Cognitive? Science?

Cognitive Science is a promising field of research that deals with one of the most fundamental questions ever: how do beings know? However, despite the long and extensive tradition of the field it has not yet become an area of knowledge with scientific identity. This is primarily due to three reasons: the lack of boundaries in defining the object of study, i.e. cognition, the lack of a precise, robust and consistent scientific methodology and results, and the inner problems derived from its interdisciplinary nature. This paper presents a background review, a theoretical frame and a humble reflection on these topics in order to arouse the internal debate among readers once more.     

Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.     

Assessing the value of Hermite densities for predictive distributions

The empirical behaviour of two Hermitian densities—the Edgeworth asymptotic expansion, and the Gallant and Nychka ( 1987 ) squared transformation—are assessed and compared to Hansen's (1994) asymmetric Student t. The comparison focuses on VaR measurements and overall probability fits. In and out of sample, Berkowitz's ( 2001 ) extended procedures are also implemented. Results are moderately favourable to the Hermitians, supporting the semi‐nonparametric interpretation, and multivariate developments. Copyright © 2009 John Wiley & Sons, Ltd.     

Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'

The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells. Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2Rα (termed CD25), IL-2Rβ and IL-2Rγ. Naive T cells express only a low density of IL-2Rβ and IL-2Rγ, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rβ and IL-2Rγ. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2Rβ. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rβ binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.     

Experimental demonstration of quantum memory for light

The information carrier of today's communications, a weak pulse of light, is an intrinsically quantum object. As a consequence, complete information about the pulse cannot be perfectly recorded in a classical memory, even in principle. In the field of quantum information, this has led to the long-standing challenge of how to achieve a high-fidelity transfer of an independently prepared quantum state of light onto an atomic quantum state. Here we propose and experimentally demonstrate a protocol for such a quantum memory based on atomic ensembles. Recording of an externally provided quantum state of light onto the atomic quantum memory is achieved with 70 per cent fidelity, significantly higher than the limit for classical recording. Quantum storage of light is achieved in three steps: first, interaction of the input pulse and an entangling field with spin-polarized caesium atoms; second, subsequent measurement of the transmitted light; and third, feedback onto the atoms using a radio-frequency magnetic pulse conditioned on the measurement result. The density of recorded states is 33 per cent higher than the best classical recording of light onto atoms, with a quantum memory lifetime of up to 4 milliseconds.     

Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1

Ras proteins regulate cellular growth and differentiation, and are mutated in 30% of cancers. We have shown recently that Ras is activated on and transmits signals from the Golgi apparatus as well as the plasma membrane but the mechanism of compartmentalized signalling was not determined. Here we show that, in response to Src-dependent activation of phospholipase Cgamma1, the Ras guanine nucleotide exchange factor RasGRP1 translocated to the Golgi where it activated Ras. Whereas Ca(2+) positively regulated Ras on the Golgi apparatus through RasGRP1, the same second messenger negatively regulated Ras on the plasma membrane by means of the Ras GTPase-activating protein CAPRI. Ras activation after T-cell receptor stimulation in Jurkat cells, rich in RasGRP1, was limited to the Golgi apparatus through the action of CAPRI, demonstrating unambiguously a physiological role for Ras on Golgi. Activation of Ras on Golgi also induced differentiation of PC12 cells, transformed fibroblasts and mediated radioresistance. Thus, activation of Ras on Golgi has important biological consequences and proceeds through a pathway distinct from the one that activates Ras on the plasma membrane.     

Following translation by single ribosomes one codon at a time

We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation--and-pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate-determining processes control each pause. Each translocation step measures three bases--one codon-and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions.     

Positive feedbacks promote power-law clustering of Kalahari vegetation

The concept of local-scale interactions driving large-scale pattern formation has been supported by numerical simulations, which have demonstrated that simple rules of interaction are capable of reproducing patterns observed in nature. These models of self-organization suggest that characteristic patterns should exist across a broad range of environmental conditions provided that local interactions do indeed dominate the development of community structure. Readily available observations that could be used to support these theoretical expectations, however, have lacked sufficient spatial extent or the necessary diversity of environmental conditions to confirm the model predictions. We use high-resolution satellite imagery to document the prevalence of self-organized vegetation patterns across a regional rainfall gradient in southern Africa, where percent tree cover ranges from 65% to 4%. Through the application of a cellular automata model, we find that the observed power-law distributions of tree canopy cluster sizes can arise from the interacting effects of global-scale resource constraints (that is, water availability) and local-scale facilitation. Positive local feedbacks result in power-law distributions without entailing threshold behaviour commonly associated with criticality. Our observations provide a framework for integrating a diverse suite of previous studies that have addressed either mean wet season rainfall or landscape-scale soil moisture variability as controls on the structural dynamics of arid and semi-arid ecosystems.     

Delayed ageing through damage protection by the Arf/p53 pathway

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.