Simultaneous quantification of depolymerization and mineralization rates by a novel 15N tracing model

The depolymerization of soil organic matter, such as proteins and (oligo-)peptides, into monomers (e.g. amino acids) is currently considered to be the rate-limiting step for nitrogen (N) availability in terrestrial ecosystems. The mineralization of free amino acids (FAAs), liberated by the depolymerization of peptides, is an important fraction of the total mineralization of organic N. Hence, the accurate assessment of peptide depolymerization and FAA mineralization rates is important in order to gain a better process-based understanding of the soil N cycle. In this paper, we present an extended numerical 15N tracing model Ntrace, which incorporates the FAA pool and related N processes in order to provide a more robust and simultaneous quantification of depolymerization and gross mineralization rates of FAAs and soil organic N. We discuss analytical and numerical approaches for two forest soils, suggest improvements of the experimental work for future studies, and conclude that (i) when about half of all depolymerized peptide N is directly mineralized, FAA mineralization can be as important a rate-limiting step for total gross N mineralization as peptide depolymerization rate; (ii) gross FAA mineralization and FAA immobilization rates can be used to develop FAA use efficiency (NUEFAA), which can reveal microbial N or carbon (C) limitation

Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells.

Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal that 3T3-L1 preadipocytes exposed to tumor-secreted factors generate a stiffer Fn matrix relative to control cells. We then show that this early matrix stiffening correlates with increased molecular unfolding in Fn fibers, as determined by Förster Resonance Energy Transfer. Finally, we assessed the resulting changes in adhesion and proangiogenic factor (VEGF) secretion of newly seeded 3T3-L1s, and we examined altered integrin specificity as a potential mechanism of modified cell-matrix interactions through integrin blockers. Our data indicate that tumor-conditioned Fn decreases adhesion while enhancing VEGF secretion by preadipocytes, and that an integrin switch is responsible for such changes. Collectively, our findings suggest that simultaneous stiffening and unfolding of initially deposited tumor-conditioned Fn alters both adhesion and proangiogenic behavior of surrounding stromal cells, likely promoting vascularization and growth of the breast tumor. This work enhances our knowledge of cell - Fn matrix interactions that may be exploited for other biomaterials-based applications, including advanced tissue engineering approaches

Coming to terms with sexual violence in institutions of growing-up. Challenges for educational research and positioning. An introduction

Die Einführung bietet einen Überblick über die Beiträge des Themenheftes, "das sich als erziehungswissenschaftlich orientierte Annäherung an die Herausforderung systematischer Aufarbeitung sexueller Gewalt in Kindheit und Jugend versteht". (DIPF/Orig.

Djurvälfärd i ekologisk produktion – vad vet vi i dag?

Ekologisk produktion bygger på en ekocentrisk grundsyn där man värderar naturlighet högt. Detta ledertill ökat fokus på att skapa produktionssystem där djuren kan få utlopp för sina naturliga beteenden. Tillexempel ska djuren ha större ytor att röra sig på, tillgång till bete och utevistelse och ha tillgång till grovfoder.Men det innebär vissa utmaningar. Till exempel leder utevistelse till att djuren i högre grad utsättsför parasiter och vissa moderna raser kan få benproblem när de rör sig mycket i ekologiska system. Dessaoch andra utmaningar behöver den ekologiska branschen adressera, och forskningen fortsätta att belysa,för att ytterligare förbättra djurhälsa och djurvälfärd i den ekologiska djurproduktionen.Den här rapporten sammanfattar den senaste forskningen kring djurvälfärd inom ekologisk djurproduktion.Den behandlar ekologisk mjölk- och nötproduktion, ekologisk får- och lammproduktion, ekologiskgrisproduktion samt ekologisk ägg- och slaktkycklingsproduktion. Sammanfattningsvis diskuterar denvilka målkonflikter som kan uppstå inom ekologisk djurproduktion. Ambitionen är att ge främst forskareoch rådgivare en uppdaterad inblick i hur forskningsbehovet och kunskapsläget ser ut inom området menäven att öka insikten hos beslutsfattare om vilka målkonflikter som finns inom ekologisk djurproduktionoch varför de uppstår.SLU Ekologisk produktion och konsumtion, Epok, har finansierat arbetet med rapporten. Huvudförfattareär Torun Wallgren, SLU, Niels Andresen, HIR Skåne AB och Magdalena Åkerfeldt, SLU. Rapportenbygger på en kunskapssammanställning som påbörjades 2019 av Magdalena. I januari 2020 hölls ett seminariumpå KSLA med titel ”Hur mår djuren i ekologisk produktion?” som gav en del inspel till fortsattarbete med sammanställningen. En vetenskaplig artikel med titel ”Health and welfare in organic livestockproduction systems – a systematic mapping of current knowledge” publicerades senare 2020 i OrganicAgriculture med Magdalena som huvudförfattare. Denna rapport som Torun och Niels färdigställt är enpopulärvetenskaplig skrift baserad på denna artikel.Uppsala april 2022Johanna Spångberg, föreståndare Epo

Functional level, physical activity and wellbeing in nursing home residents in three Nordic countries

Background and aims: The main aim of this study was to describe physical and cognitive function and wellbeing among nursing home residents in three Nordic countries. A second aim was to compare groups of differing ages, levels of dependency in daily life activities (ADL), degree of fall-related self-efficacy, wellbeing and cognitive function. Methods: 322 residents from nursing homes in Sweden, Norway and Denmark were included. Physical and cognitive function, level of physical activity and wellbeing were assessed by means of reliable and valid instruments. Results: The mean age of participants was 85 years. Sixty percent could rise from a chair and 64% could walk independently. Men were younger and more physically active than women. Participants with a high level of dependency in ADL had lower physical and cognitive functions, were less physically active, and had lower fall-related self-efficacy than participants less dependent in ADL. Participants with low cognitive function had high fall-related self-efficacy. Conclusions: These data demonstrate that elderly residents in nursing homes in Sweden, Norway and Denmark are frail but heterogeneous. Significant differences in physical activity, physical function and dependency in ADL were seen in relation to age, fall-related self-efficacy, wellbeing and cognitive function

Collagen microarchitecture mechanically controls myofibroblast differentiation.

Altered microarchitecture of collagen type I is a hallmark of wound healing and cancer that is commonly attributed to myofibroblasts. However, it remains unknown which effect collagen microarchitecture has on myofibroblast differentiation. Here, we combined experimental and computational approaches to investigate the hypothesis that the microarchitecture of fibrillar collagen networks mechanically regulates myofibroblast differentiation of adipose stromal cells (ASCs) independent of bulk stiffness. Collagen gels with controlled fiber thickness and pore size were microfabricated by adjusting the gelation temperature while keeping their concentration constant. Rheological characterization and simulation data indicated that networks with thicker fibers and larger pores exhibited increased strain-stiffening relative to networks with thinner fibers and smaller pores. Accordingly, ASCs cultured in scaffolds with thicker fibers were more contractile, expressed myofibroblast markers, and deposited more extended fibronectin fibers. Consistent with elevated myofibroblast differentiation, ASCs in scaffolds with thicker fibers exhibited a more proangiogenic phenotype that promoted endothelial sprouting in a contractility-dependent manner. Our findings suggest that changes of collagen microarchitecture regulate myofibroblast differentiation and fibrosis independent of collagen quantity and bulk stiffness by locally modulating cellular mechanosignaling. These findings have implications for regenerative medicine and anticancer treatments

Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis.

Obesity and extracellular matrix (ECM) density are considered independent risk and prognostic factors for breast cancer. Whether they are functionally linked is uncertain. We investigated the hypothesis that obesity enhances local myofibroblast content in mammary adipose tissue and that these stromal changes increase malignant potential by enhancing interstitial ECM stiffness. Indeed, mammary fat of both diet- and genetically induced mouse models of obesity were enriched for myofibroblasts and stiffness-promoting ECM components. These differences were related to varied adipose stromal cell (ASC) characteristics because ASCs isolated from obese mice contained more myofibroblasts and deposited denser and stiffer ECMs relative to ASCs from lean control mice. Accordingly, decellularized matrices from obese ASCs stimulated mechanosignaling and thereby the malignant potential of breast cancer cells. Finally, the clinical relevance and translational potential of our findings were supported by analysis of patient specimens and the observation that caloric restriction in a mouse model reduces myofibroblast content in mammary fat. Collectively, these findings suggest that obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering mammary ECM mechanics with important potential implications for anticancer therapies

Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells

Fibronectin (Fn) forms a fibrillar network that controls cell behavior in both physiological and diseased conditions including cancer. Indeed, breast cancer-associated stromal cells not only increase the quantity of deposited Fn but also modify its conformation. However, (i) the interplay between mechanical and conformational properties of early tumor-associated Fn networks and (ii) its effect on tumor vascularization remain unclear. Here, we first used the Surface Forces Apparatus to reveal that 3T3-L1 preadipocytes exposed to tumor-secreted factors generate a stiffer Fn matrix relative to control cells. We then show that this early matrix stiffening correlates with increased molecular unfolding in Fn fibers, as determined by Förster Resonance Energy Transfer. Finally, we assessed the resulting changes in adhesion and proangiogenic factor (VEGF) secretion of newly seeded 3T3-L1s, and we examined altered integrin specificity as a potential mechanism of modified cell–matrix interactions through integrin blockers. Our data indicate that tumor-conditioned Fn decreases adhesion while enhancing VEGF secretion by preadipocytes, and that an integrin switch is responsible for such changes. Collectively, our findings suggest that simultaneous stiffening and unfolding of initially deposited tumor-conditioned Fn alters both adhesion and proangiogenic behavior of surrounding stromal cells, likely promoting vascularization and growth of the breast tumor. This work enhances our knowledge of cell – Fn matrix interactions that may be exploited for other biomaterials-based applications, including advanced tissue engineering approaches

Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis

Obesity and extracellular matrix (ECM) density are considered independent risk and prognostic factors for breast cancer. Whether they are functionally linked is uncertain. We investigated the hypothesis that obesity enhances local myofibroblast content in mammary adipose tissue and that these stromal changes increase malignant potential by enhancing interstitial ECM stiffness. Indeed, mammary fat of both diet- and genetically induced mouse models of obesity were enriched for myofibroblasts and stiffness-promoting ECM components. These differences were related to varied adipose stromal cell (ASC) characteristics because ASCs isolated from obese mice contained more myofibroblasts and deposited denser and stiffer ECMs relative to ASCs from lean control mice. Accordingly, decellularized matrices from obese ASCs stimulated mechanosignaling and thereby the malignant potential of breast cancer cells. Finally, the clinical relevance and translational potential of our findings were supported by analysis of patient specimens and the observation that caloric restriction in a mouse model reduces myofibroblast content in mammary fat. Collectively, these findings suggest that obesity-induced interstitial fibrosis promotes breast tumorigenesis by altering mammary ECM mechanics with important potential implications for anticancer therapies

The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway

The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation–arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field