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  • Torrente, Laura; Maan, Gunjit; Oumkaltoum Rezig, Asma; Quinn, Jean; Jackson, Angus; Grilli, Andrea; Casares, Laura; Zhang, Ying; Kulesskiy, Evgeny; Saarela, Jani; Bicciato, Silvio; Edwards, Joanne; Dinkova-Kostova, Albena T.; de la Vega, Laureano (Multidisciplinary Digital Publishing Institute, 2020)
    Aberrant hyperactivation of nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2) is a common event in many tumour types and associates with resistance to therapy and poor patient prognosis; however, its relevance in colorectal tumours is not well-established. Measuring the expression of surrogate genes for NRF2 activity in silico, in combination with validation in patients’ samples, we show that the NRF2 pathway is upregulated in colorectal tumours and that high levels of nuclear NRF2 correlate with a poor patient prognosis. These results highlight the need to overcome the protection provided by NRF2 and present an opportunity to selectively kill cancer cells with hyperactive NRF2. Exploiting the CRISPR/Cas9 technology, we generated colorectal cancer cell lines with hyperactive NRF2 and used them to perform a drug screen. We identified AT9283, an Aurora kinase inhibitor, for its selectivity towards killing cancer cells with hyperactive NRF2 as a consequence to either genetic or pharmacological activation. Our results show that hyperactivation of NRF2 in colorectal cancer cells might present a vulnerability that could potentially be therapeutically exploited by using the Aurora kinase inhibitor AT9283.
  • Silva, Ximena; Roux, Jolanda; Asiegbu, Fred O. (Multidisciplinary Digital Publishing Institute, 2020)
    <i>Background and objectives:</i> The global forest economy is threatened by eucalypt pathogens which are often latent or cryptic species that escape common quarantine and detection methods. Plantation forestry using eucalypts is of considerable importance to Paraguay, but knowledge regarding the pests and diseases affecting these plantations is limited. This study identified fungal diseases present in these plantations. <i>Materials and Methods:</i> We surveyed eucalypt plantations in four provinces in Paraguay and collected material from diseased trees for identification of the causal agents. The samples were analyzed using a combination of morphological and molecular methods. <i>Results:</i> Diseases encountered included Botryosphaeria stem canker, Calonectria leaf blight, Chrysoporthe stem canker, myrtle/eucalypt rust, Coniella leaf spot, heartwood rot and Teratosphaeria stem canker. Contrary to expectations, the causal agent of Teratosphaeria stem canker was identified as <i>Teratosphaeria zuluensis</i> (M.J. Wingf., Crous &amp; T.A. Cout.) M.J. Wingf. &amp; Crous and not <i>Teratosphaeria gauchensis</i> (M.-N. Cortinas, Crous &amp; M.J. Wingf.) M.J. Wingf. &amp; Crous, that is commonly documented for the South American region. <i>Conclusions:</i> This study updates the knowledge on forest fungal pathogens in Paraguayan eucalypt plantations and is the first report of <i>T. zuluensis</i> in Paraguay and in South America.
  • Sidorova, Yulia; Domanskyi, Andrii (Multidisciplinary Digital Publishing Institute, 2020)
    Oxidative stress is prominent in many neurodegenerative diseases. Along with mitochondrial dysfunction and pathological protein aggregation, increased levels of reactive oxygen and nitrogen species, together with impaired antioxidant defense mechanisms, are frequently observed in Alzheimer&rsquo;s, Parkinson&rsquo;s, Huntington&rsquo;s disease and amyotrophic lateral sclerosis. The presence of oxidative stress markers in patients&rsquo; plasma and cerebrospinal fluid may aid early disease diagnoses, as well as provide clues regarding the efficacy of experimental disease-modifying therapies in clinical trials. In preclinical animal models, the detection and localization of oxidatively damaged lipids, proteins and nucleic acids helps to identify most vulnerable neuronal populations and brain areas, and elucidate the molecular pathways and the timeline of pathology progression. Here, we describe the protocol for the detection of oxidative stress markers using immunohistochemistry on formaldehyde-fixed, paraffin-embedded tissue sections, applicable to the analysis of postmortem samples and tissues from animal models. In addition, we provide a simple method for the detection of malondialdehyde in tissue lysates and body fluids, which is useful for screening and the identification of tissues and structures in the nervous system which are most affected by oxidative stress.
  • Lindholm, Juha-Matti; Laine, Ilkka; Tuuminen, Raimo (Multidisciplinary Digital Publishing Institute, 2020)
    The present study estimated the 5-year cumulative probability of Nd:YAG laser posterior capsulotomy according to the diopter power of implanted hydrophobic acrylic intraocular lenses (IOLs). Data were retrospectively collected of 15,375 eyes having cataract surgery and in-the-bag implantation of hydrophobic acrylic monofocal IOLs at the Ophthalmology Unit of Kymenlaakso Central Hospital, Kotka, Finland between the years 2007 and 2016. The cumulative probability of Nd:YAG capsulotomy was calculated by Kaplan&ndash;Meier estimates, and potential risk factors were analyzed using the Cox proportional hazards model. The 5-year cumulative probability of Nd:YAG capsulotomy after cataract surgery was 27.4% (95% confidence interval (CI) 22.9&ndash;32.6%) for low-diopter (5&ndash;16.5 D) IOLs, 14.6% (13.8&ndash;15.5%) for mid-diopter (17&ndash;24.5 D) IOLs, and 13.6% (11.7&ndash;15.6%) for high-diopter (25&ndash;30 D) IOLs. A multivariate Cox regression analysis showed that low-diopter IOLs (HR 1.76; 95% CI 1.38&ndash;2.25; <i>p</i> &lt; 0.001) were associated with an increased risk of Nd:YAG capsulotomy compared to mid-diopter IOLs over the follow-up period after accounting for other predictors. Real-world evidence shows that low-diopter IOLs are associated with significantly higher risk of Nd:YAG capsulotomy within five years following implantation. Estimation should help in evaluating the risks of cataract surgery in myopic eyes.
  • Panu, Pihkala (Multidisciplinary Digital Publishing Institute, 2020)
    Eco-anxiety and climate anxiety are widely discussed in contemporary media and are subjects of growing research interest. However, there is a lack of research about the definitions and variations of these phenomena. This article analyzes various views of eco-anxiety from a wide range of disciplines. Insights from various anxiety theories are used to discuss empirical studies about forms of eco-anxiety. The article points out that uncertainty, unpredictability, and uncontrollability seem to be important factors in eco-anxiety. Most forms of eco-anxiety appear to be non-clinical, but cases of &ldquo;pathological&rdquo; eco-anxiety are also discussed. Other relevant terms and phenomena are scrutinized, such as ecological grief, solastalgia, and ecological trauma. The relationship between studies on eco-anxiety and research about ecological emotions and affect is probed. Eco-anxiety is found to be closely connected to fear and worry, but several disciplines include discussion of its character as existential anxiety. Psychosocial and sociological perspectives point out that social dynamics shape forms of eco-anxiety in profound ways. While paralyzing forms of eco-anxiety emerge as a problem, it is noted that eco-anxiety manifests itself also as &ldquo;practical anxiety&rdquo;, which leads to gathering of new information and reassessment of behavior options. This variety of forms of eco-anxiety should be taken into account in healthcare and public discussion.
  • Yang, Fang; Feng, Weiying; Matti, Leppäranta; Yang, Yu; Merkouriadi, Ioanna; Cen, Rui; Bai, Yangwei; Li, Changyou; Liao, Haiqing (Multidisciplinary Digital Publishing Institute, 2020)
    The intra-annual heat exchange process has a considerable influence on the energy circulation, material metabolism, and ecological succession of lakes. The input and output of heat in an ice-covered lake provide the basic dynamic force driving changes in the biochemical state of the lake. Based on the heat balance between the lake surface and the atmosphere, we established a thermodynamic model for calculating the thermodynamic factors of shallow inland lakes during the ice and open seasons. The data of the Ulansuhai Lake, Inner Mongolia, from two years (2012 and 2013) are used to analyze the seasonal characteristics and associated influences of the heat budget on the ecosystem. The results indicated that the monthly mean lake temperature over the past 10 years was 1.7&ndash;2.2 &deg;C lower than in the previous 50 years. The absorbed solar radiation reached up to 210 W/m<sup>2</sup> in 2012 and 179 W/m<sup>2</sup> in 2013, and there were clear differences in the heat budget between the ice-covered and open seasons. The mean net heat fluxes in the ice season were &minus;33.8 and &minus;38.5 W/m<sup>2</sup> in 2012 and 2013, respectively; while in the open season water, these fluxes were 62.5 and 19.1 W/m<sup>2</sup>. In the simulations, the wind was an important factor for intensive evaporation in summer and the main driver of the ice cover formation patterns in winter, involving the transmission and diffusion of material and energy in the lake. The results provide a theoretical foundation for simulating ice cover growth and ablation processes in shallow lakes. They also present data on the ecological evolution in these lacustrine environments.
  • Cuenca-García, Carmen; Risbøl, Ole; Bates, C. Richard; Stamnes, Arne Anderson; Skoglund, Fredrik; Ødegård, Øyvind; Viberg, Andreas; Koivisto, Satu; Fuglsang, Mikkel; Gabler, Manuel; Schlosser Mauritsen, Esben; Perttola, Wesa; Solem, Dag-Øyvind (Multidisciplinary Digital Publishing Institute, 2020)
    In August 2018, a group of experts working with terrestrial/marine geophysics and remote sensing methods to explore archaeological sites in Denmark, Finland, Norway, Scotland and Sweden gathered together for the first time at the Workshop &lsquo;Sensing Archaeology in The North&rsquo;. The goal was to exchange experiences, discuss challenges, and consider future directions for further developing these methods and strategies for their use in archaeology. After the event, this special journal issue was arranged to publish papers that are based on the workshop presentations, but also to incorporate work that is produced by other researchers in the field. This paper closes the special issue and further aims to provide current state-of-the-art for the methods represented by the workshop. Here, we introduce the aspects that inspired the organisation of the meeting, a summary of the 12 presentations and eight paper contributions, as well as a discussion about the main outcomes of the workshop roundtables, including the production of two searchable databases (online resources and equipment). We conclude with the position that the &lsquo;North&rsquo;, together with its unique cultural heritage and thriving research community, is at the forefront of good practice in the application and development of sensing methods in archaeological research and management. However, further method development is required, so we claim the support of funding bodies to back research efforts based on testing/experimental studies to: explore unknown survey environments and identify optimal survey conditions, as well as to monitor the preservation of archaeological remains, especially those that are at risk. It is demonstrated that remote sensing and geophysics not only have an important role in the safeguarding of archaeological sites from development and within prehistorical-historical research, but the methods can be especially useful in recording and monitoring the increased impact of climate change on sites in the North.
  • Leigh, Robert S.; Kaynak, Bogac L. (Multidisciplinary Digital Publishing Institute, 2020)
    Vitamin A is a micronutrient and signaling molecule that regulates transcription, cellular differentiation, and organ homeostasis. Additionally, metabolites of Vitamin A are utilized as differentiation agents in the treatment of hematological cancers and skin disorders, necessitating further study into the effects of both nutrient deficiency and the exogenous delivery of Vitamin A and its metabolites on cardiovascular phenotypes. Though vitamin A/retinoids are well-known regulators of cardiac formation, recent evidence has emerged that supports their role as regulators of cardiac regeneration, postnatal cardiac function, and cardiovascular disease progression. We here review findings from genetic and pharmacological studies describing the regulation of both myocyte- and vascular-driven cardiac phenotypes by vitamin A signaling. We identify the relationship between retinoids and maladaptive processes during the pathological hypertrophy of the heart, with a focus on the activation of neurohormonal signaling and fetal transcription factors (Gata4, Tbx5). Finally, we assess how this information might be leveraged to develop novel therapeutic avenues.
  • Tenhu, Elina; Teräsjärvi, Johanna; Cruzeiro, Manuel Leite; Savonius, Okko; Rugemalira, Emilie; Roine, Irmeli; He, Qiushui; Pelkonen, Tuula (Multidisciplinary Digital Publishing Institute, 2020)
    Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of <i>TLR4</i> and <i>TLR9</i> are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs <i>TLR4</i> rs4986790 (896A &gt; G) and <i>TLR9</i> rs187084 (&minus;1486T &gt; C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in <i>TLR4</i> was significantly higher in patients with <i>Haemophilus influenzae</i> meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2&ndash;5.4; <i>p</i> = 0.021), whereas the frequency of variant genotypes in <i>TLR9</i> was significantly lower in patients with <i>H. influenzae</i> meningitis than controls (OR, 0.4; 95% CI, 0.2&ndash;0.9; <i>p</i> = 0.036). No such differences were found with other causative pathogens, such as <i>Streptococcus pneumoniae</i> and <i>Neisseria meningitidis</i>. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant <i>TLR4</i> genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52&ndash;109.80; <i>p</i> = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07&ndash;131.49; <i>p</i> = 0.044) than those with the wild-type <i>TLR4</i> genotype. Our study suggests an association between <i>H. influenzae</i> meningitis and genetic variation between <i>TLR4</i> and <i>TLR9</i> in Angolan children.
  • Aaronson, Alexander; Achiron, Asaf; Tuuminen, Raimo (Multidisciplinary Digital Publishing Institute, 2020)
    Background: To evaluate the clinical course of pseudophakic cystoid macular edema (PCME) treated with topical non-steroidal anti-inflammatory drugs (NSAIDs). Methods: An analysis of the clinical course of PCME consisting of 536 eyes of 536 patients from five consecutive randomized clinical trials aimed at the optimization of anti-inflammatory medication in patients undergoing routine cataract surgery. PCME was classified as (i) grade 0a; no macular thickening, (ii) grade 0b; macular thickening (central subfield macular thickness (CSMT) increase of at least 10%) without signs of macular edema, (iii) grade I; subclinical PCME, (iv) grade II; acute PCME, (v) grade III; long-standing PCME. Eyes with PCME classification from grade I onwards were treated with nepafenac 1 mg/mL t.i.d. for two months. Results: CSMT increase of at least 10% at any postoperative timepoint with cystoid changes&mdash;a criterion for PCME&mdash;was found in 19 of 536 eyes (total incidence 3.5%). Of these 19 eyes, 13 eyes (total incidence 2.4%) had clinically significant PCME. PCME was considered clinically significant when both of the following visual acuity criteria were fulfilled. At any timepoint after the cataract surgery both the corrected distance visual acuity (CDVA) gain was less than 0.4 decimals from that of preoperative CDVA, and the absolute CDVA level remained below 0.8 decimals. Only one of the 19 eyes with criteria for PCME (total incidence 0.2%, incidence of PCME eyes 5.3%) showed no macular edema resolution within 2 months after topical nepafenac administration. <b>Conclusions:</b> PCME in most cases is self-limiting using topical nepafenac without any further need for intravitreal treatment.
  • Pour-Aboughadareh, Alireza; Omidi, Mansoor; Naghavi, Mohammad Reza; Etminan, Alireza; Mehrabi, Ali Ashraf; Poczai, Peter (Multidisciplinary Digital Publishing Institute, 2020)
    Previous studies have revealed that some wild wheat accessions respond well to water deficit treatments and have a good potential in terms of photosynthetic parameters, root system architecture, and several physiological properties. However, the biochemical responses and molecular mechanisms of antioxidant-encoding genes remain to be elucidated. Herein, we investigated the most tolerant accessions from <i>A. crassa</i>, <i>Ae. tauschii</i>, and <i>Ae. cylindrica</i> previously identified from a core collection in previous studies, along with a control variety of bread wheat (<i>T. aestivum</i> cv. Sirvan) through measuring the shoot fresh and dry biomasses; the activities of antioxidant enzymes (including ascorbate peroxidase (APX), catalase (CAT), guaiacol peroxidase (GPX), and peroxidase (POD)); and the relative expression of <i>CAT</i>, superoxide dismutase (<i>MnSOD</i>), and <i>GPX</i> and <i>APX</i> genes under control and water deficit conditions. Water deficit stress caused a significant decrease in the shoot biomasses but resulted in an increase in the activity of all antioxidant enzymes and relative expression of antioxidant enzyme-encoding genes. Principal component analysis showed a strong association between the shoot dry biomass and the activity of CAT, POD, and APX, as well as <i>MnSOD</i> gene expression. Thus, these traits can be used as biomarkers to screen the tolerant plant material in the early growth stage. Taken together, our findings exposed the fact that <i>Ae. tauschii</i> and <i>Ae. crassa</i> respond better to water deficit stress than <i>Ae. cylindrica</i> and a control variety. Furthermore, these accessions can be subjected to further molecular investigation.
  • Bannai, Hideo; Gagie, Travis; Hoppenworth, Gary; Puglisi, Simon J.; Russo, Luís M. S. (Multidisciplinary Digital Publishing Institute, 2020)
    We extend recent results regarding finding shortest unique substrings (SUSs) to obtain new time-space tradeoffs for this problem and the generalization of finding <i>k</i>-mismatch SUSs. Our new results include the first algorithm for finding a <i>k</i>-mismatch SUS in sublinear space, which we obtain by extending an algorithm by Senanayaka (2019) and combining it with a result on sketching by Gawrychowski and Starikovskaya (2019). We first describe how, given a text <i>T</i> of length <i>n</i> and <i>m</i> words of workspace, with high probability we can find an SUS of length <i>L</i> in <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><mi>n</mi><mo>(</mo><mi>L</mi><mo>/</mo><mi>m</mi><mo>)</mo><mo form="prefix">log</mo><mi>L</mi><mo>)</mo></mrow></semantics></math></inline-formula> time using random access to <i>T</i>, or in <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><mi>n</mi><mrow><mo>(</mo><mi>L</mi><mo>/</mo><mi>m</mi><mo>)</mo></mrow><msup><mo form="prefix">log</mo><mn>2</mn></msup><mrow><mo>(</mo><mi>L</mi><mo>)</mo></mrow><mo form="prefix">log</mo><mo form="prefix">log</mo><mi>&sigma;</mi><mo>)</mo></mrow></semantics></math></inline-formula> time using <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><mrow><mo>(</mo><mi>L</mi><mo>/</mo><mi>m</mi><mo>)</mo></mrow><msup><mo form="prefix">log</mo><mn>2</mn></msup><mi>L</mi><mo>)</mo></mrow></semantics></math></inline-formula> sequential passes over <i>T</i>. We then describe how, for constant <i>k</i>, with high probability, we can find a <i>k</i>-mismatch SUS in <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><msup><mi>n</mi><mrow><mn>1</mn><mo>+</mo><mi>ϵ</mi></mrow></msup><mi>L</mi><mo>/</mo><mi>m</mi><mo>)</mo></mrow></semantics></math></inline-formula> time using <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><msup><mi>n</mi><mi>ϵ</mi></msup><mi>L</mi><mo>/</mo><mi>m</mi><mo>)</mo></mrow></semantics></math></inline-formula> sequential passes over <i>T</i>, again using only <i>m</i> words of workspace. Finally, we also describe a deterministic algorithm that takes <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><mi>n</mi><mi>&tau;</mi><mo form="prefix">log</mo><mi>&sigma;</mi><mo form="prefix">log</mo><mi>n</mi><mo>)</mo></mrow></semantics></math></inline-formula> time to find an SUS using <inline-formula><math display="inline"><semantics><mrow><mi>O</mi><mo>(</mo><mi>n</mi><mo>/</mo><mi>&tau;</mi><mo>)</mo></mrow></semantics></math></inline-formula> words of workspace, where <inline-formula><math display="inline"><semantics><mi>&tau;</mi></semantics></math></inline-formula> is a parameter.
  • Koponen, Ismo T. (Multidisciplinary Digital Publishing Institute, 2020)
    Nature of science (NOS) has been a central theme in science education and research on it for nearly three decades, but there is still debate on its proper focus and underpinnings. The focal points of these debates revolve around different ways of understanding the terms &ldquo;science&rdquo; and &ldquo;scientific knowledge&rdquo;. It is suggested here that the lack of agreement is at least partially related to and reflected as a lack of common vocabulary and terminology that would provide a shared basis for finding consensus. Consequently, the present study seeks motivation from the notions of centrality of lexicons in recognizing the identity of disciplinary communities and different schools of thought within NOS. Here, by using a network approach, we investigate how lexicons used by different authors to discuss NOS are confluent or divergent. The lexicons used in these texts are investigated on the basis of a network analysis. The results of the analysis reveal clear differences in the lexicons that are partially related to differences in views, as evident from the debates surrounding the consensus NOS. The most divergent views are related to epistemology, while regarding the practices and social embeddedness of science the lexicons overlap significantly. This suggests that, in consensus NOS, one can find much basis for converging views, with common understanding, where constructive communication may be possible. The basic vocabulary, in the form of a lexicon, can reveal much about the different stances and the differences and similarities between various disciplinary schools. The advantage of such an approach is its neutrality and how it keeps a distance from preferred epistemological positions and views of nature of knowledge.
  • Saarinen, Niila V. V.; Lehtonen, Jussi; Veijola, Riitta; Lempainen, Johanna; Knip, Mikael; Hyöty, Heikki; Laitinen, Olli H.; Hytönen, Vesa P. (Multidisciplinary Digital Publishing Institute, 2020)
    The authors wish to make the following corrections to this paper [...]
  • Pitkänen, Kati; Lehtimäki, Jenni; Puhakka, Riikka (Multidisciplinary Digital Publishing Institute, 2020)
    Contact with nature is associated with numerous psychological, physiological and social health and well-being benefits. Outdoor recreation, such as rural second home tourism, provides extensive exposure to the natural environment, but research around health impacts of this exposure is scattered. We review current research on health and well-being impacts of nature and discuss how the characteristics of rural second home environments and their use and users can affect these potential impacts in Finland. We discover four key issues affecting the impacts. First, health and well-being impacts depend on the users; urban people can especially benefit from rural second homes, while child development and the performance of elderly people can also be supported by contact with nature at second homes. Second, the regularity, length and season of second home visits influence the potential to receive benefits as they have an impact on the intensity of nature exposure. Third, the type and quality of second home environment affect contact with nature, such as exposure to health-supporting environmental microbes. Fourth, practices, motives and meanings modify activities and attachment and crucially affect both physical and mental well-being. We conclude that rural second homes have extensive potential to provide nature-related health and well-being benefits and further research is needed.
  • Jyske, Tuula; Brännström, Hanna; Sarjala, Tytti; Hellström, Jarkko; Halmemies, Eelis; Raitanen, Jan-Erik; Kaseva, Janne; Lagerquist, Lucas; Eklund, Patrik; Nurmi, Juha (Multidisciplinary Digital Publishing Institute, 2020)
    Softwood bark is an important by-product of forest industry. Currently, bark is under-utilized and mainly directed for energy production, although it can be extracted with hot water to obtain compounds for value-added use. In Norway spruce (<i>Picea abies</i> [L.] Karst.) bark, condensed tannins and stilbene glycosides are among the compounds that comprise majority of the antioxidative extractives. For developing feasible production chain for softwood bark extractives, knowledge on raw material quality is critical. This study examined the fate of spruce bark tannins and stilbenes during storage treatment with two seasonal replications (i.e., during winter and summer). In the experiment, mature logs were harvested and stored outside. During six-month-storage periods, samples were periodically collected for chemical analysis from both inner and outer bark layers. Additionally, bark extractives were analyzed for antioxidative activities by FRAP, ORAC, and H<sub>2</sub>O<sub>2</sub> scavenging assays. According to the results, stilbenes rapidly degraded during storage, whereas tannins were more stable: only 5&ndash;7% of the original stilbene amount and ca. 30&ndash;50% of the original amount of condensed tannins were found after 24-week-storage. Summer conditions led to the faster modification of bark chemistry than winter conditions. Changes in antioxidative activity were less pronounced than those of analyzed chemical compounds, indicating that the derivatives of the compounds contribute to the antioxidative activity. The results of the assays showed that, on average, ca. 27% of the original antioxidative capacity remained 24 weeks after the onset of the storage treatment, while a large variation (2&ndash;95% of the original capacity remaining) was found between assays, seasons, and bark layers. Inner bark preserved its activities longer than outer bark, and intact bark attached to timber is expected to maintain its activities longer than a debarked one. Thus, to ensure prolonged quality, no debarking before storage is suggested: outer bark protects the inner bark, and debarking enhances the degradation.
  • Jyske, Tuula; Järvenpää, Eila; Kunnas, Susan; Sarjala, Tytti; Raitanen, Jan-Erik; Mäki, Maarit; Pastell, Helena; Korpinen, Risto; Kaseva, Janne; Tupasela, Tuomo (Multidisciplinary Digital Publishing Institute, 2020)
    Developing shoots, i.e., sprouts, and older needles of Norway spruce (<i>Picea abies</i> (L.) Karst.) have traditionally been used for medicinal purposes due to the high content of vitamins and antioxidants. Currently, sprouts are available as, for example, superfood and supplements. However, end-product quality and nutritive value may decline in the value-chain from raw material sourcing to processing and storage. We studied (1) impacts of different drying and extraction methods on nutritional composition and antioxidative properties of sprouts and needles, (2) differences between sprouts and needles in nutritional composition and microbiological quality, and (3) production scale quality of the sprouts. Additionally, (4) sprout powder was applied in products (ice-cream and sorbet) and consumer acceptance was evaluated. According to our results, older needles have higher content of dry matter, energy, and calcium, but lower microbial quality than sprouts. Sprouts showed a higher concentration of vitamin C, magnesium, potassium, and phosphorus than older needles. Freeze-drying was the best drying method preserving the quality of both sprouts and needles, e.g., vitamin C content. The antioxidative activity of the sprout extracts were lower than that of needles. Ethanol-water extraction resulted in a higher content of active compounds in the extract than water extraction. Sensory evaluation of food products revealed that on average, 76% of consumers considered sprout-containing products very good or good, and a creamy product was preferred over a water-based sorbet.
  • Contesini, Fabiano Jares; Davanço, Marcelo Gomes; Borin, Gustavo Pagotto; Vanegas, Katherina Garcia; Cirino, João Pedro Gonçalves; Melo, Ricardo Rodrigues de; Mortensen, Uffe Hasbro; Hildén, Kristiina; Campos, Daniel Rossi; Carvalho, Patricia de Oliveira (Multidisciplinary Digital Publishing Institute, 2020)
    Lipases are one of the most used enzymes in the pharmaceutical industry due to their efficiency in organic syntheses, mainly in the production of enantiopure drugs. From an industrial viewpoint, the selection of an efficient expression system and host for recombinant lipase production is highly important. The most used hosts are <i>Escherichia coli</i> and <i>Komagataella phaffii</i> (previously known as <i>Pichia pastoris</i>) and less often reported <i>Bacillus</i> and <i>Aspergillus</i> strains. The use of efficient expression systems to overproduce homologous or heterologous lipases often require the use of strong promoters and the co-expression of chaperones. Protein engineering techniques, including rational design and directed evolution, are the most reported strategies for improving lipase characteristics. Additionally, lipases can be immobilized in different supports that enable improved properties and enzyme reuse. Here, we review approaches for strain and protein engineering, immobilization and the application of lipases in the pharmaceutical industry.
  • Liu, Xinxin; Hui, Nan; Kontro, Merja H. (Multidisciplinary Digital Publishing Institute, 2020)
    The triazine herbicide atrazine easily leaches with water through soil layers into groundwater, where it is persistent. Its behavior during short-term transport is poorly understood, and there is no in situ remediation method for it. The aim of this study was to investigate whether water circulation, or circulation combined with bioaugmentation (<i>Pseudomonas</i> sp. ADP, or four isolates from atrazine-contaminated sediments) alone or with biostimulation (Na-citrate), could enhance atrazine dissipation in subsurface sediment&ndash;water systems. Atrazine concentrations (100 mg L<sup>&minus;1</sup>) in the liquid phase of sediment slurries and in the circulating water of sediment columns were followed for 10 days. Atrazine was rapidly degraded to 53&ndash;64 mg L<sup>&minus;1</sup> in the slurries, and further to 10&ndash;18 mg L<sup>&minus;1</sup> in the circulating water, by the inherent microbes of sediments collected from 13.6 m in an atrazine-contaminated aquifer. Bioaugmentation without or with biostimulation had minor effects on atrazine degradation. The microbial number simultaneously increased in the slurries from 1.0 &times; 10<sup>3</sup> to 0.8&ndash;1.0 &times; 10<sup>8</sup> cfu mL<sup>&minus;1</sup>, and in the circulating water from 0.1&ndash;1.0 &times; 10<sup>2</sup> to 0.24&ndash;8.8 &times; 10<sup>4</sup> cfu mL<sup>&minus;1</sup>. In sediments without added atrazine, the cultivable microbial numbers remained low at 0.82&ndash;8.0 &times; 10<sup>4</sup> cfu mL<sup>&minus;1</sup> in the slurries, and at 0.1&ndash;2.8 &times; 10<sup>3</sup> cfu mL<sup>&minus;1</sup> in the circulating water. The cultivated microorganisms belonged to the nine genera <i>Acinetobacter</i>, <i>Burkholderia</i>, <i>Methylobacterium</i>, <i>Pseudomonas</i>, <i>Rhodococcus</i>, <i>Sphingomonas</i>, <i>Streptomyces</i>, <i>Variovorax</i> and <i>Williamsia</i>; i.e., biodiversity was low. Water flow through the sediments released adsorbed and complex-bound atrazine for microbial degradation, though the residual concentration of 10&ndash;64 mg L<sup>&minus;1</sup> was high and could contaminate large groundwater volumes from a point source, e.g., during heavy rain or flooding.
  • Sidorova, Yulia A.; Saarma, Mart (Multidisciplinary Digital Publishing Institute, 2020)
    Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) are able to promote the survival of multiple neuronal populations in the body and, therefore, hold considerable promise for disease-modifying treatments of diseases and conditions caused by neurodegeneration. Available data reveal the potential of GFLs for the therapy of Parkinson&rsquo;s disease, neuropathic pain and diseases caused by retinal degeneration but, also, amyotrophic lateral sclerosis and, possibly, Alzheimer&rsquo;s disease. Despite promising data collected in preclinical models, clinical translation of GFLs is yet to be conducted. The main reasons for the limited success of GFLs clinical development are the poor pharmacological characteristics of GFL proteins, such as the inability of GFLs to cross tissue barriers, poor diffusion in tissues, biphasic dose-response and activation of several receptors in the organism in different cell types, along with ethical limitations on patients&rsquo; selection in clinical trials. The development of small molecules selectively targeting particular GFL receptors with improved pharmacokinetic properties can overcome many of the difficulties and limitations associated with the clinical use of GFL proteins. The current review lists several strategies to target the GFL receptor complex with drug-like molecules, discusses their advantages, provides an overview of available chemical scaffolds and peptides able to activate GFL receptors and describes the effects of these molecules in cultured cells and animal models.

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