Type 2 diabetes mellitus and skeletal muscle metabolic function.

AB - Type 2 diabetic patients are characterized by a decreased fat oxidative capacity and high levels of circulating free fatty acids (FFAs). The latter is known to cause insulin resistance, in particularly in skeletal muscle, by reducing insulin stimulated glucose uptake, most likely via accumulation of lipid inside the muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this. Furthermore, type 2 diabetes is associated with impaired metabolic flexibility, i.e. an impaired switching from fatty acid to glucose oxidation in response to insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are important components of skeletal muscle insulin resistance. The cause of these derangements in skeletal muscle of type 2 diabetic patients remains to be elucidated. An impaired mitochondrial function is a likely candidate. Evidence from both in vivo and ex vivo studies supports the idea that an impaired skeletal muscle mitochondrial function is related to the development of insulin resistance and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of mitochondrial function using ex vivo high-resolution respirometry revealed opposite results. Future (human) studies should challenge this concept of impaired mitochondrial function underlying metabolic defects and prove if mitochondria are truly functional impaired in insulin resistance, or low in number, and whether it represents the primary starting point of pathogenesis of insulin resistance, or is just an other feature of the insulin resistant stat

Awareness of group performance in a CSCL-environment: Effects of peer feedback and reflection

Phielix, C., Prins, F. J., & Kirschner, P. A. (2010). Awareness of group performance in a CSCL-environment: Effects of peer feedback and reflection. Computers in Human Behavior, 26(2), 151-161. doi:10.1016/j.chb.2009.10.011This study investigated the effects of a peer feedback tool and a reflection tool on social and cognitive performance during computer supported collaborative learning (CSCL). A CSCL-environment was augmented with a peer feedback tool (Radar) and a reflection tool (Reflector) in order to make group members aware of both their individual and their group behavior. Radar visualizes how group members perceive their own social and cognitive performance and that of their peers during collaboration along five dimensions. Reflector stimulates group members to reflect upon their own performance and the performance of the group. A 2x2 factorial between-subjects design was used to examine whether Radar and Reflector would lead to better team development, more group satisfaction, lower levels of group conflict, more positive attitudes toward problem-based collaboration, and a better group product. Results show that groups with Radar perceived their team as being better developed, experienced lower conflict levels, and had a more positive attitude towards collaborative problem solving than groups without Radar. The quality of group products, however, did not differ. The results demonstrate that peer feedback on the social performance of individual group members can enhance the performance and attitudes of a CSCL-group

Group Awareness of Social and Cognitive Behavior in a CSCL Environment

Phielix, C., Prins, F. J., & Kirschner, P. A. (2010). Group awareness of social and cognitive behavior in a CSCL environment. In K. Gomez, L. Lyons, & J. Radinsky (Eds.), Learning in the Disciplines: Proceedings of the 9th International Conference of the Learning Sciences (ICLS 2010): Volume 1 (pp. 230-237). Chicago IL, USA: International Society of the Learning Sciences.This study investigated whether a peer feedback tool and a reflection tool would enhance group performance in a computer-supported collaborative learning environment. The underlying assumption was that group performance can be positively influenced by making group members aware of how their social and cognitive behavior is perceived by themselves, their peers, and the group as a whole. Participants were 120 fourth-year high school students working, with or without the tools, in dyads, triads and groups of 4 on a collaborative writing task. Results show that groups using tools perceived their team as being better developed, experienced higher levels of group satisfaction and lower levels of conflicts, than groups not using the tools. Results demonstrate that awareness, stimulated by peer assessment and reflection tools, enhances the social performance of a CSCL-group

Group awareness of social and cognitive performance in a CSCL environment: Effects of a peer feedback and reflection tool

Phielix, C., Prins, F. J., Kirschner, P. A., Erkens, G., & Jaspers, J. (2011). Group awareness of social and cognitive performance in a CSCL environment: Effects of a peer feedback and reflection tool. Computers in Human Behavior, 27(3), 1087-1102. doi:10.1016/j.chb.2010.06.024A peer feedback tool (Radar) and a reflection tool (Reflector) were used to enhance group performance in a computer-supported collaborative learning environment. Radar allows group members to assess themselves and their fellow group members on six traits related to social and cognitive behavior. Reflector stimulates group members to reflect on their past, present and future group functioning, stimulating them to set goals and formulate plans to improve their social and cognitive performance. The underlying assumption was that group performance would be positively influenced by making group members aware of how they, their peers and the whole group perceive their social and cognitive behavior in the group. Participants were 108 fourth-year high school students working in dyads, triads and groups of four on a collaborative writing task, with or without the tools. Results demonstrate that awareness stimulated by the peer feedback and reflection tools enhances group-process satisfaction and social performance of CSCL-groups

Fostering complex learning-task performance through scripting student use of computer supported representational tools

Slof, B., Erkens, G., Kirschner, P. A., Janssen, J., & Phielix, C. (2010). Fostering complex learning-task performance through scripting student use of computer supported representational tools. Computers & Education, 55(4), 1707-1720.This study investigated whether scripting student use of computer supported representational tools fostered students’ collaborative performance of a complex business-economics problem. Scripting the problem-solving process sequenced and made its phase-related part-task demands explicit, namely (1) determining core concepts, (2) proposing multiple solutions, and (3) coming to a final solution. The representational tools facilitated students in constructing specific representations of the domain (i.e., conceptual, causal, or mathematical) and were each suited for carrying out the part-task demands of a specific phase. Student groups in four experimental conditions had to carry out all part-tasks in a predefined order, but differed in the representational tool(s) they received during their collaborative problem-solving process. In three mismatch conditions, student groups received either a conceptual, causal, or simulation representational tool which supported them in only carrying out one of the three part-tasks. In the match condition, student groups received the three representational tools in the specified order, each matching the part-task demands of a specific problem phase. The results revealed that student groups in the match condition constructed more task-appropriate representations and had more elaborated and meaningful discussions about the domain. As a consequence, those student groups performed better on the complex learning-task. However, similar results were obtained by student groups who only received a representational tool for constructing causal representations for all part-tasks

Fostering complex learning-task performance through scripting student use of computer supported representational tools

This study investigated whether scripting student use of computer supported representational tools fostered students’ collaborative performance of a complex business-economics problem. Scripting the problem-solving process sequenced and made its phase-related part-task demands explicit, namely (1) determining core concepts, (2) proposing multiple solutions, and (3) coming to a final solution. The representational tools facilitated students in constructing specific representations of the domain (i.e., conceptual, causal, or mathematical) and were each suited for carrying out the part-task demands of a specific phase. Student groups in four experimental conditions had to carry out all part-tasks in a predefined order, but differed in the representational tool(s) they received during their collaborative problem-solving process. In three mismatch conditions, student groups received either a conceptual, causal, or simulation representational tool which supported them in only carrying out one of the three part-tasks. In the match condition, student groups received the three representational tools in the specified order, each matching the part-task demands of a specific problem phase. The results revealed that student groups in the match condition constructed more task-appropriate representations and had more elaborated and meaningful discussions about the domain. As a consequence, those student groups performed better on the complex learning-task. However, similar results were obtained by student groups who only received a representational tool for constructing causal representations for all part-tasks

Insulin sensitivity and fat mass in young male sedentary adults

We live in an obesogenic environment, spending a lot of time sitting neglecting physical activity. This study aims to determine the impact of a sedentary lifestyle on insulin sensitivity by comparing insulin sensitivity of healthy athletes and sedentary subjects. Twelve athletes and 12 sedentary subjects underwent a two-step hyperinsulinemic euglycemic clamp test to assess insulin sensitivity and a DEXA scan to assess body fat mass. Insulin sensitivity was significantly lower in sedentary subjects (p=0.009) and fat mass negatively correlated with insulin sensitivity (r=-0.57, p=0.005). This study shows that healthy sedentary subjects have an impaired insulin metabolism compared to trained athletes

Shortening the lipid A acyl chains of Bordetella pertussis enables depletion of lipopolysaccharide endotoxic activity

Whooping cough, or pertussis, is an acute respiratory infectious disease caused by the Gram-negative bacterium Bordetella pertussis. Whole-cell vaccines, which were introduced in the fifties of the previous century and proved to be effective, showed considerable reactogenicity and were replaced by subunit vaccines around the turn of the century. However, there is a considerable increase in the number of cases in industrialized countries. A possible strategy to improve vaccine-induced protection is the development of new, non-toxic, whole-cell pertussis vaccines. The reactogenicity of whole-cell pertussis vaccines is, to a large extent, derived from the lipid A moiety of the lipopolysaccharides (LPS) of the bacteria. Here, we engineered B. pertussis strains with altered lipid A structures by expressing genes for the acyltransferases LpxA, LpxD, and LpxL from other bacteria resulting in altered acyl-chain length at various positions. Whole cells and extracted LPS from the strains with shorter acyl chains showed reduced or no activation of the human Toll-like receptor 4 in HEK-Blue reporter cells, whilst a longer acyl chain increased activation. Pyrogenicity studies in rabbits confirmed the in vitro assays. These findings pave the way for the development of a new generation of whole-cell pertussis vaccines with acceptable side effects

Postexercise changes in myocellular lipid droplet characteristics of young lean individuals are affected by circulatory nonesterified fatty acids

Intramyocellular lipid (IMCL) content is an energy source during acute exercise. Nonesterified fatty acid (NEFA) levels can compete with IMCL utilization during exercise. IMCL content is stored as lipid droplets (LDs) that vary in size, number, subcellular distribution, and in coating with LD protein PLIN5. Little is known about how these factors are affected during exercise and recovery. Here, we aimed to investigate the effects of acute exercise with and without elevated NEFA levels on intramyocellular LD size and number, intracellular distribution and PLIN5 coating, using high-resolution confocal microscopy. In a crossover study, 9 healthy lean young men performed a 2-h moderate intensity cycling protocol in the fasted (high NEFA levels) and glucose-fed state (low NEFA levels). IMCL and LD parameters were measured at baseline, directly after exercise and 4 h postexercise. We found that total IMCL content was not changed directly after exercise (irrespectively of condition), but IMCL increased 4 h postexercise in the fasting condition, which was due to an increased number of LDs rather than changes in size. The effects were predominantly detected in type I muscle fibers and in LDs coated with PLIN5. Interestingly, subsarcolemmal, but not intermyofibrillar IMCL content, was decreased directly after exercise in the fasting condition and was replenished during the 4 h recovery period. In conclusion, acute exercise affects IMCL storage during exercise and recovery, particularly in type I muscle fibers, in the subsarcolemmal region and in the presence of PLIN5. Moreover, the effects of exercise on IMCL content are affected by plasma NEFA levels.NEW & NOTEWORTHY Skeletal muscle stores lipids in lipid droplets (LDs) that can vary in size, number, and location and are a source of energy during exercise. Specifically, subsarcolemmal LDs were used during exercise when fasted. Exercising in the fasted state leads to postrecovery elevation in IMCL levels due to an increase in LD number in type I muscle fibers, in subsarcolemmal region and decorated with PLIN5. These effects are blunted by glucose ingestion during exercise and recovery