Social cognition

Social cognition concerns the various psychological processes that enable individuals to take advantage of being part of a social group. Of major importance to social cognition are the various social signals that enable us to learn about the world. Such signals include facial expressions, such as fear and disgust, which warn us of danger, and eye gaze direction, which indicate where interesting things can be found. Such signals are particularly important in infant development. Social referencing, for example, refers to the phenomenon in which infants refer to their mothers' facial expressions to determine whether or not to approach a novel object. We can learn a great deal simply by observing others. Much of this signalling seems to happen automatically and unconsciously on the part of both the sender and the receiver. We can learn to fear a stimulus by observing the response of another, in the absence of awareness of that stimulus. By contrast, learning by instruction, rather than observation, does seem to depend upon awareness of the stimulus, since such learning does not generalize to situations where the stimulus is presented subliminally. Learning by instruction depends upon a meta-cognitive process through which both the sender and the receiver recognize that signals are intended to be signals. An example would be the ‘ostensive’ signals that indicate that what follows are intentional communications. Infants learn more from signals that they recognize to be instructive. I speculate that it is this ability to recognize and learn from instructions rather than mere observation which permitted that advanced ability to benefit from cultural learning that seems to be unique to the human race

In situ measurements and simulation of residual stresses and deformations in additively manufactured thin plates

In this work, the residual stresses and deformations developed during and after laser powder bed fusion (L-PBF) manufacture of thin quasi-2D metallic plates were investigated. Such thin structures are particularly susceptible to effects of residual stress development. A finite element analysis of the L-PBF process was validated with in situ force measurements for the first time for a thin horizontal plate. The predicted forces developed reached a steady growth rate in the corners of the sample of 4.25 N per layer deposited, compared to 3.1 to 3.6 N per layer measured by in situ load cells. The evolution of deformation and residual stress in a different configuration, thin vertical plates, during and after removal of support structures, was also studied numerically and experimentally. Here, the finite element results showed good qualitative and quantitative (to within about 30% on average) agreement for residual deformations and final geometries of the thin vertical structures when compared with stereoscopic digital image correlation measurements. The results from the simulations showed that through-thickness stresses and shear stresses are negligible, while in-plane stresses grow in magnitude during the build process and the subsequent cooling period but are relaxed when the supporting structures are severed and the built plates removed from the base-plate, leaving tension in first built layers and compression in the last built layers. The models provide a tool for designing support structures and processes for release of the structures from their supports and substrates

A well-conserved Plasmodium falciparum var gene shows an unusual stage-specific transcript pattern

The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere to a variety of host receptors, are thought to be important virulence factors. The predominant expression of a single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different PfEMP1 types to evade host protective antibody responses, are processes thought to be controlled at the transcriptional level. Contradictory data have been published on the timing of var gene transcription. Reverse transcription-polymerase chain reaction (RT-PCR) data suggested that transcription of the predominant var gene occurs in the later (pigmented trophozoite) stages, whereas Northern blot data indicated such transcripts only in early (ring) stages. We investigated this discrepancy by Northern blot, with probes covering a diverse var gene repertoire. We confirm that almost all var transcript types were detected only in ring stages. However, one type, the well-conserved varCSA transcript, was present constitutively in different laboratory parasites and does not appear to undergo antigenic variation. Although varCSA has been shown to encode a chondroitin sulphate A (CSA)-binding PfEMP1, we find that the presence of full-length varCSA transcripts does not correlate with the CSA-binding phenotype

Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: a morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis

The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. Purpose: The distribution and significance of caveolin 1 (CAV1) expression in different breast cell types and role in breast carcinogenesis remain poorly understood. Both tumor-suppressive and oncogenic roles have been proposed for this protein. The aims of this study were to characterize the distribution of CAV1 in normal breast, benign breast lesions, breast cancer precursors, and metaplastic breast carcinomas; to assess the prognostic significance of CAV1 expression in invasive breast carcinomas; and to define whether CAV1 gene amplification is the underlying genetic mechanism driving CAV1 overexpression in breast carcinomas. Experimental Design: CAV1 distribution in frozen and paraffin-embedded whole tissue sections of normal breast was evaluated using immunohistochemistry, immunofluorescence, and immunoelectron microscopy. CAV1 expression was immunohistochemically analyzed in benign lesions, breast cancer precursors, and metaplastic breast carcinomas and in a cohort of 245 invasive breast carcinomas from patients treated with surgery followed by anthracycline-based chemotherapy. In 25 cases, CAV1 gene amplification was assessed by chromogenic in situ hybridization. Results: In normal breast, CAV1 was expressed in myoepithelial cells, endothelial cells, and a subset of fibroblasts. Luminal epithelial cells showed negligible staining. CAV1 was expressed in 90% of 39 metaplastic breast carcinomas and in 9.4% of 245 invasive breast cancers. In the later cohort, CAV1 expression was significantly associated with ‘basal-like’ immunophenotype and with shorter disease-free and overall survival on univariate analysis. CAV1 gene amplification was found in 13% of cases with strong CAV1 expression. Conclusions: The concurrent CAV1 amplification and overexpression call into question its tumor-suppressive effects in basal-like breast carcinomas

Molecular and phenotypic characterisation of paediatric glioma cell lines as models for preclinical drug development.

Although paediatric high grade gliomas resemble their adult counterparts in many ways, there appear to be distinct clinical and biological differences. One important factor hampering the development of new targeted therapies is the relative lack of cell lines derived from childhood glioma patients, as it is unclear whether the well-established adult lines commonly used are representative of the underlying molecular genetics of childhood tumours. We have carried out a detailed molecular and phenotypic characterisation of a series of paediatric high grade glioma cell lines in comparison to routinely used adult lines

Small animal models for human immunodeficiency virus (HIV), hepatitis b, and tuberculosis: Proceedings of an NIAID workshop

The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below

2019 ESC/EAS guidelines for the management of dyslipidaemias : Lipid modification to reduce cardiovascular risk

Correction: Volume: 292 Pages: 160-162 DOI: 10.1016/j.atherosclerosis.2019.11.020 Published: JAN 2020Peer reviewe