Spatial Pattern Learning, Catastophic Forgetting and Optimal Rules of Synaptic Transmission

It is a neural network truth universally acknowledged, that the signal transmitted to a target node must be equal to the product of the path signal times a weight. Analysis of catastrophic forgetting by distributed codes leads to the unexpected conclusion that this universal synaptic transmission rule may not be optimal in certain neural networks. The distributed outstar, a network designed to support stable codes with fast or slow learning, generalizes the outstar network for spatial pattern learning. In the outstar, signals from a source node cause weights to learn and recall arbitrary patterns across a target field of nodes. The distributed outstar replaces the outstar source node with a source field, of arbitrarily many nodes, where the activity pattern may be arbitrarily distributed or compressed. Learning proceeds according to a principle of atrophy due to disuse whereby a path weight decreases in joint proportion to the transmittcd path signal and the degree of disuse of the target node. During learning, the total signal to a target node converges toward that node's activity level. Weight changes at a node are apportioned according to the distributed pattern of converging signals three types of synaptic transmission, a product rule, a capacity rule, and a threshold rule, are examined for this system. The three rules are computationally equivalent when source field activity is maximally compressed, or winner-take-all when source field activity is distributed, catastrophic forgetting may occur. Only the threshold rule solves this problem. Analysis of spatial pattern learning by distributed codes thereby leads to the conjecture that the optimal unit of long-term memory in such a system is a subtractive threshold, rather than a multiplicative weight.

Diet and Spatial Pattern of Foraging in Ectatomma opaciventre (Hymenoptera: Formicidae) in an Anthropic Area

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Oviposition pattern and within-season spatial and temporal variation of pre-dispersal seed predation in a population of Mimosa bimucronata trees

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

BPAG1 isoform-b: Complex distribution pattern in striated and heart muscle and association with plectin and α-actinin

BPAG1-b is the major muscle-specific isoform encoded by the dystonin gene, which expresses various protein isoforms belonging to the plakin protein family with complex, tissue-specific expression profiles. Recent observations in mice with either engineered or spontaneous mutations in the dystonin gene indicate that BPAG1-b serves as a cytolinker important for the establishment and maintenance of the cytoarchitecture and integrity of striated muscle. Here, we studied in detail its distribution in skeletal and cardiac muscles and assessed potential binding partners. BPAG1-b was detectable in vitro and in vivo as a high molecular mass protein in striated and heart muscle cells, co-localizing with the sarcomeric Z-disc protein alpha-actinin-2 and partially with the cytolinker plectin as well as with the intermediate filament protein desmin. Ultrastructurally, like alpha-actinin-2, BPAG1-b was predominantly localized at the Z-discs, adjacent to desmin-containing structures. BPAG1-b was able to form complexes with both plectin and alpha-actinin-2, and its NH(2)-terminus, which contains an actin-binding domain, directly interacted with that of plectin and alpha-actinin. Moreover, the protein level of BPAG1-b was reduced in muscle tissues from plectin-null mutant mice versus wild-type mice. These studies provide new insights into the role of BPAG1-b in the cytoskeletal organization of striated muscle.

Competition may explain the fine-scale spatial patterns and genetic structure of two co-occurring plant congeners

1. The spatial distribution of individual plants within a population and the population’s genetic structure are determined by several factors, like dispersal, reproduction mode or biotic interactions. The role of interspecific interactions in shaping the spatial genetic structure of plant populations remains largely unknown. 2. Species with a common evolutionary history are known to interact more closely with each other than unrelated species due to the greater number of traits they share. We hypothesize that plant interactions may shape the fine genetic structure of closely related congeners. 3. We used spatial statistics (georeferenced design) and molecular techniques (ISSR markers) to understand how two closely related congeners, Thymus vulgaris (widespread species) and T. loscosii (narrow endemic) interact at the local scale. Specific cover, number of individuals of both study species and several community attributes were measured in a 10 × 10 m plot. 4. Both species showed similar levels of genetic variation, but differed in their spatial genetic structure. Thymus vulgaris showed spatial aggregation but no spatial genetic structure, while T. loscosii showed spatial genetic structure (positive genetic autocorrelation) at short distances. The spatial pattern of T. vulgaris’ cover showed significant dissociation with that of T. loscosii. The same was true between the spatial patterns of the cover of T. vulgaris and the abundance of T. loscosii and between the abundance of each species. Most importantly, we found a correlation between the genetic structure of T. loscosii and the abundance of T. vulgaris: T. loscosii plants were genetically more similar when they were surrounded by a similar number of T. vulgaris plants. 5. Synthesis. Our results reveal spatially complex genetic structures of both congeners at small spatial scales. The negative association among the spatial patterns of the two species and the genetic structure found for T. loscosii in relation to the abundance of T. vulgaris indicate that competition between the two species may account for the presence of adapted ecotypes of T. loscosii to the abundance of a competing congeneric species. This suggests that the presence and abundance of close congeners can influence the genetic spatial structure of plant species at fine scales.

Water Deficit and Spatial Pattern of Leaf Development. Variability in Responses Can Be Simulated Using a Simple Model of Leaf Development1

We analyzed the effect of short-term water deficits at different periods of sunflower (Helianthus annuus L.) leaf development on the spatial and temporal patterns of tissue expansion and epidermal cell division. Six water-deficit periods were imposed with similar and constant values of soil water content, predawn leaf water potential and [ABA] in the xylem sap, and with negligible reduction of the rate of photosynthesis. Water deficit did not affect the duration of expansion and division. Regardless of their timing, deficits reduced relative expansion rate by 36% and relative cell division rate by 39% (cells blocked at the G0-G1 phase) in all positions within the leaf. However, reductions in final leaf area and cell number in a given zone of the leaf largely differed with the timing of deficit, with a maximum effect for earliest deficits. Individual cell area was only affected during the periods when division slowed down. These behaviors could be simulated in all leaf zones and for all timings by assuming that water deficit affects relative cell division rate and relative expansion rate independently, and that leaf development in each zone follows a stable three-phase pattern in which duration of each phase is stable if expressed in thermal time (C. Granier and F. Tardieu [1998b] Plant Cell Environ 21: 695–703).

The spatial pattern of senile plaques, neurofibrillary tangles and A4 deposits in Alzheimer's disease

The spatial patterns of senile plaques (SP) and neurofibrillary tangles (NFT) as visualised using the Gallyas stain and of discrete A4 protein deposits were determined in coronal serial sections from a variety of brain regions in six elderly patients with Alzheimer's disease (AD). These lesions showed clustering in virtually all tissues examined with many of the clusters being regularly spaced. These spatial patterns were compared with the clustering observed for SP and NFT stained by the Glees and Marsland method in the same tissues. The data suggest that on average, while the regular clusters of A4 deposits and NFT were of approximately the same mean diameter (3600 microns), clusters of both Glees and Gallyas SP were approximately half this diameter (1800 - 2000 microns). If SP develop in local areas of the brain where both A4 deposition and neurofibrillary changes have occurred, the data suggest that the SP clusters would represent the region of overlap of the A4 deposits and neurofibrillary changes. Various hypothese are advocated to explain the regular clsuetring of the A4 deposits.

Density and spatial pattern of β-amyloid (Aβ) deposits in corticobasal degeneration

Corticobasal degeneration (CBD) is a rare, progressive movement disorder characterized neuropathologically by widespread neuronal and glial pathology including tau-immunoreactive neuronal cytoplasmic inclusions (NCI), oligodendroglial inclusions (GI), and astrocytic plaques (AP). However, ß -amyloid (A ß) deposits have been observed in the cerebral cortex and/or hippocampus in some cases of CBD. To clarify the role of Aß deposition in CBD, the densities and spatial patterns of the Aß deposits were studied in three cases. In two cases, expressing apolipoprotein E (APOE) genotypes 2/3 or 3/3, the densities of the Aß deposits were similar to those in normal elderly brain. In the remaining case, expressing APOE genotype 3/4, Aß deposition was observed throughout the cerebral cortex, sectors CA1 and CA2 of the hippocampus, and the molecular layer of the dentate gyrus. The densities of the Aß deposits in this case were typical of those observed in Alzheimer's disease (AD). In the three cases, clustering of Aß deposits, with clusters ranging in size from 200 to >6400 µm in diameter, was evident in 25/27 (93%) of analyses. In addition, the clusters of Aß deposits were regularly distributed parallel to the tissue boundary in 52% of analyses, a spatial pattern similar to that observed in AD. These results suggest: (1) in some CBD cases, Aß pathology is age-related, (2) more extensive Aß deposition is observed in some cases, the density and spatial patterns of the Aß deposits being similar to AD, and (3) extensive deposition of Aß in CBD may be associated with APOE allele e4.

Density and spatial pattern of the neuropathological changes in the cerebellum in the prion disease variant Creutzfeldt-Jakob disease (vCJD)

The objective of this chapter is to quantify the neuropathology of the cerebellar cortex in cases of the prion disease variant Creutzfeldt-Jakob disease (vCJD). Hence, sequential sections of the cerebellum of 15 cases of vCJD were stained with H/E, or immunolabelled with a monoclonal antibody 12F10 against prion protein (PrP) and studied using quantitative techniques and spatial pattern analysis. A significant loss of Purkinje cells was evident in all cases. Densities of the vacuolation and the protease resistant form of prion protein (PrPSc) in the form of diffuse and florid plaques were greater in the granule cell layer (GL) than the molecular layer (ML). In the ML, vacuoles and PrPSc plaques, occurred in clusters which were regularly distributed along the folia, larger clusters of vacuoles and diffuse plaques being present in the GL. There was a negative spatial correlation between the vacuoles and the surviving Purkinje cells in the ML and a positive spatial correlation between the clusters of vacuoles and the diffuse PrPSc plaques in the ML and GL in five and six cases respectively. A canonical variate analysis (CVA) suggested a negative correlation between the densities of the vacuolation in the GL and the diffuse PrPSc plaques in the ML. The data suggest: 1) all laminae of the cerebellar cortex were affected by the pathology of vCJD, the GL more severely than the ML, 2) the pathology was topographically distributed especially in the Purkinje cell layer and GL, 3) pathological spread may occur in relation to a loop of anatomical projections connecting the cerebellum, thalamus, cerebral cortex, and pons, and 4) there are differences in the pathology of the cerebellum in vCJD compared with the M/M1 subtype of sporadic CJD (sCJD).

Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

Socio-environmental factors and suicide in Queensland, Australia

Suicide has drawn much attention from both the scientific community and the public. Examining the impact of socio-environmental factors on suicide is essential in developing suicide prevention strategies and interventions, because it will provide health authorities with important information for their decision-making. However, previous studies did not examine the impact of socio-environmental factors on suicide using a spatial analysis approach. The purpose of this study was to identify the patterns of suicide and to examine how socio-environmental factors impact on suicide over time and space at the Local Governmental Area (LGA) level in Queensland. The suicide data between 1999 and 2003 were collected from the Australian Bureau of Statistics (ABS). Socio-environmental variables at the LGA level included climate (rainfall, maximum and minimum temperature), Socioeconomic Indexes for Areas (SEIFA) and demographic variables (proportion of Indigenous population, unemployment rate, proportion of population with low income and low education level). Climate data were obtained from Australian Bureau of Meteorology. SEIFA and demographic variables were acquired from ABS. A series of statistical and geographical information system (GIS) approaches were applied in the analysis. This study included two stages. The first stage used average annual data to view the spatial pattern of suicide and to examine the association between socio-environmental factors and suicide over space. The second stage examined the spatiotemporal pattern of suicide and assessed the socio-environmental determinants of suicide, using more detailed seasonal data. In this research, 2,445 suicide cases were included, with 1,957 males (80.0%) and 488 females (20.0%). In the first stage, we examined the spatial pattern and the determinants of suicide using 5-year aggregated data. Spearman correlations were used to assess associations between variables. Then a Poisson regression model was applied in the multivariable analysis, as the occurrence of suicide is a small probability event and this model fitted the data quite well. Suicide mortality varied across LGAs and was associated with a range of socio-environmental factors. The multivariable analysis showed that maximum temperature was significantly and positively associated with male suicide (relative risk [RR] = 1.03, 95% CI: 1.00 to 1.07). Higher proportion of Indigenous population was accompanied with more suicide in male population (male: RR = 1.02, 95% CI: 1.01 to 1.03). There was a positive association between unemployment rate and suicide in both genders (male: RR = 1.04, 95% CI: 1.02 to 1.06; female: RR = 1.07, 95% CI: 1.00 to 1.16). No significant association was observed for rainfall, minimum temperature, SEIFA, proportion of population with low individual income and low educational attainment. In the second stage of this study, we undertook a preliminary spatiotemporal analysis of suicide using seasonal data. Firstly, we assessed the interrelations between variables. Secondly, a generalised estimating equations (GEE) model was used to examine the socio-environmental impact on suicide over time and space, as this model is well suited to analyze repeated longitudinal data (e.g., seasonal suicide mortality in a certain LGA) and it fitted the data better than other models (e.g., Poisson model). The suicide pattern varied with season and LGA. The north of Queensland had the highest suicide mortality rate in all the seasons, while there was no suicide case occurred in the southwest. Northwest had consistently higher suicide mortality in spring, autumn and winter. In other areas, suicide mortality varied between seasons. This analysis showed that maximum temperature was positively associated with suicide among male population (RR = 1.24, 95% CI: 1.04 to 1.47) and total population (RR = 1.15, 95% CI: 1.00 to 1.32). Higher proportion of Indigenous population was accompanied with more suicide among total population (RR = 1.16, 95% CI: 1.13 to 1.19) and by gender (male: RR = 1.07, 95% CI: 1.01 to 1.13; female: RR = 1.23, 95% CI: 1.03 to 1.48). Unemployment rate was positively associated with total (RR = 1.40, 95% CI: 1.24 to 1.59) and female (RR=1.09, 95% CI: 1.01 to 1.18) suicide. There was also a positive association between proportion of population with low individual income and suicide in total (RR = 1.28, 95% CI: 1.10 to 1.48) and male (RR = 1.45, 95% CI: 1.23 to 1.72) population. Rainfall was only positively associated with suicide in total population (RR = 1.11, 95% CI: 1.04 to 1.19). There was no significant association for rainfall, minimum temperature, SEIFA, proportion of population with low educational attainment. The second stage is the extension of the first stage. Different spatial scales of dataset were used between the two stages (i.e., mean yearly data in the first stage, and seasonal data in the second stage), but the results are generally consistent with each other. Compared with other studies, this research explored the variety of the impact of a wide range of socio-environmental factors on suicide in different geographical units. Maximum temperature, proportion of Indigenous population, unemployment rate and proportion of population with low individual income were among the major determinants of suicide in Queensland. However, the influence from other factors (e.g. socio-culture background, alcohol and drug use) influencing suicide cannot be ignored. An in-depth understanding of these factors is vital in planning and implementing suicide prevention strategies. Five recommendations for future research are derived from this study: (1) It is vital to acquire detailed personal information on each suicide case and relevant information among the population in assessing the key socio-environmental determinants of suicide; (2) Bayesian model could be applied to compare mortality rates and their socio-environmental determinants across LGAs in future research; (3) In the LGAs with warm weather, high proportion of Indigenous population and/or unemployment rate, concerted efforts need to be made to control and prevent suicide and other mental health problems; (4) The current surveillance, forecasting and early warning system needs to be strengthened, to trace the climate and socioeconomic change over time and space and its impact on population health; (5) It is necessary to evaluate and improve the facilities of mental health care, psychological consultation, suicide prevention and control programs; especially in the areas with low socio-economic status, high unemployment rate, extreme weather events and natural disasters.

Developing the Pattern and Structure Assessment (PASA) interview to inform early mathematics learning

The Pattern and Structure Mathematical Awareness Program(PASMAP) stems from a 2-year longitudinal study on students’ early mathematical development. The paper outlines the interview assessment the Pattern and Structure Assessment(PASA) designed to describe students’ awareness of mathematical pattern and structure across a range of concepts. An overview of students’ performance across items and descriptions of their structural development are described.