Are faces special? A case of pure prosopagnosia

The ability to recognize individual faces is of crucial social importance for humans and evolutionarily necessary for survival. Consequently, faces may be “special” stimuli, for which we have developed unique modular perceptual and recognition processes. Some of the strongest evidence for face processing being modular comes from cases of prosopagnosia, where patients are unable to recognize faces whilst retaining the ability to recognize other objects. Here we present the case of an acquired prosopagnosic whose poor recognition was linked to a perceptual impairment in face processing. Despite this, she had intact object recognition, even at a subordinate level. She also showed a normal ability to learn and to generalize learning of nonfacial exemplars differing in the nature and arrangement of their parts, along with impaired learning and generalization of facial exemplars. The case provides evidence for modular perceptual processes for faces.

The scaffold protein KSR1, a novel therapeutic target for the treatment of Merlin-deficient tumors

Merlin has broad tumor-suppressor functions as its mutations have been identified in multiple benign tumors and malignant cancers. In all schwannomas, the majority of meningiomas and 1/3 of ependymomas Merlin loss is causative. In neurofibromatosis type 2, a dominantly inherited tumor disease because of the loss of Merlin, patients suffer from multiple nervous system tumors and die on average around age 40. Chemotherapy is not effective and tumor localization and multiplicity make surgery and radiosurgery challenging and morbidity is often considerable. Thus, a new therapeutic approach is needed for these tumors. Using a primary human in vitro model for Merlin-deficient tumors, we report that the Ras/Raf/mitogen-activated protein, extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) scaffold, kinase suppressor of Ras 1 (KSR1), has a vital role in promoting schwannomas development. We show that KSR1 overexpression is involved in many pathological phenotypes caused by Merlin loss, namely multipolar morphology, enhanced cell-matrix adhesion, focal adhesion and, most importantly, increased proliferation and survival. Our data demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesion is more dependent on KSR1 than MEK1/2. Immunoprecipitation analysis reveals that KSR1 is a novel binding partner of Merlin, which suppresses KSR1's function by inhibiting the binding between KSR1 and c-Raf. Our proteomic analysis also demonstrates that KSR1 interacts with several Merlin downstream effectors, including E3 ubiquitin ligase CRL4DCAF1. Further functional studies suggests that KSR1 and DCAF1 may co-operate to regulate schwannomas formation. Taken together, these findings suggest that KSR1 serves as a potential therapeutic target for Merlin-deficient tumors.

Service to an interdisciplinary need-group from computerised secondary services

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Drug action on anxiety models with special reference to serotonergic mechanisms

A study has been made of drugs acting at 5-HT receptors on animal models of anxiety. An elevated X-maze was used as a model of anxiety for rats and the actions of various ligands for the 5-HT receptor, and its subtypes, were examined in this model. 5-HT agonists, with varying affinities for the 5-HT receptor subtypes, were demonstrated to have anxiogenic-like activity. The 5-HT2 receptor antagonists ritanserin and ketanserin exhibited an anxiolytic-like profile. The new putatuve anxiolytics ipsapirone and buspirone, which are believed to be selective for 5-HT1 receptors, were also examined. The former had an anxiolytic profile whilst the latter was without effect. Antagonism studies showed the anxiogenic response to 8-hydroxy-2-(Di-n-propylamino)tetralin (8-OH-DPAT) to be antagonised by ipsapirone, pindolol, alprenolol and para-chlorophenylalanine, but not by diazepam, ritanserin, metoprolol, ICI118,551 or buspirone. To confirm some of the results obtained in the elevated X-maze the Social Interaction Test of anxiety was used. Results in this test mirrored the effects seen with the 5-HT agonists, ipsapirone and pindolol, whilst the 5-HT2 receptor antagonists were without effect. Studies using operant conflict models of anxiety produced marginal and varying results which appear to be in agreement with recent criticisms of such models. Finally, lesions of the dorsal raphe nucleus (DRN) were performed in order to investigate the mechanisms involved in the production of the anxiogenic response to 8-OH-DPAT. Overall the results lend support to the involvement of 5-HT, and more precisely 5-HT1, receptors in the manifestation of anxiety in such animal models.

The Effect of low-grade aggregates on the abrasion resistance of concrete

Three types of crushed rock aggregate were appraised, these being Carboniferous Sandstone, Magnesian Limestone and Jurassic Limestone. A comprehensive aggregate testing programme assessed the properties of these materials. Two series of specimen slabs were cast and power finished using recognised site procedures to assess firstly the influence of these aggregates as the coarse fraction, and secondly as the fine fraction. Each specimen slab was tested at 28 days under three regimes to simulate 2-body abrasion, 3-body abrasion and the effect of water on the abrasion of concrete. The abrasion resistance was measured using a recognised accelerated abrasion testing apparatus employing rotating steel wheels. Relationships between the aggregate and concrete properties and the abrasion resistance have been developed with the following properties being particularly important - Los Angeles Abrasion and grading of the coarse aggregate, hardness of the fine aggregate and water-cement ratio of the concrete. The sole use of cube strength as a measure of abrasion resistance has been shown to be unreliable by this work. A graphical method for predicting the potential abrasion resistance of concrete using various aggregate and concrete properties has been proposed. The effect of varying the proportion of low-grade aggregate in the mix has also been investigated. Possible mechanisms involved during abrasion have been discussed, including localised crushing and failure of the aggregate/paste bond. Aggregates from each of the groups were found to satisfy current specifications for direct finished concrete floors. This work strengthens the case for the increased use of low-grade aggregates in the future.

Pre-conception care : current practice and methods of provision

This thesis examines the present provisions for pre-conception care and the views of the providers of services. Pre-conception care is seen by some clinicians and health educators as a means of making any necessary changes in life style, corrections to imbalances in the nutritional status of the prospective mother (and father) and the assessment of any medical problems, thus maximizing the likelihood of the normal development of the baby. Pre-conception care may be described as a service to bridge the gap between the family planning clinic and the first ante-natal booking appointment. There were three separate foci for the empirical research - the Foresight organisation (a charity which has pioneered pre-conception care in Britain); the pre-conception care clinic at the West London Hospital, Hammersmith; and the West Midlands Regional Health Authority. The six main sources of data were: twenty five clinicians operating Foresight pre-conception clinics, couples attending pre-conception clinics, committee members of the Foresight organisation, staff of the West London Hospital pre-conception clinic, Hammersmith, District Health Education Officers working in the West Midlands Regional Health Authority and the members of the Ante-Natal Care Action Group, a sub-group of the Regional Health Advisory Group on Health Promotion and Preventive Medicine. A range of research methods were adopted. These were as follows: questionnaires and report forms used in co-operation with the Foresight clinicians, interviews, participant observation discussions and informal meetings and, finally, literature and official documentation. The research findings illustrated that pre-conception care services provided at the predominantly private Foresight clinics were of a rather `ad hoc' nature. The type of provision varied considerably and clearly reflected the views held by its providers. The protocol which had been developed to assist in the standardization of results was not followed by the clinicians. The pre-conception service provided at the West London Hospital shared some similarities in its approach with the Foresight provision; a major difference was that it did not advocate the use of routine hair trace metal analysis. Interviews with District Health Education Officers and with members of the Ante Natal Care Action Group revealed a tentative and cautious approach to pre-conception care generally and to the Foresight approach in particular. The thesis concludes with a consideration of the future of pre-conception care and the prospects for the establishment of a comprehensive pre-conception care service.

Remote-controlled experiments with cloud chemistry

Developing cleaner chemical processes often involves sophisticated flow-chemistry equipment that is not available in many economically developing countries. For reactions where it is the data that are important rather than the physical product, the networking of chemists across the internet to allow remote experimentation offers a viable solution to this problem.

Fabrication of high aspect ratio microfluidic devices using direct fs ablation

We present a single stage direct fs ablation results which show that it is possible to make high quality and high aspect ratio devices in a single stage process using a CAD optimised approach. © 2008 Optical Society of America.

An in vitro comparison of the incorporation, growth, and chondrogenic potential of human bone marrow versus adipose tissue mesenchymal stem cells in clinically relevant cell scaffolds used for cartilage repair

Aim. To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair. Methods. Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively. Results. A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro- Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source. Conclusion. Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue.