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  • Amaghnouje, Amal; Mechchate, Hamza; Es-safi, Imane; Alotaibi, Amal A.; Noman, Omar M.; Nasr, Fahd A.; Al-zharani, Mohammed; Cerruti, Pierfrancesco; Calarco, Anna; EL Fatemi, Hinde; Grafov, Andriy; Bousta, Dalila (Multidisciplinary Digital Publishing Institute, 2020)
    Marjoram (<i>Origanum majorana</i> L.) infusion has been used as folk medicine against depression and anxiety. However, no studies have been carried out yet to prove those activities scientifically. In this study, the anxiolytic, antidepressant-like effects, and memory impact of the hydro-ethanolic extracts of marjoram were evaluated in mice. The hydro-ethanolic extracts (250 and 500 mg/kg) were evaluated for their central nervous effect using six different behavioral tests such as light&ndash;dark box (LDB) and open field (OF) for anxiety, forced swim test (FST), and tail suspension test (TST) for depression, and object recognition test (ORT), Morris water maze (MWM) for the impact on memory. The experiments were realized on days 1, 7, 14, and 21 of treatments and compared with bromazepam for anxiety (1 mg/kg) and paroxetine for depression (11.5 mg/kg). The phytochemical screening was performed by HPLC, and the acute and sub-acute toxicities were performed following OCED guidelines (N&deg;423 and 407) with biochemical parameters evaluation and histopathological analysis. Oral administration of marjoram hydro-ethanolic extract induced significant anxiolytic and antidepressant-like effects without memory impairment, increasing the exploration and time spent in the light area in the LDB test in a similar way to that of bromazepam. In the FST and TST, the extract was as effective as paroxetine (11.5 mg/kg, p.o.) in reducing immobility. The phytochemical screening showed the presence of ferulic acid, naringin, hydroxytyrosol, geraniol, and quercetin. This study approves the traditional use of this plant and encourages further investigation on its bioactive compounds.
  • Bernard, Guillaume; Kauppi, Laura; Lavesque, Nicolas; Ciutat, Aurélie; Grémare, Antoine; Massé, Cécile; Maire, Olivier (Multidisciplinary Digital Publishing Institute, 2020)
    The invasive mussel <i>Arcuatula senhousia</i> has successfully colonized shallow soft sediments worldwide. This filter feeding mussel modifies sedimentary habitats while forming dense populations and efficiently contributes to nutrient cycling. In the present study, the density of <i>A. senhousia</i> was manipulated in intact sediment cores taken within an intertidal <i>Zostera noltei</i> seagrass meadow in Arcachon Bay (French Atlantic coast), where the species currently occurs at levels corresponding to an early invasion stage. It aimed at testing the effects of a future invasion on (1) bioturbation (bioirrigation and sediment mixing) as well as on (2) total benthic solute fluxes across the sediment&ndash;water interface. Results showed that increasing densities of <i>A. senhousia</i> clearly enhanced phosphate and ammonium effluxes, but conversely did not significantly affect community bioturbation rates, highlighting the ability of <i>A. senhousia</i> to control nutrient cycling through strong excretion rates with potential important consequences for nutrient cycling and benthic&ndash;pelagic coupling at a broader scale. However, it appears that the variability in the different measured solute fluxes were underpinned by different interactions between the manipulated density of <i>A. senhousia</i> and several faunal and/or environmental drivers, therefore underlining the complexity of anticipating the effects of an invasion process on ecosystem functioning within a realistic context.
  • Kartalou, Georgia-Ioanna; Salgueiro-Pereira, Ana Rita; Endres, Thomas; Lesnikova, Angelina; Casarotto, Plinio; Pousinha, Paula; Delanoe, Kevin; Edelmann, Elke; Castrén, Eero; Gottmann, Kurt; Marie, Hélène; Lessmann, Volkmar (Multidisciplinary Digital Publishing Institute, 2020)
    Therapeutic approaches providing effective medication for Alzheimer&rsquo;s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of A&beta; accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.
  • Jawhari, Fatima Zahra; El Moussaoui, Abdelfattah; Bourhia, Mohammed; Imtara, Hamada; Mechchate, Hamza; Es-Safi, Imane; Ullah, Riaz; Ezzeldin, Essam; Mostafa, Gamal A.; Grafov, Andriy; Ibenmoussa, Samir; Bousta, Dalila; Bari, Amina (Multidisciplinary Digital Publishing Institute, 2020)
    Background: <i>Anacyclus pyrethrum</i> (<i>A. pyrethrum</i>) is a wild species belonging to the family Asteraceae, which is used in traditional medicines. Aim of the study: This work was undertaken to study the chemical composition, analgesic, anti-inflammatory, and wound healing properties of hydroalcoholic extracts of different parts (roots, seeds, leaves, and capitula) of <i>A. pyrethrum.</i> Material and Methods: The phytochemical analysis of the studied extracts was conducted by GC-MS. The analgesic activity was evaluated in mice using acetic acid and formaldehyde methods. The anti-inflammatory activity was tested using the inhibitory method of edema induced in rats. The healing activity of the hydroethanolic extracts was explored by excision and incision wound healing models in rats. Results: The phytochemical analysis of the studied plant extracts affirmed the presence of interesting compounds, including some newly detected elements, such as sarcosine, <i>N</i>-(trifluoroacetyl)-butyl ester, levulinic acid, malonic acid, palmitic acid, morphinan-6-One, 4,5.alpha.-epoxy-3-hydroxy-17-methyl, 2,4-undecadiene-8,10-diyne-<i>N</i>-tyramide, and isovaleric acid. The extracts of different parts (roots, seeds, leaves, and capitula) exhibited promising anti-inflammatory, analgesic, and wound healing effects, with percentages of inhibition up to 98%, 94%, and 100%, respectively. Conclusion: This study might contribute towards the well-being of society as it provides evidence on the potential analgesic, anti-inflammatory, and wound healing properties of <i>A. pyrethrum</i>.
  • Gilbert-Girard, Shella; Savijoki, Kirsi; Yli-Kauhaluoma, Jari; Fallarero, Adyary (Multidisciplinary Digital Publishing Institute, 2020)
    In an effort to find new repurposed antibacterial compounds, we performed the screening of an FDA-approved compounds library against <i>Staphylococcus aureus</i> American Type Culture Collection (ATCC) 25923. Compounds were evaluated for their capacity to prevent both planktonic growth and biofilm formation as well as to disrupt pre-formed biofilms. One of the identified initial hits was fingolimod (FTY720), an immunomodulator approved for the treatment of multiple sclerosis, which was then selected for follow-up studies. Fingolimod displayed a potent activity against <i>S. aureus</i> and <i>S. epidermidis</i> with a minimum inhibitory concentration (MIC) within the range of 12&ndash;15 &micro;M at which concentration killing of all the bacteria was confirmed. A time&ndash;kill kinetic study revealed that fingolimod started to drastically reduce the viable bacterial count within two hours and we showed that no resistance developed against this compound for up to 20 days. Fingolimod also displayed a high activity against <i>Acinetobacter baumannii</i> (MIC 25 &micro;M) as well as a modest activity against <i>Escherichia coli</i> and <i>Pseudomonas aeruginosa</i>. In addition, fingolimod inhibited quorum sensing in <i>Chromobacterium violaceum</i> and might therefore target this signaling pathway in certain Gram-negative bacteria. In conclusion, we present the identification of fingolimod from a compound library and its evaluation as a potential repurposed antibacterial compound.
  • Honkimaa, Anni; Kimura, Bryn; Sioofy-Khojine, Amir-Babak; Lin, Jake; Laiho, Jutta; Oikarinen, Sami; Hyöty, Heikki (Multidisciplinary Digital Publishing Institute, 2020)
    Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical isolates. We sequenced 5&prime; untranslated region (UTR) and regions coding for structural and non-structural proteins and the second single open reading frame (ORF) protein of all persisting CVB1 strains using next generation sequencing to identify mutations that are common for all of these strains. One mutation, K257R in VP1, was found from all persisting CVB1 strains. The mutations were mainly accumulated in viral structural proteins, especially at BC, DE, EF loops and C-terminus of viral capsid protein 1 (VP1), the puff region of VP2, the knob region of VP3 and infection-enhancing epitope of VP4. This showed that the capsid region of the viruses sustains various changes during persistency some of which could be hallmark(s) of persistency.
  • Hossein Motlagh, Naser; Khatibi, Ali; Aslani, Alireza (Multidisciplinary Digital Publishing Institute, 2020)
    Buildings are one of the primary consumers of energy. In addition to the electricity grids, renewable energies can be used to supply the energy demand of buildings. Intelligent systems such as the Internet of Things (IoT) and wireless sensor technologies can also be applied to manage the energy consumption in buildings. Fortunately, integrating renewable energies with these intelligent systems enables creating nearly zero-energy buildings. In this paper, we present the results of our experimentation to demonstrate forming such a building and showing the benefits for building users and the society. We create a system by integrating photovoltaic (PV) technology with an IoT-based control mechanism to supply and consume energy. We further illustrate &ldquo;how the integration of IoT and PV technology can bring added value to the users?&rdquo;. To this end, we evaluate the performance of our system against conventional ways of energy supply and consumption for a lighting use case in a dairy store. We also investigate the environmental and economic impacts of our system. In our implementation, for the IoT-based control system, we have used a set of sensors, a server, and a wireless network to control the energy consumption. We developed a web application for user interaction and software-based settings. To control the lighting system, we developed an algorithm that utilizes the ambient light, users&rsquo; movements inside the store and a historical dataset. The historical dataset was collected from the users&rsquo; behaviour as a training set for the algorithm for turning on and off the lights. We also designed an electricity management system that computes the energy generation by the PV panels, controls the energy supply, and imports and exports electricity to the grid. The results show that our system is an efficient approach for creating energy-independent buildings by integrating renewable energies with IoT-based control systems. The results also show that our system not only responds to the internal demand by using domestic supply, but it also (i) offers economic benefit by exporting extra renewable electricity to the grid, and (ii) prevents producing huge amounts of CO<inline-formula><math display="inline"><semantics><msub><mrow></mrow><mn>2</mn></msub></semantics></math></inline-formula>. Our system is one of the first works to achieve a nearly zero-energy building in the developing countries with low electricity accessibility.
  • Hänninen, Joonas; Kouvonen, Anne; Sumanen, Hilla (Multidisciplinary Digital Publishing Institute, 2020)
    Community paramedic (CP) units are becoming more popular in enhancing a person&rsquo;s access to the need for care assessment and treatment in acute but non-life-threatening health issues. Simultaneously CP units can reduce the strain on emergency departments (EDs) by treating patients effectively at home. The efficacy of CP units is proven in previous studies, but the details of conditions patients seek retreatment at the ED after a CP unit visit are largely unknown. This study aimed to categorize CP unit patients (<i>n</i> = 229) seeking retreatment after a CP unit visit and investigate links between CP unit actions and patients seeking retreatment. The study was based on a data set from a six-month CP unit pilot program in Finland. The main results show that 82% of the patients assessed and treated by the CP unit did not seek retreatment. Low back symptoms and nausea were the main problems patients presented to the ED within 96 h after the CP visit. On-call physician consultation (<i>p</i> = 0.335) or CP unit treatment time (<i>p</i> = 0.629) were not associated with the frequency of ED presentation. Further studies are needed in order to investigate which types of emergency medical missions are the most suitable for CP units. The findings of this study support the effectiveness of community paramedicine programs.
  • Cameli, Matteo; Miglioranza, Marcelo Haertel; Magne, Julien; Mandoli, Giulia Elena; Benfari, Giovanni; Ancona, Roberta; Sibilio, Gerolamo; Reskovic Luksic, Vlatka; Dejan, Dosen; Griseli, Leonardo; Van De Heyning, Caroline M.; Mortelmans, Philippe; Michalski, Blazej; Kupczynska, Karolina; Di Giannuario, Giovanna; Devito, Fiorella; Dulgheru, Raluca; Ilardi, Federica; Salustri, Alessandro; Abushahba, Galal; Morrone, Doralisa; Fabiani, Iacopo; Penicka, Martin; Katbeh, Asim; Sammarco, Giuseppe; Esposito, Roberta; Santoro, Ciro; Pastore, Maria Concetta; Comenale Pinto, Salvatore; Kalinin, Artem; Pičkure, Žanna; Ažman Juvan, Katja; Zupan Mežnar, Anja; Coisne, Augustine; Coppin, Amandine; Opris, Mihaela Maria; Nistor, Dan Octavian; Paakkanen, Riitta; Biering-Sørensen, Tor; Olsen, Flemming Javier; Lapinskas, Tomas; Vaškelyté, Jolanta Justina; Galian-Gay, Laura; Casas, Guillem; Motoc, Andreea Iulia; Papadopoulos, Constantinos Hristou; Loizos, Savvas; Ágoston, Gergely; Szabó, Istvan; Hristova, Krasimira; Tsonev, Svetlin Netkov; Galli, Elena; Vinereanu, Dragos; Mihaila Baldea, Sorina; Muraru, Denisa; Mondillo, Sergio; Donal, Erwan; Galderisi, Maurizio; Cosyns, Bernard; Edvardsen, Thor; Popescu, Bogdan A. (Multidisciplinary Digital Publishing Institute, 2020)
    Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume&ndash;pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference.
  • Huang, Xin; Ma, Kaiyue; Leinonen, Sara; Sontag-Strohm, Tuula (Multidisciplinary Digital Publishing Institute, 2020)
    The lack of certified reference materials has been one major challenge for gluten quantification in gluten-free products. In this study, the feasibility of using barley C-hordein as the calibrant for wheat gluten in R5 sandwich enzyme-linked immunosorbent assay (ELISA) was investigated. The gluten composition and total gluten R5 reactivity ranged largely depending on the genotypes and the growing environment. The conversion factor of gliadin to gluten averaged 1.31 for common wheat, which is smaller than the theoretical factor of 2. Each gluten group had varying reactivity against the R5 antibody, where &omega;1.2-, &gamma;- and &alpha;-gliadins were the main reactive groups from wheat gluten. A mixture of wheat cultivars or one single cultivar as the reference material can be difficult to keep current. Based on the average R5 reactivity of total gluten from the 27 common wheat cultivars, here we proposed 10% C-hordein mixed with an inert protein as the calibrant for wheat gluten quantification. In spiking tests of gluten-free oat flour and biscuits, calibration using 10% C-hordein achieved the same recovery as the gliadin standard with its cultivar-specific conversion factor. For its good solubility and good affinity to the R5 antibody, the application of C-hordein increases the probability of developing a series of reference materials for various food matrices.
  • Tang, Jin; Sipiläinen, Timo; Fu, Gang (Multidisciplinary Digital Publishing Institute, 2020)
    Social responsibility is a natural obligation of cooperatives, and fulfilling social responsibility is of great meaning to the sustainable development of cooperatives and society. This article constructs a &ldquo;life cycle-cooperative social responsibility framework (LC-CoopSRF)&rdquo; and analyzes the framework with the case of Chongxin Apiculture Specialized Cooperative of Sichuan Province, China. The research results show that cooperatives should respect the law of life cycle, consider conditions such as operational capabilities and ethical expectations, and fulfill social responsibility in a reasonable manner. The successful cooperative highlights the bottom-line responsibility in the establishment phase, internal responsibility in the growth phase, system responsibility in the maturity phase, and the differentiation phase is the phase of system responsibility.
  • Reigada, Inés; Guarch-Pérez, Clara; Patel, Jayendra Z.; Riool, Martijn; Savijoki, Kirsi; Yli-Kauhaluoma, Jari; Zaat, Sebastian A. J.; Fallarero, Adyary (Multidisciplinary Digital Publishing Institute, 2020)
    Nosocomial diseases represent a huge health and economic burden. A significant portion is associated with the use of medical devices, with 80% of these infections being caused by a bacterial biofilm. The insertion of a foreign material usually elicits inflammation, which can result in hampered antimicrobial capacity of the host immunity due to the effort of immune cells being directed to degrade the material. The ineffective clearance by immune cells is a perfect opportunity for bacteria to attach and form a biofilm. In this study, we analyzed the antibiofilm capacity of three naturally derived biofilm inhibitors when combined with immune cells in order to assess their applicability in implantable titanium devices and low-density polyethylene (LDPE) endotracheal tubes. To this end, we used a system based on the coculture of HL-60 cells differentiated into polymorphonuclear leukocytes (PMNs) and <i>Staphylococcus aureus</i> (laboratory and clinical strains) on titanium, as well as LDPE surfaces. Out of the three inhibitors, the one coded <b>DHA1</b> showed the highest potential to be incorporated into implantable devices, as it displayed a combined activity with the immune cells, preventing bacterial attachment on the titanium and LDPE. The other two inhibitors seemed to also be good candidates for incorporation into LDPE endotracheal tubes.
  • Hong, Jinsu; Han, Taehee; Kim, Yoo Yong (Multidisciplinary Digital Publishing Institute, 2020)
    Edible insects have been used as an alternative protein source for food and animal feed, and the market size for edible insects has increased. <i>Tenebrio molitor</i> larvae, also known as mealworm and yellow mealworm, are considered a good protein source with nutritional value, digestibility, flavor, and a functional ability. Additionally, they are easy to breed and feed for having a stable protein content, regardless of their diets. Therefore, <i>T. molitor</i> larvae have been produced industrially as feed for pets, zoo animals, and even for production animals. To maintain the nutrient composition and safety of <i>T. molitor</i> larvae, slaughtering (heating or freezing) and post-slaughtering (drying and grinding) procedures should be improved for animal feed. <i>T. molitor</i> larvae are also processed with defatting or hydrolysis before grinding. They have a high quality and quantity of protein and amino acid profile, so are considered a highly sustainable protein source for replacing soybean meal or fishmeal. <i>T. molitor</i> has a chitin in its cuticle, which is an indigestible fiber with positive effects on the immune system. In studies of poultry, the supplementation of <i>T. molitor</i> larvae improved the growth performance of broiler chickens, without having negative effects on carcass traits, whereas some studies have reported that there were no significant differences in the growth performance and carcass yield of broiler chickens. In studies of swine, the supplementation of <i>T. molitor</i> larvae improved the growth performance and protein utilization of weaning pigs. Furthermore, 10% of <i>T. molitor</i> larvae showed greater amino acid digestibility than conventional animal proteins in growing pigs. However, there are some challenges regarding the biosafety, consumer&rsquo;s acceptance, and price for the use of <i>T. moiltor</i> larvae in animal feed. Consequently, <i>T. molitor</i> larvae could be used as an alternative or sustainable protein source in monogastric animal feed with a consideration of the nutritional values, biosafety, consumer&rsquo;s acceptance, and market price of <i>T. molitor</i> larvae products.
  • Beyer, Hannes M.; Virtanen, Salla I.; Aranko, A. Sesilja; Mikula, Kornelia M.; Lountos, George T.; Wlodawer, Alexander; Ollila, O. H. Samuli; Iwaï, Hideo (Multidisciplinary Digital Publishing Institute, 2020)
    Protein splicing catalyzed by inteins utilizes many different combinations of amino-acid types at active sites. Inteins have been classified into three classes based on their characteristic sequences. We investigated the structural basis of the protein splicing mechanism of class 3 inteins by determining crystal structures of variants of a class 3 intein from <i>Mycobacterium chimaera</i> and molecular dynamics simulations, which suggested that the class 3 intein utilizes a different splicing mechanism from that of class 1 and 2 inteins. The class 3 intein uses a bond cleavage strategy reminiscent of proteases but share the same Hedgehog/INTein (HINT) fold of other intein classes. Engineering of class 3 inteins from a class 1 intein indicated that a class 3 intein would unlikely evolve directly from a class 1 or 2 intein. The HINT fold appears as structural and functional solution for <i>trans</i>-peptidyl and <i>trans</i>-esterification reactions commonly exploited by diverse mechanisms using different combinations of amino-acid types for the active-site residues.
  • Paterno, Jussi J.; Koskela, Ali; Hyttinen, Juha M.T.; Vattulainen, Elina; Synowiec, Ewelina; Tuuminen, Raimo; Watala, Cezary; Blasiak, Janusz; Kaarniranta, Kai (Multidisciplinary Digital Publishing Institute, 2020)
    Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the <i>mTOR</i> (Mechanistic Target of Rapamycin), <i>ATG5</i> (Autophagy Related 5), <i>ULK1</i> (Unc-51-Like Autophagy Activating Kinase 1), <i>MAP1LC3A</i> (Microtubule Associated Protein 1 Light Chain 3 &alpha;), <i>SQSTM1</i> (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.
  • Palviainen, Mari; Laukkanen, Kirsi; Tavukcuoglu, Zeynep; Velagapudi, Vidya; Kärkkäinen, Olli; Hanhineva, Kati; Auriola, Seppo; Ranki, Annamari; Siljander, Pia (Multidisciplinary Digital Publishing Institute, 2020)
    Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.
  • Kallio, Sonja; Eskola, Tiina; Pohjanoksa-Mäntylä, Marika; Airaksinen, Marja (Multidisciplinary Digital Publishing Institute, 2020)
    Community pharmacists have a duty to contribute to medication risk management in outpatient care. This study aimed to investigate the actions taken by pharmacists in routine dispensing to manage medication risks. The study was conducted as a national cross-sectional online survey targeted at all community pharmacies in Finland (<i>n </i>=<i> </i>576) in October 2015. One pharmacist from each pharmacy was recommended to be the spokesperson for the outlet to describe their practices. Responses were received from 169 pharmacies (response rate of 29%). Pharmacists were oriented to solving poor adherence and technical problems in prescriptions, whereas responsibility for therapeutic risks was transferred to the patient to resolve them with the physician. Pharmacists have access to a wide range of electronic medication risk management tools, but they are rarely utilized in daily dispensing. Attention was paid to drug&ndash;drug interactions and the frequency of dispensing with regard to high-risk medicines. Pharmacies rarely had local agreements with other healthcare providers to solve medication-related risks. In routine dispensing, more attention needs to be given to the identification and solving of therapeutic risks in medications, especially those of older adults. Better participation of community pharmacists in medication risk management requires stronger integration and an explicit mandate to solve the therapeutic risks.
  • Surakhi, Ola M.; Zaidan, Martha Arbayani; Serhan, Sami; Salah, Imad; Hussein, Tareq (Multidisciplinary Digital Publishing Institute, 2020)
    Time-series prediction is an important area that inspires numerous research disciplines for various applications, including air quality databases. Developing a robust and accurate model for time-series data becomes a challenging task, because it involves training different models and optimization. In this paper, we proposed and tested three machine learning techniques&mdash;recurrent neural networks (RNN), heuristic algorithm and ensemble learning&mdash;to develop a predictive model for estimating atmospheric particle number concentrations in the form of a time-series database. Here, the RNN included three variants&mdash;Long-Short Term Memory, Gated Recurrent Network, and Bi-directional Recurrent Neural Network&mdash;with various configurations. A Genetic Algorithm (GA) was then used to find the optimal time-lag in order to enhance the model&rsquo;s performance. The optimized models were used to construct a stacked ensemble model as well as to perform the final prediction. The results demonstrated that the time-lag value can be optimized by using the heuristic algorithm; consequently, this improved the model prediction accuracy. Further improvement can be achieved by using ensemble learning that combines several models for better performance and more accurate predictions.
  • Kaartinen, Mari T.; Arora, Mansi; Heinonen, Sini; Rissanen, Aila; Kaprio, Jaakko; Pietiläinen, Kirsi H. (Multidisciplinary Digital Publishing Institute, 2020)
    Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of <i>TGM</i> family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy&ndash;lean twin pairs. We report that <i>F13A1</i> is the only <i>TGM</i> family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte <i>F13A1</i> to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of <i>F13A1</i> to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of <i>F13A1</i> (&Delta;Heavy&ndash;Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of <i>F13A1</i> in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.
  • Papale, Maria; Rappazzo, Alessandro Ciro; Mikkonen, Anu; Rizzo, Carmen; Moscheo, Federica; Conte, Antonella; Michaud, Luigi; Lo Giudice, Angelina (Multidisciplinary Digital Publishing Institute, 2020)
    Microbial communities promptly respond to the environmental perturbations, especially in the Arctic and sub-Arctic systems that are highly impacted by climate change, and fluctuations in the diversity level of microbial assemblages could give insights on their expected response. 16S rRNA gene amplicon sequencing was applied to describe the bacterial community composition in water and sediment through the sub-Arctic Pasvik River. Our results showed that river water and sediment harbored distinct communities in terms of diversity and composition at genus level. The distribution of the bacterial communities was mainly affected by both salinity and temperature in sediment samples, and by oxygen in water samples. Glacial meltwaters and runoff waters from melting ice probably influenced the composition of the bacterial community at upper and middle river sites. Interestingly, marine-derived bacteria consistently accounted for a small proportion of the total sequences and were also more prominent in the inner part of the river. Results evidenced that particular conditions occurring at sampling sites (such as algal blooms, heavy metal contamination and anaerobiosis) may select species at local scale from a shared bacterial pool, thus favoring certain bacterial taxa. Conversely, the few phylotypes specifically detected in some sites are probably due to localized external inputs introducing allochthonous microbial groups.

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