The “practice turn” in philosophy of science has strengthened the connections between philosophy and scientific practice. Apart from reinvigorating philosophy of science, this also increases the ...relevance of philosophical research for science, society, and science education. In this paper, we reflect on our extensive experience with teaching mandatory philosophy of science courses to science students from a range of programs at University of Copenhagen. We highlight some of the lessons we have learned in making philosophy of science “fit for teaching” outside of philosophy circles by taking selected cases from the students’ own field as the starting point. We argue for adapting philosophy of science teaching to particular audiences of science students, and discuss the benefits of drawing on research within science education to inform curriculum and course design. This involves reconsidering teaching resources, assumptions about students, intended learning outcomes, and teaching formats. We also argue that to make philosophy of science relevant and engaging to science students, it is important to consider their potential career trajectories. By anticipating future contexts and situations in which methodological, conceptual, and ethical questions could be relevant, philosophy of science can demonstrate its value in the education of science students.
Abnormal cellular Ca2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca2+ transient amplitude due to decreased sarcoplasmic reticulum Ca2+ content is ...a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca2+ release events which occur when sarcoplasmic reticulum Ca2+ content exceeds a certain threshold level. Such Ca2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls. Video edge-detection, whole-cell Ca2+ imaging and confocal line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca2+ transients and Ca2+ waves. In baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with large myocardial infarction, but without heart failure, did not differ from sham-operated animals in any of these aspects of cellular function. However, when exposed to beta-adrenoceptor stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca2+ content, decreased Ca2+ transient amplitude, and increased frequency of Ca2+ waves. These results are in line with a decreased threshold for diastolic Ca2+ release established by other studies. In the present study, factors that might contribute to a lower threshold for diastolic Ca2+ release were increased THR286 phosphorylation of Ca2+/calmodulin-dependent protein kinase II and increased protein phosphatase 1 abundance. In conclusion, this study demonstrates both decreased sarcoplasmic reticulum Ca2+ content and increased propensity for diastolic Ca2+ release events in ventricular cardiomyocytes from rats with heart failure after myocardial infarction, and that these phenomena are also found in rats with large myocardial infarctions without heart failure development. Importantly, beta-adrenoceptor stimulation is necessary to reveal these perturbations in Ca2+ handling after a myocardial infarction.
Aim:
Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca
2+
release in cardiomyocytes that ...contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca
2+
release in rats with post-myocardial infarction HF.
Materials and Methods:
We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO
2max
test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca
2+
release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.
Results:
ET increased VO
2max
in HF-ET rats to 127% of HF-SED (
P
< 0.05). This coincided with attenuated spontaneous SR Ca
2+
release in left ventricular cardiomyocytes from HF-ET but also reduced Ca
2+
transient amplitude and slowed Ca
2+
reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca
2+
homeostasis and major proteins involved in the regulation of SR Ca
2+
release and reuptake could not explain the attenuated spontaneous SR Ca
2+
release or reduced Ca
2+
transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta
1
-adrenoceptor density and beta
1
:beta
2
-adrenoceptor ratio in HF-ET.
Conclusion:
ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca
2+
release. Our data show that these effects of ET can be gained without major alterations in SR Ca
2+
regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway.
For the past decade, philosophers of mathematical practice have examined the nature and function of proofs in mathematical practice, most often in mathematical research practice. More recently they ...have examined how mathematicians assess and get to know a proof not just by reading it, but through active engagement with the proof. For example, mathematicians traverse gaps in the proof by filling in details. This paper examines the relevance of this literature to the teaching of mathematics. In particular, it examines how reader engagement can be taught as an aspect of proofs in the context of upper-secondary mathematics education, and the argument is illustrated by teaching material on Hero’s formula, which was developed for and tested in Danish upper-secondary mathematics teaching.
Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) predisposes to ventricular tachyarrhythmias (VTs) during high heart rates due to physical or psychological stress. The essential ...role of catecholaminergic effects on ventricular cardiomyocytes in this situation is well documented, but the importance of heart rate per se for arrhythmia initiation in CPVT1 is largely unexplored.
Sixteen CPVT1 patients performed a bicycle stress-test. Occurrence of VT triggers, i.e. premature ventricular complexes (PVC), depended on high heart rate, with individual thresholds. Atrial pacing above the individual PVC threshold in three patients did not induce PVCs. The underlying mechanism for the clinical observation was explored using cardiomyocytes from mice with the RyR2-R2474S (RyR2-RS) mutation, which exhibit exercise-induced VTs. While rapid pacing increased the number of Ca2+ waves in both RyR2-RS and wild-type (p<0.05), β-adrenoceptor (βAR) stimulation induced more Ca2+ waves in RyR2-RS (p<0.05). Notably, Ca2+ waves occurred despite decreased sarcoplasmic reticulum (SR) Ca2+ content in RyR2-RS (p<0.05), suggesting increased cytosolic RyR2 Ca2+ sensitivity. A computational model of mouse ventricular cardiomyocyte electrophysiology reproduced the cellular CPVT1 phenotype when RyR2 Ca2+ sensitivity was increased. Importantly, diastolic fluctuations in phosphorylation of RyR2 and SR Ca2+ content determined Ca2+ wave initiation. These factors were modulated towards increased propensity for arrhythmia initiation by increased pacing rates, but even more by βAR stimulation.
In CPVT1, VT propensity depends on individual heart rate thresholds for PVCs. Through converging data from clinical exercise stress-testing, cellular studies and computational modelling, we confirm the heart rate-independent pro-arrhythmic effects of βAR stimulation in CPVT1, but also identify an independent and synergistic contribution from effects of high heart rate.
Abnormal cellular Ca.sup.2+ handling contributes to both contractile dysfunction and arrhythmias in heart failure. Reduced Ca.sup.2+ transient amplitude due to decreased sarcoplasmic reticulum ...Ca.sup.2+ content is a common finding in heart failure models. However, heart failure models also show increased propensity for diastolic Ca.sup.2+ release events which occur when sarcoplasmic reticulum Ca.sup.2+ content exceeds a certain threshold level. Such Ca.sup.2+ release events can initiate arrhythmias. In this study we aimed to investigate if both of these aspects of altered Ca.sup.2+ homeostasis could be found in left ventricular cardiomyocytes from rats with different states of cardiac function six weeks after myocardial infarction when compared to sham-operated controls. Video edge-detection, whole-cell Ca.sup.2+ imaging and confocal line-scan imaging were used to investigate cardiomyocyte contractile properties, Ca.sup.2+ transients and Ca.sup.2+ waves. In baseline conditions, i.e. without beta-adrenoceptor stimulation, cardiomyocytes from rats with large myocardial infarction, but without heart failure, did not differ from sham-operated animals in any of these aspects of cellular function. However, when exposed to beta-adrenoceptor stimulation, cardiomyocytes from both non-failing and failing rat hearts showed decreased sarcoplasmic reticulum Ca.sup.2+ content, decreased Ca.sup.2+ transient amplitude, and increased frequency of Ca.sup.2+ waves. These results are in line with a decreased threshold for diastolic Ca.sup.2+ release established by other studies. In the present study, factors that might contribute to a lower threshold for diastolic Ca.sup.2+ release were increased THR286 phosphorylation of Ca.sup.2+ /calmodulin-dependent protein kinase II and increased protein phosphatase 1 abundance. In conclusion, this study demonstrates both decreased sarcoplasmic reticulum Ca.sup.2+ content and increased propensity for diastolic Ca.sup.2+ release events in ventricular cardiomyocytes from rats with heart failure after myocardial infarction, and that these phenomena are also found in rats with large myocardial infarctions without heart failure development. Importantly, beta-adrenoceptor stimulation is necessary to reveal these perturbations in Ca.sup.2+ handling after a myocardial infarction.
Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca
release in cardiomyocytes that contributes to ...contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca
release in rats with post-myocardial infarction HF.
We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO
test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca
release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.
ET increased VO
in HF-ET rats to 127% of HF-SED (
< 0.05). This coincided with attenuated spontaneous SR Ca
release in left ventricular cardiomyocytes from HF-ET but also reduced Ca
transient amplitude and slowed Ca
reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca
homeostasis and major proteins involved in the regulation of SR Ca
release and reuptake could not explain the attenuated spontaneous SR Ca
release or reduced Ca
transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta
-adrenoceptor density and beta
:beta
-adrenoceptor ratio in HF-ET.
ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca
release. Our data show that these effects of ET can be gained without major alterations in SR Ca
regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway.
Aim: To examine the association between skipping meals and snacking events and dietary and clinical characteristics in children and adolescents using modern insulin treatment.
Methods: Dietary ...intake was recorded for 4 d in food diaries in 655 young diabetic patients. Number of meals and snacking events was recorded in a separated questionnaire, while clinical data were obtained from case record forms. Skipping meals refer to consuming a main meal (e.g., breakfast) five times a week or less.
Results: Modern insulin treatment may favor a more flexible lifestyle. This study shows that there are fewer young diabetic patients who skip meals than non‐diabetic controls (p < 0.001) even when using modern intensified insulin treatment. However, skipping meals among young diabetic patients was associated with negative characteristics such as having suboptimal hemoglobin A1c (HbA1c) (OR 4.7, p = 0.02), higher low‐density lipoprotein (LDL) cholesterol levels (OR 4.0, p < 0.001), watching more TV (OR 3.6, p < 0.001), being overweight (OR 2.8, p = 0.03), as well as having a higher intake of added sugar (OR 2.1, p = 0.01) and lower intake of fiber (OR 0.2, p = 0.04) compared with those not skipping meals. Having more than two snacking events during the day was associated with higher HbA1c, higher intake of added sugar and sweets, and spending more hours in front of the TV or personal computer.
Conclusions: In general, fewer children and adolescents with type 1 diabetes skip meals compared with healthy peers. Those who skip meals and have more snacking events have poorer glycemic control and less healthy dietary and leisure habits.
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