biniou (a FoxF transcription factor) and Bagpipe (an Nkx factor) activity, as a first step to deciphering the developmental program regulating Drosophila visceral muscle development. A time course of chromatin immunoprecipitatation followed by microarray analysis (ChIP-on-chip) experiments and expression profiling of mutant embryos reveal a dynamic map of in vivo bound enhancers and direct target genes. While Biniou is broadly expressed, it regulates enhancers driving temporally and spatially restricted expression. In vivo reporter assays indicate that the timing of Biniou binding is a key trigger for the time span of enhancer activity. Although bagpipe and biniou mutants phenocopy each other, their regulatory potential is quite different. This network architecture was not apparent from genetic studies, and highlights Biniou as a universal regulator in all visceral muscle, regardless of its developmental origin or subsequent function. The regulatory connection of a number of Biniou target genes is conserved in mice, suggesting an ancient wiring of this developmental program.
43.	Larsson, Åke, 1944, et al. (author) Kustfisk - hälsa 2012 In: HAVET 2012 - Om miljötillståndet i svenska havsområden. - 1654-6741. ; år 2012 Research review (peer-reviewed)
44.	Lindholm, Ljubica, et al. (author) Effect of lipid bilayer properties on the photocycle of green proteorhodopsin 2015 In: Biochimica et Biophysica Acta - Bioenergetics. - : Elsevier BV. - 0005-2728 .- 1879-2650. ; 1847:8, s. 698-708 Journal article (peer-reviewed)abstract The significance of specific lipids for proton pumping by the bacterial rhodopsin proteorhodopsin (pR) was studied. To this end, it was examined whether pR preferentially binds certain lipids and whether molecular properties of the lipid environment affect the photocycle. pR's photocyde was followed by microsecond flash-photolysis in the visible spectral range. It was fastest in phosphatidylcholine liposomes (soy bean lipid), intermediate in 3-[(3-cholamidopropyl) dimethylammonio] propanesulfonate (CHAPS): 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bicelles and in Triton X-100, and slowest when pR was solubilized in CHAPS. In bicelles with different lipid compositions, the nature of the head groups, the unsaturation level and the fatty acid chain length had small effects on the photocycle. The specific affinity of pR for lipids of the expression host Eschetichia coil was investigated by an optimized method of lipid isolation from purified membrane protein using two different concentrations of the detergent N-dodecyl-beta-D-maltoside (DDM). We found that 11 lipids were copurified per pR molecule at 0.1% DDM, whereas essentially all lipids were stripped off from pR by 1% DDM. The relative amounts of copurifled phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin did not correlate with the molar percentages normally present in E. coil cells. The results indicate a predominance of phosphatidylethanolamine species in the lipid annulus around recombinant pR that are less polar than the dominant species in the cell membrane of the expression host E. coli.
45.	Matson Dzebo, Maria, 1985, et al. (author) Extended functional repertoire for human copper chaperones 2016 In: Biomolecular Concepts. - : Walter de Gruyter GmbH. - 1868-5021 .- 1868-503X. ; 7:1, s. 29-39 Journal article (peer-reviewed)abstract Copper (Cu) ions are cofactors in many essential enzymes. As free Cu ions are toxic, most organisms have highly specialized Cu transport systems involving dedicated proteins. The human cytoplasmic Cu chaperone Atox1 delivers Cu to P1B-type ATPases in the Golgi network, for incorporation into Cu-dependent enzymes following the secretory path. Atox1 homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein that binds Cu in a conserved surface-exposed CXXC motif. In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). Many mechanistic aspects have been resolved with respect to how Cu ions are moved between these proteins. In addition to the primary cytoplasmic Cu chaperone function, all three cytoplasmic chaperones have been reported to have other interaction partners that are involved in signaling pathways that modulate cell growth and development. These new discoveries imply that humans have evolved a highly sophisticated network of control mechanisms that connect Cu transport with cell regulatory processes. This knowledge may eventually be exploited for future drug developments towards diseases such as cancer and neurodegenerative disorders.
46.	Nyström, Thomas, 1960, et al. (author) Protein quality control in time and space - links to cellular aging. 2014 In: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356. ; 14:1, s. 40-48 Journal article (peer-reviewed)abstract The evolutionary theory of aging regards aging as an evolved characteristic of the soma, and proponents of the theory state that selection does not allow the evolution of aging in unicellular species lacking a soma–germ demarcation. However, the life history of some microorganisms, reproducing vegetatively by either budding or binary fission, has been demonstrated to encompass an ordered, polar-dependent, segregation of damage leading to an aging cell lineage within the clonal population. In the yeast Saccharomyces cerevisiae and the bacterium Escherichia coli, such segregation is under genetic control and includes an asymmetrical inheritance of protein aggregates and inclusions. Herein, the ultimate and proximate causation for such an asymmetrical inheritance, with special emphasis on damaged/aggregated proteins in budding yeast, is reviewed.
47.	Panagaki, Dimitra, et al. (author) Nuclear envelope budding is a response to cellular stress. 2021 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 118:30 Journal article (peer-reviewed)abstract Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast Saccharomyces cerevisiae, NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited. Yeast cells treated with azetidine-2-carboxylic acid, a proline analog that induces protein misfolding, display the most dramatic increase in NEB, suggesting a causal link to protein quality control. This link was further supported by both localization of ubiquitin and Hsp104 to protein aggregates and NEB events, and the evolution of these structures during heat shock. We hypothesize that NEB is part of normal cellular physiology in a vast range of species and that in S. cerevisiae NEB comprises a stress response aiding the transport of protein aggregates across the nuclear envelope.
48.	Salmon, Pablo, et al. (author) Effects of the Urban Environment on Oxidative Stress in Early Life : Insights from a Cross-fostering Experiment 2018 In: Integrative and Comparative Biology. - : Oxford University Press (OUP). - 1557-7023 .- 1540-7063. ; , s. 986-994 Journal article (peer-reviewed)abstract As urban areas expand rapidly worldwide, wildlife is exposed to a wide range of novel environmental stressors, such as increased air pollution and artificial light at night. Birds in highly polluted and/or urbanized habitats have been found to have increased antioxidant protection, which is likely important to avoid accumulation of oxidative damage, which can have negative fitness consequences. Yet, the current knowledge about the ontogeny of antioxidant protection in urban areas is limited; i.e., is the capacity to up-regulate the antioxidant defences already established during pre-natal development, or does it manifest itself during post-natal development? We cross-fostered great tit (Parus major) nestlings within and between urban and rural habitats, to determine if oxidative stress (measured as non-enzymatic total antioxidant capacity, superoxide dismutase (SOD), and plasma lipid peroxidation) is affected by habitat of origin and/or by habitat of rearing. The results demonstrate that being reared in the urban environment triggers an increase in SOD (an intracellular, enzymatic antioxidant) independent of natal habitat. Oxidative damage increased with hatching date in urban-reared nestlings, but there was little seasonal change in rural-reared nestlings. Total antioxidant capacity was neither affected by habitat of rearing or habitat of origin, but we observed a decline with hatching date in both rearing habitats. Taken together, our results support the growing evidence that the urban environment induces a direct plastic adjustment in antioxidant protection, but that up-regulation is not sufficient to avoid increased oxidative damage in late-hatched broods. Future studies should explore the underlying causes for this effect in late-hatched broods and whether it has any negative long-term implications, both at the individual- and the population level.
49.	Szabò, Ildikò, et al. (author) Impact of the ion transportome of chloroplasts on the optimization of photosynthesis. 2017 In: Journal of experimental botany. - : Oxford University Press (OUP). - 1460-2431 .- 0022-0957. ; 68:12, s. 3115-3128 Research review (peer-reviewed)abstract Ions play fundamental roles in all living cells, and their gradients are often essential to fuel transport, regulate enzyme activities, and transduce energy within cells. Regulation of their homeostasis is essential for cell metabolism. Recent results indicate that modulation of ion fluxes might also represent a useful strategy to regulate one of the most important physiological processes taking place in chloroplasts, photosynthesis. Photosynthesis is highly regulated, due to its unique role as a cellular engine for growth in the light. Controlling the balance between ATP and NADPH synthesis is a critical task, and availability of these molecules can limit the overall photosynthetic yield. Photosynthetic organisms optimize photosynthesis in low light, where excitation energy limits CO2 fixation, and minimize photo-oxidative damage in high light by dissipating excess photons. Despite extensive studies of these phenomena, the mechanism governing light utilization in plants is still poorly understood. In this review, we provide an update of the recently identified chloroplast-located ion channels and transporters whose function impacts photosynthetic efficiency in plants.
50.	Tamás, Markus J., 1970 (author) Cellular and molecular mechanisms of antimony transport, toxicity and resistance 2016 In: Environmental Chemistry. - 1448-2517. ; 13:6, s. 955-962 Research review (peer-reviewed)abstract Antimony is a toxic metalloid that is naturally present in low amounts in the environment, but can locally reach high concentrations at mining and processing sites. Today, antimony is used in a wide range of modern technology applications and is also an important constituent of pharmacological drugs. The increasing use of antimony has led to concerns about human and environmental exposure. Yet little is known about the biological properties of antimony and its mechanisms of actions in cells. This review will provide a brief summary of how antimony enters and affects cells, and how cells deal with the presence of this metalloid to acquire resistance.

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