Environmental impacts — Lake ecosystems

The North Sea region contains a vast number of lakes; from shallow, highly eutrophic water bodies in agricultural areas to deep, oligotrophic systems in pristine high-latitude or high-altitude areas. These freshwaters and the biota they contain are highly vulnerable to climate change. As largely closed systems, lakes are ideally suited to studying climate-induced effects via changes in ice cover, hydrology and temperature, as well as via biological communities (phenology, species and size distribution, food-web dynamics, life-history traits, growth and respiration, nutrient dynamics and ecosystem metabolism). This chapter focuses on change in natural lakes and on parameters for which their climate-driven responses have major impacts on ecosystem properties such as productivity, community composition, metabolism and biodiversity. It also points to the importance of addressing different temporal scales and variability in driving and response variables along with threshold-driven responses to environmental forces. Exceedance of critical thresholds may result in abrupt changes in particular elements of an ecosystem. Modelling climate-driven physical responses like ice-cover duration, stratification periods and thermal profiles in lakes have shown major advances, and the chapter provide recent achievements in this field for northern lakes. Finally, there is a tentative summary of the level of certainty for key climatic impacts on freshwater ecosystems. Wherever possible, data and examples are drawn from the North Sea region

Advancing projections of phytoplankton responses to climate change through ensemble modelling

A global trend of increasing health hazards associated with proliferation of toxin-producing cyanobacteria makes the ability to project phytoplankton dynamics of paramount importance. Whilst ensemble (multi-)modelling approaches have been used for a number of years to improve the robustness of weather forecasts this approach has until now never been adopted for ecosystem modelling. We show that the average simulated phytoplankton biomass derived from three different aquatic ecosystem models is generally superior to any of the three individual models in describing observed phytoplankton biomass in a typical temperate lake ecosystem, and we simulate a series of climate change projections. While this is the first multi-model ensemble approach applied for some of the most complex aquatic ecosystem models available, we consider it sets a precedent for what will become commonplace methodology in the future, as it enables increased robustness of model projections, and scenario uncertainty estimation due to differences in model structures

Antisense locked nucleic acid gapmers to control Candida albicans filamentation

Whereas locked nucleic acid (LNA) has been extensively used to control gene expression, it has never been exploited to control Candida virulence genes. Thus, the main goal of this work was to compare the efficacy of five different LNA-based antisense oligonucleotides (ASO) with respect to the ability to control EFG1 gene expression, to modulate filamentation and to reduce C. albicans virulence. In vitro, all LNA-ASOs were able to significantly reduce C. albicans filamentation and to control EFG1 gene expression. Using the in vivo Galleria mellonella model, important differences among the five LNA-ASOs were revealed in terms of C. albicans virulence reduction. The inclusion of PS-linkage and palmitoyl-2-amino-LNA chemical modification in these five LNA gapmers proved to be the most promising combination, increasing the survival of G. mellonella by 40%. Our work confirms that LNA-ASOs are useful tools for research and therapeutic development in the candidiasis field.This study was supported by the Portuguese Foundation forScience and Technology (FCT) under the strategic funding of UIDB/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European RegionalDevelopment Fund under the scope of Norte2020-ProgramaOperacional Regional do Norte and Daniela Eira Araújo [SFRH/BD/121417/2016] PhD grant. The authors also acknowledge theproject funding by the“02/SAICT/2017–Projetos de Investiga-ção Científica e Desenvolvimento Tecnológico (IC&DT)–POCI-01-0145-FEDER-028893”. VILLUM Fonden is acknowledgedfor funding the Biomolecular Nano-scale Engineering Center(BioNEC), a Villum center of excellence, grant numberVKR18333. Funding received by iBB-Institute for Bioengineer-ing and Biosciences from FCT (UID/BIO/04565/2020) andPrograma Operacional Regional de Lisboa 2020 (Project No.007317) is also acknowledged. We acknowledge Dr. LucíliaGoreti Pinto, Life and Health Sciences Research Institute(ICVS), School of Medicine, University of Minho, forprocessing and sectioningG. mellonellatissue samples.The authors declare no conflict of interest.info:eu-repo/semantics/publishedVersio

Intervention effects on dietary intake among children by maternal education level: results of the Copenhagen School Child Intervention Study (CoSCIS)

Dietary intake among Danish children, in general, does not comply with the official recommendations. The objectives of the present study were to evaluate the 3-year effect of a multi-component school-based intervention on nutrient intake in children, and to examine whether an intervention effect depended on maternal education level. A total of 307 children (intervention group: n 184; comparison group: n 123) were included in the present study. All had information on dietary intake pre- and post-intervention (mean age 6·8 and 9·5 years for intervention and comparison groups, respectively) assessed by a 7-d food record. Analyses were conducted based on the daily intake of macronutrients (energy percentage (E%)), fatty acids (E%), added sugar (E%) and dietary fibre (g/d and g/MJ). Analyses were stratified by maternal education level into three categories. Changes in nutrient intake were observed in the intervention group, mainly among children of mothers with a short education ( < 10 years). Here, intake of dietary fibre increased (β = 2·1 g/d, 95 % CI 0·5, 3·6, P= 0·01). Intake of protein tended to increase (β = 0·6 E%, 95 % CI − 0·01, 1·2, P= 0·05), while intake of fat (β = − 1·7 E%, 95 % CI − 3·8, 0·3, P= 0·09) and SFA (β = − 0·9, 95 % CI − 2·0, 0·2, P= 0·10) tended to decrease. Also, a significant intervention effect was observed on the intake of SFA among children of mothers with a long education (β = − 0·8, 95 % CI − 1·5, − 0·03, P= 0·04). This multi-component school-based intervention resulted in changes in the dietary intake, particularly among children of mothers with a short education. As the dietary intake of this subgroup generally differs most from the recommendations, the results of the present study are particularly encouraging

KEYNOTE - D36: Personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma

Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall response after initial stable disease or partial response to pembrolizumab treatment, in patients with advanced melanoma. The novel end points ensure a decisive readout which may prove helpful before making major investments in phase III trials with limited phase I data. Clinical Trial Registration: NCT05309421 (ClinicalTrials.gov)

Characteristics of Canteens at Elementary Schools, Upper Secondary Schools and Workplaces that Comply with Food Service Guidelines and Have a Greater Focus on Food Waste

Policy actions to improve the nutritional environment include the provision of official food service guidelines. This study aimed to examine compliance with food service guidelines for hot meals as well as self-evaluated focus on food waste reduction across settings, i.e., elementary schools, upper secondary schools and workplaces, and different canteen characteristics. The same five criteria for hot meals were applied for all settings with regard to serving of fruit and vegetables, fish, wholegrain product and high fat meat and dairy products. A self-administered questionnaire survey was conducted as a cross-sectional study among 680 Danish canteens. Canteens having a high degree of organic food procurement were more likely to comply with the five criteria for hot meals combined (OR 2.00 (Cl 1.13,3.53)). Also, the use of organic food together with having a meal policy was associated with reported focus on food waste reduction (OR 1.91 (CI 1.12,3.25) and 1.84 (Cl 1.31,2.59), respectively). Compliance with individual criteria varied across settings with elementary schools being more likely to comply with criteria on, e.g., maximum serving of non-wholegrain products, whereas workplaces were more likely to comply with criteria on, e.g., minimum fruit and vegetable content and serving of fish. In addition, specific characteristics, e.g., serving system, were found to predict compliance with some of the criteria. These findings highlight the need to address differences in canteen characteristics when planning implementation support for both guideline and food waste reduction initiatives

The association between seafood intake and fecundability: Analysis from two prospective studies

Background: Seafood is an important source of omega\u20103 fatty acids, which have been associated with improved oocyte quality and embryo morphology in some studies. However, seafood is also a source of persistent organic pollutants and heavy metals, which may adversely affect fecundity. Previous studies of seafood intake and fecundity have generated inconsistent results. Methods: In two prospective cohort studies of 7836 female pregnancy planners from Denmark (Snart Foraeldre, n = 2709) and North America (PRESTO, n = 5127), we evaluated the association of dietary intake of total seafood and marine\u2010sourced long\u2010chain omega\u20103 fatty acids (eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid) with fecundability. Participants completed a baseline questionnaire on sociodemographics, behavioral factors, anthropometrics, and medical history, and a food frequency questionnaire. Pregnancy status was updated bimonthly for up to 12 months or until reported conception. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) using proportional probabilities regression models, adjusted for energy intake and other potential confounders. We restricted analyses to women with 646 menstrual cycles of attempt time at enrollment. Results: Intake of total seafood or marine\u2010sourced long\u2010chain omega\u20103 fatty acids was not appreciably associated with fecundability in either cohort ( 65200 vs. &lt;50 g/week total seafood: FR = 0.94, 95% CI: 0.79\u20131.10 in Snart Foraeldre; FR = 1.00, 95% CI: 0.90\u20131.13 in PRESTO; marine fatty acids: 6590th vs. &lt;25th percentile: FR = 1.00, 95% CI: 0.85\u20131.18 in Snart Foraeldre; FR = 0.97, 95% CI: 0.86\u20131.09 in PRESTO). In PRESTO, where we collected additional data on seafood preparation, we observed an inverse association between fecundability and fried shellfish ( 6510 g/week vs. none: FR = 0.77, 95% CI: 0.61\u20130.98), but not unfried shellfish ( 6520 g/week vs. none: FR = 0.98, 95% CI: 0.89\u20131.07); in Snart Foraeldre, there was no association with total shellfish intake. Conclusions: We found little association between seafood intake and fecundability overall, but greater intake of fried shellfish was associated with reduced fecundability among North American participants

Growth of unidirectional molecular rows of cysteine on Au(110)-(1x2) driven by adsorbate-induced surface rearrangements

Kühnle A, Molina LM, Linderoth TR, Hammer B, Besenbacher F. Growth of unidirectional molecular rows of cysteine on Au(110)-(1x2) driven by adsorbate-induced surface rearrangements. Physical Review Letters. 2004;93(8):086101.Using scanning tunneling microscopy we have studied the nucleation and growth of unidirectional molecular rows upon adsorption of the amino acid cysteine onto the anisotropic Au(110)-(1x2) surface under ultrahigh vacuum conditions. By modeling a large variety of possible molecular adsorption geometries using density-functional theory calculations, we find that in the optimum, lowest energy configuration, no significant intermolecular interactions exist along the growth direction. Instead the driving force for formation of the unidirectional molecular rows is an adsorbate-induced surface rearrangement, providing favorable adsorption sites for the molecules

<i>Toxoplasma gondii</i> peptide ligands open the gate of the HLA class I binding groove

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions