CSR i små och medelstora företag - Spelar storleken roll?

Fem Nyckelord: CSR, SME, U-formad teori, resurstillgång, hållbarhet Syfte: Syftet med uppsatsen är att studera hur små och medelstora bolag definierar CSR och varför de engagerar sig. Metod: Studien bygger på en kvalitativ forskningsstrategi med semi-strukturerade intervjuer. Ambitionen är att ha en deduktiv forskningsansats, dock med en del induktiva inslag. Teoretiska perspektiv: Studiens teoretiska referensram tar stöd i forskningsartiklar och kurslitteratur. Empiri: Studiens empiri baseras på sex intervjuer. Två av intervjuerna ägde rum på plats hos respektive företag, och övriga fyra per telefon. Resultat: I kort visar resultatet att de små företagen i studien uppvisar ett mindre aktivt hållbarhetsarbete i relation till de medelstora företagen. Vi konstaterar att Borglund et als teori stämmer bättre än Udayasankars för samtliga företag.Key words: CSR, SME, U-shaped theory, resource access, sustainability. Purpose: The purpose of this essay is to examine whether there are any differences between small and medium-sized enterprises regarding their sustainability work. Methodology: The study is based on a qualitative academic strategy with semi-structured interviews. Our ambition is to have an deductive academic approach that have inductive approach as well to a certain extent. Theoretical perspectives: The theoretical perspectives of the study take support from academic journals and course literature. Empirical foundation: The empirical foundation is based on six interviews. Two of them were performed at the companies and four of them on telephone. Conclusion: The study shows that small entities exhibit a less active sustainability work, compared to medium-sized entities. Further, we could establish that Borglund et als theory was more applicable than Udayasankars in the context of the companies within the study

Novel Zn²⁺ Modulated GPR39 Receptor Agonists Do Not Drive Acute Insulin Secretion in Rodents

<div><p>Type 2 diabetes (T2D) occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion <i>in vivo</i>. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn²⁺ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO) mice and Zucker fatty rats. It is concluded that Zn²⁺ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.</p></div

Design of Selective sPLA₂‑X Inhibitor (−)-2-{2-[Carbamoyl-6-(trifluoromethoxy)‑1<i>H</i>‑indol-1-yl]pyridine-2-yl}propanoic Acid

A lead generation campaign identified indole-based sPLA₂-X inhibitors with a promising selectivity profile against other sPLA₂ isoforms. Further optimization of sPLA₂ selectivity and metabolic stability resulted in the design of (−)-<b>17</b>, a novel, potent, and selective sPLA₂-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (−)-<b>17</b> was tested in an ApoE^–/– murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA₂-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (−)-<b>17</b> did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis

Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing

Abstract Genome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing

IPGTT in C57BL/6J mice; AZ7914 (<i>A</i>), AZ4237 (<i>B</i>), AZ1395 (<i>C</i>).

<p>Compounds (black triangles: 30 mg/kg, black circles: 100 mg/kg, grey circles: exendin-4, 1 μg/kg) or vehicle (white circles) were IP administered to fasted C57BL/6J mice at -30 min. Glucose solution (1.5 g/kg) was given IP at 0 min. Values are mean ± SEM (n = 7). ^#<i>P</i><0.05, ^##<i>P</i><0.01, ^###<i>P</i><0.001 <i>versus</i> vehicle (repeated measures ANOVA followed by student’s t-test).*<i>P</i><0.05, **<i>P</i><0.01, ***<i>P</i><0.001 <i>versus</i> vehicle (repeated measures ANOVA followed by Dunnett).</p

Plasma concentration–time profile of test compounds in the IPGTT using C57BL/6J mice; AZ7914 (<i>A</i>), AZ4237 (<i>B</i>), AZ1395 (<i>C</i>).

<p>Compounds were IP administered to fasted C57BL/6J mice at -30 min as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145849#pone.0145849.g007" target="_blank">Fig 7</a> legend. Data represent the value of pooled samples from 7 animals.</p

Insulin secretion assays in mouse islets.

<p>Effect on insulin secretion by each compound. Islets were treated with 1 and 10 μM of AZ7914 (<i>A</i>), AZ4237 (<i>B</i>), AZ1395 (<i>C</i>). The assays were performed in the absence or presence of 5 μM of Zn²⁺. Values were calculated as the ratio of insulin concentration compared to the basal control and expressed as the average of three separate measurements ± SEM.</p

Binding parameters for Zn²⁺-interaction with AZ1395, AZ4237 and AZ7914 determined by ITC at 30°C.

<p>Binding parameters for Zn²⁺-interaction with AZ1395, AZ4237 and AZ7914 determined by ITC at 30°C.</p

<i>In vivo</i> exposures <i>versus in vitro</i> potencies for AZ7914 (<i>A</i>), AZ4237 (<i>B</i>), AZ1395 (<i>C</i>).

<p>C_<i>u</i>,_<i>av</i> (μM) / EC₅₀ (μM) and C_<i>u</i>,_<i>av</i> (μM) / <i>K</i>_D (μM) calculated for different compound doses (30 or 100 mg/kg) IP administered to normal C57BL/6J mice. EC₅₀ and <i>K</i>_D values were from <i>in vitro</i> assays (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145849#pone.0145849.t001" target="_blank">Table 1</a>) performed in the absence (w/o) or presence of 5 μM Zn²⁺ (+) and adjusted for protein binding. a) Compound weakly active in <i>in vitro</i> assay: Potency >33 μM, E_max ≥ 8%. b) Compound inactive in <i>in vitro</i> assay: Potency >33 μM, E_max < 2%. For bars labeled with a) and b), EC₅₀ = 33 μM has been used for calculations, resulting in overestimation of C_<i>u</i>,_<i>av</i> / EC₅₀ ratios. This is indicated with open bars. Closed bars indicate that EC₅₀ values have been determined to a defined value. ND, not determined.</p

Plasma concentration–time profile of test compounds in the IPGTT using DIO mice; AZ7914 (<i>A</i>), AZ4237 (<i>B</i>), AZ1395 (<i>C</i>).

<p>Compounds were IP administered to fasted DIO mice at -30 min as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0145849#pone.0145849.g008" target="_blank">Fig 8</a> legend. Data represent the value of pooled samples from 7 animals.</p