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  • Shchemeleva, Irina (Multidisciplinary Digital Publishing Institute, 2021)
    This paper reports on the study of multilingual speakers’ perception of their research writing practices in English and in their local language—Russian—and the publication process in English. It is based on interviews with 18 scholars from social sciences and humanities working in a leading university in Russia. The study discusses social factors influencing multilingual scholars’ choice of languages as well as their personal motivation to choose English as the main language of publication. Special attention is given to their attitude to proofreading as part of the publication process. The interview results suggest that, from the participants’ perspective, the benefits they gain by publishing research in English seem to outweigh costs they experience in the process of writing and publishing. The study contributes to the on-going debate about the position of multilingual scholars in the competition to publish in top-rated journals, suggesting that the traditional doctrine of linguistic injustice, from the participants’ point-of-view, does not seem to be relevant for every multilingual scholar.
  • Postuma, Ian; González, Sara; Herrera, Maria S; Provenzano, Lucas; Ferrarini, Michele; Magni, Chiara; Protti, Nicoletta; Fatemi, Setareh; Vercesi, Valerio; Battistoni, Giuseppe; Anselmi Tamburini, Umberto; Liu, Yuan Hao; Kankaanranta, Leena; Koivunoro, Hanna; Altieri, Saverio; Bortolussi, Silva (Multidisciplinary Digital Publishing Institute, 2021)
    (1) Background:The quality of neutron beams for Boron Neutron Capture Therapy (BNCT) is currently defined by its physical characteristics in air. Recommendations exist to define whether a designed beam is useful for clinical treatment. This work presents a new way to evaluate neutron beams based on their clinical performance and on their safety, employing radiobiological quantities. (2) Methods: The case study is a neutron beam for deep-seated tumors from a 5 MeV proton beam coupled to a beryllium target. Physical Figures of Merit were used to design five beams; however, they did not allow a clear ranking of their quality in terms of therapeutic potential. The latter was then evaluated based on in-phantom dose distributions and on the calculation of the Uncomplicated Tumor Control Probability (UTCP). The safety of the beams was also evaluated calculating the in-patient out-of-beam dosimetry. (3) Results: All the beams ensured a UTCP comparable to the one of a clinical beam in phantom; the safety criterion allowed to choose the best candidate. When this was tested in the treatment planning of a real patient treated in Finland, the UTCP was still comparable to the one of the clinical beam. (4) Conclusions: Even when standard physical recommendations are not met, radiobiological and dosimetric criteria demonstrate to be a valid tool to select an effective and safe beam for patient treatment.
  • Sadeghi, Mohammadreza; Tomaru, Yuji; Ahola, Tero (Multidisciplinary Digital Publishing Institute, 2021)
    Increasing sequence information indicates that RNA viruses constitute a major fraction of marine virus assemblages. However, only 12 RNA virus species have been described, infecting known host species of marine single-celled eukaryotes. Eight of these use diatoms as hosts, while four are resident in dinoflagellate, raphidophyte, thraustochytrid, or prasinophyte species. Most of these belong to the order <i>Picornavirales</i>, while two are divergent and fall into the families <i>Alvernaviridae</i> and <i>Reoviridae</i>. However, a very recent study has suggested that there is extraordinary diversity in aquatic RNA viromes, describing thousands of viruses, many of which likely use protist hosts. Thus, RNA viruses are expected to play a major ecological role for marine unicellular eukaryotic hosts. In this review, we describe in detail what has to date been discovered concerning viruses with RNA genomes that infect aquatic unicellular eukaryotes.
  • Szanto, Timea; Lassila, Riitta; Lemponen, Marja; Lehtinen, Elina; Neerman-Arbez, Marguerite; Casini, Alessandro (Multidisciplinary Digital Publishing Institute, 2021)
    The outcome of congenital fibrinogen defects (CFD) is often unpredictable. Standard coagulation assays fail to predict the clinical phenotype. We aimed to&nbsp;assess the pheno- and genotypic associations of thrombin generation (TG) and ROTEM in CFD. We measured fibrinogen (Fg) activity and antigen, prothrombin fragments F1+2, and TG by ST Genesia® with both Bleed- and ThromboScreen in 22 patients. ROTEM was available for 11 patients. All patients were genotyped for fibrinogen mutations. Ten patients were diagnosed with hypofibrinogenemia, nine with dysfibrinogenemia, and three with hypodysfibrinogenemia. Among the 17 mutations, eight were affecting the Fg γ chain, four the Fg Bβ chain, and five the Fg Aα chain. No statistical difference according to the clinical phenotypes was observed among <i>FGG</i> and <i>FGA</i> mutations. Median F1+2 and TG levels were normal among the different groups. Fg levels correlated negatively with F1+2 and peak height, and positively with lag time and time to peak. The pheno- and genotypes of the patients did not associate with TG. FIBTEM by ROTEM detected hypofibrinogenemia. Our study suggests an inverse link between low fibrinogen activity levels and enhanced TG, which could modify the structure–function relationship of fibrin to support hemostasis.
  • Li, Hao; Hohenstein, Peter; Kuure, Satu (Multidisciplinary Digital Publishing Institute, 2021)
    The adult mammalian kidney is a poorly regenerating organ that lacks the stem cells that could replenish functional homeostasis similarly to, e.g., skin or the hematopoietic system. Unlike a mature kidney, the embryonic kidney hosts at least three types of lineage-specific stem cells that give rise to (a) a ureter and collecting duct system, (b) nephrons, and (c) mesangial cells together with connective tissue of the stroma. Extensive interest has been raised towards these embryonic progenitor cells, which are normally lost before birth in humans but remain part of the undifferentiated nephrogenic rests in the pediatric renal cancer Wilms tumor. Here, we discuss the current understanding of kidney-specific embryonic progenitor regulation in the innate environment of the developing kidney and the types of disruptions in their balanced regulation that lead to the formation of Wilms tumor.
  • Magalhães, Joana; Franko, Nina; Raboni, Samanta; Annunziato, Giannamaria; Tammela, Päivi; Bruno, Agostino; Bettati, Stefano; Armao, Stefano; Spadini, Costanza; Cabassi, Clotilde Silvia; Mozzarelli, Andrea; Pieroni, Marco; Campanini, Barbara; Costantino, Gabriele (Multidisciplinary Digital Publishing Institute, 2021)
    Many bacteria and actinomycetales use L-cysteine biosynthesis to increase their tolerance to antibacterial treatment and establish a long-lasting infection. In turn, this might lead to the onset of antimicrobial resistance that currently represents one of the most menacing threats to public health worldwide. The biosynthetic machinery required to synthesise L-cysteine is absent in mammals; therefore, its exploitation as a drug target is particularly promising. In this article, we report a series of inhibitors of <i>Salmonella thyphimurium</i> serine acetyltransferase (SAT), the enzyme that catalyzes the rate-limiting step of L-cysteine biosynthesis. The development of such inhibitors started with the virtual screening of an in-house library of compounds that led to the selection of seven structurally unrelated hit derivatives. A set of molecules structurally related to hit compound <b>5</b>, coming either from the original library or from medicinal chemistry efforts, were tested to determine a preliminary structure–activity relationship and, especially, to improve the inhibitory potency of the derivatives, that was indeed ameliorated by several folds compared to hit compound <b>5</b> Despite these progresses, at this stage, the most promising compound failed to interfere with bacterial growth when tested on a Gram-negative model organism, anticipating the need for further research efforts.
  • Künnapuu, Jaana; Bokharaie, Honey; Jeltsch, Michael (Multidisciplinary Digital Publishing Institute, 2021)
    Specific proteolytic cleavages turn on, modify, or turn off the activity of vascular endothelial growth factors (VEGFs). Proteolysis is most prominent among the lymph­angiogenic VEGF-C and VEGF-D, which are synthesized as precursors that need to undergo enzymatic removal of their C- and N-terminal propeptides before they can activate their receptors. At least five different proteases mediate the activating cleavage of VEGF-C: plasmin, ADAMTS3, prostate-specific antigen, cathepsin D, and thrombin. All of these proteases except for ADAMTS3 can also activate VEGF-D. Processing by different proteases results in distinct forms of the “mature” growth factors, which differ in affinity and receptor activation potential. The “default” VEGF-C-activating enzyme ADAMTS3 does not activate VEGF-D, and therefore, VEGF-C and VEGF-D do function in different contexts. VEGF-C itself is also regulated in different contexts by distinct proteases. During embryonic development, ADAMTS3 activates VEGF-C. The other activating proteases are likely important for non-developmental lymphangiogenesis during, e.g., tissue regeneration, inflammation, immune response, and pathological tumor-associated lymphangiogenesis. The better we understand these events at the molecular level, the greater our chances of developing successful therapies targeting VEGF-C and VEGF-D for diseases involving the lymphatics such as lymphedema or cancer.
  • Willberg, Elias; Järv, Olle; Väisänen, Tuomas; Toivonen, Tuuli (Multidisciplinary Digital Publishing Institute, 2021)
    The coronavirus disease 2019 (COVID-19) crisis resulted in unprecedented changes in the spatial mobility of people across societies due to the restrictions imposed. This also resulted in unexpected mobility and population dynamics that created a challenge for crisis preparedness, including the mobility from cities during the crisis due to the underlying phenomenon of multi-local living. People changing their residences can spread the virus between regions and create situations in which health and emergency services are not prepared for the population increase. Here, our focus is on urban–rural mobility and the influence of multi-local living on population dynamics in Finland during the COVID-19 crisis in 2020. Results, based on three mobile phone datasets, showed a significant drop in inter-municipal mobility and a shift in the presence of people—a population decline in urban centres and an increase in rural areas, which is strongly correlated to secondary housing. This study highlights the need to improve crisis preparedness by: (1) acknowledging the growing importance of multi-local living, and (2) improving the use of novel data sources for monitoring population dynamics and mobility. Mobile phone data products have enormous potential, but attention should be paid to the varying methodologies and their possible impact on analysis.
  • Han, Kyung M.; Jung, Chang H.; Park, Rae-Seol; Park, Soon-Young; Lee, Sojin; Kulmala, Markku; Petäjä, Tuukka; Karasiński, Grzegorz; Sobolewski, Piotr; Yoon, Young Jun; Lee, Bang Young; Kim, Kiyeon; Kim, Hyun S. (Multidisciplinary Digital Publishing Institute, 2021)
    In this study, more accurate information on the levels of aerosol optical depth (AOD) was calculated from the assimilation of the modeled AOD based on the optimal interpolation method. Additionally, more realistic levels of surface particulate matters over the Arctic were estimated using the assimilated AOD based on the linear relationship between the particulate matters and AODs. In comparison to the MODIS observation, the assimilated AOD was much improved compared with the modeled AOD (e.g., increase in correlation coefficients from −0.15–0.26 to 0.17–0.76 over the Arctic). The newly inferred monthly averages of PM<sub>10</sub> and PM<sub>2.5</sub> for April–September 2008 were 2.18–3.70 μg m<sup>−3</sup> and 0.85–1.68 μg m<sup>−3</sup> over the Arctic, respectively. These corresponded to an increase of 140–180%, compared with the modeled PMs. In comparison to in-situ observation, the inferred PMs showed better performances than those from the simulations, particularly at Hyytiala station. Therefore, combining the model simulation and data assimilation provided more accurate concentrations of AOD, PM<sub>10</sub>, and PM<sub>2.5</sub> than those only calculated from the model simulations.
  • Siddiqui, Farid Ahmad; Parkkola, Hanna; Vukic, Vladimir; Oetken-Lindholm, Christina; Jaiswal, Alok; Kiriazis, Alexandros; Pavic, Karolina; Aittokallio, Tero; Salminen, Tiina A.; Abankwa, Daniel (Multidisciplinary Digital Publishing Institute, 2021)
    The ATP-competitive inhibitors of Hsp90 have been tested predominantly in kinase addicted cancers; however, they have had limited success. A mechanistic connection between Hsp90 and oncogenic K-Ras is not known. Here, we show that K-Ras selectivity is enabled by the loss of the K-Ras membrane nanocluster modulator galectin-3 downstream of the Hsp90 client HIF-1α. This mechanism suggests a higher drug sensitivity in the context of KRAS mutant, HIF-1α-high and/or Gal3-high cancer cells, such as those found, in particular, in pancreatic adenocarcinoma. The low toxicity of conglobatin further indicates a beneficial on-target toxicity profile for Hsp90/Cdc37 interface inhibitors. We therefore computationally screened &gt;7 M compounds, and identified four novel small molecules with activities of 4 μM–44 μM in vitro. All of the compounds were K-Ras selective, and potently decreased the Hsp90 client protein levels without inducing the heat shock response. Moreover, they all inhibited the 2D proliferation of breast, pancreatic, and lung cancer cell lines. The most active compounds from each scaffold, furthermore, significantly blocked 3D spheroids and the growth of K-Ras-dependent microtumors. We foresee new opportunities for improved Hsp90/Cdc37 interface inhibitors in cancer and other aging-associated diseases.
  • Evans, Claire; Brandsma, Joost; Meredith, Michael P.; Thomas, David N.; Venables, Hugh J.; Pond, David W.; Brussaard, Corina P. D. (Multidisciplinary Digital Publishing Institute, 2021)
    The relative flow of carbon through the viral shunt and the microbial loop is a pivotal factor controlling the contribution of secondary production to the food web and to rates of nutrient remineralization and respiration. The current study examines the significance of these processes in the coastal waters of the Antarctic during the productive austral summer months. Throughout the study a general trend towards lower bacterioplankton and heterotrophic nanoflagellate (HNF) abundances was observed, whereas virioplankton concentration increased. A corresponding decline of HNF grazing rates and shift towards viral production, indicative of viral infection, was measured. Carbon flow mediated by HNF grazing decreased by more than half from 5.7 µg C L<sup>−1</sup> day<sup>−1</sup> on average in December and January to 2.4 µg C L<sup>−1</sup> day<sup>−1</sup> in February. Conversely, carbon flow through the viral shunt increased substantially over the study from on average 0.9 µg C L<sup>−1</sup> day<sup>−1</sup> in December to 7.6 µg C L<sup>−1</sup> day<sup>−1</sup> in February. This study shows that functioning of the coastal Antarctic microbial community varied considerably over the productive summer months. In early summer, the system favors transfer of matter and energy to higher trophic levels via the microbial loop, however towards the end of summer carbon flow is redirected towards the viral shunt, causing a switch towards more recycling and therefore increased respiration and regeneration.
  • Yu, Jennifer Chun; Mietzsch, Mario; Singh, Amriti; Jimenez Ybargollin, Alberto; Kailasan, Shweta; Chipman, Paul; Bhattacharya, Nilakshee; Fakhiri, Julia; Grimm, Dirk; Kapoor, Amit; Kučinskaitė-Kodzė, Indrė; Žvirblienė, Aurelija; Söderlund-Venermo, Maria; McKenna, Robert; Agbandje-McKenna, Mavis (Multidisciplinary Digital Publishing Institute, 2021)
    Human bocavirus 1 (HBoV1) has gained attention as a gene delivery vector with its ability to infect polarized human airway epithelia and 5.5 kb genome packaging capacity. Gorilla bocavirus 1 (GBoV1) VP3 shares 86% amino acid sequence identity with HBoV1 but has better transduction efficiency in several human cell types. Here, we report the capsid structure of GBoV1 determined to 2.76 Å resolution using cryo-electron microscopy (cryo-EM) and its interaction with mouse monoclonal antibodies (mAbs) and human sera. GBoV1 shares capsid surface morphologies with other parvoviruses, with a channel at the 5-fold symmetry axis, protrusions surrounding the 3-fold axis and a depression at the 2-fold axis. A 2/5-fold wall separates the 2-fold and 5-fold axes. Compared to HBoV1, differences are localized to the 3-fold protrusions. Consistently, native dot immunoblots and cryo-EM showed cross-reactivity and binding, respectively, by a 5-fold targeted HBoV1 mAb, 15C6. Surprisingly, recognition was observed for one out of three 3-fold targeted mAbs, 12C1, indicating some structural similarity at this region. In addition, GBoV1, tested against 40 human sera, showed the similar rates of seropositivity as HBoV1. Immunogenic reactivity against parvoviral vectors is a significant barrier to efficient gene delivery. This study is a step towards optimizing bocaparvovirus vectors with antibody escape properties.
  • Wang, Lanhui; Cui, Zichan; Kuuluvainen, Jari; Sun, Yongyu (Multidisciplinary Digital Publishing Institute, 2021)
    Forests and the forest products industry contribute to climate change mitigation by sequestering carbon from the atmosphere and storing it in biomass, and by fabricating products that substitute other, more greenhouse-gas-emission-intensive materials and energy. This study investigates primary wood-working industries (panel, furniture, pulp and paper) in order to determine the development of carbon emissions in China during the last two decades. The input–output approach is used and the factors driving the changes in CO<sub>2</sub> emissions are analyzed by Index Decomposition Analysis–Log Mean Divisia Index (LMDI). The results show that carbon emissions in forest product industries have been declining during the last twenty years and that the driving factor of this change is the energy intensity of production and economic input, which have changed dramatically.
  • Tiekstra, Sanne; Dopico-Parada, Ana; Koivula, Hanna; Lahti, Johanna; Buntinx, Mieke (Multidisciplinary Digital Publishing Institute, 2021)
    Market implementation of active and intelligent packaging (AIP) technologies specifically for fiber-based food packaging can be hindered by various factors. This paper highlights those from a social, economic, environmental, and legislative point of view, and elaborates upon the following aspects mainly related to interactions among food packaging value chain stakeholders: (i) market drivers that affect developments, (ii) the gap between science and industry, (iii) the gap between legislation and practice, (iv) cooperation between the producing stakeholders within the value chain, and (v) the gap between the industry and consumers. We perceive these as the most influential aspects in successful market implementation at a socioeconomic level. The findings are supported by results from quantitative studies analyzing consumer buying expectations about active and intelligent packaging (value perception of packaging functions, intentions to purchase AIP, and willingness to pay more) executed in 16 European countries. Finally, in this paper, we discuss approaches that could direct future activities in the field towards industrial implementation.
  • Mönttinen, Heli A. M.; Ravantti, Janne J.; Poranen, Minna M. (Multidisciplinary Digital Publishing Institute, 2021)
    RNA viruses are the fastest evolving known biological entities. Consequently, the sequence similarity between homologous viral proteins disappears quickly, limiting the usability of traditional sequence-based phylogenetic methods in the reconstruction of relationships and evolutionary history among RNA viruses. Protein structures, however, typically evolve more slowly than sequences, and structural similarity can still be evident, when no sequence similarity can be detected. Here, we used an automated structural comparison method, homologous structure finder, for comprehensive comparisons of viral RNA-dependent RNA polymerases (RdRps). We identified a common structural core of 231 residues for all the structurally characterized viral RdRps, covering segmented and non-segmented negative-sense, positive-sense, and double-stranded RNA viruses infecting both prokaryotic and eukaryotic hosts. The grouping and branching of the viral RdRps in the structure-based phylogenetic tree follow their functional differentiation. The RdRps using protein primer, RNA primer, or self-priming mechanisms have evolved independently of each other, and the RdRps cluster into two large branches based on the used transcription mechanism. The structure-based distance tree presented here follows the recently established RdRp-based RNA virus classification at genus, subfamily, family, order, class and subphylum ranks. However, the topology of our phylogenetic tree suggests an alternative phylum level organization.
  • Latva-Mäenpää, Harri; Wufu, Riziwanguli; Mulat, Daniel; Sarjala, Tytti; Saranpää, Pekka; Wähälä, Kristiina (Multidisciplinary Digital Publishing Institute, 2021)
    Stilbenes or stilbenoids, major polyphenolic compounds of the bark of Norway spruce (<i>Picea abies</i> L. Karst), have potential future applications as drugs, preservatives and other functional ingredients due to their antioxidative, antibacterial and antifungal properties. Stilbenes are photosensitive and UV and fluorescent light induce <i>trans</i> to <i>cis</i> isomerisation via intramolecular cyclization. So far, the characterizations of possible new compounds derived from <i>trans</i>-stilbenes under UV light exposure have been mainly tentative based only on UV or MS spectra without utilizing more detailed structural spectroscopy techniques such as NMR. The objective of this work was to study the stability of biologically interesting and readily available stilbenes such as astringin and isorhapontin and their aglucones piceatannol and isorhapontigenin, which have not been studied previously. The effects of fluorescent and UV light and storage on the stability of <i>trans</i> stilbenes were assessed and the identification and characterisation of new compounds formed during our experiments were carried out by chromatographic (HPLC, GC) and spectroscopic techniques (UV, MS, NMR). The stilbenes undergo a <i>trans</i> to <i>cis</i> isomerisation under extended UV irradiation by intramolecular cyclisation (by the formation of a new C-C bond and the loss of two hydrogens) to phenanthrene structures. The characterised compounds are novel and not described previously.
  • Boyle, John H.; Rastas, Pasi M. A.; Huang, Xin; Garner, Austin G.; Vythilingam, Indra; Armbruster, Peter A. (Multidisciplinary Digital Publishing Institute, 2021)
    The Asian tiger mosquito, <i>Aedes albopictus</i>, is an invasive vector mosquito of substantial public health concern. The large genome size (~1.19–1.28 Gb by cytofluorometric estimates), comprised of ~68% repetitive DNA sequences, has made it difficult to produce a high-quality genome assembly for this species. We constructed a high-density linkage map for <i>Ae. albopictus</i> based on 111,328 informative SNPs obtained by RNAseq. We then performed a linkage-map anchored reassembly of AalbF2, the genome assembly produced by Palatini et al. (2020). Our reassembled genome sequence, AalbF3, represents several improvements relative to AalbF2. First, the size of the AalbF3 assembly is 1.45 Gb, almost half the size of AalbF2. Furthermore, relative to AalbF2, AalbF3 contains a higher proportion of complete and single-copy BUSCO genes (84.3%) and a higher proportion of aligned RNAseq reads that map concordantly to a single location of the genome (46%). We demonstrate the utility of AalbF3 by using it as a reference for a bulk-segregant-based comparative genomics analysis that identifies chromosomal regions with clusters of candidate SNPs putatively associated with photoperiodic diapause, a crucial ecological adaptation underpinning the rapid range expansion and climatic adaptation of <i>A. albopictus</i>.
  • Salem, Mabruka; Pajunen, Maria I.; Jun, Jin Woo; Skurnik, Mikael (Multidisciplinary Digital Publishing Institute, 2021)
    The <i>Yersinia</i> bacteriophages fPS-2, fPS-65, and fPS-90, isolated from pig stools, have long contractile tails and elongated heads, and they belong to genus Tequatroviruses in the order <i>Caudovirales</i>. The phages exhibited relatively wide host ranges among <i>Yersinia pseudotuberculosis</i> and related species. One-step growth curve experiments revealed that the phages have latent periods of 50–80 min with burst sizes of 44–65 virions per infected cell. The phage genomes consist of circularly permuted dsDNA of 169,060, 167,058, and 167,132 bp in size, respectively, with a G + C content 35.3%. The number of predicted genes range from 267 to 271. The phage genomes are 84–92% identical to each other and ca 85% identical to phage T4. The phage receptors were identified by whole genome sequencing of spontaneous phage-resistant mutants. The phage-resistant strains had mutations in the <i>ompF, galU, hldD,</i> or <i>hldE</i> genes. OmpF is a porin, and the other genes encode lipopolysaccharide (LPS) biosynthetic enzymes. The <i>ompF</i>, <i>galU</i>, and <i>hldE</i> mutants were successfully complemented <i>in trans</i> with respective wild-type genes. The host recognition was assigned to long tail fiber tip protein Gp38, analogous to that of T-even phages such as <i>Salmonella</i> phage S16, specifically to the distal β-helices connecting loops.
  • Julku, Ulrika H.; Jäntti, Maria; Svarcbahs, Reinis; Myöhänen, Timo T. (Multidisciplinary Digital Publishing Institute, 2021)
    Prolyl oligopeptidase (PREP) is a serine protease that binds to alpha-synuclein (aSyn) and induces its aggregation. PREP inhibitors have been shown to have beneficial effects in Parkinson’s disease models by enhancing the clearance of aSyn aggregates and modulating striatal dopamine. Additionally, we have shown that PREP regulates phosphorylation and internalization of dopamine transporter (DAT) in mice. In this study, we clarified the mechanism behind this by using HEK-293 and PREP knock-out HEK-293 cells with DAT transfection. We tested the effects of PREP, PREP inhibition, and alpha-synuclein on PREP-related DAT regulation by using Western blot analysis and a dopamine uptake assay, and characterized the impact of PREP on protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) by using PKC assay and Western blot, respectively, as these kinases regulate DAT phosphorylation. Our results confirmed our previous findings that a lack of PREP can increase phosphorylation and internalization of DAT and decrease uptake of dopamine. PREP inhibition had a variable impact on phosphorylation of ERK dependent on the metabolic state of cells, but did not have an effect on phosphorylation or function of DAT. PREP modifications did not affect PKC activity either. Additionally, a lack of PREP elevated a DAT oligomerization that is associated with intracellular trafficking of DAT. Our results suggest that PREP-mediated phosphorylation, oligomerization, and internalization of DAT is not dependent on PKC or ERK.
  • Brylka, Asteria; Wolke, Dieter; Ludyga, Sebastian; Bilgin, Ayten; Spiegler, Juliane; Trower, Hayley; Gkiouleka, Anna; Gerber, Markus; Brand, Serge; Grob, Alexander; Weber, Peter; Heinonen, Kati; Kajantie, Eero; Räikkönen, Katri; Lemola, Sakari (Multidisciplinary Digital Publishing Institute, 2021)
    This study examined whether physical activity is associated with better mental health and well-being among very preterm (≤32 weeks) and term born (≥37 weeks) adolescents alike or whether the associations are stronger in either of the groups. Physical activity was measured with accelerometry in children born very preterm and at term in two cohorts, the Basel Study of Preterm Children (BSPC; 40 adolescents born ≤32 weeks of gestation and 59 term born controls aged 12.3 years) and the Millennium Cohort Study (MCS; 45 adolescents born ≤32 weeks of gestation and 3137 term born controls aged 14.2 years on average). In both cohorts, emotional and behavioral problems were mother-reported using the Strengths and Difficulties Questionnaire. Subjective well-being was self-reported using the Kidscreen-52 Questionnaire in the BSPC and single items in the MCS. Hierarchical regressions with ‘preterm status × physical activity’-interaction effects were subjected to individual participant data (IPD) meta-analysis. IPD meta-analysis showed that higher levels of physical activity were associated with lower levels of peer problems, and higher levels of psychological well-being, better self-perception/body image, and school related well-being. Overall, the effect-sizes were small and the associations did not differ significantly between very preterm and term born adolescents. Future research may examine the mechanisms behind effects of physical activity on mental health and wellbeing in adolescence as well as which type of physical activity might be most beneficial for term and preterm born children.

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