Neurodevelopmental synaptopathies: Insights from behaviour in rodent models of synapse gene mutations.

The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated. Specifically, we focus on the main behavioural phenotypes that have been documented in these animal models, to consolidate our current understanding of how synapse genes regulate key behavioural and cognitive domains. These studies provide insights into better understanding the basis of the overlapping genetic and cognitive heterogeneity observed in neurodevelopmental disorders.

The oncogenic potential of human papillomaviruses: a review on the role of host genetics and environmental cofactors.

Human papillomaviruses (HPVs), with over 100 genotypes, are a very complex group of human pathogenic viruses. In most cases, HPV infection results in benign epithelial proliferations (verrucae). However, oncogenic types of HPV may induce malignant transformation in the presence of cofactors. For example, over 99% of all cervical cancers and a majority of vulval, vaginal, anal and penile cancers are the result of oncogenic HPV types. Such HPV types have been increasingly linked to other epithelial cancers involving the skin, larynx and oesophagus. Although viral infection is necessary for neoplastic transformation, evidence suggests that host and environmental cofactors are also required. Research investigating HPV oncogenesis is complex and quite extensive. The inability to produce mature HPV virions in animal models has been a major limitation in fully elucidating the oncogenic potential and role of associated cofactors in promoting malignant transformation in HPV-infected cells. We have reviewed the literature and provide a brief account of the current understanding of HPV oncogenesis, emphasizing the role of genetic susceptibility, immune response, and environmental and infectious cofactors.

Development of a standardised approach to river habitat assessment in Australia.

Despite the demonstrated utility of the Australian River Assessment Scheme (AUSRIVAS) to provide national-scale information on the biological condition of rivers, there is no commensurate scheme that can provide standardised information on physical habitat. Existing habitat assessment methods are not suitable for implementation on a national scale, so we present a new habitat assessment protocol that incorporates favorable elements of existing methods. Habitat Predictive Modelling forms the basis for the protocol because it can predict the occurrence of local-scale features from large-scale data, uses the reference condition concept, can be modified to incorporate a range of biologically and geomorphologically relevant variables, and employs a rapid survey approach. However, the protocol has been augmented with geomorphological variables and incorporates principles of hierarchy and geomorphological river zonation. There are four sequential components to the implementation of the protocol: reference site selection, data collection, predictive model construction and assessment of test sites using the predictive models. Once implemented, the habitat assessment protocol will provide a standardised tool for the assessment of river habitat condition at a variety of governance levels.

Framework for designing sampling programs.

A general framework for designing sampling programs is described. As part of the sampling program the problem of concern, or reason for sampling, needs to be clearly stated and objectives specified. The development of a conceptual model will assist the clarification of objectives and the choice of indicators to be sampled.Objectives can then be stated as testable hypotheses and decisions made about the samallest difference/changes that are to be detected/observed by the sampling.To allow the collection of representative samples, and the statistical analysis of data to be collected, the potential sources of variability in the data must be considered. Site, selection, frequency and replication must account for the expected variability.Before field collection of samples occurs, the sample collection device needs to be tested as to its efficiency to collect a representative sample. It also will usually be necessary to consider how samples are to be preserved to inhibit biological and chemical change. All sample programs require a quality assurance program to identify, measure and control errors.As well as the above the cost-effectiveness of the program should be evaluated in terms of maximizing the information obtained/cost.

The effect of oculomotor training on reading efficiency.

The purpose of this study was to record and measure, by means of a microcomputer, the reading eye movements and reading efficiency of a sample of "poor readers" from an adult, professional school population. A program of oculomotor skill enhancement training was given to 10 students who failed an academically appropriate reading test. Their pre- and post-training reading performance was compared to that of a group of students who also failed the reading test but received no such training. All subjects' eye movements were monitored and recorded individually while reading, using a Visagraph Eye-Movement Recording System. The subjects were split into an experimental group (receiving training) and a control group (receiving no training). Following a 12-hour program of "in office" and "home" training, the group receiving oculomotor training showed trends toward improved reading eye movement efficiency (number of regressions, number of fixations and span of recognition), compared to that of the untrained group.

Water quality assessment programs in Australia deciding what to measure, and how and where to use bioindicators.

Effective water quality assessment programs require the formulation of common objectives between managers who are making decisions and scientists who are obtaining the information on which those decisions are to be made. The data collected must be apropriate for use in the decision making process. After the objectives have been formulated a number of testable hypotheses can be proposed and evaluated in terms of what information is required for decision making.From a management perspective it is important to know if an impact occurs and what management strategy to adopt to reduce or eliminate the impact. When bioaccumulators are used to indicate environmental quality the organisms proposed need to be fully evaluated before being used. Communities, which are often used to assess levels of impact, have the capacity to assimilate pollutants and they will function under pollutant stress. Thus managers need to make value judgements about when a community structure or function has shifted from acceptable to adverse. Bioassays in which the effects of pollutants on growth, biochemistry and behaviour are measured, give an indication of the sub-lethal effects of a pollutant, but it is difficult to set meaningful levels that are not to be exceeded for use by managers.Difficulties in using chemical and biological data mainly arise from a lack of appreciation of environmental heterogeneity. The data obtained must meet the needs for statistically testing hypotheses. Before programs can be designed to meet statistical needs the potential sources of variability must be considered. Once the minimum differences that are seen as important have been determined, the number of replicates needed can be calculated. Data verification is also needed, as if the validity of data is questioned, so will any decisions that have been made based on those data. Finally programs should be designed to minimize the sampling effort/cost to meet the objectives.

Effectiveness of mine rehabilitation in relation to water quality.

When mining is completed the sites may be completely restored to the original ecosystem, rehabilitated for some desirable environmental characteristics, desirable alternative ecosystems created or just neglected. The strategy adopted will depend on the intended uses of the parts of the environment (including water) affected by the mining. An example of rehabilitation of a metal mine near the Australian Federal Capital is used to illustrate the problems that may be encountered. These include: lack of controls while mining is underway; catastrophic events, such as the collapse of a settling dam, lack of site specific understanding of pyrite oxidation processes, particularly those that are biologically enhanced; the need for adequate biological information on which to base decisions to meet biological information on which to base decisions to meet biological objectives. Experience has shown that biological collections such studies should be stored in museums where they will be valuable for comparisons of changes over long periods.