No description available.

Mammary gland (MG) is a dynamic organ that is essential for the production and secretion of breast milk. During pregnancy the MG undergoes a critical phase of remodeling, which is accompanied by the differentiation of mammary epithelial cells (MECs). During lactation, the MG requires high level of energy for proper folding of proteins in the secretory pathway, which takes place in the endoplasmic reticulum (ER). Limited evidence has been reported on the impact of cannabis or its components, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), on the differentiation of MECs. However, both THC and CBD have been reported to induce ER stress in various cell types, resulting in impacting cellular function. Furthermore, consequences of cannabis use in the perinatal period on breast milk composition have not been reported. Using the HC11 cell line, we investigated whether THC and CBD evoke ER stress in MECs resulting in the impaired cellular function. We also reported on the effects of cannabis use during pregnancy and lactation on the levels of macronutrients and bioactive factors in the breast milk of cannabis users. Relative to control, 10μM THC and 10μM CBD reduced mRNA levels of milk proteins (CSN2 and WAP) and lipid synthesizing enzymes (FASN, FABP4, PLIN2 and LPL), as well as whey acidic protein and lipid levels. In addition, 10μM THC, 10μM CBD, and the combination of 10μM THC + 10μM CBD significantly induced the expression of ER stress genes in HC11 cells. Furthermore, in the milk of women who used cannabis during pregnancy and lactation, the levels of secretory immunoglobulin A (SIgA) were decreased, relative to non-users. Altogether, our findings indicate that cannabis use in the perinatal period may have implications on breast milk composition and infant health. / Thesis / Doctor of Philosophy (Medical Science) / Breast milk is crucial to the nutrition and immunity of the newborn. It is produced by the mammary gland (MG), which is composed of mammary epithelial cells (MEC) that play a key role in producing and secreting proteins and factors into the milk. During pregnancy, the MG undergoes remodeling which is accompanied by differentiation of the MECs (change from unspecialized to a specialized stage that allows the MECs to produce milk proteins and other factors). The disruption in MEC differentiation can result in altered milk production and composition. Cannabis is used by women during pregnancy and breastfeeding. In this study, we investigated the impact of cannabinoids on the MEC differentiation and examined the effect of cannabis use in the perinatal period on the breast milk composition in humans. We reported that cannabinoids reduced the differentiation of MECs and maternal cannabis use during breastfeeding reduced levels of an essential immune factor.

No description available.

Background: The p53-up-regulated modulator of apoptosis (PUMA) protein is a pro-apoptotic, BH3-only member of the BCL2 family of effector proteins responsible for promoting organized cell death. PUMA is required for resolution of pneumococcal pneumonia in mice, as mice deficient of PUMA exhibit greater numbers of S. pneumoniae CFU within tissues and higher mortality rates than observed in Puma+/+ mice. Methods: Puma+/+ and Puma-/- mice were intranasally challenged with TIGR4 pneumococcus and sacrificed 24 h post-infection. Differences in cytokine levels from blood and whole lung tissue were detected by MILLIPLEX MAP Mouse Cytokine/Chemokine Magnetic Bead Panel. Lung transcriptomes from Puma+/+ and Puma-/- mice were prepared from total lung RNA using NEBNext Poly(A) mRNA Magnetic Isolation Module and NEBNext Ultra RNA Library Prep Kit for Illumina. Libraries were read by Illumina NovaSeq and transcript reads were referenced to Mus musculus. Results: Puma-/- mice exhibited significant differences in G-CSF, GM-CSF, IFN-gamma, IL-1-alpha and -beta, -6, -9, -10, -12 (p40 and p70), -13, and -17, IP-10, KC, MCP-1, MIP- iv 1alpha and -beta, MIP-2, RANTES, and TNF-alpha compared to Puma+/+ mice. Puma-/- lungs exhibited higher levels of IL-12, IFN-gamma, and IP-10. Loss of PUMA also resulted in expression of the pro-angiogenic genes Adam19 and Neurexin2. Additionally, Puma+/+ and Puma-/- mice displayed similar levels of colonization, but Puma-/- mice were more susceptible to subsequent dissemination to the lungs and blood. Conclusion: Polymorphonuclear cells (PMNs) were previously demonstrated to be one of the innate cell types responsible for Puma-dependent resolution of pneumococcal pneumonia in mice. Observations reported here suggest that this resolution is propelled by suppressing the inflammatory response via the inhibition of IL-12/IFN-gamma/IP-10 pro-inflammatory axis. Pulmonary tissue transcriptomic analysis also suggests PUMA-dependent positive regulation of homeostatic control of pulmonary vasculature, smooth muscle innervation, and maintenance of the interstitium. Gene ontological analysis further demonstrated Puma's modulatory role in Type I and II IFN signaling. For the first time, we report Puma's regulatory effects on pro-inflammatory cytokine signaling and gene expression during pneumococcal pneumonia.

No description available.

This study aims to contribute to the research field in the cross-border region of Oresund, between Helsingborg and Helsingor. The study aims to research politicians’ views on the cooperation between the two cities and to answer how politicians in Helsingborg and Helsingor view cross-border cooperation in the region based on driving forces, visions, and obstacles. The purpose is also to see if there are any differences between the politicians' views, in each city, on the cooperation and if the cross-border cooperation is being driven by instrumental ideas or value-based ideas.The study does this by qualitative interviews with politicians on each side of the border in the two cities. The interviews and the analysis of the material are based on the three carrying concepts: driving forces, visions, and obstacles. The analysis is being done with the help of the theory based on instrumental driving forces and value-based ideas.From the analysis, the conclusion is that the driving forces behind this cooperation is connected to the geographical proximity between the countries. The vision is based on the goal of becoming a strong seamless-region and that there are obstacles such as taxes. The study concludes that the cooperation is mostly driven by instrumental ideas but that some of these driving forces have their origin in some type of value-based idea. The conclusion is also that the politicians in the two cities view the cooperation in a mostly similar way.

No description available.

No description available.

No description available.

No description available.