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Hantaan virus glycoprotein Gc induces NEDD4-dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation
No full textHantaan virus (HTNV) infection causes severe hemorrhagic fever with renal syndrome (HFRS) in humans and the infectious process can be regulated by autophagy. The phosphatase and tensin homolog (PTEN) protein has antiviral effects and plays a critical role in the autophagy pathway. However, the relationship between PTEN and HTNV infection is not clear and whether PTEN-regulated autophagy involves in HTNV replication is unknown. Here, we identified that HTNV infection inhibits PTEN expression in vitro and in vivo. The HTNV glycoprotein Gc promotes PTEN ubiquitination and degradation through 26S-proteasome pathway via the E3 ubiquitin ligase NEDD4. In addition, knockdown of PTEN prevents autophagy and increases HTNV production, while overexpression of PTEN induces autophagosome formation which can wrap HTNV particles, thus leading to restrain the production of progeny viruses. Altogether, our findings reveal the role of PTEN in HTNV infection by autophagy, highlighting the potential importance of PTEN and autophagy in the treatment of HFRS diseases.Peer reviewe
A tale of two worlds : spatial arrangement of avian communities in a Neotropical city
No full textUrbanization is considered one of the most critical processes related to biodiversity loss worldwide. Birds are one of the most commonly studied groups in urban ecosystems due to their quick response to environmental changes. Despite the current knowledge related to urban bird communities, information associated with the specific factors shaping avian communities in cities is still scarce, especially in the Neotropics. In this study, we performed a citywide survey for birds in the city of Xalapa (Mexico), to compare the species composition of urban communities with those of two reference sites adjacent to the urban area. We hypothesized that the compositional similarity would either be defined by their spatial proximity to their respective reference site or that it would be shaped by resources intrinsic to the city. Considering the nature of our data, we performed a subgroup analysis using randomly selected groups for the urban and reference sites to compare similar samples. We used S & oslash;rensen (incidence-based) and Bray-Curtis (abundance-based) cluster analyses and found that the urban bird community composition is better explained by the vegetation cover than by the proximity to the reference sites. We confirmed this association with the results of the GLM, showing a statistically significant association with the vegetation cover. Our results are relevant in terms of urban design, considering that promoting the improvement of vegetation in cities could potentially help avian communities in these changing environments.Peer reviewe
Estimating the atmospheric aerosol number size distribution using deep learning
No full textThe submicron aerosol number size distribution significantly impacts human health, air quality, weather, and climate. However, its measurement requires sophisticated and expensive instrumentation that demands substantial maintenance efforts, leading to limited data availability. To tackle this challenge, we developed estimation models using advanced deep learning algorithms to estimate the aerosol number size distribution based on trace gas concentrations, meteorological parameters, and total aerosol number concentration. These models were trained and validated with 15 years of ambient data from three distinct environments, and data from a fourth station were exclusively used for testing. Our estimative models successfully replicated the trends in the test data, capturing the temporal variations of particles ranging from approximately 10-500 nm, and accurately deriving total number, surface area, and mass concentrations. The model's accuracy for particles below 75 nm is limited without the inclusion of total particle number concentration as training input, highlighting the importance of this parameter for capturing the dynamics of smaller particles. The reliance on total particle number concentration, a parameter not routinely measured at all in air quality monitoring sites, as a key input for accurate estimation of smaller particles presents a practical challenge for broader application of the models. Our models demonstrated a robust generalization capability, offering valuable data for health assessments, regional pollution studies, and climate modeling. The estimation models developed in this work are representative of ambient conditions in Finland, but the methodology in general can be applied in broader regions.Peer reviewe
Non-analogue Neotropical communities : Large herbivore ecometrics in northern South America
No full textThe modern Neotropics contain many of the most biodiverse areas in the world, encompassing a range of habitats including rainforests, dry forests, wetlands, savannahs and deserts, each with its own set of mammal communities. The
relationships between the traits of these modern mammals and their environment are consistent with those on other continents. However, the composition of the mammal assemblages in the South American fossil record is very distinct
from elsewhere because of its ‘punctuated isolation’ for most of the last 65 million years.
In general, the teeth of large herbivores can be used to reconstruct palaeoenvironments because of known functional relationships between molar shape/structure and the environment. These relationships are the foundation of the study of ecometrics. For example, in other continents, higher-crowned (hypsodont) molars are an adaptationto increase durability and are correlated with environmental aridity. In the fossil record of South America, several groups have hypsodont teeth
because of their evolutionary history, even when they lived in tropical wetlands or rainforests.
The Neotropical fossil mammal record has been historically understudied compared to the diverse, well-preserved record from higher latitudes due to a variety of biases, including the relatively low preservation potential of fossils in rainforests compared to many other environments. However, the Neotropics are particularly important to our understanding of environmental and faunal change in South America. This
region contains a range of habitat types and is close to the Isthmus of Panama, through which a series of migration events have driven dramatic changes in the South American mammal faunas. The plant fossil record has provided some evidence for environmental change, but in some cases plant fossils aren’t available so it is critical to be able to use mammals to reconstruct palaeoenvironments.
Interpreting the environmental signal of some dental traits, including tooth crown height, has specific challenges in South America. However, dental traits vary between sites that have known environmental differences. Therefore, there is scope for further use of these methods in the Neotropics with more tailored models relating them to the environment. An alternative is the application of more universal traits, particularly diet and body mass. These can be estimated using relatively simple methods, even for fragmentary fossil teeth.
New multivariate statistical approaches to mapping differences in body mass distributions in mammal communities through generalised linear latent variable models (GLLVMs) reveal that modern mammal communities (and those where Pleistocene megafauna are included in the models assuming they had avoided extinction) differ in their body mass distributions in a way that is predictable according to environmental conditions. These GLLVM approaches therefore offer an opportunity for palaeoenvironmental reconstruction using relatively little information. However, they seem to perform best for more diverse fossil assemblages, which should be accounted for given the biases in the Neotropical record.
Novel mesowear angle methods indicate the diet of herbivores and these mesowear angles can be used to predict the palaeoenvironment. For example, a greater proportion of grazers, reflected by higher mesowear angles, should indicate greater availability of grasses. Previously, mesowear angles have only been applied to
a limited number of groups that have teeth with multiple lophs, particularly proboscideans, but the methods are useful for other types of teeth. Combining
mesowear angles across herbivores with different tooth morphologies in a given location should give an accurate reflection of the plants there. These approaches are potentially applicable across continents and timescales.
Investigations in the Neotropical fossil record from the Late Oligocene to the Late Pleistocene highlight that both traditional dental functional traits (e.g. hypsodonty) and these new universal traits have utility for palaeoenvironmental reconstruction, given concordance with independent proxies. However, further research is needed to calibrate the trait-environment relationships in a more quantified way. Further discoveries continue to be made in the Neotropics, both through reassessment of museum collections and new fieldwork. As the mammal fossil record grows, so too will our understanding of the palaeoenvironments of the Neotropics, through application of these ecometric approaches.Nykyinen neotropiikki kattaa monia maailman biologisesti monimuotoisimpia alueita, joihin lukeutuu erilaisia elinympäristöjä, kuten sademetsiä, kuivia metsiä, kosteikkoja, savanneja ja aavikoita, joista jokaisella on omat nisäkäsyhteisönsä. Nykyään neotropiikissa elävien nisäkkäiden ominaisuuksien ja elinympäristöjen vastaavuudet ovat yhdenmukaisia muiden maanosien kanssa. Etelä-Amerikan fossiilisten nisäkäsyhteisöjen koostumus on kuitenkin hyvin erilainen kuin muualla, koska manner oli eristyksissä suurimman osan viimeisistä 65 vuosimiljoonasta.
Yleisesti ottaen suurten kasvinsyöjien hampaita voidaan käyttää paleoympäristöjen rekonstruoimiseen, koska poskihampaiden muoto ja rakenne ovat sopeutumia kasviravinnon syömiseen erilaisissa kasvillisuus- ja ympäristöoloissa ja heijastavat näin muinaisten ympäristöjen ominaisuuksia. Tämä yhteys on ekometrisen tutkimuksen perusta. Esimerkiksi muilla mantereilla korkeakruunuiset hampaat yhdistetään kuivempiin ympäristöihin, koska korkeakru unuiset (hypsodontit) hampaat ovat sopeuma kuluttavampaan ravintoon. Etelä-Amerikan fossiiliaineistossa useilla ryhmillä on evoluution myötä kehittynyt hypsodontit hampaat, vaikka ne elivät
trooppisissa kosteikoissa tai sademetsissä.
Neotrooppisia fossiilisia nisäkkäitä on aiemmin tutkittu suhteellisen vähän verrattuna monimuotoiseen, hyvin säilyneeseen fossiiliaineistoon korkeammilla leveysasteilla. Tämä johtunee erilaisista aineiston vinoumista, kuten fossiilien heikommasta säilymispotentiaalista sademetsissä verrattuna moniin muihin ympäristöihin.
Neotrooppiikin fossiiliaineisto on kuitenkin erityisen tärkeä Etelä-Amerikan ympäristöjen ja eläimistön muutosten ymmärtämisen kannalta. Aluella on erilaisia elinympäristötyyppejä ja se sijaitsee Etelä-Amerikan pohjoisosassa lähellä Panaman kannasta, jonka kautta useat muuttotapahtumat ovat aikaansaaneet dramaattisia
muutoksia Etelä-Amerikan nisäkäslajistossa. Kasvifossiilit antavat tietoa ympäristön muutoksista, mutta kaikkialla kasvifossiileja ei ole säilynyt, jolloin nisäkäsfossiilit ovat ratkaisevassa asemassa palaeoympäristöjen rekonstruoimiseen.
Vaikka joillakin hampaiden ominaisuuksilla, kuten hampaiden kruunun korkeudella, on tulkinnallisia haasteita Etelä-Amerikassa, hampaiden ominaisuuksissa on kuitenkin muuntelua sellaisten paikkojen välillä, joiden paleoympäristöt tunnetaan. Näin ollen ekometrisiä menetelmiä voidaan käyttää neotrooppisiin ympäristöihin räätälöityjen mallien avulla. Vaihtoehtoisesti voidaan soveltaa yleisemmin kaikille nisäkkäille yhtenäisiä ominaisuuksia, kuten ruokavaliota ja ruumiinpainoa. Molem-
pia voidaan arvioida jopa osittain säilyneistä fossiilisista hampaista suhteellisen yksinkertai sin menetelmin.
Uudet tilastolliset monimuuttujamenetelmät erojen kartoittamiseen nisäkäsyhteisöjen ruumiinpainojakaumissa yleisten lineaaristen latenttimuuttujamallien (GLLVM) avulla paljastavat, että nykyiset nisäkäsyhteisöt (ja ne yhteisöt, joissa pleistoseenin megafauna on sisällytetty malleihin olettaen, että ne olisivat välttäneet sukupuu-
ton) eroavat ruumiinpainojakaumiltaan tavalla, joka on ennustettavissa ympäristöolosuhteiden perusteella. Nämä GLLVM-lähestymistavat siten mahdollistavat paleoympäristön ominaisuuksien, kuten lämpötilan, sadannan, kasvillisuuden tuottavuuden ja puuston peittävyyden, arvioimisen suhteellisen vähäisen tiedon pohjalta. Mallit soveltunevat kuitenkin parhaiten
monipuolisempiin fossiiliaineistoihin, mikä on muistettava, kun otetaan huomioon neotrooppisen aineiston vinoumat.
Uudenlaiset kuluneista hampaista mitattavien mesowear-kulmien mittausmenetelmät ilmentävät kasvinsyöjien ruokavaliota, ja mitattuja mesowear-kulmia voidaan käyttää paleoympäristöjen rekonstruoimiseen. Esimerkiksi heinänsyöjien suurempi osuus eläinyhteisöstä viittaisi parempaan heinien saatavuuteen elinympäristössä. Aikaisemmin mesowearkulmia on sovellettu vain joillekin nisäkäsryhmille, kuten norsueläimille, joiden hampaiden purupinnat koostuvat lukuisista kiilleharjanteista, mutta menetelmä osoittautui hyödylliseksi myös muun tyyppisille hampaille. Mesowear-kulmien yhdistäminen tietoihin fossiililajistosta ja sen hampaiden toiminnallisista ominaisuuksista antaa suhteellisen hyvän kuvan muinaisesta kasvillisuudesta. Samanlaista lähestymistapaa voidaan mahdollisesti soveltaa eri mantereilla ja laajoilla aikaskaaloilla.
Neotrooppisten fossiilien tarkastelu aikajänteellä myöhäisestä oligoseenista myöhäiseen pleistoseeniin korostaa, että paleoympäristöjen rekonstruktiossa voidaan hyödyntää sekä perinteisiä hampaiden toiminnallisia ominaisuuksia (esim. hypsodontia) että uusia yleisluontoisia (pidemmälle nisäkkäiden evoluutiohistoriassa ulottuvia) ominaisuuksia (kuten mesowear-kulmia ja ruumiinkokoa), jos ne ovat yhdenmukaisia proksiaineiston kanssa. Lisätutkimusta kuitenkin tarvitaan näiden ominaisuuksien ja ympäristön välisten suhteiden kvantitatiiviseen määrittämiseen. Neotropiikin alueella tehdään edelleen uusia löytöjä sekä museokokoelmien.
delleenarvioinnin että uusien kenttätöiden seurauksena. Nisäkäsfossiilien määrän lisääntyessä, myös ymmärryksemme neotrooppisista paleoympäristöistä kasvaa näiden ekometristen lähestymistapojen avulla.ei saavutettavaVäitöskirjan yhteenveto-osa on saavutettav
Requirements and special considerations for drug trials with children across six jurisdictions : 2. Ethics review in the regulatory approval process
No full textBackground Conducting clinical drug trials (CTs) with children presents several challenges. A major challenge is the need to enroll participants at multiple sites across different jurisdictions. Recruiting the required number of children within a reasonable timeframe requires the study to be reviewed by Research Ethics Boards (REB) or Institutional Review Boards (IRB) at multiple sites across various jurisdictions. This work, undertaken by the Working Group (WG) on International Collaborations at the European Network of Pediatric Research at the European Medicines Agency (Enpr-EMA) aims to describe the research ethics review requirements including any pediatric specific requirements, as well as current or upcoming changes across six jurisdictions - the European Union (EU), United Kingdom (UK), United States of America (USA), Canada, Japan, and Australia.Methods An open questionnaire developed by the WG and directed at both the Competent Authorities (CA) and the national pediatric clinical trial networks arranged by jurisdictions.Results A synopsis of the current regulatory requirements covers centralized versus independent review, comparisons between investigator initiated and industry sponsored clinical trials, timelines, review board members requirements and the consenting/assent process for clinical trial (CT) applications, application submission processes and application requirements for each of the six jurisdictions. It also describes changes currently or soon to be implemented in some jurisdictions.Conclusion This environmental scan highlights the differences in ethics review for CTs in pediatric medicine development across six jurisdictions. While there is a growing trend for centralized ethics review, it is not universally permitted due to institutional, state/provincial, or national policies. Even where central review is allowed, local review may still be required for vulnerable populations like children. Harmonized and centralized ethics reviews offer advantages such as expert pediatric reviewers and efficient and consistent evaluations.Peer reviewe
Developing a medication-safety self-assessment tool for rural primary care units - a case from Finnish Lapland
No full textAbstract Background In rural areas, primary care faces several challenges, and medication therapy is one of the most complex processes in primary care. With a specific, proactive, medication-safety self-assessment tool designed for rural primary care units, healthcare professionals could identify development needs in their medication processes. Methods The Delphi consensus method with two Delphi rounds was used to create a medication-safety self-assessment tool for rural primary care units in Finnish Lapland. A preliminary tool was designed based on three national and international risk management tools. Statements of the preliminary tool were evaluated with a two-round Delphi panel by 12 experts in primary care and patient safety. Evaluated aspects were suitability for primary care settings, medication safety relevance, and the necessity of the statements to be included in the developed rural, primary care, medication-safety self-assessment tool. Results In the first Delphi round, a consensus of ≥ 85% on being “sufficiently important and essential” was reached on 39% of the statements (n = 118/304), of which 86% (n = 101/118) were included, and 14% (n = 17/118) were excluded from the final primary care medication- safety self-assessment tool. In the second round, 84% of the statements (n = 141/167) reached a consensus, of which 70% (n = 98/141) were excluded and 30% (n = 43/141) included in the final tool. The included 144 statements were divided into 12 thematic sub-groups: (1) Patient information, (2) Drug information, (3) Communication of drug orders and other drug information; (4) Drug labeling, packaging and nomenclature; (5) Drug storage and distribution, (6) Medication device acquisition and use, (7) Environmental factors, workflow and staffing patterns; (8) Staff competency and education, (9) Patient education, (10) Preventive risk management, 11. Learning from medication safety incidents, and 12. Electronic health record. Conclusions The developed medication-safety self-assessment tool is targeted for proactive medication risk management in rural primary care settings. While experts reached a consensus for the Primary care Medication Safety Self Assessment tool contents, adopting the tool to suit the rural primary care environments in different countries should be further investigated
Cosmological Simulations with Resolved Supermassive Black Hole Binary Dynamics and Accretion
No full textThis thesis investigates the properties of galaxies and supermassive black hole (SMBH) binaries in cosmological zoom-in simulations. The focus of the study is twofold: first, the agreement between simulated galaxies and observed scaling relations is assessed, followed by an analysis of the impact of different mass accretion models on SMBH binaries. To achieve these objectives, numerical simulations were run using the GADGET-3 and KETJU codes on the Mahti supercomputer hosted at the Finnish IT Centre for Science (CSC).
Hydrodynamical cosmological simulations provide essential constraints and improvements for galaxy formation and evolution models by enabling direct comparisons with observations. For reliable results, simulated galaxies must resemble those in the real Universe. Here, it is found that the galaxies produced by KETJU generally follow observed relations, such as the specific stellar angular momentum -- stellar mass relation and the evolution of the size-mass relation. However, the supernova feedback in the simulation is found to be too inefficient, particularly in low-mass galaxies, resulting in excessive star formation and, consequently, over-massive galaxies and SMBHs.
This work also presents the first implementation of a new KETJU binary mass accretion model in a cosmological simulation. A new simulation run of the original simulation volume was performed to evaluate the impact of a more physically motivated model on the SMBH binary properties. SMBHs coalesce as a result of a three-phased binary merger process, during which they interact with their surroundings via gas accretion and feedback. The results demonstrate that the new binary accretion model is necessary in order to resolve the SMBH binary evolution more accurately.
In comparison with the old single accretion model, the binary accretion model produces more physically motivated mass ratios of the SMBHs by applying preferential accretion on to the secondary black hole. Additionally, it eliminates discontinuities in the mass accretion rates and black hole properties during the binary phase and prevents excessive star formation by maintaining gas densities below the star formation threshold. Contrary to previous expectations, the differences produced by the two models are also seen in gas-poor binaries. We find that fixing the binary eccentricity significantly reduces the discrepancies between different models. Overall, this study highlights the need for more complex SMBH accretion and feedback models to fully capture the co-evolution of galaxies and SMBH binaries in a cosmological context
Childhood Lifestyle Behaviors and Mental Health Symptoms in Adolescence
No full textImportance Mental health problems often arise during adolescence and early adulthood, affecting up to 25% to 30% of young people. Enhancing the ability to identify children and adolescents at increased risk of mental health problems and uncover factors that promote mental health from childhood to adolescence is important. Objective To investigate if cumulative lifestyle behaviors from childhood to adolescence are associated with perceived stress and depressive symptoms in adolescence. Design, Setting, and Participants Prospective cohort study in Finland using baseline data collected between October 2007 and November 2009 and 8-year follow-up data collected between December 2015 and December 2017 as part of the Physical Activity and Nutrition in Children (PANIC) study of children aged 6 to 9 years. Data were analyzed from January to February 2024. Exposures Cumulative physical activity (PA), sedentary behavior (SB), sleep, and diet quality from childhood to adolescence. PA and screen time (ST) assessed by a questionnaire; PA at different intensities, SB, and sleep duration assessed by a combined movement and heart rate sensor; diet quality assessed by 4-day food records and the Baltic Sea Diet Score computed at baseline, 2-year follow-up, and 8-year follow-up examinations. Main Outcomes and Measures Perceived stress assessed by the Finnish version of the Cohen Perceived Stress Scale, and depressive symptoms by the Beck Depression Inventory at 8-year follow-up examinations. Linear regression analyses were used to evaluate associations between cumulative lifestyle behaviors over 8 years with the outcomes. Results Altogether, 187 adolescents (97 boys [51.9%]; mean age, 15.8 [0.4] years) had valid data on self-reported lifestyle behaviors, and 170 adolescents had valid data on device-assessed lifestyle behaviors. Perceived stress scores ranged from 2 to 33 and depressive symptoms scores from 0 to 31. Self-reported total PA and supervised exercise were inversely associated with perceived stress (standardized regression coefficient [β] = −0.15; 95% CI, −0.31 to −0.01 and β = −0.15; 95% CI, −0.29 to −0.01, respectively) and depressive symptoms (β = −0.17; 95% CI, −0.31 to −0.02 and β = −0.14; 95% CI, −0.29 to −0.0, respectively). Total ST (β = 0.27; 95% CI, 0.13 to 0.41), computer use (β = 0.16; 95% CI, 0.01 to 0.30), and mobile device use (β = 0.28; 95% CI, 0.16 to 0.41) were positively associated with perceived stress. Total ST (β = 0.30; 95% CI, 0.15 to 0.44) and mobile device use (β = 0.33; 95% CI, 0.19 to 0.46) were positively associated with depressive symptoms. Conclusions and Relevance This cohort study of Finnish children and adolescents found that higher PA and lower ST from childhood were associated with perceived stress and depressive symptoms in adolescence. These findings emphasize reducing screen time and increasing PA to promote mental health in youth.Peer reviewe
Leadership Education in Finland : A Critical Examination of Well-Being Management Approaches
No full textThis study examines how work well-being is addressed in Finnish leadership education programs. The data consist of 91 publicly available course descriptions from Finnish leadership education programs in 2023, including those for master’s degrees from universities of applied sciences, traditional university-level leadership programs, and specialist vocational qualifications in leadership and business management. The study uses content analysis to examine the role of work well-being in leadership training. The results indicate that work well-being is often linked to organizational performance and treated as a tool for achieving economic goals, with less emphasis on the inherent value of employee well-being. This instrumental approach is prevalent across the different types of leadership training programs, including those found in the universities of applied sciences, traditional universities, and programs for specialist vocational qualifications in leadership and business management. The study also finds that leadership training programs often emphasize self-leadership and personal development, which can perpetuate a culture of individual responsibility for well-being and may lead to superficial leadership practices. The study concludes that Finnish leadership educators should prioritize holistic approaches to work well-being in leadership training, emphasizing its intrinsic value alongside its role in organizational performance, while researchers could explore methods to integrate and evaluate these balanced perspectives in diverse educational contexts.Peer reviewe
