Simple heuristics: From one infinite regress to another?

Gigerenzer, Todd, and the ABC Research Group argue that optimisation under constraints leads to an infinite regress due to decisions about how much information to consider when deciding. In certain cases, however, their fast and frugal heuristics lead instead to an endless series of decisions about how best to decide.

Ai Weiwei: La recepción de su producción artística

Actualmente Ai Weiwei es el creador con mayor proyección dentro y fuera de China, destacando especialmente por su prolífica, heterogénea, comprometida y polémica producción artística. Sus propuestas suscitan un gran interés y obtienen una destacada repercusión tanto en China como en un escenario internacional. Precisamente, es uno de los artistas contemporáneos chinos que ha logrado una mayor presencia en los medios de comunicación y en los espacios expositivos españoles, siendo un ejemplo de ello la organización de la primera exposición museística de su obra en el Centro Andaluz de Arte Contemporáneo (2013) y el estreno de la película documental sobre su vida y su obra Never Sorry (2013), dirigida por Alison Klayman. Ai Weiwei es un autor mediático y su visibilidad deviene una plataforma desde donde articular proyectos artísticos que enfocan determinadas problemáticas sociales. A la vez, la crítica política de Ai Weiwei resulta especialmente atractiva en un contexto euroamericano que subraya su papel de disidente y agitador. Dentro de tales parámetros se ahondará en la recepción de la producción artística de Ai Weiwei en el marco internacional y en el contexto español, analizando la aproximación que la prensa esboza sobre dicho autor.

The conflict between realism and abstraction in the field of spanish art as an iteration of la "Querelle des Anciens et des Modernes"

Based on the analysis model favored by the study of the conditions in which the seventeenth century Querelle des Anciens et des Modernes took place, we examine the case of confrontation between realism and abstraction, which occurred in the context of Spanish art in the nineties of the twentieth century. Connections are established with other aesthetic conflicts which are considered part of a genealogy whose most explicit antecedent could be placed in the before mentioned complaint, such as the confrontation between realism and abstraction in the American art scene, which occurred in the fifties of the last century, and the more recent controversy on pluralism and the end of art.

Joaquim Mir y la tienda de juguetes: microhistoria de un retrato

¿Puede un retrato pictórico suscitar un ejercicio de microhistoria? Nuestra investigación tratará de aportar una respuesta positiva a esta cuestión, analizando para ello uno de los pocos retratos del pintor postimpresionista Joaquim Mir Trinxet, fechado en 1926. El protagonista representado no es otro que el suegro del pintor, Antoni Estalella i Trinxet, un insigne personaje de Vilanova y la Geltrú (Barcelona) que vivió entre dos siglos. La obra está ambientada en la tienda de juguetes de la familia, convirtiéndose así en una de las escasas pinturas que han captado el interior de una juguetería en la España anterior a la Guerra Civil. Gracias a los trabajos de archivo realizados, este artículo reúne diversos documentos inéditos que permiten reconstruir no sólo la vida del retratado, que llegó a ser corresponsal de Francisco Pi y Margall, sino también el ambiente social, artístico y comercial de Vilanova, en un período que abarca desde la década de 1870 a la primera mitad del siglo XX, en plena “Edad de Oro” de la industria juguetera. Es esta una propuesta de metodología historiográfica cuyo recorrido comienza en el oficio arcaico de la tonelería para desembocar al fin en los albores del comercio moderno de juguetes.

Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma.

Background Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. Methods In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients. Results In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity. Conclusion Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

Genomic insights into the origin of parasitism in the emerging plant pathogen Bursaphelenchus xylophilus.

Bursaphelenchus xylophilus is the nematode responsible for a devastating epidemic of pine wilt disease in Asia and Europe, and represents a recent, independent origin of plant parasitism in nematodes, ecologically and taxonomically distinct from other nematodes for which genomic data is available. As well as being an important pathogen, the B. xylophilus genome thus provides a unique opportunity to study the evolution and mechanism of plant parasitism. Here, we present a high-quality draft genome sequence from an inbred line of B. xylophilus, and use this to investigate the biological basis of its complex ecology which combines fungal feeding, plant parasitic and insect-associated stages. We focus particularly on putative parasitism genes as well as those linked to other key biological processes and demonstrate that B. xylophilus is well endowed with RNA interference effectors, peptidergic neurotransmitters (including the first description of ins genes in a parasite) stress response and developmental genes and has a contracted set of chemosensory receptors. B. xylophilus has the largest number of digestive proteases known for any nematode and displays expanded families of lysosome pathway genes, ABC transporters and cytochrome P450 pathway genes. This expansion in digestive and detoxification proteins may reflect the unusual diversity in foods it exploits and environments it encounters during its life cycle. In addition, B. xylophilus possesses a unique complement of plant cell wall modifying proteins acquired by horizontal gene transfer, underscoring the impact of this process on the evolution of plant parasitism by nematodes. Together with the lack of proteins homologous to effectors from other plant parasitic nematodes, this confirms the distinctive molecular basis of plant parasitism in the Bursaphelenchus lineage. The genome sequence of B. xylophilus adds to the diversity of genomic data for nematodes, and will be an important resource in understanding the biology of this unusual parasite.

Two distinct but interchangeable mechanisms for flipping of lipid-linked oligosaccharides

Translocation of lipid-linked oligosaccharide (LLO) intermediates across membranes is an essential but poorly understood process in eukaryotic and bacterial glycosylation pathways. Membrane proteins defined as translocases or flippases are implicated to mediate the translocation reaction. The membrane protein Wzx has been proposed to mediate the translocation across the plasma membrane of lipopolysaccharide (LPS) O antigen subunits, which are assembled on an undecaprenyl pyrophosphate lipid carrier. Similarly, PglK (formerly WlaB) is a Campylobacter jejuni-encoded ABC-type transporter proposed to mediate the translocation of the undecaprenylpyrophosphate-linked heptasaccharide intermediate involved in the recently identified bacterial N-linked protein glycosylation pathway. A combination of genetic and carbohydrate structural analyses defined and characterized flippase activities in the C. jejuni N-linked protein glycosylation and the Escherichia coli LPS O antigen biosynthesis. PglK displayed relaxed substrate specificity with respect to the oligosaccharide structure of the LLO intermediate and complemented a wzx deficiency in E. coli O-antigen biosynthesis. Our experiments provide strong genetic evidence that LLO translocation across membranes can be catalyzed by two distinct proteins that do not share any sequence similarity.

An amino acid substitution in Fasciola hepatica P-glycoprotein from triclabendazole-resistant and triclabendazole-susceptible populations

Control of fasciolosis is threatened by the development of anthelmintic resistance. Enhanced triclabendazole (TCBZ) efflux by ABC transporters such as P-glycoprotein (Pgp) has been implicated in this process. A putative full length cDNA coding for a Pgp expressed in adult Fasciola hepatica has been constructed and used to design a primer set capable of amplifying a region encoding part of the second nucleotide binding domain of Pgp when genomic DNA was used as a template. Application of this primer set to genomic DNA from TCBZ-resistant and -susceptible field populations has shown a significant difference in the alleles present. Analysis of an allele occurring at a three-fold higher frequency in the "resistant" population revealed that it was characterised by a serine to arginine substitution at residue 1144. Homology modelling studies have been used to locate this site in the Pgp structure and hence assess its potential to modify functional activity. © 2012 Elsevier B.V.

Sensory-motor problems in Autism

Despite being largely characterised as a social and cognitive disorder, strong evidence indicates the presence of significant sensory-motor problems in Autism Spectrum Disorder (ASD). This paper outlines our progression from initial, broad assessment using the Movement Assessment Battery for Children (M-ABC) to subsequent targeted kinematic assessment. In particular, pronounced ASD impairment seen in the broad categories of manual dexterity and ball skills was found to be routed in specific difficulties on isolated tasks, which were translated into focused experimental assessment. Kinematic results from both subsequent studies highlight impaired use of perception-action coupling to guide, adapt and tailor movement to task demands, resulting in inflexible and rigid motor profiles. In particular difficulties with the use of temporal adaption are shown, with "hyperdexterity" witnessed in ballistic movement profiles, often at the cost of spatial accuracy and task performance. By linearly progressing from the use of a standardised assessment tool to targeted kinematic assessment, clear and defined links are drawn between measureable difficulties and underlying sensory-motor assessment. Results are specifically viewed in-light of perception-action coupling and its role in early infant development suggesting that rather than being 'secondary' level impairment, sensory-motor problems may be fundamental in the progression of ASD. This logical and systematic process thus allows a further understanding into the potential route of observable motor problems in ASD; a vital step if underlying motor problems are to be considered a fundamental aspect of autism and allow a route of non-invasive preliminary diagnosis.

Newly Acquired Fear of Falling Leads to Altered Eye Movement Patterns and Reduced Stepping Safety: A Case Study

This opportune case study describes visual and stepping behaviours of an 87 year old female (P8), both prior to, and following two falls. Before falling, when asked to walk along a path containing two stepping guides positioned before and after an obstacle, P8 generally visually fixated the first stepping guide until after foot contact inside it. However, after falling P8 consistently looked away from the stepping guide before completing the step into it in order to fixate the upcoming obstacle in her path. The timing of gaze redirection away from the target (in relation to foot contact inside it) correlated with absolute stepping error. No differences in eyesight, cognitive function, or balance were found between pre- and post-fall recordings. However, P8 did report large increases in fall-related anxiety and reduced balance confidence, supporting previously suggested links between anxiety/increased fear or falling and maladaptive visual/stepping behaviours. The results represent a novel insight into how psychological and related behavioural factors can change in older adults following a fall, and provide a possible partial rationalisation for why recent fallers are more likely to fall again in the following 12 months. These findings highlight novel possibilities for falls prevention and rehabilitation.

Successful balance training is associated with improved multisensory function in fall-prone older adults

Balance maintenance relies on a complex interplay between many different sensory modalities. Although optimal multisensory processing is thought to decline with ageing, inefficient integration is particularly associated with falls in older adults. We investigated whether improved balance control, following a novel balance training intervention, was associated with more efficient multisensory integration in older adults, particularly those who have fallen in the past. Specifically, 76 healthy and fall-prone older adults were allocated to either a balance training programme conducted over 5 weeks or to a passive control condition. Balance training involved a VR display in which the on-screen position of a target object was controlled by shifts in postural balance on a Wii balance board. Susceptibility to the sound-induced flash illusion, before and after the intervention (or control condition), was used as a measure of multisensory function. Whilst balance and postural control improved for all participants assigned to the Intervention group, improved functional balance was correlated with more efficient multisensory processing in the fall-prone older adults only. Our findings add to growing evidence suggesting important links between balance control and multisensory interactions in the ageing brain and have implications for the development of interventions designed to reduce the risk of falls.

Unique mitochondrial DNA lineages in Irish stickleback populations: cryptic refugium or rapid recolonization?

Repeated recolonization of freshwater environments following Pleistocene glaciations has played a major role in the evolution and adaptation of anadromous taxa. Located at the western fringe of Europe, Ireland and Britain were likely recolonized rapidly by anadromous fishes from the North Atlantic following the last glacial maximum (LGM). While the presence of unique mitochondrial haplotypes in Ireland suggests that a cryptic northern refugium may have played a role in recolonization, no explicit test of this hypothesis has been conducted. The three-spined stickleback is native and ubiquitous to aquatic ecosystems throughout Ireland, making it an excellent model species with which to examine the biogeographical history of anadromous fishes in the region. We used mitochondrial and microsatellite markers to examine the presence of divergent evolutionary lineages and to assess broad-scale patterns of geographical clustering among postglacially isolated populations. Our results confirm that Ireland is a region of secondary contact for divergent mitochondrial lineages and that endemic haplotypes occur in populations in Central and Southern Ireland. To test whether a putative Irish lineage arose from a cryptic Irish refugium, we used approximate Bayesian computation (ABC). However, we found no support for this hypothesis. Instead, the Irish lineage likely diverged from the European lineage as a result of postglacial isolation of freshwater populations by rising sea levels. These findings emphasize the need to rigorously test biogeographical hypothesis and contribute further evidence that postglacial processes may have shaped genetic diversity in temperate fauna.

Novel microtubule-targeting agents, pyrrolo-1,5-benzoxazepines, induce apoptosis in multi-drug-resistant cancer cells

PURPOSE: The development of multi-drug resistance (MDR) due to the expression of members of the ATP binding cassette (ABC) transporter family is a major obstacle in cancer treatment. The broad range of substrate specificities associated with these transporters leads to the efflux of many anti-cancer drugs from tumour cells. Therefore, the development of new chemotherapeutic agents that are not substrates of these transporters is important. We have recently demonstrated that some members of a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds are microtubule-depolymerising agents that potently induce apoptosis in several cancer cell lines and impair growth of mouse breast tumours. The aim of this current study was to establish whether PBOXs were capable of inducing apoptosis in cancer cells expressing either P-glycoprotein or breast cancer resistance protein (BCRP), two of the main ABC transporters associated with MDR.

METHODS: We performed in vitro studies to assess the effects of PBOXs on cell proliferation, cell cycle and apoptosis in human cancer cell lines and their drug-resistant substrains expressing either P-glycoprotein or BCRP. In addition, we performed a preliminary molecular docking study to examine interactions between PBOXs and P-glycoprotein.

RESULTS: We established that three representative PBOXs, PBOX-6, -15 and -16 were capable of inducing apoptosis in drug-resistant HL60-MDR1 cells (expressing P-glycoprotein) and HL60-ABCG2 cells (expressing BCRP) with similar potencies as in parental human promyelocytic leukaemia HL60 cells. Likewise, resistance to PBOX-6 and -16 was not evident in P-glycoprotein-expressing A2780-ADR cells in comparison with parent human ovarian carcinoma A2780 cells. Finally, we deduced by molecular docking that PBOX-6 is not likely to form favourable interactions with the substrate binding site of P-glycoprotein.

CONCLUSION: Our results suggest that pro-apoptotic PBOX compounds may be potential candidates for the treatment of P-glycoprotein- or BCRP-associated MDR cancers.