Browsing by Subject "GENE-EXPRESSION"

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  • Thompson, Luke R.; Sanders, Jon G.; McDonald, Daniel; Amir, Amnon; Ladau, Joshua; Locey, Kenneth J.; Prill, Robert J.; Tripathi, Anupriya; Gibbons, Sean M.; Ackermann, Gail; Navas-Molina, Jose A.; Janssen, Stefan; Kopylova, Evguenia; Vazquez-Baeza, Yoshiki; Gonzalez, Antonio; Morton, James T.; Mirarab, Siavash; Xu, Zhenjiang Zech; Jiang, Lingjing; Haroon, Mohamed F.; Kanbar, Jad; Zhu, Qiyun; Song, Se Jin; Kosciolek, Tomasz; Bokulich, Nicholas A.; Lefler, Joshua; Brislawn, Colin J.; Humphrey, Gregory; Owens, Sarah M.; Hampton-Marcell, Jarrad; Berg-Lyons, Donna; McKenzie, Valerie; Fierer, Noah; Fuhrman, Jed A.; Clauset, Aaron; Stevens, Rick L.; Shade, Ashley; Pollard, Katherine S.; Goodwin, Kelly D.; Jansson, Janet K.; Gilbert, Jack A.; Knight, Rob; Earth Microbiome Project Consortiu; Hultman, Jenni (2017)
    Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.
  • Kvist, Jouni; Athanasio, Camila Goncalves; Pfrender, Michael E.; Brown, James B.; Colbourne, John K.; Mirbahai, Leda (2020)
    Background Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. Results In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine 4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine 27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. Conclusions The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.
  • Lahtinen, Alexandra; Puttonen, Sampsa; Vanttola, Päivi; Viitasalo, Katriina; Sulkava, Sonja; Pervjakova, Natalia; Joensuu, Anni; Salo, Perttu; Toivola, Auli; Härmä, Mikko; Milani, Lili; Perola, Markus; Paunio, Tiina (2019)
    Short sleep duration or insomnia may lead to an increased risk of various psychiatric and cardio-metabolic conditions. Since DNA methylation plays a critical role in the regulation of gene expression, studies of differentially methylated positions (DMPs) might be valuable for understanding the mechanisms underlying insomnia. We performed a cross-sectional genome-wide analysis of DNA methylation in relation to self-reported insufficient sleep in individuals from a community-based sample (79 men, aged 39.3 +/- 7.3), and in relation to shift work disorder in an occupational cohort (26 men, aged 44.9 +/- 9.0). The analysis of DNA methylation data revealed that genes corresponding to selected DMPs form a distinctive pathway: "Nervous System Development" (FDR P value <0.05). We found that 78% of the DMPs were hypomethylated in cases in both cohorts, suggesting that insufficient sleep may be associated with loss of DNA methylation. A karyoplot revealed clusters of DMPs at various chromosomal regions, including 12 DMPs on chromosome 17, previously associated with Smith-Magenis syndrome, a rare condition comprising disturbed sleep and inverse circadian rhythm. Our findings give novel insights into the DNA methylation patterns associated with sleep loss, possibly modifying processes related to neuroplasticity and neurodegeneration. Future prospective studies are needed to confirm the observed associations.
  • Lahti, Leo; Torrente, Aurora; Elo, Laura L.; Brazma, Alvis; Rung, Johan (2013)
  • Coviello, Andrea D.; Haring, Robin; Wellons, Melissa; Vaidya, Dhananjay; Lehtimaki, Terho; Keildson, Sarah; Lunetta, Kathryn L.; He, Chunyan; Fornage, Myriam; Lagou, Vasiliki; Mangino, Massimo; Onland-Moret, N. Charlotte; Chen, Brian; Eriksson, Joel; Garcia, Melissa; Mei, Yong; Koster, Annemarie; Lohman, Kurt; Lyytikainen, Leo-Pekka; Petersen, Ann-Kristin; Prescott, Jennifer; Stolk, Lisette; Vandenput, Liesbeth; Wood, Andrew R.; Zhuang, Wei Vivian; Ruokonen, Aimo; Hartikainen, Anna-Liisa; Pouta, Anneli; Bandinelli, Stefania; Biffar, Reiner; Brabant, Georg; Cox, David G.; Chen, Yuhui; Cummings, Steven; Ferrucci, Luigi; Gunter, Marc J.; Hankinson, Susan E.; Martikainen, Hannu; Hofman, Albert; Homuth, Georg; Illig, Thomas; Jansson, John-Olov; Johnson, Andrew D.; Karasik, David; Karlsson, Magnus; Kettunen, Johannes; Kiel, Douglas P.; Kraft, Peter; Liu, Jingmin; Ljunggren, Osten; Lorentzon, Mattias; Maggio, Marcello; Markus, Marcello R. P.; Mellstrom, Dan; Miljkovic, Iva; Mirel, Daniel; Nelson, Sarah; Papunen, Laure Morin; Peeters, Petra H. M.; Prokopenko, Inga; Raffel, Leslie; Reincke, Martin; Reiner, Alex P.; Rexrode, Kathryn; Rivadeneira, Fernando; Schwartz, Stephen M.; Siscovick, David; Soranzo, Nicole; Stockl, Doris; Tworoger, Shelley; Uitterlinden, Andre G.; van Gils, Carla H.; Vasan, Ramachandran S.; Wichmann, H. -Erich; Zhai, Guangju; Bhasin, Shalender; Bidlingmaier, Martin; Chanock, Stephen J.; De Vivo, Immaculata; Harris, Tamara B.; Hunter, David J.; Kahonen, Mika; Liu, Simin; Ouyang, Pamela; Spector, Tim D.; van der Schouw, Yvonne T.; Viikari, Jorma; Wallaschofski, Henri; McCarthy, Mark I.; Frayling, Timothy M.; Murray, Anna; Franks, Steve; Jarvelin, Marjo-Riitta; de Jong, Frank H.; Raitakari, Olli; Teumer, Alexander; Ohlsson, Claes; Murabito, Joanne M.; Perry, John R. B. (2012)
  • Vanlandewijck, Michael; He, Liqun; Mäe, Maarj A. Andaloussi; Andrae, Johanna; Ando, Koji; Del Gaudio, Francesca; Nahar, Khayrun; Lebouvier, Thibaud; Lavina, Barbara; Gouveia, Leonor; Sun, Ying; Raschperger, Elisabeth; Räsänen, Markus; Zarb, Yvette; Mochizuki, Naoki; Keller, Annika; Lendahl, Urban; Betsholtz, Christer (2018)
    Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.
  • McGarvey, Alison C.; Rybtsov, Stanislav; Souilhol, Celine; Tamagno, Sara; Rice, Ritva; Hills, David; Godwin, Duncan; Rice, David; Tomlinson, Simon R.; Medvinsky, Alexander (2017)
    In the developing embryo, hematopoietic stem cells (HSCs) emerge from the aorta-gonad-mesonephros (AGM) region, but the molecular regulation of this process is poorly understood. Recently, the progression from E9.5 to E10.5 and polarity along the dorso-ventral axis have been identified as clear demarcations of the supportive HSC niche. To identify novel secreted regulators of HSC maturation, we performed RNA sequencing over these spatiotemporal transitions in the AGM region and supportive OP9 cell line. Screening several proteins through an ex vivo reaggregate culture system, we identify BMP ER as a novel positive regulator of HSC development. We demonstrate that BMP ER is associated with BMP signaling inhibition, but is transcriptionally induced by BMP4, suggesting that BMP ER contributes to the precise control of BMP activity within the AGM region, enabling the maturation of HSCs within a BMP-negative environment. These findings and the availability of our transcriptional data through an accessible interface should provide insight into the maintenance and potential derivation of HSCs in culture.
  • Robson, T. Matthew; Aphalo, Pedro J.; Banas, Agnieszka Katarzyna; Barnes, Paul W.; Brelsford, Craig C.; Jenkins, Gareth I.; Kotilainen, Titta K.; Labuz, Justyna; Martinez-Abaigar, Javier; Morales, Luis O.; Neugart, Susanne; Pieriste, Marta; Rai, Neha; Vandenbussche, Filip; Jansen, Marcel A. K. (2019)
    Plants perceive ultraviolet-B (UV-B) radiation through the UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8), and initiate regulatory responses via associated signalling networks, gene expression and metabolic pathways. Various regulatory adaptations to UV-B radiation enable plants to harvest information about fluctuations in UV-B irradiance and spectral composition in natural environments, and to defend themselves against UV-B exposure. Given that UVR8 is present across plant organs and tissues, knowledge of the systemic signalling involved in its activation and function throughout the plant is important for understanding the context of specific responses. Fine-scale understanding of both UV-B irradiance and perception within tissues and cells requires improved application of knowledge about UV-attenuation in leaves and canopies, warranting greater consideration when designing experiments. In this context, reciprocal crosstalk among photoreceptor-induced pathways also needs to be considered, as this appears to produce particularly complex patterns of physiological and morphological response. Through crosstalk, plant responses to UV-B radiation go beyond simply UV-protection or amelioration of damage, but may give cross-protection over a suite of environmental stressors. Overall, there is emerging knowledge showing how information captured by UVR8 is used to regulate molecular and physiological processes, although understanding of upscaling to higher levels of organisation, i.e. organisms, canopies and communities remains poor. Achieving this will require further studies using model plant species beyond Arabidopsis, and that represent a broad range of functional types. More attention should also be given to plants in natural environments in all their complexity, as such studies are needed to acquire an improved understanding of the impact of climate change in the context of plant-UV responses. Furthermore, broadening the scope of experiments into the regulation of plant-UV responses will facilitate the application of UV radiation in commercial plant production. By considering the progress made in plant-UV research, this perspective highlights prescient topics in plant-UV photobiology where future research efforts can profitably be focussed. This perspective also emphasises burgeoning interdisciplinary links that will assist in understanding of UV-B effects across organisational scales and gaps in knowledge that need to be filled so as to achieve an integrated vision of plant responses to UV-radiation.
  • Tguiko, Olga; Jatsenko, Tatjana; Grace, Lalit Kumar Parameswaran; Kurg, Ants; Vermeesch, Joris Robert; Lanner, Fredrik; Altmae, Signe; Salumets, Andres (2019)
    The journey of embryonic development starts at oocyte fertilization, which triggers a complex cascade of events and cellular pathways that guide early embryogenesis. Recent technological advances have greatly expanded our knowledge of cleavage-stage embryo development, which is characterized by an increased rate of whole-chromosome losses and gains, mixoploidy, and atypical cleavage morphokinetics. Embryonic aneuploidy significantly contributes to implantation failure, spontaneous miscarriage, stillbirth or congenital birth defects in both natural and assisted human reproduction. Essentially, early embryo development is strongly determined by maternal factors. Owing to considerable limitations associated with human oocyte and embryo research, the use of animal models is inevitable. However, cellular and molecular mechanisms driving the error-prone early stages of development are still poorly described. In this review, we describe known events that lead to aneuploidy in mammalian oocytes and preimplantation embryos. As the processes of oocyte and embryo development are rigorously regulated by multiple signal-transduction pathways, we explore the putative role of signaling pathways in genomic integrity maintenance. Based on the existing evidence from human and animal data, we investigate whether critical early developmental pathways, like Wnt, Hippo and MAPK, together with distinct DNA damage response and DNA repair pathways can be associated with embryo genomic instability, a question that has, so far, remained largely unexplored.
  • Larson, Eric D.; Magno, Jose Pedrito M.; Steritz, Matthew J.; Llanes, Erasmo Gonzalo d; Cardwell, Jonathan; Pedro, Melquiadesa; Roberts, Tori Bootpetch; Einarsdottir, Elisabet; Rosanes, Rose Anne Q.; Greenlee, Christopher; Santos, Rachel Ann P.; Yousaf, Ayesha; Streubel, Sven-Olrik; Santos, Aileen Trinidad R.; Ruiz, Amanda G.; Mae Lagrana-Villagracia, Sheryl; Ray, Dylan; Yarza, Talitha Karisse L.; Scholes, Melissa A.; Anderson, Catherine B.; Acharya, Anushree; Gubbels, Samuel P.; Bamshad, Michael J.; Cass, Stephen P.; Lee, Nanette R.; Shaikh, Rehan S.; Nickerson, Deborah A.; Mohlke, Karen L.; Prager, Jeremy D.; Cruz, Teresa Luisa G.; Yoon, Patricia J.; Abes, Generoso T.; Schwartz, David A.; Chan, Abner L.; Wine, Todd M.; Maria Cutiongco-de la Paz, Eva; Friedman, Norman; Kechris, Katerina; Kere, Juha; Leal, Suzanne M.; Yang, Ivana; Patel, Janak A.; Tantoco, Ma Leah C.; Riazuddin, Saima; Chan, Kenny H.; Mattila, Petri S.; Reyes-Quintos, Maria Rina T.; Ahmed, Zubair M.; Jenkins, Herman A.; Chonmaitree, Tasnee; Hafren, Lena; Chiong, Charlotte M.; Santos-Cortez, Regie Lyn P. (2019)
    A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.
  • Sola-Carvajal, Agustin; Revechon, Gwladys; Helgadottir, Hafdis T.; Whisenant, Daniel; Hagblom, Robin; Döhla, Julia; Katajisto, Pekka; Brodin, David; Fagerstrom-Billai, Fredrik; Viceconte, Nikenza; Eriksson, Maria (2019)
    Hutchinson-Gilford progeria syndrome (HGPS) is the result of a defective form of the lamin A protein called progerin. While progerin is known to disrupt the properties of the nuclear lamina, the underlying mechanisms responsible for the pathophysiology of HGPS remain less clear. Previous studies in our laboratory have shown that progerin expression in murine epidermal basal cells results in impaired stratification and halted development of the skin. Stratification and differentiation of the epidermis is regulated by asymmetric stem cell division. Here, we show that expression of progerin impairs the ability of stem cells to maintain tissue homeostasis as a result of altered cell division. Quantification of basal skin cells showed an increase in symmetric cell division that correlated with progerin accumulation in HGPS mice. Investigation of the mechanisms underlying this phenomenon revealed a putative role of Wnt/beta-catenin signaling. Further analysis suggested an alteration in the nuclear translocation of beta-catenin involving the inner and outer nuclear membrane proteins, emerin and nesprin-2. Taken together, our results suggest a direct involvement of progerin in the transmission of Wnt signaling and normal stem cell division. These insights into the molecular mechanisms of progerin may help develop new treatment strategies for HGPS.
  • Pascual, Jesus; Rahikainen, Moona; Angeleri, Martina; Alegre, Sara; Gossens, Richard; Shapiguzov, Alexey; Heinonen, Arttu; Trotta, Andrea; Durian, Guido; Winter, Zsofia; Sinkkonen, Jari; Kangasjarvi, Jaakko; Whelan, James; Kangasjärvi, Saijaliisa (2021)
    Mitochondria are tightly embedded within metabolic and regulatory networks that optimize plant performance in response to environmental challenges. The best-known mitochondrial retrograde signaling pathway involves stress-induced activation of the transcription factor NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), which initiates protective responses to stress-induced mitochondrial dysfunction in Arabidopsis (Arabidopsis thaliana). Posttranslational control of the elicited responses, however, remains poorly understood. Previous studies linked protein phosphatase 2A subunit PP2A-B'gamma, a key negative regulator of stress responses, with reversible phosphorylation of ACONITASE 3 (ACO3). Here we report on ACO3 and its phosphorylation at Ser91 as key components of stress regulation that are induced by mitochondrial dysfunction. Targeted mass spectrometry-based proteomics revealed that the abundance and phosphorylation of ACO3 increased under stress, which required signaling through ANAC017. Phosphomimetic mutation at ACO3-Ser91 and accumulation of ACO3(S91D)-YFP promoted the expression of genes related to mitochondrial dysfunction. Furthermore, ACO3 contributed to plant tolerance against ultraviolet B (UV-B) or antimycin A-induced mitochondrial dysfunction. These findings demonstrate that ACO3 is both a target and mediator of mitochondrial dysfunction signaling, and critical for achieving stress tolerance in Arabidopsis leaves.
  • Kovalchuk, Andriy; Raffaello, Tommaso; Jaber, Emad; Keriö, Susanna; Ghimire, Rajendra; Lorenz, W. Walter; Dean, Jeffrey F. D.; Holopainen, Jarmo K.; Asiegbu, Fred O. (2015)
    Background: During their lifetime, conifer trees are exposed to numerous herbivorous insects. To protect themselves against pests, trees have developed a broad repertoire of protective mechanisms. Many of the plant's defence reactions are activated upon an insect attack, and the underlying regulatory mechanisms are not entirely understood yet, in particular in conifer trees. Here, we present the results of our studies on the transcriptional response and the volatile compounds production of Scots pine (Pinus sylvestris) upon the large pine weevil (Hylobius abietis) feeding. Results: Transcriptional response of Scots pine to the weevil attack was investigated using a novel customised 36.4 K Pinus taeda microarray. The weevil feeding caused large-scale changes in the pine transcriptome. In total, 774 genes were significantly up-regulated more than 4-fold (p = 0.05), whereas 64 genes were significantly down-regulated more than 4-fold. Among the up-regulated genes, we could identify genes involved in signal perception, signalling pathways, transcriptional regulation, plant hormone homeostasis, secondary metabolism and defence responses. The weevil feeding on stem bark of pine significantly increased the total emission of volatile organic compounds from the undamaged stem bark area. The emission levels of monoterpenes and sesquiterpenes were also increased. Interestingly, we could not observe any correlation between the increased production of the terpenoid compounds and expression levels of the terpene synthase-encoding genes. Conclusions: The obtained data provide an important insight into the transcriptional response of conifer trees to insect herbivory and illustrate the massive changes in the host transcriptome upon insect attacks. Moreover, many of the induced pathways are common between conifers and angiosperms. The presented results are the first ones obtained by the use of a microarray platform with an extended coverage of pine transcriptome (36.4 K cDNA elements). The platform will further facilitate the identification of resistance markers with the direct relevance for conifer tree breeding.
  • Yu, Nancy Y.; Bieder, Andrea; Raman, Amitha; Mileti, Enrichetta; Katayama, Shintaro; Einarsdottir, Elisabet; Fredholm, Bertil B.; Falk, Anna; Tapia-Paez, Isabel; Daub, Carsten O.; Kere, Juha (2017)
    Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 mu M and 10 mu M), over a period of 9 h. We found dosage-dependent activation of immediate early genes after 1 h. Neuronal projection development processes were up-regulated and negative regulation of axon extension processes were down-regulated at 3 h. In addition, genes involved in extracellular matrix organization, response for wound healing, and regulation of immune system processes were down-regulated by caffeine at 3 h. This study identified novel genes within the neuronal projection guidance pathways that respond to acute caffeine stimulation and suggests potential mechanisms for the effects of caffeine on neuronal cells.
  • Ouwerkerk, Janneke P.; van der Ark, Kees C. H.; Davids, Mark; Claassens, Nico J.; Finestra, Teresa Robert; de Vos, Willem M.; Belzer, Clara (2016)
    Akkermansia muciniphila colonizes the mucus layer of the gastrointestinal tract, where the organism can be exposed to the oxygen that diffuses from epithelial cells. To understand how A. muciniphila is able to survive and grow at this oxic-anoxic interface, its oxygen tolerance and response and reduction capacities were studied. A. muciniphila was found to be oxygen tolerant. On top of this, under aerated conditions, A. muciniphila showed significant oxygen reduction capacities and its growth rate and yield were increased compared to those seen under strict anaerobic conditions. Transcriptome analysis revealed an initial oxygen stress response upon exposure to oxygen. Thereafter, genes related to respiration were expressed, including those coding for the cytochrome bd complex, which can function as a terminal oxidase. The functionality of A. muciniphila cytochrome bd genes was proven by successfully complementing cytochrome-deficient Escherichia coli strain ECOM4. We conclude that A. muciniphila can use oxygen when it is present at nanomolar concentrations. IMPORTANCE This article explains how Akkermansia muciniphila, previously described as a strictly anaerobic bacterium, is able to tolerate and even benefit from low levels of oxygen. Interestingly, we measured growth enhancement of A. muciniphila and changes in metabolism as a result of the oxygen exposure. In this article, we discuss similarities and differences of this oxygen-responsive mechanism with respect to those of other intestinal anaerobic isolates. Taken together, we think that these are valuable data that indicate how anaerobic intestinal colonizing bacteria can exploit low levels of oxygen present in the mucus layer and that our results have direct relevance for applicability, as addition of low oxygen concentrations could benefit the in vitro growth of certain anaerobic organisms.
  • Laulajainen-Hongisto, Anu; Toppila-Salmi, Sanna Katriina; Luukkainen, Annika; Kern, Robert (2020)
    Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.
  • van der Lugt, Benthe; van Beek, Adriaan A.; Aalvink, Steven; Meijer, Ben; Sovran, Bruno; Vermeij, Wilbert P.; Brandt, Renata M. C.; de Vos, Willem M.; Savelkoul, Huub F. J.; Steegenga, Wilma T.; Belzer, Clara (2019)
    BackgroundThe use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1(-/7) mice with A. muciniphila for 10weeks and investigated histological, transcriptional and immunological aspects of intestinal health.ResultsThe thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80(+)CD273(-) B cells in Peyer's patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6C(int) monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila.ConclusionsAltogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
  • Aminoff, Anna; Ledmyr, Helena; Thulin, Petra; Lundell, Kerstin; Nunez, Leyla; Strandhagen, Elisabeth; Murphy, Charlotte; Lidberg, Ulf; Westerbacka, Jukka; Franco-Cereceda, Anders; Liska, Jan; Nielsen, Lars Bo; Gafvels, Mats; Mannila, Maria Nastase; Hamsten, Anders; Yki-Järvinen, Hannele; Thelle, Dag; Eriksson, Per; Boren, Jan; Ehrenborg, Ewa (2010)
  • Castillejo, Cristina; Waurich, Veronika; Wagner, Henning; Ramos, Ruben; Oiza, Nicolas; Munoz, Pilar; Trivino, Juan C.; Caruana, Julie; Liu, Zhongchi; Cobo, Nicolas; Hardigan, Michael A.; Knapp, Steven J.; Vallarino, Jose G.; Osorio, Sonia; Martin-Pizarro, Carmen; Pose, David; Toivainen, Tuomas; Hytonen, Timo; Oh, Youngjae; Barbey, Christopher R.; Whitaker, Vance M.; Lee, Seonghee; Olbricht, Klaus; Sanchez-Sevilla, Jose F.; Amaya, Iraida (2020)
    Independent mutations in the transcription factor MYB10 cause most of the anthocyanin variation observed in diploid woodland strawberry (Fragaria vesca) and octoploid cultivated strawberry (Fragaria x ananassa). The fruits of diploid and octoploid strawberry (Fragaria spp) show substantial natural variation in color due to distinct anthocyanin accumulation and distribution patterns. Anthocyanin biosynthesis is controlled by a clade of R2R3 MYB transcription factors, among which MYB10 is the main activator in strawberry fruit. Here, we show that mutations in MYB10 cause most of the variation in anthocyanin accumulation and distribution observed in diploid woodland strawberry (F. vesca) and octoploid cultivated strawberry (F. xananassa). Using a mapping-by-sequencing approach, we identified a gypsy-transposon in MYB10 that truncates the protein and knocks out anthocyanin biosynthesis in a white-fruited F. vesca ecotype. Two additional loss-of-function mutations in MYB10 were identified among geographically diverse white-fruited F. vesca ecotypes. Genetic and transcriptomic analyses of octoploid Fragaria spp revealed that FaMYB10-2, one of three MYB10 homoeologs identified, regulates anthocyanin biosynthesis in developing fruit. Furthermore, independent mutations in MYB10-2 are the underlying cause of natural variation in fruit skin and flesh color in octoploid strawberry. We identified a CACTA-like transposon (FaEnSpm-2) insertion in the MYB10-2 promoter of red-fleshed accessions that was associated with enhanced expression. Our findings suggest that cis-regulatory elements in FaEnSpm-2 are responsible for enhanced MYB10-2 expression and anthocyanin biosynthesis in strawberry fruit flesh.
  • Liu, Jiao; Puolanne, Eero; Schwartzkopf, Matthias; Arner, Anders (2020)
    The "Woody" or "Wooden" breast disease is a severe myopathy of pectoralis major muscle recently identified within rapidly growing broiler lines all around the world with a prevalence rate around 20%, or even higher. Although of significant ethical and economic impact, little is known regarding the structural and functional aspects of the contractile apparatus in the woody breast muscle. The aim of the present study was to determine physiological properties of the contractile system in the morphologically intact muscle fibers of focally damaged woody breast in comparison with normal muscle fibers to gain insight into the muscle function of the animal and possibly mechanisms involved in the disease development. Muscle samples were taken from woody breast (non-lesioned areas) and normal breast muscles from broilers. Length-tension curves, maximal active stress, maximal shortening velocity, calcium sensitivity, rate of tension development, lattice spacing and muscle biochemical composition were investigated on single skinned fibers. Sarcomeres of woody breast fibers were more compliant, which is very likely related to the wider spacing (18% wider compared to controls) between thick and thin filament. No differences were found in optimal sarcomere length (2.68 +/- 0.04 vs. 2.65 +/- 0.05 mu m) nor in maximal active stress (116 +/- 17 vs. 125 +/- 19 mN mm(-2)). However, woody breast fibers had less steep descending arm as shown in length-tension curve. Woody breast muscle fibers had 40% bigger sarcomeric volume compared to controls. Content of contractile proteins (myosin and actin), and maximal shortening velocity were unchanged indicating that the growth in woody breast muscle fiber was associated with synthesis of new contractile units with unaltered kinetics. Calcium sensitivity was decreased in woody breast muscle fibers significantly. In conclusion, the results show that the rapid growth of muscle in woody breast disease is associated with significant structural and functional changes in the pectoralis major musculature, associated with alterations in the mechanical anchoring of contractile filaments.