1,535 research outputs found

    Haptic Edge Detection Through Shear

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    Most tactile sensors are based on the assumption that touch depends on measuring pressure. However, the pressure distribution at the surface of a tactile sensor cannot be acquired directly and must be inferred from the deformation field induced by the touched object in the sensor medium. Currently, there is no consensus as to which components of strain are most informative for tactile sensing. Here, we propose that shape-related tactile information is more suitably recovered from shear strain than normal strain. Based on a contact mechanics analysis, we demonstrate that the elastic behavior of a haptic probe provides a robust edge detection mechanism when shear strain is sensed. We used a jamming-based robot gripper as a tactile sensor to empirically validate that shear strain processing gives accurate edge information that is invariant to changes in pressure, as predicted by the contact mechanics study. This result has implications for the design of effective tactile sensors as well as for the understanding of the early somatosensory processing in mammals

    The Cost of Sex: Quantifying Energetic Investment in Gamete Production by Males and Females

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    The relative energetic investment in reproduction between the sexes forms the basis of sexual selection and life history theories in evolutionary biology. It is often assumed that males invest considerably less in gametes than females, but quantifying the energetic cost of gamete production in both sexes has remained a difficult challenge. For a broad diversity of species (invertebrates, reptiles, amphibians, fishes, birds, and mammals), we compared the cost of gamete production between the sexes in terms of the investment in gonad tissue and the rate of gamete biomass production. Investment in gonad biomass was nearly proportional to body mass in both sexes, but gamete biomass production rate was approximately two to four orders of magnitude higher in females. In both males and females, gamete biomass production rate increased with organism mass as a power law, much like individual metabolic rate. This suggests that whole-organism energetics may act as a primary constraint on gamete production among species. Residual variation in sperm production rate was positively correlated with relative testes size. Together, these results suggest that understanding the heterogeneity in rates of gamete production among species requires joint consideration of the effects of gonad mass and metabolism

    Barriers to disseminating brief CBT for voices from a lived experience and clinician perspective

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    Access to psychological therapies continues to be poor for people experiencing psychosis. To address this problem, researchers are developing brief interventions that address the specific symptoms associated with psychosis, i.e., hearing voices. As part of the development work for a brief Cognitive Behaviour Therapy (CBT) intervention for voices we collected qualitative data from people who hear voices (study 1) and clinicians (study 2) on the potential barriers and facilitators to implementation and engagement. Thematic analysis of the responses from both groups revealed a number of anticipated barriers to implementation and engagement. Both groups believed the presenting problem (voices and psychosis symptoms) may impede engagement. Furthermore clinicians identified a lack of resources to be a barrier to implementation. The only facilitator to engagement was reported by people who hear voices who believed a compassionate, experienced and trustworthy therapist would promote engagement. The results are discussed in relation to how these barriers could be addressed in the context of a brief intervention using CBT techniques

    A new tool for the chemical genetic investigation of the Plasmodium falciparum Pfnek-2 NIMA-related kinase

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    Background: Examining essential biochemical pathways in Plasmodium falciparum presents serious challenges, as standard molecular techniques such as siRNA cannot be employed in this organism, and generating gene knock-outs of essential proteins requires specialized conditional approaches. In the study of protein kinases, pharmacological inhibition presents a feasible alternative option. However, as in mammalian systems, inhibitors often lack the desired selectivity. Described here is a chemical genetic approach to selectively inhibit Pfnek-2 in P. falciparum, a member of the NIMA-related kinase family that is essential for completion of the sexual development of the parasite. Results: Introduction of a valine to cysteine mutation at position 24 in the glycine rich loop of Pfnek-2 does not affect kinase activity but confers sensitivity to the protein kinase inhibitor 4-(6-ethynyl-9H-purin-2-ylamino) benzene sulfonamide (NCL-00016066). Using a combination of in vitro kinase assays and mass spectrometry, (including phosphoproteomics) the study shows that this compound acts as an irreversible inhibitor to the mutant Pfnek2 likely through a covalent link with the introduced cysteine residue. In particular, this was shown by analysis of total protein mass using mass spectrometry which showed a shift in molecular weight of the mutant kinase in the presence of the inhibitor to be precisely equivalent to the molecular weight of NCL-00016066. A similar molecular weight shift was not observed in the wild type kinase. Importantly, this inhibitor has little activity towards the wild type Pfnek-2 and, therefore, has all the properties of an effective chemical genetic tool that could be employed to determine the cellular targets for Pfnek-2. Conclusions: Allelic replacement of wild-type Pfnek-2 with the mutated kinase will allow for targeted inhibition of Pfnek-2 with NCL-00016066 and hence pave the way for comparative studies aimed at understanding the biological role and transmission-blocking potential of Pfnek-2. © 2016 The Author(s)

    Gaze following in multiagent contexts: Evidence for a quorum-like principle

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    Research shows that humans spontaneously follow another individual’s gaze. However, little remains known on how they respond when multiple gaze cues diverge across members of a social group. To address this question, we presented participants with displays depicting three (Experiment 1) or five (Experiment 2) agents showing diverging social cues. In a three-person group, one individual looking at the target (33% of the group) was sufficient to elicit gaze-facilitated target responses. With a five-person group, however, three individuals looking at the target (60% of the group) were necessary to produce the same effect. Gaze following in small groups therefore appears to be based on a quorum-like principle, whereby the critical level of social information needed for gaze following is determined by a proportion of consistent social cues scaled as a function of group size. As group size grows, greater agreement is needed to evoke joint attention

    Paul Nizan: conspiracy and the contemplation of crime

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    Paul Nizan (1905-1940) is also known in France as the ‘impossible communist’, for his long-term allegiance to the Party and the abrupt cancellation of his membership, in the late 1930s, following the Nazi-Soviet pact. This paper discusses a number of his writings, focusing particularly on his best known novel, The Conspiracy, where a revolutionary cell plans illegal political action. Conflict, nihilism, suicide and betrayal are among the topics stemming from the novel, which will be examined from a criminological perspective. The analysis will primarily address ‘cultural’ aspects of crime and refer to notions such as ‘thrill’ and ‘seductions of crime’ among others. These notions, it will be argued, require some revision in the face of the imagined or actual criminality described in the novel

    Cooperation between Wnt and Notch signalling in human breast cancer

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    The Wnt and Notch signalling pathways play major roles in mammary gland development and tumourigenesis. During development, these pathways have opposing effects. However, in a recent paper Ayyanan and coworkers show that expression of Wnt1 is sufficient to transform primary human mammary epithelial cells, and that this is in part due to activation of the Notch pathway. This indicates that during tumourigenesis the two pathways cooperate. Here we ask why activation of Wnt signalling alone is sufficient to cause transformation; whether there is evidence for inhibitory crosstalk between the pathways during tumourigenesis; and whether cooperation between these pathways occurs in other forms of cancer

    Gyrodactylus salinae n. sp. (Platyhelminthes: Monogenea) infecting the south European toothcarp Aphanius fasciatus (Valenciennes) (Teleostei, Cyprinodontidae) from a hypersaline environment in Italy

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    Background: Historically, non-native species of Gambusia (Poeciliidae) have been used to control larval stages of the Asian tiger mosquito, Stegomyia albopicta Reinert, Harbach et Kitching, 2004 throughout Italy. The potential utility of indigenous populations of Aphanius fasciatus (Valenciennes) (Teleostei: Cyprinodontidae) as an appropriate alternative biological control is currently being explored. A sub-sample of ten fish collected from Cervia Saline, Italy (salinity 65 ppt; 30°C) to assess their reproductive capability in captivity, harboured a moderate infection of Gyrodactylus von Nordmann, 1832 (Platyhelminthes, Monogenea). A subsequent morphological and molecular study identified this as being a new species. Results: Gyrodactylus salinae n. sp. is described from the skin, fins and gills of A. fasciatus. Light and scanning electron microscopical (SEM) examination of the opisthaptoral armature and their comparison with all other recorded species suggested morphological similarities to Gyrodactylus rugiensoides Huyse et Volckaert, 2002 from Pomatoschistus minutus (Pallas). Features of the ventral bar, however, permit its discrimination from G. rugiensoides. Sequencing of the nuclear ribosomal DNA internal transcribed spacers 1 and 2 and the 5.8S rRNA gene and a comparison with all species listed in GenBank confirmed they are unique and represent a new species (most similar to Gyrodactylus anguillae Ergens, 1960, 8.3% pair-wise distance based on 5.8S+ITS2). This represents the first species of Gyrodactylus to be described from Aphanius and, to date, has the longest ITS1 (774 bp) sequenced from any Gyrodactylus. Additional sampling of Cervia Saline throughout the year, found G. salinae n. sp. to persist in conditions ranging from 35 ppt and 5°C in December to 65 ppt and 30°C in July, while in captivity a low level of infection was present, even in freshwater conditions (0 ppt). Conclusions: The ability of G. salinae n. sp. to tolerate a wide range of salinities and temperatures shows its potential to readily adapt to several environmental conditions. These findings, together with the fact that A. fasciatus is a protected species and is considered as a biological control organism, necessitate further studies on the ecology and virulence of G. salinae n. sp

    A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells

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    Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells.When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo.Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells

    Domain Swapping and Different Oligomeric States for the Complex Between Calmodulin and the Calmodulin-Binding Domain of Calcineurin A

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    BACKGROUND: Calmodulin (CaM) is a ubiquitously expressed calcium sensor that engages in regulatory interactions with a large number of cellular proteins. Previously, a unique mode of CaM target recognition has been observed in the crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A. METHODOLOGY/PRINCIPAL FINDINGS: We have solved a high-resolution crystal structure of a complex between CaM and the CaM-binding domain of calcineurin A in a novel crystal form, which shows a dimeric assembly of calmodulin, as observed before in the crystal state. We note that the conformation of CaM in this complex is very similar to that of unliganded CaM, and a detailed analysis revels that the CaM-binding motif in calcineurin A is of a novel '1-11' type. However, using small-angle X-ray scattering (SAXS), we show that the complex is fully monomeric in solution, and a structure of a canonically collapsed CaM-peptide complex can easily be fitted into the SAXS data. This result is also supported by size exclusion chromatography, where the addition of the ligand peptide decreases the apparent size of CaM. In addition, we studied the energetics of binding by isothermal titration calorimetry and found them to closely resemble those observed previously for ligand peptides from CaM-dependent kinases. CONCLUSIONS/SIGNIFICANCE: Our results implicate that CaM can also form a complex with the CaM-binding domain of calcineurin in a 1 ratio 1 stoichiometry, in addition to the previously observed 2 ratio 2 arrangement in the crystal state. At the structural level, going from 2 ratio 2 association to two 1 ratio 1 complexes will require domain swapping in CaM, accompanied by the characteristic bending of the central linker helix between the two lobes of CaM
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