Introduction to the thematical section: Articles from SSK 2015

The Student Conference of Language Sciences (Den Sprogvidenskabelige Studenterkonference, SSK) is a conference for and by students. Since its inception in 2013, the goal has been to create a space for students to cultivate their common interest in linguistics outside formal university education

Temaintroduktion: Artikler fra SSK 2015

Den Sprogvidenskabelige Studenterkonference (SSK) er en konference for og af studerende. Siden konferencens spæde start i 2013 har det været vores mål at skabe et rum, hvor studerende kan dyrke deres fælles interesse for sprogvidenskab uden for semesterplanens og pensumlistens faste rammer. Her kan vi stille hinanden de spørgsmål, som der ikke altid er plads til i undervisningen, og her kan vi ikke mindst inspirere og blive inspireret af hinanden

Importance of Conserved N-domain Residues Thr 441 , Glu 442 , Lys 515 , Arg 560 , and Leu 562 of Sarcoplasmic Reticulum Ca 2+ -ATPase for MgATP Binding and Subsequent Catalytic Steps: PLASTICITY OF THE NUCLEOTIDE-BINDING SITE

Nine single mutations were introduced to amino acid residues Thr441, Glu442, Lys515, Arg560, Cys561, and Leu562 located in the nucleotide-binding domain of sarcoplasmic reticulum Ca2+-ATPase, and the functional consequences were studied in a direct nucleotide binding assay, as well as by steady-state and transient kinetic measurements of the overall and partial reactions of the transport cycle. Some partial reaction steps were also examined in mutants with alterations to Phe487, Arg489, and Lys492. The results implicate all these residues, except Cys561, in high affinity nucleotide binding at the substrate site. Mutations Thr441 --> Ala, Glu442 --> Ala, and Leu562 --> Phe were more detrimental to MgATP binding than to ATP binding, thus pointing to a role for these residues in the binding of Mg2+ or to a difference between the interactions with MgATP and ATP. Subsequent catalytic steps were also selectively affected by the mutations, showing the involvement of the nucleotide-binding domain in these reactions. Mutation of Arg560 inhibited phosphoryl transfer but enhanced the E1PCa2 --> E2P conformational transition, whereas mutations Thr441 --> Ala, Glu442 --> Ala, Lys492 --> Leu, and Lys515 --> Ala inhibited the E1PCa2 --> E2P transition. Hydrolysis of the E2P phosphoenzyme intermediate was enhanced in Glu442 --> Ala, Lys492 --> Leu, Lys515 --> Ala, and Arg560 --> Glu. None of the mutations affected the low affinity activation by nucleotide of the phosphoenzyme-processing steps, indicating that modulatory nucleotide interacts differently from substrate nucleotide. Mutation Glu442 --> Ala greatly enhanced reaction of Lys515 with fluorescein isothiocyanate, indicating that the two residues form a salt link in the native protein

Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice

<p>Abstract</p> <p>Background</p> <p>Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are expressed by microglia and infiltrating macrophages following ischemic stroke. Whereas IL-1β is primarily neurotoxic in ischemic stroke, TNF-α may have neurotoxic and/or neuroprotective effects. We investigated whether IL-1β and TNF-α are synthesized by overlapping or segregated populations of cells after ischemic stroke in mice.</p> <p>Methods</p> <p>We used flow cytometry and immunohistochemistry to examine cellular co-expression of IL-1β and TNF-α at 6, 12 and 24 hours after permanent middle cerebral artery occlusion in mice, validating the results by the use of bone marrow chimeric mice.</p> <p>Results</p> <p>We found that IL-1β and TNF-α were expressed in largely segregated populations of CD11b⁺CD45^dimmicroglia and CD11b⁺CD45^highmacrophages, with cells expressing both cytokines only rarely. The number of Gr1⁺granulocytes producing IL-1β or TNF-α was very low, and we observed no IL-1β- or TNF-α-expressing T cells or astrocytes.</p> <p>Conclusion</p> <p>Taken together, the results show that IL-1β and TNF-α are produced by largely segregated populations of microglia and macrophages after ischemic stroke in mice. Our findings provide evidence of a functional diversity among different subsets of microglia and macrophages that is potentially relevant to future design of anti-inflammatory therapies in stroke.</p

Spontaneous ischaemic stroke lesions in a dog brain: neuropathological characterisation and comparison to human ischaemic stroke

Abstract Background Dogs develop spontaneous ischaemic stroke with a clinical picture closely resembling human ischaemic stroke patients. Animal stroke models have been developed, but it has proved difficult to translate results obtained from such models into successful therapeutic strategies in human stroke patients. In order to face this apparent translational gap within stroke research, dogs with ischaemic stroke constitute an opportunity to study the neuropathology of ischaemic stroke in an animal species. Case presentation A 7\ua0years and 8\ua0months old female neutered Rottweiler dog suffered a middle cerebral artery infarct and was euthanized 3\ua0days after onset of neurological signs. The brain was subjected to histopathology and immunohistochemistry. Neuropathological changes were characterised by a pan-necrotic infarct surrounded by peri-infarct injured neurons and reactive microglia/macrophages and astrocytes. Conclusions The neuropathological changes reported in the present study were similar to findings in human patients with ischaemic stroke. The dog with spontaneous ischaemic stroke is of interest as a complementary spontaneous animal model for further neuropathological studies

No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

BACKGROUND: Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. METHODS: The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively. RESULTS: Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice. CONCLUSIONS: SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had no effect on ischemic cerebral infarction

Physical activity in pregnancy:a mixed methods process evaluation of the FitMum randomised controlled trial interventions

BACKGROUND: Physical activity (PA) at moderate intensity is recommended for healthy pregnant women. The three-arm FitMum randomised controlled trial showed that it was possible to increase PA level during pregnancy with structured supervised exercise training (EXE) compared to standard care. Motivational counselling on PA (MOT) did not increase PA. This process evaluation aims to understand the implementation and mechanisms of impact of EXE and MOT. METHODS: A mixed methods process evaluation was conducted using the UK Medical Research Council’s process evaluation framework by assessing implementation (reach, fidelity, and dose) and mechanisms of impact of the two interventions provided to pregnant women in FitMum. Data was collected both quantitatively (n = 220) and qualitatively (n = 20). RESULTS: The FitMum trial reached educated pregnant women (80% having an educational level ≥ bachelor’s degree) with high autonomy of everyday life. Most participants (58%) were recruited at their first-trimester ultrasonic scan. Reasons to participate were personal (91%) and altruistic (56%). The intervention dose was delivered as intended with high fidelity in the original physical intervention setup and in the altered online setup during the COVID-19 restrictions. A low dose received in EXE (1.3 [95% CI, 1.1; 1.5] sessions/week) was partly explained by the pre-scheduled EXE sessions favouring participants with a flexible everyday life and a supportive social network. Dose received in EXE increased during online intervention delivery. Participants in MOT received 5.2 [4.7; 5.7] of 7 sessions. Mechanisms of impact comprised a perception of intervention commitment among participants in EXE due to the scheduled EXE sessions, whereas participants in MOT considered themselves as PA self-determined. PA was considered as constrained activities in EXE and included in daily activities in MOT. CONCLUSION: The FitMum interventions was delivered with high fidelity. During COVID-19, the dose received in EXE increased compared to the previous physical setup. Mechanisms of impact as commitment, perception of empowerment and perception of PA as well as the paradox between prioritising PA and family and the need of a flexible everyday life need to be considered when offering pregnant women PA interventions. Future interventions should consider a combination of physical and online exercise training for pregnant women. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-14717-1

The Danish National Lymphoma Registry:Coverage and Data Quality

BACKGROUND:The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM:To test the coverage and data quality of the LYFO. METHODS:The coverage was tested by merging data of the LYFO with the Danish Cancer Register and the Danish National Patient Register, respectively. The validity of the LYFO was assessed by crosschecking with information from medical records in subgroups of patients. A random sample of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive values (PPVs) and completeness of selected variables were calculated for each subgroup and for the entire cohort of patients. RESULTS:The comparison of data from the LYFO with the Danish Cancer Register and the Danish National Patient Register revealed a high coverage. In addition, the data quality was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION:The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research