48 research outputs found
Functional and regulatory profiling of energy metabolism in fission yeast
Background: The control of energy metabolism is fundamental for cell growth and function and anomalies in it
are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying
different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells
growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration.
Results: We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth.
Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the
mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling
approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to
respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently
tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that
acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated
the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde
response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from
mitochondrial malfunction.
Conclusions: This study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission
yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As
a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast
DOPPLER ULTRASONOGRAPHIC ESTIMATION OF RENAL AND OCULAR RESISTIVE AND PULSATILITY INDICES IN NORMAL DOGS AND CATS
Encoding microcarriers : present and future technologies
In answer to the ever-increasing need to carry out many assays simultaneously in drug screening and drug discovery, several microcarrier-based multiplex technologies have arisen in the past few years. The compounds to be screened are attached to the surface of microcarriers, which can be mixed together in a vessel that contains the target analyte. Each microcarrier has to be encoded to know which compound is attached to its surface. In this article, the methods that have been developed for the encoding of microcarriers are reviewed and discussed
Modulation of brain activity during a Stroop inhibitory task by the kind of cognitive control required
This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus