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Genomic editing of metformin efficacy-associated genetic variants in SLC47A1 does not alter SLC47A1 expression

Several pharmacogenetics studies have identified an association between a greater metformin-dependent reduction in HbA1c levels and the minor A allele at rs2289669 in intron 10 of SLC47A1, encoding multidrug and toxin extrusion 1 (MATE1), a presumed metformin transporter. It is currently unknown if the rs2289669 locus is a cis-eQTL, which would validate its role as predictor of metformin efficacy.

Headline indicators for global climate monitoring

The World Meteorological Organization has developed a set of headline indicators for global climate monitoring. These seven indicators are a subset of the existing set of essential climate variables (ECVs) established by the Global Climate Observing System and are intended to provide the most essential parameters representing the state of the climate system. These indicators include global mean su

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

Pathogens possess the ability to adapt and survive in some host species but not in others–an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanism

Truly United in Diversity: The European Union Thriving in Crisis? An Interview Study on Problem-Solving Behaviour in the European Union During the Ukraine Crisis

The European Union (EU) has faced numerous severe crises during the 21st century. Rather than standing united and finding joint solutions, the intergovernmental negotiations have often revolved around furthering member state preferences, and maximising individual outcomes. Surprisingly, when Russia invaded Ukraine, in the spring of 2022, the EU managed to field a relatively successful and united r

Salt-inducible kinases are required for glucose uptake and insulin signaling in human adipocytes

OBJECTIVE: Salt-inducible kinase 2 (SIK2) is abundantly expressed in adipocytes and downregulated in adipose tissue from individuals with obesity or insulin resistance. The main aims of this work were to investigate the involvement of SIKs in the regulation of glucose uptake in primary mature human adipocytes and to identify mechanisms underlying this regulation.METHODS: Primary mature adipocytes

Defining and implementing a sufficient level of accessibility : What’s stopping us?

Recent transport equity literature has proposed a sufficientarian approach to transport planning, according to which all individuals would be entitled to a minimum level of accessibility deemed adequate or sufficient. The implementation of this approach would require the adoption of an accessibility standard as a key performance indicator guiding transport investments, land use planning and servic

Format för Vatten

I takt med klimatförändringarna förväntas mer extrema nederbörd komma oftare och med en högre intensitet. De system som ska ta hand om allt regnvatten är inte dimensionerade för sådana skyfall, vilket kommer leda till att de svämmar över. Dessa förändrade förutsättningar gör att planeringen och byggandet för urbana miljöer blir viktigare än någonsin. Vattenhanteringsstrategier i landskapet och ruIn line with climate change, more extreme precipitation is expected to occur more often and with a higher intensity than before, historically. The systems that are supposed to take care of all the rainwater are not designed for such torrential rains, which will lead to flooding. These changed conditions make the planning and construction of urban environments more important than ever. There are m

Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes

Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabe

Ethical and Legal Challenges of Holographic Communication Technologies

The paper presents ethical and legal challenges of holographic communication technologies and suggests a framework to address them. Holographic communications enable the capturing of a user’s 3D depiction via special equipment, and its high-quality transmission to another user located elsewhere, introducing a distinctive data communication experience. Their wrongful use could compromise basic huma

Mechanism of TNFα-induced downregulation of salt-inducible kinase 2 in adipocytes

Salt-inducible kinase 2 (SIK2) is highly expressed in white adipocytes, but downregulated in individuals with obesity and insulin resistance. These conditions are often associated with a low-grade inflammation in adipose tissue. We and others have previously shown that SIK2 is downregulated by tumor necrosis factor α (TNFα), however, involvement of other pro-inflammatory cytokines, or the mechanis

Gut hormone-based pharmacology : novel formulations and future possibilities for metabolic disease therapy

Glucagon-like peptide-1 (GLP-1) receptor agonists are established pharmaceutical therapies for the treatment of type 2 diabetes and obesity. They mimic the action of GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also reduce body weight by inducing satiety through central actions. The GLP-1 receptor agonists used clinically are ba

The impact of certification on the reduction of information asymmetry, during and post-IPO

Purpose: The purpose of this study is to investigate the existence of information asymmetry displayed in the initial return, and post-IPO financing. Additionally, how sponsor certification influences IPOs and in the post-IPO financing as a means to reduce information asymmetry. Methodology: The study was conducted based on a quantitative research method, followed by a deductive approach, which in