PirB regulates a structural substrate for cortical plasticity

Experience-driven circuit changes underlie learning and memory. Monocular deprivation (MD) engages synaptic mechanisms of ocular dominance (OD) plasticity and generates robust increases in dendritic spine density on L5 pyramidal neurons. Here we show that the paired immunoglobulin-like receptor B (PirB) negatively regulates spine density, as well as the threshold for adult OD plasticity. In PirB(-/-) mice, spine density and stability are significantly greater than WT, associated with higher-frequency miniature synaptic currents, larger long-term potentiation, and deficient long-term depression. Although MD generates the expected increase in spine density in WT, in PirB(-/-) this increase is occluded. In adult PirB(-/-), OD plasticity is larger and more rapid than in WT, consistent with the maintenance of elevated spine density. Thus, PirB normally regulates spine and excitatory synapse density and consequently the threshold for new learning throughout life

Agents in decentralised information ecosystems: the DIET approach

The complexity of the current global information infrastructure requires novel means of understanding and exploiting the dynamics of information. One means may be through the concept of an information ecosystem. An information ecosystem is analo gous to a natural ecosystem in which there are flo ws of materials and energy analo gous to information flow between many interacting individuals. This paper describes a multi-agent platform, DIET (Decentralised Information Ecosystem Technologies) that can be used to implement open, robust, adaptive and scalable ecosystem-inspired systems. We describe the design principles of the DIET software architecture, and present a simple example application based upon it. We go on to consider how the DIET system can be used to develop information brokering agents, and how these can contribute to the implementation of economic interactions between agents, as well as identifying some open questions relating to research in these areas. In this way we show the capacity of the DIET system to support applications using information agents.Future and Emerging Technologies arm of the IST Programme of the European Union, under the FET Proactive Initiative – Universal Information Ecosystems (FET, 1999), through project DIET (IST -1999-10088), BTexaCT Intelligent Systems Laboratory for stimulating discussion and comment

Relationship between the Sensory-Determined Astringency and the Flavanolic Composition of Red Wines

[EN] The relationship between the proanthocyanidin profile and the perceived astringency was assessed in 13 commercial Tempranillo red wines. The concentration and compositional information were obtained by liquid chromatography with diode array detection coupled to electrospray ionization mass spectrometry after acid-catalyzed depolymerization of wine proanthocyanidins in the presence of excess phloroglucinol. Statistical analysis of the results showed significant correlations between sensory and chemical determinations. Astringency was more affected by the subunit composition than by the total concentration or the average degree of polymerization of wine proanthocyanidins. Higher proportions of epicatechin (EC) subunits in extension positions and gallocatechin (GC) subunits in terminal positions were shown to increase astringency. On the contrary, the amount of epigallocatechin (EGC) in both extension and terminal positions was negatively correlated with the perceived astringency

Mammalian Ste20-Like Kinase and SAV1 Promote 3T3-L1 Adipocyte Differentiation by Activation of PPARγ

The mammalian ste20 kinase (MST) signaling pathway plays an important role in the regulation of apoptosis and cell cycle control. We sought to understand the role of MST2 kinase and Salvador homolog 1 (SAV1), a scaffolding protein that functions in the MST pathway, in adipocyte differentiation. MST2 and MST1 stimulated the binding of SAV1 to peroxisome proliferator-activated receptor γ (PPARγ), a transcription factor that plays a key role in adipogenesis. The interaction of endogenous SAV1 and PPARγ was detected in differentiating 3T3-L1 adipocytes. This binding required the kinase activity of MST2 and was mediated by the WW domains of SAV1 and the PPYY motif of PPARγ. Overexpression of MST2 and SAV1 increased PPARγ levels by stabilizing the protein, and the knockdown of SAV1 resulted in a decrease of endogenous PPARγ protein in 3T3-L1 adipocytes. During the differentiation of 3T3-L1 cells into adipocytes, MST2 and SAV1 expression began to increase at 2 days when PPARγ expression also begins to increase. MST2 and SAV1 significantly increased PPARγ transactivation, and SAV1 was shown to be required for the activation of PPARγ by rosiglitazone. Finally, differentiation of 3T3-L1 cells was augmented by MST2 and SAV1 expression and inhibited by knockdown of MST1/2 or SAV1. These results suggest that PPARγ activation by the MST signaling pathway may be a novel regulatory mechanism of adipogenesis

Nitrate regulates floral induction in Arabidopsis, acting independently of light, gibberellin and autonomous pathways

The transition from vegetative growth to reproduction is a major developmental event in plants. To maximise reproductive success, its timing is determined by complex interactions between environmental cues like the photoperiod, temperature and nutrient availability and internal genetic programs. While the photoperiod- and temperature- and gibberellic acid-signalling pathways have been subjected to extensive analysis, little is known about how nutrients regulate floral induction. This is partly because nutrient supply also has large effects on vegetative growth, making it difficult to distinguish primary and secondary influences on flowering. A growth system using glutamine supplementation was established to allow nitrate to be varied without a large effect on amino acid and protein levels, or the rate of growth. Under nitrate-limiting conditions, flowering was more rapid in neutral (12/12) or short (8/16) day conditions in C24, Col-0 and Laer. Low nitrate still accelerated flowering in late-flowering mutants impaired in the photoperiod, temperature, gibberellic acid and autonomous flowering pathways, in the fca co-2 ga1-3 triple mutant and in the ft-7 soc1-1 double mutant, showing that nitrate acts downstream of other known floral induction pathways. Several other abiotic stresses did not trigger flowering in fca co-2 ga1-3, suggesting that nitrate is not acting via general stress pathways. Low nitrate did not further accelerate flowering in long days (16/8) or in 35S::CO lines, and did override the late-flowering phenotype of 35S::FLC lines. We conclude that low nitrate induces flowering via a novel signalling pathway that acts downstream of, but interacts with, the known floral induction pathways

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field