Browsing by Subject "ACCUMULATION"

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  • West, Gun; Turunen, Minttu; Aalto, Anna; Virtanen, Laura; Li, Song-Ping; Heliö, Tiina; Meinander, Annika; Taimen, Pekka (2022)
    Lamins A and C are nuclear intermediate filament proteins that form a proteinaceous meshwork called lamina beneath the inner nuclear membrane. Mutations in the LMNA gene encoding lamins A and C cause a heterogenous group of inherited degenerative diseases known as laminopathies. Previous studies have revealed altered cell signaling pathways in lamin-mutant patient cells, but little is known about the fate of mutant lamins A and C within the cells. Here, we analyzed the turnover of lamins A and C in cells derived from a dilated cardiomyopathy patient with a heterozygous p.S143P mutation in LMNA. We found that transcriptional activation and mRNA levels of LMNA are increased in the primary patient fibroblasts, but the protein levels of lamins A and C remain equal in control and patient cells because of a meticulous interplay between autophagy and the ubiquitin-proteasome system (UPS). Both endogenous and ectopic expression of p.S143P lamins A and C cause significantly reduced activity of UPS and an accumulation of K48-ubiquitin chains in the nucleus. Furthermore, K48-ubiquitinated lamins A and C are degraded by compensatory enhanced autophagy, as shown by increased autophagosome formation and binding of lamins A and C to microtubule-associated protein 1A/1B-light chain 3. Finally, chaperone 4-PBA augmented protein degradation by restoring UPS activity as well as autophagy in the patient cells. In summary, our results suggest that the p.S143P-mutant lamins A and C have overloading and deleterious effects on protein degradation machinery and pharmacological interventions with compounds enhancing protein degradation may be beneficial for cell homeostasis.
  • Guzman, Erika Avendano; Bouter, Yvonne; Richard, Bernhard C.; Lannfelt, Lars; Ingelsson, Martin; Paetau, Anders; Verkkoniemi-Ahola, Auli; Wirths, Oliver; Bayer, Thomas A. (2014)
  • 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.
  • FALS Sequencing Consortium; Amer Genome Ctr; Int ALS Genomics Consortium; ITALSGEN Consortium; Johnson, Janel O.; Chia, Ruth; Miller, Danny E.; Tienari, Pentti J.; Laaksovirta, Hannu; Valori, Miko; Jansson, Lilja (2021)
    IMPORTANCE Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. OBJECTIVE To identify the genetic variants associated with juvenile ALS. DESIGN, SETTING, AND PARTICIPANTS In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. MAIN OUTCOMES AND MEASURES De novo variants present only in the index case and not in unaffected family members. RESULTS Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p. Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. CONCLUSIONS AND RELEVANCE These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.
  • Rehman, Sidra; Mansoora, Nida; Al-Dhumri, Sami A.; Amjad, Syeda F.; Al-Shammari, Wasimah B.; Almutari, Mohammad M.; Alhusayni, Fatimah S.; Al Bakre, Dhafer A.; Lalarukh, Irfana; Alshahri, Abdullah H.; Poczai, Peter; Galal, Tarek M.; Abdelhafez, Ahmed A. (2022)
    Heavy metal stress and less nutrient availability are some of the major concerns in agriculture. Both abiotic stresses have potential to decrease the crops productivity. On the other hand, organic fertilizers i.e., activated carbon biochar (ACB) and arbuscular mycorrhizal fungi (AMF) increase nutritional and heavy metal like Nickel (Ni) stress tolerance and provide immunity to plants for their survival in unfavorable environments. Previous studies have only looked at single applications of either ACB or AMF thus far. There is limited evidence of their synergistic effects, especially in plants growing in soil contaminated with nickel (Ni). To cover the knowledge gap of combined use of AMF inoculation (Glomus intraradices) and/or wheat straw biochar amendments on wheat growth, antioxidant activities and osmolytes concentration, present study is conducted. The use of either the AMF inoculant or the ACB alone resulted in improved wheat growth and decreased Ni uptake. Furthermore, sole AMF or ACB also reduced Ni stress effectively, allowing wheat to grow faster and reducing soil Ni transfer into plant tissue. In comparison to a control, adding ACB with AMF inoculant considerably increased fungal populations. The most significant increase in wheat growth and decrease in tissue Ni contents came from amending soil with AMF inoculant and biochar. Inducing soil alkalinization and causing Ni immobilization, as well as decreasing Ni phyto-availability, the combination treatment had a synergistic impact. These findings imply that AMF inoculation in ACB treatment could be used not only for wheat production but also for Ni-contaminated soil phyto-stabilization. (C) 2022 The Author(s). Published by Elsevier B.V.
  • Landolt, Lea; Furriol, Jessica; Babickova, Janka; Ahmed, Lavina; Eikrem, Oystein; Skogstrand, Trude; Scherer, Andreas; Suliman, Salwa; Leh, Sabine; Lorens, J. B.; Gausdal, Gro; Marti, H.P.; Osman, Tarig (2019)
    The AXL receptor tyrosine kinase (RTK) is involved in partial epithelial-to-mesenchymal transition (EMT) and inflammation - both main promoters of renal fibrosis development. The study aim was to investigate the role of AXL inhibition in kidney fibrosis due to unilateral ureteral obstruction (UUO). Eight weeks old male C57BL/6 mice underwent UUO and were treated with oral AXL inhibitor bemcentinib (n = 22), Angiotensin-converting enzyme inhibitor (ACEI, n = 10), ACEI and bemcentinib (n = 10) or vehicle alone (n = 22). Mice were sacrificed after 7 or 15 days and kidney tissues were analyzed by immunohistochemistry (IHC), western blot, ELISA, Sirius Red (SR) staining, and hydroxyproline (Hyp) quantification. RNA was extracted from frozen kidney tissues and sequenced on an Illumina HiSeq4000 platform. After 15 days the ligated bemcentinib-treated kidneys showed less fibrosis compared to the ligated vehicle-treated kidneys in SR analyses and Hyp quantification. Reduced IHC staining for Vimentin (VIM) and alpha smooth muscle actin (alpha SMA), as well as reduced mRNA abundance of key regulators of fibrosis such as transforming growth factor (Tgf beta), matrix metalloproteinase 2 (Mmp2), Smad2, Smad4, myofibroblast activation (Aldh1a2, Crlf1), and EMT (Snai1,2, Twist), in ligated bemcentinib-treated kidneys was compatible with reduced (partial) EMT induction. Furthermore, less F4/80 positive cells, less activity of pathways related to the immune system and lower abundance of MCP1, MCP3, MCP5, and TARC in ligated bemcentinib-treated kidneys was compatible with reduction in inflammatory infiltrates by bemcentinib treatment. The AXL RTK pathway represents a promising target for pharmacologic therapy of kidney fibrosis.
  • Blomqvist, Kim H.; Lundbom, Jesper; Lundbom, Nina; Sepponen, Raimo E. (2011)
  • Kaila, Kai; Löscher, Wolfgang (2022)
    In his editorial, Kevin Staley criticizes our recent work demonstrating the lack of effect of bumetanide in a novel model of neonatal seizures. The main points in our response are that (1) our work is on an asphyxia model, not one on "hypercarbia only"; (2) clinically relevant parenteral doses of bumetanide applied in vivo lead to concentrations in the brain parenchyma that are at least an order of magnitude lower than what would be sufficient to exert any direct effect-even a transient one-on neuronal functions, including neonatal seizures; and (3) moreover, bumetanide's molecular target in the brain is the Na-K-2Cl cotransporter NKCC1, which has vital functions in neurons, astrocytes, and oligodendrocytes as well as microglia. This would make it impossible even for highly brain-permeant NKCC1 blockers to specifically target depolarizing and excitatory actions of gamma-aminobutyric acid in principal neurons of the brain, which is postulated as the rationale of clinical trials on neonatal seizures.
  • Lang, Adam R.; Engelberg, Dirk L.; Walther, Clemens; Weiss, Martin; Bosco, Hauke; Jenkins, Alex; Livens, Francis R.; Law, Gareth T. W. (2019)
    Stainless steels can become contaminated with radionuclides at nuclear sites. Their disposal as radioactive waste would be costly. If the nature of steel contamination could be understood, effective decontamination strategies could be designed and implemented during nuclear site decommissioning in an effort to release the steels from regulatory control. Here, batch uptake experiments have been used to understand Sr and Cs (fission product radionuclides) uptake onto AISI Type 304 stainless steel under conditions representative of spent nuclear fuel storage (alkaline ponds) and PUREX nuclear fuel reprocessing (HNO3). Solution (ICP-MS) and surface measurements (GD-OES depth profiling, TOF-SIMS, and XPS) and kinetic modeling of Sr and Cs removal from solution were used to characterize their uptake onto the steel and define the chemical composition and structure of the passive layer formed on the steel surfaces. Under passivating conditions (when the steel was exposed to solutions representative of alkaline ponds and 3 and 6 M HNO3), Sr and Cs were maintained at the steel surface by sorption/selective incorporation into the Cr-rich passive film. In 12 M HNO3, corrosion and severe intergranular attack led to Sr diffusion into the passive layer and steel bulk. In HNO3, Sr and Cs accumulation was also commensurate with corrosion product (Fe and Cr) readsorption, and in the 12 M HNO3 system, XPS documented the presence of Sr and Cs chromates.
  • Ahonen, Salla; Hayden, Brian; Leppänen, Jaakko Johannes; Kahilainen, Kimmo Kalevi (2018)
    Climate change is resulting in increased temperatures and precipitation in subarctic regions of Europe. These changes are extending tree lines to higher altitudes and latitudes, and enhancing tree growth enabling intensification of forestry into previously inhospitable subarctic regions. The combined effects of climate change and land-use intensification extend the warm, open-water season in subarctic lakes and increase lake productivity and may also increase leaching andmethylation activity of mercury within the lakes. To assess the joint effects of climate and productivity on total mercury (THg) bioaccumulation in fish, we conducted a space-for-time substitution study in 18 tributary lakes of a subarcticwatercourse forming a gradient fromcold pristine oligotrophic lakes in the northern headwaters to warmer and increasingly human-altered mesotrophic and eutrophic systems in the southern lower reaches. Increasing temperature, precipitation, and lake productivity were predicted to elevate length-and age-adjusted THg concentrations, as well as THg bioaccumulation rate (the rate of THg bioaccumulation relative to length or age) in muscle tissue of European whitefish (Coregonus lavaretus), vendace (Coregonus albula), perch (Perca fluviatilis), pike (Esox lucius), roach (Rutilus rutilus) and ruffe (Gymnocephalus cernua). A significant positive relationship was observed between age-adjusted THg concentration and lake climateproductivity in vendace (r(2) = 0.50), perch (r(2) = 0.51), pike (r(2) = 0.55) and roach (r(2) = 0.61). Higher climate-productivity values of the lakes also had a positive linear (pike; r(2) = 0.40 and whitefish; r(2)= 0.72) or u-shaped (perch; r(2) = 0.64 and ruffe; r(2) = 0.50) relationship with THg bioaccumulation rate. Our findings of increased adjusted THg concentrations in planktivores and piscivores reveal adverse effects of warming climate and increasing productivity on these subarctic fishes, whereas less distinct trends in THg bioaccumulation rate suggest more complex underlying processes. Joint environmental stressors such as climate and productivity should be considered in ongoing and future monitoring of mercury concentrations. (C) 2018 Elsevier B.V. All rights reserved.
  • Salmela, Jouni; Saarni, Saija; Blafield, Linnea; Katainen, Markus; Kasvi, Elina; Alho, Petteri (2022)
    In this study, we investigated sedimentation differences between two distinctive cold seasons, in terms of hydmmeteorological and hydrodynamic conditions, in a coastal area of the Northern Baltic Sea in 2018-2020. A combination of sediment trap data, hydmmeteorological data and hydrodynamic modelling provided a unique set-up to discover differences in sedimentation rates and compositions. Our study shows that the averaged sedimentation accumulation rate (SAR) was nearly three times higher during warmer cold season (30.9 g m(-2) day(-1)), characterised by higher precipitation, especially rain and discharge, as well as snowless and open water conditions, compared to regular cold season (10.6 g m(-2) day(-1)). While sedimentation was higher during the warmer season, the mean sediment grain size (D-50) was higher during the regular cold season with permanent snow and ice cover. Similarly, while sediments of the regular cold season were organically rich, the total amount of organic matter accumulation was larger during the warmer cold season. Sediments consisted mostly of elastic matter (85-89%), of which the mean grain size varied from clay to fine silt (0.3-3.0 mu m). Sedimentation differences between the cold seasons can be explained by differences in precipitation, river flow, wind-induced resuspension and a low air pressure system forcing sea level changes. Sedimentation differences along the study bay were found to be connected to channel cross-sectional area and flow conditions caused by river input and sea level changes.
  • Tossavainen, Marika; Nykänen, Anne; Valkonen, Kalle Santeri; Ojala, Anne; Silja, Kostia; Romantschuk, Martin (2017)
    Growth and fatty acid production of microalga Selenastrum sp. with associated bacteria was studied in lab-scale experiments in three composting leachate liquids. Nutrient reduction in cultures was measured at different initial substrate strengths. A small, pilot-scale photobioreactor (PBR) was used to verify labscale results. Similar growth conditions supported growth of both Selenastrum and bacteria. CO2 feed enhanced the production of biomass and lipids in PBR (2.4 g L-1 and 17% DW) compared to lab-scale (0.1-1.6 g L-1 and 4.0-6.5% DW) experiments. Also prolonged cultivation time increased lipid content in PBR. At both scales, NH4-N with an initial concentration of ca. 40 mg L-1 was completely removed from the biowaste leachate. In lab-scale, maximal COD reduction was over 2000 mg L-1, indicating mixotrophic growth of Selenastrum. Co-cultures are efficient in composting leachate liquid treatment, and conversion of waste to biomass is a promising approach to improve the bioeconomy of composting plants. (C) 2017 The Authors. Published by Elsevier Ltd.
  • Ayvaz, Muavviz; Guven, Avni; Fagerstedt, Kurt Valter (2015)
    Potato crop production in Turkey ranks on the thirteenth place in the world. Toxicity is a problematic issue for some parts of the Turkish soils. Hence, it is very important to clarify the physiological responses of plants to toxic mineral stress. In this study, two different potato cultivars - Solanum tuberosum cv. Resy and Solanum tuberosum cv. Agria - were used as a study material. Excess boron was applied in two different concentrations (5 mmol/L and 12.5 mmol/L) 32 days after planting the tubers. Plants were harvested at the end of 15 days of excess boron application. Chlorophyll fluorescence (Fv/Fm) was measured. Shoot height and shoot-root fresh weight contents were determined. Analyses were carried out for the contents of the endogenous hormones indole-3-acetic acid (IAA) and abscisic acid (ABA) by using gas chromatography-mass spectrophotometry (GS-MS). According to the obtained data, plants' shoot height did not change, whereas the shoot's fresh weight decreased significantly with increasing of the boron concentrations in cv Resy, by applying 12.5 mmol/L boron. With 12.5 mmol/L boron, the photosynthesis was negatively affected in both cultivars. Boron application led to increased endogenous IAA and ABA content in both cultivars. As a result, cv. Resy showed more resistance to excess boron. Findings on the hormone metabolism and chlorophyll fluorescence in different cultivars will shed a light on understanding the physiological response to excess mineral stress.
  • Kahilainen, Kimmo K.; Thomas, Stephen M.; Nystedt, Elina K. M.; Keva, Ossi; Malinen, Tommi; Hayden, Brian (2017)
    Resource polymorphism, whereby ancestral trophic generalists undergo divergence into multiple specialist morphs, is common in salmonid fish populations inhabiting subarctic lakes. However, the extent to which such resource specialization into the three principal lake habitats (littoral, profundal, and pelagic) affects patterns of contaminant bioaccumulation remains largely unexplored. We assessed total mercury concentrations (THg) of European whitefish (Coregonus lavaretus (L)) and their invertebrate prey in relation to potential explanatory variables across 6 subarctic lakes, of which three are inhabited by polymorphic (comprised of four morphs) and three by monomorphic populations. Among invertebrate prey, the highest THg concentrations were observed in profundal benthic macroinvertebrates, followed by pelagic zooplankton, with concentrations lowest in littoral benthic macroinvertebrates in both lake types. Broadly similar patterns were apparent in whitefish in polymorphic systems, where average age-corrected THg concentrations and bioaccumulation rates were the highest in pelagic morphs, intermediate in the profundal morph, and the lowest in the littoral morph. In monomorphic systems, age-corrected THg concentrations were generally lower, and showed pronounced lake-specific variation. In the polymorphic systems, we found significant relationships between whitefish muscle tissue THg concentration and gill raker count, resource use, lipid content and maximum length, whilst no such relationships were apparent in the monomorphic systems. Across all polymorphic lakes, the major variables explaining THg in whitefish were gill raker count and age, whereas in monomorphic systems, the factors were lake-specific. Whitefish resource polymorphism across the three main lake habitats therefore appears to have profound impacts on THg concentration and bioaccumulation rate. This highlights the importance of recognizing such intraspecific diversity in both future scientific studies and mercury monitoring programs. (C) 2017 Elsevier B.V. All rights reserved.
  • Esterhuizen, Maranda; Kim, Young Jun (2022)
    Plastic waste is recognised as hazardous, with the risk increasing as the polymers break down in nature to secondary microplastics or even nanoplastics. The number of studies reporting on the prevalence of microplastic in every perceivable niche and bioavailable to biota is dramatically increasing. Knowledge of the ecotoxicology of microplastic is advancing as well; however, information regarding plants, specifically aquatic macrophytes, is still lacking. The present study aimed to gain more information on the ecotoxicological effects of six different polymer types as 4 mm microplastic on the morphology (germination and growth) and the physiology (catalase and glutathione S-transferase activity) of the rooted aquatic macrophyte, Nelumbo nucifera. The role of sediment was also considered by conducting all exposure both in a sediment-containing and sediment-free exposure system. Polyvinyl chloride and polyurethane exposures caused the highest inhibition of germination and growth compared to the control. However, the presence of sediment significantly decreased the adverse effects. Catalase activity was increased with exposure to polyvinyl chloride, polyurethane, and polystyrene, both in the presence and absence of sediment but more so in the sediment-free system. Glutathione S-transferase activity was significantly increased with exposure to polypropylene, polyvinyl chloride, and polyethylene terephthalate in the sediment-free system and exposure to polyethylene terephthalate and polyurethane in the absence of sediment. There was no clear correlation between the morphological and physiological effects observed. Further studies are required to understand the underlying toxicity mechanism of microplastics.
  • Kuittinen, Matti; Hautamaki, Ranja; Tuhkanen, Eeva-Maria; Riikonen, Anu; Ariluoma, Mari (2021)
    Purpose Currently, no clear guidance exists for ISO and EN standards of calculating, verifying, and reporting the climate impacts of plants, mulches, and soils used in landscape design and construction. In order to optimise the potential of ecosystem services in the mitigation of greenhouse gas emissions in the built environment, we unequivocally propose their inclusion when assessing sustainability. Methods We analysed the life cycle phases of plants, soils, and mulches from the viewpoint of compiling standard-based Environmental Product Declarations. In comparison to other construction products, the differences of both mass and carbon flows were identified in these products. Results Living and organic products of green infrastructure require an LCA approach of their own. Most importantly, if conventional life cycle guidance for Environmental Product Declarations were to be followed, over time, the asymmetric mass and carbon flows would lead to skewed conclusions. Moreover, the ability of plants to reproduce raises additional questions for allocating environmental impacts. Conclusions We present a set of recommendations that are required for compiling Environmental Product Declarations for the studied products of green infrastructure. In order to enable the quantification of the climate change mitigation potential of these products, it is essential that work for further development of LCA guidance be mandated.
  • Ajoolabady, Amir; Lindholm, Dan; Ren, Jun; Pratico, Domenico (2022)
    Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes a heavy burden on the healthcare system globally. Current therapeutics to interfere with the underlying disease process in AD is still under development. Although many efforts have centered on the toxic forms of A beta to effectively tackle AD, considering the unsatisfactory results so far it is vital to examine other targets and therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers to the build-up of unfolded or misfolded proteins within the ER, thus, perturbing the ER and cellular homeostasis. Emerging evidence indicates that ER stress contributes to the onset and development of AD. A thorough elucidation of ER stress machinery in AD pathology may help to open up new therapeutic avenues in the management of this devastating condition to relieve the cognitive dementia symptoms. Herein, we aim at deciphering the unique role of ER stress in AD pathogenesis, reviewing key findings, and existing controversy in an attempt to summarize plausible therapeutic interventions in the management of AD pathophysiology.
  • Loisel, J.; Loisel, J.; Amesbury, Matthew J.; Magnan, G.; Anshari, G.; Beilman, D. W.; Benavides, J. C.; Blewett, J.; Camill, P.; Charman, D. J.; Chawchai, S.; Hedgpeth, A.; Kleinen, T.; Korhola, Atte; Large, D.; Mansilla, C. A.; Muller, J.; van Bellen, S.; West, J. B.; Yu, Z.; Bubier, J. L.; Garneau, M.; Moore, T.; Sannel, A. B. K.; Page, S.; Väliranta, Minna; Bechtold, M.; Brovkin, Victor; Cole, L. E. S.; Chanton, J. P.; Christensen, T. R.; Davies, M. A.; De Vleeschouwer, F.; Finkelstein, S. A.; Frolking, S.; Galka, M.; Gandois, L.; Girkin, N.; Harris, L.; Heinemeyer, A.; Hoyt, A. M.; Jones, M. C.; Joos, F.; Juutinen, Sari; Kaiser, K.; Lacourse, T.; Lamentowicz, M.; Larmola, T.; Leifeld, J.; Lohila, Annalea Katriina; Milner, A. M.; Minkkinen, Kari; Moss, P.; Naafs, B. D. A.; Nichols, J.; O'Donnell, J.; Payne, R.; Philben, M.; Piilo, Sanna; Quillet, A.; Ratnayake, A. S.; Roland, T. P.; Sjogersten, S.; Sonnentag, O.; Swindles, G. T.; Swinnen, W.; Talbot, J.; Treat, C.; Valach, A. C.; Wu, J. (2021)
    Peatlands are impacted by climate and land-use changes, with feedback to warming by acting as either sources or sinks of carbon. Expert elicitation combined with literature review reveals key drivers of change that alter peatland carbon dynamics, with implications for improving models. The carbon balance of peatlands is predicted to shift from a sink to a source this century. However, peatland ecosystems are still omitted from the main Earth system models that are used for future climate change projections, and they are not considered in integrated assessment models that are used in impact and mitigation studies. By using evidence synthesized from the literature and an expert elicitation, we define and quantify the leading drivers of change that have impacted peatland carbon stocks during the Holocene and predict their effect during this century and in the far future. We also identify uncertainties and knowledge gaps in the scientific community and provide insight towards better integration of peatlands into modelling frameworks. Given the importance of the contribution by peatlands to the global carbon cycle, this study shows that peatland science is a critical research area and that we still have a long way to go to fully understand the peatland-carbon-climate nexus.
  • Törnblom, Sanna; Wiersema, Renske; Prowle, John R.; Haapio, Mikko; Pettilä, Ville; Vaara, Suvi T. (2021)
    Background Acute kidney injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjustments lead to a different incidence of AKI when used in conjunction with urine output (UO) criteria is unknown. Methods This was a post hoc analysis of the Finnish Acute Kidney Injury study. Hourly UO and daily plasma Cr were measured during the first 5 days of intensive care unit admission. Cr values were adjusted following the previously used formula and combined with the UO criteria. Resulting incidences and mortality rates were compared with the results based on unadjusted values. Results In total, 2044 critically ill patients were analyzed. The mean difference between the adjusted and unadjusted Cr of all 7279 observations was 5 (+/- 15) mu mol/L. Using adjusted Cr in combination with UO and renal replacement therapy criteria resulted in the diagnosis of 19 (1%) additional AKI patients. The absolute difference in the incidence was 0.9% (95% confidence interval [CI]: 0.3%-1.6%). Mortality rates were not significantly different between the reclassified AKI patients using the full set of Kidney Disease: Improving Global Outcomes criteria. Conclusion Fluid balance-adjusted Cr resulted in little change in AKI incidence, and only minor differences in mortality between patients who changed category after adjustment and those who did not. Using adjusted Cr values to diagnose AKI does not seem worthwhile in critically ill patients.