Chlorophylls of the c family: absolute configuration and inhibition of NADPH:protochlorophyllide oxidoreductase

AbstractUsing circular dichroism (CD) spectroscopy, the stereochemistry at C-132 of members of the chlorophyll (Chl) c family, namely Chls c1, c2, c3 and [8-vinyl]-protochlorophyllide a (Pchlide a) was determined. By comparison with spectra of known enantiomers, all Chl c members turned out to have the (R) configuration, which is in agreement with considerations drawn from chlorophyll biosynthesis. Except for a double bond in the side chain at C-17, the chemical structure of Chl c1 is identical with Pchlide a, the natural substrate of the light-dependent NADPH:protochlorophyllide oxidoreductase (POR). Thus, lack of binding to the active site due to the wrong configuration at C-132, which had been proposed previously, cannot be an explanation for inactivity of Chl c in this enzymic reaction. Our results show rather that Chl c1 is a competitive inhibitor for this enzyme, tested with Pchlide a and Zn-protopheophorbide a (Zn-Ppheide a) as substrates

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria (MMAuria), present unique challenges to energetic homeostasis by disrupting energy producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut) type MMAuria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared to littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator-activated receptor and Fgf21-controlled pathways. Together, these indicate hypometabolism, energetic inflexibility and increased stores at the expense of active tissue as energy shortage consequences

Data-Informed Case Formulation with the Trier Treatment Navigator

The current article presents a way of practising case formulation using technology augmentation in the context of data-informed psychotherapy. First, we explain how case formulation guides the decision-making processes in psychotherapy and how decisions made under an intuitive clinical judgement can be biased. The use of actuarial methods is pointed out as a way of addressing these biases, mainly through clinical decision support systems based on statistical tools and machine learning algorithms. We present the Trier Treatment Navigator (TTN), a clinical decision support system developed in a University research-based clinical training programme. We show how the TTN can contribute to an initial case formulation and its dynamic adaptations during treatment with a clinical case. Finally, we discuss how case formulation and data-informed psychotherapy are aimed at the same goal: treatment personalisation. We argue that case formulation and data-informed psychotherapy enrich and feedback on each other.El artículo presenta una forma de practicar la formulación de caso a través del uso de aumentación tecnológica en el contexto de una psicoterapia informada por datos. Primero explicamos cómo la formulación de caso guía el proceso de toma de decisiones en psicoterapia y cómo las decisiones tomadas a partir de un juicio clínico intuitivo pueden estar sesgadas. El uso de métodos actuariales se muestra como una forma de abordar estos sesgos, principalmente a través de sistemas de apoyo a las decisiones clínicas basados en herramientas estadísticas y algoritmos de aprendizaje automático. Presentamos el Trier Treatmnent Navigator (TTN), un sistema de apoyo a las decisiones clínicas desarrollado en un programa universitario de formación basado en investigación. A través de un caso clínico mostramos cómo el TTN puede contribuir a una formulación de caso inicial y a sus adaptaciones dinámicas durante el tratamiento. Finalmente discutimos cómo la formulación de caso y la psicoterapia informada por datos están orientadas hacia un mismo objetivo: la personalización del tratamiento. Argumentamos que la formulación de caso y la psicoterapia informada por datos se enriquecen y retroalimentan la una a la otra

Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria

Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)–type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator–activated receptor and Fgf21-controlled pathways. Together, these shed light on the mechanisms and adaptations behind energy imbalance in methylmalonic aciduria and provide insight into metabolic responses to chronic energy shortage, which may have important implications for disease understanding and patient management.ISSN:0964-6906ISSN:1460-208