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G Wallis

Publications and source records attributed to G Wallis.

At least 19 recordsLinked to original sources
PubMed2002

Identification of a locus for a form of spondyloepiphyseal dysplasia on chromosome 15q26.1: exclusion of aggrecan as a candidate gene.

We have investigated a family with an autosomal dominant form of spondyloepiphyseal dysplasia (SED) characterised by short stature and severe premature degenerative arthropathy. Previous studies have excluded linkage between this condition and the locus for the type II collagen gene. Here we report the identification of linkage between this disorder and a locus on the long arm of chromosome 15 between markers D15S979 and D15S1004. According to current linkage maps and sequence data, this locus includes that of the aggrecan gene (AGC1). Our linkage data from the SED family show, however, that AGC1 maps to a locus that is proximal to D15S979. This proximal location for AGC1 is further supported by linkage data from a second family with an autosomal recessive form of multiple epiphyseal dysplasia that also maps to the SED locus. In both families AGC1 is therefore excluded as a candidate gene.

Aggrecans↗
PubMed2001

Effects of temporal association on recognition memory.

The influence of temporal association on the representation and recognition of objects was investigated. Observers were shown sequences of novel faces in which the identity of the face changed as the head rotated. As a result, observers showed a tendency to treat the views as if they were of the same person. Additional experiments revealed that this was only true if the training sequences depicted head rotations rather than jumbled views; in other words, the sequence had to be spatially as well as temporally smooth. Results suggest that we are continuously associating views of objects to support later recognition, and that we do so not only on the basis of the physical similarity, but also the correlated appearance in time of the objects.

Analysis of Variance↗
PubMed2001

Production of tissue plasminogen activator (t-PA) in Aspergillus niger.

A protease-deficient strain of Aspergillus niger has been used as a host for the production of human tissue plasminogen activator (t-PA). In defined medium, up to 0.07 mg t-PA (g biomass)(-1) was produced in batch and fed-batch cultures and production was increased two- to threefold in two-phase batch cultures in which additional glucose was provided as a single pulse at the end of the first batch growth phase. Production was increased [up to 1.9 mg t-PA (g biomass)(-1)] by the addition of soy peptone to the defined medium. The rate of t-PA production in batch cultures supplemented with soy peptone (0.2 to 0.6 mg t-PA L(-1) h(-1)) was comparable to rates observed previously in high-producing mammalian or insect cell cultures. In glucose-limited chemostat culture supplemented with soy peptone, t-PA was produced at a rate of 0.7 mg t-PA L(-1) h(-1). Expression of t-PA in A. niger resulted in increased expression of genes (bipA, pdiA, and cypB) involved in the unfolded protein response (UPR). However, when cypB was overexpressed in a t-PA-producing strain, t-PA production was not increased. The t-PA produced in A. niger was cleaved into two chains of similar molecular weight to two-chain human melanoma t-PA. The two chains appeared to be stable for at least 16 h in culture supernatant of the host strain. However, in general, <1% of the t-PA produced in A. niger was active, and active t-PA disappeared from the culture supernatant during the stationary phase of batch cultures, suggesting that the two-chain t-PA may have been incorrectly processed or that initial proteolytic cleavage occurred within the proteolytic domain of the protein. Total t-PA (detected by enzyme-linked immunoassay) also eventually disappeared from culture supernatants, confirming significant extracellular proteolytic activity, even though the host strain was protease-deficient.

Aspergillus niger↗
PubMed2001

Deletions and duplications of Gly-Xaa-Yaa triplet repeats in the triple helical domains of type I collagen chains disrupt helix formation and result in several types of osteogenesis imperfecta.

Triple helix formation is a prerequisite for the passage of type I procollagen from the endoplasmic reticulum and secretion from the cell to form extracellular fibrils that will support mineral deposition in bone. Analysis of cDNA from 11 unrelated individuals with osteogenesis imperfecta (OI) revealed the presence of 11 novel, short in-frame deletions or duplications of three, nine, or 18 nucleotides in the helical coding regions of the COL1A1 and COL1A2 collagen genes. Triple helix formation was impaired, type I collagen alpha chains were post-translationally overmodified, and extracellular secretion was markedly reduced. With one exception, the obligate Gly-Xaa-Yaa repeat pattern of amino acids in the helical domains was not altered, but the Xaa- and Yaa position residues were out of register relative to the amino acid sequences of adjacent chains in the triple helix. Thus, the identity of these amino acids, in addition to third position glycines, is important for normal helix formation. These findings expand the known repertoire of uncommon in-frame deletions and duplications in OI, and provide insight into normal collagen biosynthesis and collagen triple helix formation.

Amino Acid Motifs↗
PubMed2001

Linear models of simple cells: correspondence to real cell responses and space spanning properties.

Despite their limitations, linear filter models continue to be used to simulate the receptive field properties of cortical simple cells. For theoreticians interested in large scale models of visual cortex, a family of self-similar filters represents a convenient way in which to characterise simple cells in one basic model. This paper reviews research on the suitability of such models, and goes on to advance biologically motivated reasons for adopting a particular group of models in preference to all others. In particular, the paper describes why the Gabor model, so often used in network simulations, should be dropped in favour of a Cauchy model, both on the grounds of frequency response and mutual filter orthogonality.

Animals↗
PubMed1999

DNA discovery.

Explore the source record for details and available documents.

DNA↗
PubMed1999

Phenyl-N-tert-butylnitrone demonstrates broad-spectrum inhibition of apoptosis-associated gene expression in endotoxin-treated rats.

Systemic exposure to gram-negative bacterial substances such as lipopolysaccharide (LPS, or endotoxin) induces an uncontrolled, massive inflammatory reaction which culminates in multiple system organ failure and death. Septic shock often does not respond to corticosteroids; however, certain low-molecular-weight antioxidant compounds have been discovered to possess potent anti-inflammatory action, and some of these novel compounds can rescue animals from experimentally induced septic shock. Phenyl-N-tert-butylnitrone (PBN) is the archetype of the nitrone class of antioxidants which we have previously shown to suppress LPS-induced cytokine biosynthesis in vivo. Using a multiprobe ribonuclease protection assay, we now demonstrate the ability of PBN to suppress proapoptotic gene expression in the LPS-induced model of endotoxic shock. The broad-spectrum gene-suppressive affects of PBN are discussed in the context of inflammatory signal transduction and models are proposed to explain why certain antioxidants may also possess anti-inflammatory and antiapoptotic properties.

Animals↗
PubMed1999

Learning to recognize objects.

Evidence from neurophysiological and psychological studies is coming together to shed light on how we represent and recognize objects. This review describes evidence supporting two major hypotheses: the first is that objects are represented in a mosaic-like form in which objects are encoded by combinations of complex, reusable features, rather than two-dimensional templates, or three-dimensional models. The second hypothesis is that transform-invariant representations of objects are learnt through experience, and that this learning is affected by the temporal sequence in which different views of the objects are seen, as well as by their physical appearance.

Journal Article↗
PubMed1998

Evidence for genetic anticipation in nodal osteoarthritis.

OBJECTIVE: Evidence was sought for genetic anticipation (disease occurring at an earlier age in subsequent generations, with increasing severity) in nodal osteoarthritis (NOA). METHODS: Age at symptom onset and disease severity was compared within 30 parent/offspring pairs with NOA. Correlation between the offspring age of disease onset and the parental age at conception was also assessed. RESULTS: The age at onset of nodal symptoms was earlier in the offspring (43 years (95% confidence intervals (CI) 38 to 47) v 61 (CI 58 to 65); mean difference 18 years (CI 13 to 22): p < 0.001) as was larger joint symptom onset (48 years (CI 41 to 55) v 67 (CI 61 to 73); mean difference 20 years (CI 13 to 27): p < 0.01). A negative correlation existed between age of offspring symptom onset and parental age at conception. Fifteen (50%) offspring had similar or more extensive disease than their parents. CONCLUSIONS: These results suggest genetic anticipation occurs in NOA and if confirmed a search for trinucleotide repeats is warranted.

Adult↗
PubMed1998

Spatio-temporal influences at the neural level of object recognition.

In late 1988, Miyashita published work reporting recordings of single cells in the inferotemporal cortex of the macaque monkey (Miyashita 1988 Nature 335 817-20). He described the responses of neurons to a sequence of random fractal pattern images, and how many of the neurons tested were seen to respond strongly to a subset of the images on the basis of sequence presentation order, i.e. appearance in time, rather than their spatial similarity. In this work, I describe a local Hebb-like learning rule which in conjunction with a simple feedforward neural architecture is capable of replicating the type of temporal-order association apparent in the cells from which he made recordings. The paper also advances reasons for requiring such learning by describing its possible role in establishing transformation invariant representations of objects.

Animals↗
PubMed1997

Optimal, unsupervised learning in invariant object recognition.

A means for establishing transformation-invariant representations of objects is proposed and analyzed, in which different views are associated on the basis of the temporal order of the presentation of these views, as well as their spatial similarity. Assuming knowledge of the distribution of presentation times, an optimal linear learning rule is derived. Simulations of a competitive network trained on a character recognition task are then used t highlight the success of this learning rule in relation to simple Hebbian learning and to show that the theory can give accurate quantitative predictions for the optimal parameters for such networks.

Animals↗
PubMed1997

Spin trapping agent phenyl N-tert-butylnitrone protects against the onset of drug-induced insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus is an autoimmune disease believed to be caused by an inflammatory process in the pancreas leading to selective destruction of the beta-cells. Cytokines and nitric oxide (NO) have been shown to be involved in this destruction. Phenyl N-tert-butylnitrone (PBN) has demonstrated protective effects against several pathological conditions including ischemia-reperfusion injury and endotoxin-induced shock. We report here that PBN co-administration can prevent the onset of the STZ-induced diabetes in mice. PBN co-treatment inhibited the streptozotocin (STZ)-induced hyperglycemia, the elevation in the level of glycated hemoglobin and weight loss in the treated mice. Histological observations indicated destruction of B-cells in the STZ-treated animals and its prevention by PBN co-treatment. EPR spin trapping experiments in the pancreas indicated the in vivo formation of NO in STZ-treated animals and its attenuation by PBN treatment.

Animals↗
PubMed1997

Invariant face and object recognition in the visual system.

Neurophysiological evidence is described, showing that some neurons in the macaque temporal cortical visual areas have responses that are invariant with respect to the position, size and view of faces and objects, and that these neurons show rapid processing and rapid learning. A theory is then described of how such invariant representations may be produced in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory proposes that neurons in these visual areas use a modified Hebb synaptic modification rule with a short-term memory trace to capture whatever can be captured at each stage that is invariant about objects as the object changes in retinal position, size, rotation and view. Simulations are then described which explore the operation of the architecture. The simulations show that such a processing system can build invariant representations of objects.

Animals↗
PubMed1996

In vivo spin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: a time-course study.

Spin trapping of nitric oxide (NO.) in vivo in liver, small intestine, kidney, and plasma of intact rats was accomplished using diethyldithiocarbamate (DETC) administered intraperitoneally. DETC combines with Fe2+ to form (DETC)2-Fe and is an excellent trapping agent for nitric oxide. DETC distribution and uptake by the organs of interest was determined and the formation of the active trapping agent (DETC)2-Fe was assayed in the various organs and plasma. The capacity of this spin trap to capture NO. in vivo was demonstrated by administering sodium nitroprusside to the animals. The trapping procedure was then used to assess the course of NO. generation during a 6 h period in animals that had been treated with endotoxin. The rate of NO. generation/gram tissue was determined during the last 15 min of each time period. The results indicate that induction of nitric oxide generation begins earliest in the small intestine, then in the liver, and still later in the kidney and plasma. Nitric oxide production was most intense in the liver and was still increasing at the end of the experiment. Control animals receiving the spin trapping agent showed only little or no evidence of nitric oxide production except for the small intestine. The results show that induction of NO. generation caused by endotoxin begins at different times in different organs.

Animals↗