Searching for the fountain of autophagy-dependent youth

One of the most exciting aspects of autophagy is its connection with aging, and the possibility of manipulating autophagy to extend life span. Many studies now demonstrate a general decrease in autophagy with age and offer some very interesting indications that reversing this trend, either genetically or pharmacologically, can have a beneficial effect with regard to aging. One of the first researchers to consider the connection between diet, aging and autophagy is Ettore Bergamini, the subject of this interview.     

Apical meristems: the plant's fountain of youth

During postembryonic development, all organs of a plant are ultimately derived from a few pluripotent stem cells found in specialized structures called apical meristems. Here we discuss our current knowledge about the regulation of plant stem cells and their environments with main emphasis on the shoot apical meristem of Arabidopsis thaliana. Recent studies suggest that stem cells are localized in specialized niches where signals from surrounding cells maintain their undifferentiated state. In the shoot meristem, initiation of stem cells during embryogenesis, regulation of stem-cell homeostasis and termination of stem-cell maintenance during flower development appear to primarily involve regulation of the stem-cell niche.     

Embryonic stem cells: taming the fountain of youth

Embryonic stem cells readily generate neurons in vitro, but steering their differentiation into specific neuronal subtypes is a major challenge. It has now been shown that mechanisms that regulate neuronal specification during development can be applied to embryonic stem cells in vitro; this may lead to new ways of generating cells for therapy.     

Emerging bioinformatics for the metabolome

Metabolic profiling applied to functional genomics (metabolomics) is in an early stage of development. Here, the technologies used for metabolite profiling are briefly covered, illustrated by a few pioneering studies. Issues related to bioinformatics, namely data analysis, visualisation and archival, are the main focus of this review. Arguably there is already a need for databases containing metabolite profiles specific for a single organism, and a generic repository containing all metabolite profiling results, regardless of species. Data analyses and visualisations that combine the biological context with chemistry details are suggested as being the most promising.     

Hypothesis assessment with qualitative reasoning: Modelling the Fontestorbes fountain

This paper demonstrates the utility of the Qualitative Reasoning approach for hypothesis testing in the domain of ecology regarding the functioning of ‘black box’ systems. As a test case, we refer to the study performed by Mangin (1969) with scale models to investigate the hidden mechanism of the Fontestorbes fountain, a spring that exhibits a periodic flow situated in the south of France. In our approach, a Qualitative Reasoning method (and hence a qualitative model) is used to test the ‘siphon-hypothesis’, which traditionally explains the oscillations of the flow rate of a periodic spring by the principle of filling and emptying an underground reservoir through a siphon action. Parts of the simulation results show that the hypothesis is qualitatively accurate; in particular the model produces a cyclic behaviour that matches with the observed one. However, the qualitative model also exhibits a contradictory behaviour (true negative) that challenges the hypothesis consistency. The causal account of this true negative denotes and explains a flaw in the siphon-hypothesis. The paper concludes that, with the Qualitative Reasoning method, models can be constructed for hypothesis testing. Such models should generate the desired behaviour as a first and necessary step to support the viability of the hypothesis. However, the occurrence of unexpected behaviours provides information that challenges the hypothesis, and may lead to having to discard it.     

Emerging Technologies for the Electrochemical Detection of Bacteria

Infections are a huge economic liability to the health care system, although real‐time detection can allow early treatment protocols to avoid some of this cost and patient morbidity and mortality. Pseudomonas aeruginosa (PA) is a drug‐resistant gram‐negative bacterium found ubiquitously in clinical settings, accounting for up to 27% of hospital acquired infections. PA secretes a vast array of molecules, ranging from secondary metabolites to quorum sensing molecules, of which many can be exploited to monitor bacterial presence. In addition to electrochemical immunoassays to sense bacteria via antigen–antibody interactions, PA pertains a distinct redox‐active virulence factor called pyocyanin (PYO), allowing a direct electrochemical detection of the bacteria. There has been a surge of publications relating to the electrochemical tracing of PA via a myriad of novel biosensing techniques, materials, and methodologies. In addition to indirect methods, research approaches where PYO has been sensitively detected using surface modified electrodes are reviewed and compared with conventional PA‐sensing methodologies. This review aims at presenting indirect and direct electrochemical methods currently developed using various surface modified electrodes, materials, and electrochemical configurations on their electrocatalytic effects on sensing of PA and in particular PYO.     

Restoring cell polarity: an HSC fountain of youth

Until recently, aging was viewed as a fixed and irreversible process. However, in this issue of Cell Stem Cell, Florian et?al. (2012) reveal a link between increased activity of the RhoGTPase Cdc42, hematopoietic stem cell polarity, and aging that can be regulated by pharmacological inhibition of Cdc42.     

Emerging computational approaches for the study of protein allostery

Allosteric regulation of protein function is key in controlling cellular processes so its underlying mechanisms are of primary concern to research in areas spanning protein engineering and drug design. However, due to the complex nature of allosteric mechanisms, a clear and predictive understanding of the relationship between protein structure and allosteric function remains elusive. Well established experimental approaches are available to offer a limited degree of characterization of mechanical properties within proteins, but the analytical capabilities of computational methods are evolving rapidly in their ability to accurately define the subtle and concerted structural dynamics that comprise allostery. This review includes a brief overview of allostery in proteins and an exploration of relevant experimental methods. An explanation of the transition from experimental toward computational methods for allostery is discussed, followed by a review of existing and emerging methods.     

Emerging rules for the distributions of active dendritic conductances

A key goal in neuroscience is to explain how the operations of a neuron emerge from sets of active channels with specific dendritic distributions. If general principles can be identified for these distributions, dendritic channels should reflect the computational role of a given cell type within its functional neural circuit. Here, we discuss insights from experimental and computational data on the distribution of voltage-gated channels in dendrites, and attempt to derive rules for how their interactions implement different dendritic functions. We propose that this type of analysis will be important for understanding behavioural processes in terms of single-neuron properties, and that it constitutes a step towards a 'functional proteomics' of nerve cells, which will be essential for defining neuronal phenotypes.     

Emerging methods for the rapid determination of enantiomeric excess

Methods for enantiomeric excess determination using a variety of spectroscopic techniques are summarized. Particular attention is paid to techniques that have promise for application to problems of combinatorial catalyst discovery but have not yet been so employed.