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Defining neuroblastoma : From origin to precision medicine

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations

Loop Motion in Triosephosphate Isomerase Is Not a Simple Open and Shut Case

Conformational changes are crucial for the catalytic action of many enzymes. A prototypical and well-studied example is loop opening and closure in triosephosphate isomerase (TIM), which is thought to determine the rate of catalytic turnover in many circumstances. Specifically, TIM loop 6 "grips" the phosphodianion of the substrate and, together with a change in loop 7, sets up the TIM active site

Uppsägning som hänför sig till arbetstagarens uppförande och bristande arbetsinsats - En utredning om vad som anses utgöra sakliga skäl vid uppsägning på grund av bristande arbetsprestation, samarbetssvårigheter och misskötsamhet

Enligt 7§ LAS behöver det föreligga sakliga skäl för att en uppsägning ska vara godtagbar. Sakliga skäl har i och med 2022 år reform ersatt saklig grund. Innan reformen var 7§ LAS en tvingande lagregel, men genom införandet av 2c § LAS blev 7 § LAS semidispositiv. Ändringen har lett till att kollektivavtal, med avvikande bestämmelser från 7§ LAS, numera kan slutas på huvudavtalsnivå. Den 22 juni 2

From pastures to plates: The thorny path to achieving deforestation-free cattle from Brazil to European consumers

The EU regulation on Deforestation-Free Products (EUDR) enacted in 2023 aims to reduce deforestation connected to commodities imported to the EU, including cattle products. In Brazil, the EUDR pressures the local cattle supply chain towards more sustainable production. However, the potential effects of the EUDR on reducing deforestation in this sector are unclear and require scrutiny. Drawing on t

Different situations, similar outcomes : Heritage grammars across the lifespan

The rise of scientific inquiry focusing on bilingualism over the past few decades has also borne witness to an increase in the study of individuals and communities who speak a native language that is not the sociolinguistically dominant language of the environment in which they grew up. While it is common practice to refer to these diverse groups and individuals as “heritage speakers”, it is uncle

Computer simulations of the catalytic mechanism of wild-type and mutant β-phosphoglucomutase

β-Phosphoglucomutase (β-PGM) has served as an important model system for understanding biological phosphoryl transfer. This enzyme catalyzes the isomerization of β-glucose-1-phosphate to β-glucose-6-phosphate in a two-step process proceeding via a bisphosphate intermediate. The conventionally accepted mechanism is that both steps are concerted processes involving acid-base catalysis from a nearby

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En reflektion over forfatterens mormors historie og det dengang begynde folkemord i Gaza.

Sexually divergent selection, allometric constraints, and the evolution of sexual dimorphism in cichlids from Lake Tanganyika

The evolution of sexual dimorphism is widely acknowledged as a manifestation of sex-specific genetic architecture. Although empirical studies suggested that sexual dimorphism evolves as a joint consequence of constraints arising from genetic architecture and sexually divergent selection, it remains unclear whether and how these established microevolutionary processes scale up to the macroevolution

Similar Active Sites and Mechanisms Do Not Lead to Cross-Promiscuity in Organophosphate Hydrolysis : Implications for Biotherapeutic Engineering

Organophosphate hydrolases are proficient catalysts of the breakdown of neurotoxic organophosphates and have great potential as both biotherapeutics for treating acute organophosphate toxicity and as bioremediation agents. However, proficient organophosphatases such as serum paraoxonase 1 (PON1) and the organophosphate-hydrolyzing lactonase SsoPox are unable to hydrolyze bulkyorganophosphates with

Extending the Nonbonded Cationic Dummy Model to Account for Ion-Induced Dipole Interactions

Modeling metalloproteins often requires classical molecular dynamics (MD) simulations in order to capture their relevant motions, which in turn necessitates reliable descriptions of the metal centers involved. One of the most successful approaches to date is provided by the "cationic dummy model", where the positive charge of the metal ion is transferred toward dummy particles that are bonded to t

Simulating the reactions of substituted pyridinio-N-phosphonates with pyridine as a model for biological phosphoryl transfer

Phosphoryl transfer reactions can proceed through several plausible mechanisms, and the potential for both solvent and substrate-assisted pathways (involving proton transfer to the phosphoryl oxygens) complicates both experimental and computational interpretations. To avoid this problem, we have used electronic structure calculations to probe the mechanisms of the reactions of pyridinio-N-phosphon

Economisation as boundary work: Integrating climate change into IMF surveillance

In 2021, the International Monetary Fund (IMF) moved to integrate climate risks into its Article IV surveillance of member states. While the IMF has not traditionally been at the forefront of climate change efforts, this decision involved defining climate change as a risk to macro-economic stability. I argue that the integration of climate change into IMF surveillance can be understood as a case o

Barriers to establishing teledermatoscopy in primary health care in Sweden

Introduction: Teledermatoscopy (TDS) has proven to be effective and reliable for diagnosis of skin malignancies. The factors that determine the success of implementation of TDS are largely unknown. Objectives: To investigate barriers to implementation of TDS in primary health care (PHC) at center and individual level. Methods: Following introduction of TDS, cross-sectional quantitative data and fr

Comparing Treatment Outcomes of Eligible Patients Consenting to or Declining Randomization in a Randomized Clinical Trial A Secondary Analysis of the FISH Trial on Humeral Shaft Fractures

Background: The Finnish Shaft of the Humerus (FISH) trial compared open reduction and internal plate fixation (ORIF) with functional bracing in adult patients with displaced, closed humeral shaft fractures. Here, we compare the results of the patients in the randomized clinical trial (RCT [the randomized cohort]) with those of the cohort of patients who were also eligible but declined randomizatio

Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis

AIMS: Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection aga

High leptin levels in blood are associated with chronic widespread pain in rheumatoid arthritis

Background: High body mass index (BMI) has been shown to have an association with chronic widespread pain (CWP), both in Rheumatoid arthritis (RA) and in other pain conditions such as fibromyalgia. Research on the adipose tissue and it’s adipokines, for example the well described leptin, is emerging. The objective of this study was to determine if there is an association between leptin levels in b