The very C-terminus of PRK1/PKN is essential for its activation by RhoA and downstream signaling

PRK1 is a lipid- and Rho GTPase-activated serine/threonine protein kinase implicated in the regulation of receptor trafficking, cytoskeletal dynamics and tumorigenesis. Although Rho binding has been mapped to the HR1 region in the regulatory domain of PRK1, the mechanism involved in the control of PRK1 activation following Rho binding is poorly understood. We now provide the first evidence that the very C-terminus beyond the hydrophobic motif in PRK1 is essential for the activation of this kinase by RhoA. Deletion of the HR1 region did not completely abolish the binding of PRK1-ΔHR1 to GTPγS-RhoA nor the activation of this mutant by GTPγS-RhoA in vitro. In contrast, removing of the last six amino acid residues from the C-terminus of PRK1 or truncating of a single C-terminal residue from PRK1-ΔHR1 completely abrogated the activation of these mutants by RhoA both in vitro and in vivo. The critical dependence of the very C-terminus of PRK1 on the signaling downstream of RhoA was further demonstrated by the failure of the PRK1 mutant lacking its six C-terminal residues to augment lisophosphatidic acid-elicited neurite retraction in neuronal cells. Thus, we show that the HR1 region is necessary but not sufficient in eliciting a full activation of PRK1 upon binding of RhoA. Instead, such activation is controlled by the very C-terminus of PRK1. Our results also suggest that the very C-terminus of PRK1, which is the least conserved among members of the protein kinase C superfamily, is a potential drug target for pharmacological intervention of RhoA-mediated signaling pathways

Woodlot Ownership and Forest Cover in Maine

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A guide to interviewing children : essential skills for counsellors, police, lawyers and social workers

This book has been written by two people who really understand children. [They show how to] create opportunities to reduce the trauma of the interview and significantly improve the quality of the information obtained. Chief Constable A.J. Butler Gloucestershire Constabulary A few years ago, a Chief Justice said that it was unnecessary to educate lawyers and judges in the techniques of interviewing children because it was 'just common sense'. The authors show that successful interviewing requires much more than 'common sense'. Freda Briggs, Professor of Child Development, University of South Australia...an excellent book for students and professionals in forensic psychology, policing and social work.Helen Westcott, PhD, The Open UniversityIt is critical that children are interviewed properly in cases of suspected abuse or where the children may be witnesses to or victims of a crime. Poor questioning can upset the child further and contaminate evidence that may be needed in court. Interviewing Children is a practical guide to interviewing techniques for a range of professionals including welfare workers, psychologists, schoolteachers and counsellors, police officers and lawyers. Step by step, it outlines the key stages of an interview, and how to respond to the child's needs during an interview. It explains how to deal with children of different ages and from different backgrounds, and also how to work with their parents. Particular attention is paid to the sensitive issue of sexual abuse, and the problems created by multiple interviews.Clare Wilson lectures in the Department of Psychology at the University of Sydney. Martine Powell lectures in the School of Psychology at Deakin University. Both have trained police officers, social workers and legal professionals in interviewing techniques in Australia and the UK.------------------Full quotes to go on half-title page:This book has been written by two people who really understand children. In passing on their knowledge to professionals who engage with children in the interview room, they create opportunities to reduce the trauma of the interview and significantly improve the quality of the information obtained. Writing in a clear and fresh style, the authors have produced a book which is valuable as a point of reference, a day to day tool and as a training aid to develop skills.Chief Constable A.J. Butler Gloucestershire ConstabularyThis book should be read by all professionals who work with children and could findthemselves receiving disclosures of abuse. It is practical, easy to read and full of examples and hints. It should be a compulsory text for social work studen

Income tax test, materials & essential cases

A comprehensive cases and materials book intended for commerce or law students undertaking semester-length courses in Australian income tax law.

Corporations law text and essential cases

Corporations Law: Text and Essential Cases is designed as a student text but will be a useful book for practitioners seeking a good, current, concise book on corporations law. Author Julie Cassidy is a proven, successful author and has carefully ensured that the case extracts in this book are long enough to be useful to lawyers needing to cite case authorities in opinions and court submissions.

Regional-scale models for relating land cover to basin surface-water quality using remotely sensed data in a GIS

Plant-based management systems implementing deep-rooted, perennial vegetation have been identified as important in mitigating the spread of secondary dryland salinity due to its capacity to influence water table depth. The Glenelg Hopkins catchment is a highly modified watershed in the southwest region of Victoria, where dryland salinity management has been identified as a priority. Empirical relationships between the proportion of native vegetation and in-stream salinity were examined in the Glenelg Hopkins catchment using a linear regression approach. Whilst investigations of these relationships are not unique, this is the first comprehensive attempt to establish a link between land use and in-stream salinity in the study area. The results indicate that higher percentage land cover with native vegetation was negatively correlated with elevated in-stream salinity. This inverse correlation was consistent across the 3 years examined (1980, 1995, and 2002). Recognising the potential for erroneously inferring causal relationships, the methodology outlined here was both a time and cost-effective tool to inform management strategies at a regional scale, particularly in areas where processes may be operating at scales not easily addressed with on-site studies.

Appraisal of random and systematic land cover transitions for regional water balance and revegetation strategies

This study describes the use of landscape transition analysis as a means for effective basin management. Land cover transitions from 1995 to 2002 were analyzed using a cross-tabulation matrix for an important economic zone in south-west Victoria, Australia. Specifically, the matrix was used to determine whether the transitions were random or systematic. Random landscape transitions occur when a land cover replaces other land covers in proportion to their availability. Systematic landscape transitions occur when there are deviations from random patterns, and land use types ‘target’ other land use types for replacement. The analysis was conducted with 11 land cover categories and showed that dryland pastures have been systematically losing area to dryland crops and blue gum (Eucalyptus globulus) plantations. Dryland crops have systematically expanded in the north-east of the catchment, an area where increasing in-stream salinization has occurred concurrently with this transition. The systematic expansion of the blue gum plantations has been predominantly in the south-west of the catchment and has the potential to reduce stream flows and groundwater recharge in an already water-stressed region, as blue gums use more water than the dryland pastures they are replacing. All other transitions were largely random. These findings have implications for land use planning in the study area for regional water balance and revegetation strategies. Landscape transition analysis is a cost-effective means of contributing to the management of water resources at a regional scale, and is highly recommended for future basin planning.

Association of reduced riparian vegetation cover in agricultural landscapes with coarse detritus dynamics in lowland streams

Studies were conducted on streams flowing through agricultural floodplains in south-eastern Australia to quantify whether reductions in riparian canopy cover were associated with alterations to the input and benthic standing stocks of coarse allochthonous detritus. Comparisons were made among three farmland reaches and three reaches within reserves with intact cover of remnant overstorey trees. Detritus inputs to these reaches were measured monthly over 2 years using litter traps. Direct inputs to streams within the reserves were relatively high (550–617 g ash free dry weight (AFDW) m^–2 year^–1), but were lower at farmland reaches with the lowest canopy covers (83–117 gAFDW m^–2 year^–1). Only a minor fraction of the total allochthonous input (<10%) entered any of the study reaches laterally. The mean amounts of benthic detritus were lowest in the most open farmland reaches. Standing stocks of benthic detritus were found to be highly patchy across a large number of agricultural streams, but were consistently very low where the streamside canopy cover was below ~35%. Canopy cover should be restored along cleared agricultural streams because allochthonous detritus is a major source of food and habitat for aquatic ecosystems. Given the absence of pristine lowland streams in south-eastern Australia, those reaches with the most intact remnant overstorey canopies should be used to guide restoration.

Human sympathetic nerve biology : parallel influences of stress and epigenetics in essential hypertension and panic disorder

Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress—a disputed proposition—we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation-related inhibitory transcription factor MeCP2.

Chronic mental stress is a cause of essential hypertension : presence of biological markers of stress

1. In searching for biological evidence that essential hypertension is caused by chronic mental stress, a disputed proposition, parallels are noted with panic disorder, which provides an explicit clinical model of recurring stress responses.
2. There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. Plasma cortisol is elevated in both.
3. In panic disorder and essential hypertension, but not in health, single sympathetic nerve fibres commonly fire repeatedly within an individual cardiac cycle; this appears to be a signature of stress exposure. For both conditions, adrenaline cotransmission is present in sympathetic nerves.
4. Tissue nerve growth factor is increased in both (nerve growth factor is a stress reactant). There is induction of the adrenaline synthesizing enzyme, phenylethanolamine-N-methyltransferase, in sympathetic nerves, an explicit indicator of mental stress exposure.
5. The question of whether chronic mental stress causes high blood pressure, still hotly debated, has been reviewed by an Australian Government body, the Specialist Medical Review Council. Despite the challenging medicolegal implications, the Council determined that stress is one proven cause of hypertension, this ruling being published in the 27 March 2002 Australian Government Gazette. This judgement was reached after consideration of the epidemiological evidence, but in particular after review of the specific elements of the neural pathophysiology of essential hypertension, described above.

Corporations law : text and essential cases

Corporations Law: Text and Essential Cases is designed specifically to meet the needs of students undertaking one-semester, case-based courses in Corporations Law. The 13 chapters each contain extracts from the leading cases supported by commentary, further readings, and review questions.

The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice

Although mdx mice share the same genetic defect and lack dystrophin expression as in Duchenne muscular dystrophy (DMD), their limb muscles have a high regenerative capacity that ensures a more benign phenotype and essentially normal function. The cellular pathways responsible for this enhanced regenerative capacity are unknown. We tested the hypothesis that the calcineurin signal transduction pathway is essential for the successful regeneration following severe degeneration observed in the limb muscles of young mdx mice (2–4 weeks old) and that inhibition of this pathway using cyclosporine A (CsA) would exacerbate the dystrophic pathology. Eighteen-day-old mdx and C57BL/10 mice were treated with CsA for 16 days. CsA administration severely disrupted muscle regeneration in mdx mice, but had minimal effect in C57BL/10 mice. Muscles from CsA-treated mdx mice had fewer centrally nucleated fibers and extensive collagen, connective tissue, and mononuclear cell infiltration than muscles from vehicle-treated littermates. The deleterious effects of CsA on muscle morphology were accompanied by a 30–35% decrease in maximal force producing capacity. Taken together, these observations indicate that the calcineurin signal transduction pathway is a significant determinant of successful skeletal muscle regeneration in young mdx mice. Up-regulating this pathway may have clinical significance for DMD.