Browsing by Subject "TOLERANCE"

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  • Clement, Cristina C.; D'Alessandro, Angelo; Thangaswamy, Sangeetha; Chalmers, Samantha; Furtado, Raquel; Spada, Sheila; Mondanelli, Giada; Ianni, Federica; Gehrke, Sarah; Gargaro, Marco; Manni, Giorgia; Lopez Cara, Luisa Carlota; Runge, Peter; Tsai, Wanxia Li; Karaman, Sinem; Arasa, Jorge; Fernandez-Rodriguez, Ruben; Beck, Amanda; Macchiarulo, Antonio; Gadina, Massimo; Halin, Cornelia; Fallarino, Francesca; Skobe, Mihaela; Veldhoen, Marc; Moretti, Simone; Formenti, Silvia; Demaria, Sandra; Soni, Rajesh K.; Galarini, Roberta; Sardella, Roccaldo; Lauvau, Gregoire; Putterman, Chaim; Alitalo, Kari; Grohmann, Ursula; Santambrogio, Laura (2021)
    Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-gamma mediated STAT1/NF-kappa Beta pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1 beta, IFN-gamma, and IL-17 production, and inhibiting generation of effector CD8(+) T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.
  • Lalarukh, Irfana; Al-Dhumri, Sami A.; Al-Ani, Laith Khalil Tawfeeq; Hussain, Rashid; Al Mutairi, Khalid Awadh; Mansoora, Nida; Amjad, Syeda Fasiha; Abbas, Mohamed H. H.; Abdelhafez, Ahmed A.; Poczai, Peter; Meena, Khem Raj; Galal, Tarek M. M.; Galal, Tarek M. (2022)
    Less nutrient availability and drought stress are some serious concerns of agriculture. Both biotic and abiotic stress factors have the potential to limit crop productivity. However, several organic extracts obtained from moringa leaves may induce immunity in plants under nutritional and drought stress for increasing their survival. Additionally, some rhizobacterial strains have the ability to enhance root growth for better nutrient and water uptake in stress conditions. To cover the knowledge gap on the interactive effects of beneficial rhizobacteria and moringa leaf extracts (MLEs), this study was conducted. The aim of this experimental study was to investigate the effectiveness of sole and combined use of rhizobacteria and MLEs against nutritional and drought stress in wheat. Nitrogen-fixing bacteria Pseudomonas aeruginosa (Pa) (10(8) CFU ml(-1)) was inoculated to wheat plants with and without foliar-applied MLEs at two different concentrations (MLE 1 = 1:15 v/v and MLE 2 = 1:30 v/v) twice at 25 and 35 days after seed sowing (50 ml per plant) after the establishment of drought stress. Results revealed that Pa + MLE 2 significantly increased fresh weight (FW), dry weight (DW), lengths of roots and shoot and photosynthetic contents of wheat. A significant enhancement in total soluble sugars, total soluble proteins, calcium, potassium, phosphate, and nitrate contents validated the efficacious effect of Pa + MLE 2 over control-treated plants. Significant decrease in sodium, proline, glycine betaine, electrolyte leakage, malondialdehyde, hydrogen peroxide, superoxide dismutase (SOD), and peroxide (POD) concentrations in wheat cultivated under drought stress conditions also represents the imperative role of Pa + MLE 2 over control. In conclusion, Pa + MLE 2 can alleviate nutritional stress and drought effects in wheat. More research in this field is required to proclaim Pa + MLE 2 as the most effective amendment against drought stress in distinct agroecological zones, different soil types, and contrasting wheat cultivars worldwide.
  • Khazaei, Hamid; Stoddard, Frederick L.; Purves, Randy W.; Vandenberg, Albert (2018)
    Faba bean (Viciafaba L.) is a valuable grain legume and a staple protein crop in many countries. Its large and complex genome requires novel approaches for its genetic dissection. Here we introduce a multi-parent population developed from four founders (ILB 938/2, Disco/2, IG 114476 and IG 132238). The selection of parental lines was based on geographic (Colombia, France, Bangladesh and China), genetic and phenotypic diversity. The parental lines were inbred and then genotyped using 875 single nucleotide polymorphism (SNP) markers. Based on molecular data, the parents had high homozygosity and high genetic distance among them. The population segregates for several important traits such as seed morphology, seed chemistry, phenology, plant architecture, drought response, yield and its components, and resistance to Botrytis fabae. The population was checked for unbiased segregation in each generation by observing simply inherited Mendelian traits such as stipule spot pigmentation (SSP) and flower colour at different generations. All 1200 four-way cross Fl plants had pigmented flowers and stipule spots. The segregation ratios for white flower colour (single gene, zt2) fit 7:1, 13:3 and 25:7 at F2, F3 and F4 generations, respectively, and the segregation ratio of SSP (two recessive unlinked genes, ssp1 and ssp2) fit 49:15 and 169:87 at the F2 and F3 generations, respectively, demonstrating unbiased generation advance. We will subject the F5 generation of this population to a high-throughput SNP array and make it available for further phenotyping and genotyping.
  • Sageman-Furnas, Katelyn; Nurmi, Markus; Contag, Meike; Ploetner, Bjoern; Alseekh, Saleh; Wiszniewski, Andrew; Fernie, Alisdair R.; Smith, Lisa M.; Laitinen, Roosa A. E. (2022)
    Hybrids between Arabidopsis thaliana accessions are important in revealing the consequences of epistatic interactions in plants. F-1 hybrids between the A. thaliana accessions displaying either defense or developmental phenotypes have been revealing the roles of the underlying epistatic genes. The interaction of two naturally occurring alleles of the OUTGROWTH-ASSOCIATED KINASE (OAK) gene in Sha and Lag2-2, previously shown to cause a similar phenotype in a different allelic combination in A. thaliana, was required for the hybrid phenotype. Outgrowth formation in the hybrids was associated with reduced levels of salicylic acid, jasmonic acid and abscisic acid in petioles and the application of these hormones mitigated the formation of the outgrowths. Moreover, different abiotic stresses were found to mitigate the outgrowth phenotype. The involvement of stress and hormone signaling in outgrowth formation was supported by a global transcriptome analysis, which additionally revealed that TCP1, a transcription factor known to regulate leaf growth and symmetry, was downregulated in the outgrowth tissue. These results demonstrate that a combination of natural alleles of OAK regulates growth and development through the integration of hormone and stress signals and highlight the importance of natural variation as a resource to discover the function of gene variants that are not present in the most studied accessions of A. thaliana.
  • 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.
  • Pollari, Marjukka; Pellinen, Teijo; Karjalainen-Lindsberg, Marja-Liisa; Kellokumpu-Lehtinen, Pirkko-Liisa; Leivonen, Suvi-Katri; Leppä, Sirpa (2020)
    Objectives Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive extranodal lymphoma. We have previously shown that high content of tumor-infiltrating lymphocytes (TILs) and PD-1 expressing TILs associate with better survival in T-DLBCL. In this study, we have further characterized distinct TIL subtypes and their proportions in association with patient demographics and survival. Methods We used multiplex immunohistochemistry to characterize TIL phenotypes, including cytotoxic T-cells (CTLs; CD8(+), OX40(+), Granzyme B+, Ki-67(+), LAG-3(+), TIM-3(+), PD-1(+)), CD4(+)T-cells (CD3(+), CD4(+), TIM-3(+), LAG-3(+)), regulatory T-cells (Tregs; CD3(+), CD4(+), FoxP3(+)), and T helper 1 cells (Th1; CD3(+), CD4(+), T-bet(+)) in 79 T-DLBCLs, and correlated the findings with patient demographics and outcome. Results We observed a substantial variation in TIL phenotypes between the patients. The most prominent CD8(+)TILs were Ki-67(+)and TIM-3(+)CTLs, whereas the most prominent CD4(+)TILs were FoxP3(+)Tregs. Despite the overall favorable prognostic impact of high TIL content, we found a subpopulation of T-bet(+)FoxP3(+)Tregs that had a significant adverse impact on survival. Lower content of CTLs with activated or exhausted phenotypes correlated with aggressive clinical features. Conclusions Our results demonstrate significant variation in TIL phenotypes and emphasize the adverse prognostic impact of Tregs in T-DLBCL.
  • Pflugmacher, Stephan; Tallinen, Saila; Kim, Young Jun; Kim, Sanghun; Esterhuizen, Maranda (2021)
    Plastic has been an environmental pollutant far longer than claimed by the first reports surfacing in 1979, meaning some plastic materials have been decaying in nature for decades. Nevertheless, the threat posed to biota is not fully understood, especially from aged microplastic. The question considered in this study was whether the adverse effects of new plastic differ from those of old plastic material. Therefore, the morphological and physiological effects on Lepidium sativum with exposure to both new and aged polycarbonate were considered against a known stressor leaching from polycarbonate with time, bisphenol-A. Exposure to new and short-term aged polycarbonate (up to 80 days) elicited the most severe effects such as germination inhibition, reduced seedling growth, decreased chlorophyll concentrations, and increased catalase activity. These adverse effects in L. sativum associated with polycarbonate exposure were reduced as a function of the ageing time applied to the polycarbonate. The chemical substances that lend new polycarbonate material its toxicity were likely leached with time during the ageing process. Based on the results obtained, temperature and humidity based artificial ageing significantly reduced the phytotoxicity of the microplastic particles
  • Mehmood, Shiraz; Din, Israr Ud; Ullah, Izhar; Mohamed, Heba; Basit, Abdul; Khan, Mudassar Nawaz; Shah, Syed Saad Hussain; Rehman, Attiq ur (2021)
    Background Knowledge of the genetic diversity and population structure of germplasm collections is an important foundation for crop improvement. Rice production across a broad range of rice-growing environments results in a diverse array of local rice varieties. Many rice varieties have been lost as a result of biodiversity loss and are now grown in Pakistan. Methods and results To protect the biodiversity of rice varieties, an experiment was carried out to check the genetic and morphological variations between 8 exotic and 7 local rice genotypes, using 5 different SSR markers, i.e., RM3, RM259, RM341, RM520, and RM11943. The analysis of morphological and quality traits of rice observed significant variation across genotypes. The results revealed that genotype Irri-Pak attained the highest plant height and primary branch plant-1, while genotype Mushkan produced a higher number of productive tillers and obtained a higher fertility factor (%). Similarly, the highest value for panicle length was observed for genotype Faker-e-Malakand, 1000-grains weight in genotype Calmochi, and maximum days to maturity was noticed in genotype Swati-2014. Moreover, the genotype Brio attained the highest value of stem diameter, while maximum seed length was noted in the genotype Sug Dasi. The highest number of primary branches plant(-1) in genotype Ibge-I and secondary branches plant(-1) in genotype Calmochi were noticed. A higher concentration of sodium and potassium was observed for the genotype Marte, while the genotype Muskan attained the maximum content of copper. Moreover, the highest concentration of iron in genotype Originario, zinc in genotype JP-5, and cadmium content were noticed in genotype Ibge. Similarly, the dendrogram analysis for quantitative parameters showed three clusters at 74.13% similarities. Whereas all the genotypes of European origin formed a separate cluster. A set of 5 simple sequence repeat primers, covering four chromosomes, amplified a total of 14 alleles and showed 100% polymorphism with an average PIC value ranging from 0.39 to 0.91. The UPGMA cluster analysis separated the 15 rice genotypes into 3 main groups based on 32.5% similarities and the highest genetic distance (45.1%) was observed between two genotypes (Fakher-e-malakand and Musa), having different geographical origins. There was no genetic distance between the genotypes Marte and Brio, irrespective of having the same origin. Conclusions The maximum genetic distances were noted for genotype, Fakhre-e-Malakand and Musa having a different origin, while the minimum genetic distance was shown by genotypes, Marte and Onice, from the same origin.
  • Koivisto, Maarit K.; Miettunen, Jouko; Levola, Jonna; Mustonen, Antti; Alakokkare, Anni-Emilia; Salom, Caroline L.; Niemelä, Solja (2022)
    Background Overdoses and poisonings are among the most common causes of death in young adults. Adolescent problem drinking has been associated with psychiatric morbidity in young adulthood as well as with elevated risk for suicide attempts. There is limited knowledge on adolescent alcohol use as a risk factor for alcohol and/or drug overdoses in later life. Methods Here, data from The Northern Finland Birth Cohort 1986 study with a follow-up from adolescence to early adulthood were used to assess the associations between adolescent alcohol use and subsequent alcohol or drug overdose. Three predictors were used: age of first intoxication, self-reported alcohol tolerance and frequency of alcohol intoxication in adolescence. ICD-10-coded overdose diagnoses were obtained from nationwide registers. Use of illicit drugs or misuse of medication, Youth Self Report total score, family structure and mother's education in adolescence were used as covariates. Results In multivariate analyses, early age of first alcohol intoxication [hazard ratios (HR) 4.5, 95% confidence intervals (CI) 2.2-9.2, P < 0.001], high alcohol tolerance (HR 3.1, 95% CI 1.6-6.0, P = 0.001) and frequent alcohol intoxication (HR 1.9, 95% CI 1.0-3.4, P = 0.035) all associated with the risk of overdoses. Early age of first intoxication (HR 5.2, 95% CI 1.9-14.7, P = 0.002) and high alcohol tolerance (HR 4.4, 95% CI 1.7-11.5, P = 0.002) also associated with intentional overdoses. Conclusions Alcohol use in adolescence associated prospectively with increased risk of overdose in later life. Early age of first intoxication, high alcohol tolerance and frequent alcohol intoxication are all predictors of overdoses.
  • Melicher, Pavol; Dvorak, Petr; Krasylenko, Yuliya; Shapiguzov, Alexey; Kangasjärvi, Jaakko; Samaj, Jozef; Takac, Tomas (2022)
    Iron superoxide dismutase 1 (FSD1) was recently characterized as a plastidial, cytoplasmic, and nuclear enzyme with osmoprotective and antioxidant functions. However, the current knowledge on its role in oxidative stress tolerance is ambiguous. Here, we characterized the role of FSD1 in response to methyl viologen (MV)-induced oxidative stress in Arabidopsis thaliana. In accordance with the known regulation of FSD1 expression, abundance, and activity, the findings demonstrated that the antioxidant function of FSD1 depends on the availability of Cu2+ in growth media. Arabidopsis fsdl mutants showed lower capacity to decompose superoxide at low Cu2+ concentrations in the medium. Prolonged exposure to MV led to reduced ascorbate levels and higher protein carbonylation in fsdl mutants and transgenic plants lacking a plastid FSD1 pool as compared to the wild type. MV induced a rapid increase in FSD1 activity, followed by a decrease after 4 h long exposure. Genetic disruption of FSD1 negatively affected the hydrogen peroxide-decomposing ascorbate peroxidase in fsdl mutants. Chloroplastic localization of FSD1 is crucial to maintain redox homeostasis. Proteomic analysis showed that the sensitivity of fsd1 mutants to MV coincided with decreased abundances of ferredoxin and photosystem II light-harvesting complex proteins. These mutants have higher levels of chloroplastic proteases indicating an altered protein turnover in chloroplasts. Moreover, FSD1 disruption affects the abundance of proteins involved in the defense response. Collectively, the study provides evidence for the conditional antioxidative function of FSD1 and its possible role in signaling.
  • Liu, Miao; Liu, Xingxing; Kang, Jieyu; Korpelainen, Helena; Li, Chunyang (2020)
    This study clarifies the mechanisms of Cd uptake, translocation and detoxification in Populus cathayana Rehder females and males, and reveals a novel strategy for dioecious plants to cope with Cd contamination. Females exhibited a high degree of Cd uptake and root-to-shoot translocation, while males showed extensive Cd accumulation in roots, elevated antioxidative capacity, and effective cellular and bark Cd sequestration. Our study also found that Cd is largely located in epidermal and cortical tissues of male roots and leaves, while in females, more Cd was present in vascular tissues of roots and leaves, as well as in leaf mesophyll. In addition, the distributions of sulphur (S) and phosphorus (P) were very similar as that of Cd in males, but the associations were weak in females. Scanning electron microscopy and energy spectroscopy analyses suggested that the amounts of tissue Cd were positively correlated with P and S amounts in males, but not in females (a weak correlation between S and Cd). Transcriptional data suggested that Cd stress promoted the upregulation of genes related to Cd uptake and translocation in females, and that of genes related to cell wall biosynthesis, metal tolerance and secondary metabolism in males. Our results indicated that coordinated physiological, microstructural and transcriptional responses to Cd stress endowed superior Cd tolerance in males compared with females, and provided new insights into mechanisms underlying sexually differential responses to Cd stress.
  • Turunen, Antti; Kuuliala, Antti; Mustonen, Harri; Puolakkainen, Pauli; Kylänpää, Leena; Kuuliala, Krista (2021)
    Objectives Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP. Methods A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-kappa B (NF-kappa B), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry. Results The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-kappa B, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-kappa B in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8(+) T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-kappa B in lymphocytes predicted secondary infections. Conclusions Leukocyte STAT3, STAT1, STAT6, and NF-kappa Beta phosphorylations are potential predictors of AP severity.
  • Egamberdieva, Dilfuza; Wirth, Stephan; Jabborova, Dilfuza; Rasanen, Leena A.; Liao, Hong (2017)
    It is a well accepted strategy to improve plant salt tolerance through inoculation with beneficial microorganisms. However, its underlying mechanisms still remain unclear. In the present study, hydroponic experiments were conducted to evaluate the effects of Bradyrhizobium japonicum USDA 110 with salt-tolerant Pseudomonas putida TSAU1 on growth, protein content, nitrogen, and phosphorus uptake as well as root system architecture of soybean (Glycine max L.) under salt stress. The results indicated that the combined inoculation with USDA 110 and TSAU1 significantly improved plant growth, nitrogen and phosphorus contents, and contents of soluble leaf proteins under salt stress compared to the inoculation with the symbiont alone or compared to un-inoculated ones. The root architectural traits, like root length, surface area, project area, and root volume; as well as nodulation traits were also significantly increased by co-inoculation with USDA 110 and TSAU1. The plant-growth promoting rhizobacteria (PGPR) P. putida strain TSAU1 could improve the symbiotic interaction between the salt-stressed soybean and B. japonicum USDA 110. In conclusion, inoculation with B. japonicum and salt-tolerant P. putida synergistically improved soybean salt tolerance through altering root system architecture facilitating nitrogen and phosphorus acquisition, and nodule formation.
  • Nieminen, Janne K.; Niemi, Mirja; Sipponen, Taina; Salo, Harri M.; Klemetti, Paula; Färkkilä, Martti Antero; Vakkila, Jukka; Vaarala, Outi (2013)
  • Lim, Ives Yubin; Lin, Xinyi; Teh, Ai Ling; Wu, Yonghui; Chen, Li; He, Menglan; Chan, Shiao-Yng; MacIsaac, Julia L.; Chan, Jerry K. Y.; Tan, Kok Hian; Chong, Mary Foong Fong; Kobor, Michael S.; Godfrey, Keith M.; Meaney, Michael J.; Lee, Yung Seng; Eriksson, Johan G.; Gluckman, Peter D.; Chong, Yap Seng; Karnani, Neerja (2022)
    Context Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring's epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. Objective We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation. Research Design and Methods This study included 830 mother-offspring dyads from the Growing Up in Singapore Towards Healthy Outcomes cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (fasting plasma glucose [FPG]) and 2-hour plasma glucose (2hPG) after a 75-g oral glucose challenge with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. Results Maternal age, prepregnancy body mass index, and blood pressure measures were associated with both FPG and 2hPG, whereas Chinese ethnicity (P = 1.9 x 10(-4)), maternal height (P = 1.1 x 10(-4)), pregnancy weight gain (P = 2.2 x 10(-3)), prepregnancy alcohol consumption (P = 4.6 x 10(-4)), and tobacco exposure (P = 1.9 x 10(-3)) showed significantly opposite associations between the 2 glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the 2 measures also reflected differences in gene ontologies and had different associations with offspring birthweight. Conclusions Our findings suggest that 2 traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring's DNA methylome.
  • Yang, Kun; Wen, Xiaopeng; Mudunuri, Suresh; Varma, G. P. Saradhi; Sablok, Gaurav (2019)
    Plants have an amazing ability to cope with wide variety of stresses by regulating the expression of genes and thus by altering the physiological status. In the past few years, canonical microRNA variants (isomiRs) have been shown to play pivotal roles by acting as regulators of the transcriptional machinery. In the present research, we present Diff isomiRs, a web-based exploratory repository of differential isomiRs across 16 sequenced plant species representing a total of 433 datasets across 21 different stresses and 158 experimental states. Diff isomiRs provides the high-throughput detection of differential isomiRs using mapping-based and model-based differential analysis revealing a total of 16,157 and 2,028 differential isomiRs, respectively. Easy-to-use and web-based exploration of differential isomiRs provides several features such as browsing of the differential isomiRs according to stress or species, as well as association of the differential isomiRs to targets and plant endogenous target mimics (PeTMs). Diff isomiRs also provides the relationship between the canonical miRNAs, isomiRs and the miRNA-target interactions. This is the first web-based large-scale repository for browsing differential isomiRs and will facilitate better understanding of the regulatory role of the isomiRs with respect to the canonical microRNAs. Diff isomiRs can be accessed at:
  • Seppanen, Mervi M.; Ebrahimi, Nashmin; Kontturi, Juha; Hartikainen, Helina; Lopez Heras, Isabel; Camara, Carmen; Madrid, Yolanda (2018)
  • e-PREDICE Consortium; Gabriel, Rafael; Lindström, Jaana; Tuomilehto, Jaakko (2020)
    Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45–74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. Registration - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39
  • Pacwa-Plociniczak, Magdalena; Plociniczak, Tomasz; Yu, Dan; Kurola, Jukka Mikael; Sinkkonen, Aki Tapio; Piotrowska-Seget, Zofia; Romantschuk, Martin L. (2018)
    In this study, we analysed the impact of heavy metals and plant rhizodeposition on the structure of indigenous microbial communities in rhizosphere and bulk soil that had been exposed to heavy metals for more than 150 years. Samples of the rhizosphere of Silene vulgaris and non-rhizosphere soils 250 and 450 m from the source of emission that had different metal concentrations were collected for analyses. The results showed that soils were collected 250 m from the smelter had a higher number of Cd-resistant CFU compared with the samples that were collected from 450 m, but no significant differences were observed in the number of total and oligotrophic CFU or the equivalent cell numbers between rhizosphere and non-rhizosphere soils that were taken 250 and 450 m from the emitter. Unweighted pair group method with arithmetic mean (UPGMA) cluster analysis of the denaturing gradient gel electrophoresis (DGGE) profiles, as well as a cluster analysis that was generated on the phospholipid fatty acid (PLFA) profiles, showed that the bacterial community structure of rhizosphere soils depended more on the plant than on the distance and metal concentrations. The sequencing of the 16S rDNA fragments that were excised from the DGGE gel revealed representatives of the phyla Bacteroidetes, Acidobacteria, Gemmatimonadetes, Actinobacteria and Betaproteobacteria in the analysed soil with a predominance of the first three groups. The obtained results demonstrated that the presence of S. vulgaris did not affect the number of CFUs, except for those of Cd-resistant bacteria. However, the presence of S. vulgaris altered the soil bacterial community structure, regardless of the sampling site, which supported the thesis that plants have a higher impact on soil microbial community than metal contamination.
  • Trotta, Luca; Hautala, Timo; Hamalainen, Sari; Syrjanen, Jaana; Viskari, Hanna; Almusa, Henrikki; Lepisto, Maija; Kaustio, Meri; Porkka, Kimmo; Palotie, Aarno; Seppanen, Mikko; Saarela, Janna (2016)
    Antibody class-switch recombination and somatic hypermutation critically depend on the function of activation-induced cytidine deaminase (AID). Rare variants in its gene AICDA have been reported to cause autosomal recessive AID deficiency (autosomal recessive hyper-IgM syndrome type 2 (HIGM2)). Exome sequencing of a multicase Finnish family with an HIGM2 phenotype identified a rare, homozygous, variant (c.416T > C, p.(Met139Thr)) in the AICDA gene, found to be significantly enriched in the Finnish population compared with other populations of European origin (38.56-fold, P <0.001). The population history of Finland, characterized by a restricted number of founders, isolation and several population bottlenecks, has caused enrichment of certain rare disease-causing variants and losses of others, as part of a phenomenon called the Finnish Disease Heritage. Accordingly, rare founder mutations cause the majority of observed Finnish cases in these mostly autosomal recessive disorders that consequently are more frequent in Finland than elsewhere. Screening of all currently known Finnish patients with an HIGM2 phenotype showed them to be homozygous for p.(Met139Thr). All the Finnish p.(Met139Thr) carriers with available data on their geographic descent originated from the eastern and northeastern parts of Finland. They were observed to share more of their genome identity by descent (IBD) than Finns in general (P <0.001), and they all carried a 207.5-kb ancestral haplotype containing the variant. In conclusion, the identified p.(Met139Thr) variant is significantly enriched in Finns and explains all thus far found AID deficiencies in Finland.