The Monitoring Illicit Substance Use Consortium: A Study Protocol.

Objective: The global impact of substance use, including cannabis, amphetamine, cocaine, ecstasy, hallucinogens, and opioids, is increasing, although the overall prevalence is low. Australia and New Zealand are among the few regions of the world in which use (typically illicit) of these classes of substances remains within the top 10 causes of disease burden. The period of adolescence and young adulthood, during which substance use behaviors accelerate in prevalence, is associated with a particular risk for harm.

The Metaphysical Irreversibility of Death.

The popularization of the term "clinical death" for the absence of vital signs suggests the possibility of a radical change in our understanding of death. While death used to be considered something that we do not have the power to reverse, contemporary optimism suggests that we may be able to restore life to a dead organism. In this article, I examine how the term "death" is used today to clarify what kind of irreversibility we ought to assign to it.

Polyneuropathy in Young Siberian Huskies Caused by Degenerative and Inflammatory Diseases.

Polyneuropathy is defined as the simultaneous dysfunction of several peripheral nerves. In dogs, a number of breeds are predisposed to a variety of immune-mediated and/or degenerative inherited forms of polyneuropathy, with laryngeal paralysis and/or megaesophagus as important clinical features of many of these conditions. This case series describes degenerative and inflammatory polyneuropathies in 7 young Siberian huskies that were categorized based on clinicopathological characteristics as follows: (1) slowly progressive laryngeal paralysis and megaesophagus caused by primary axonal degeneration with large fiber loss (n = 2); (2) slowly progressive polyneuropathy without megaesophagus or laryngeal paralysis caused by primary axonal degeneration with large fiber loss (n = 2); (3) acute inflammatory demyelinating neuropathy causing sensory, motor and autonomic nerve deficits (n = 2); and (4) ganglioradiculitis (sensory neuronopathy; n = 1).

Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes.

An X-linked muscular dystrophy, with deficiency of full-length dystrophin and expression of a low molecular weight dystrophin-related protein, has been described in Japanese Spitz dogs. The aim of this study was to identify the causative mutation and develop a specific test to identify affected cases and carrier animals. Gene expression studies in skeletal muscle of an affected animal indicated aberrant expression of the Duchenne muscular dystrophy (dystrophin) gene and an anomaly in intron 19 of the gene.

An exon splice enhancer primes IGF2:IGF2R binding site structure and function evolution.

Placental development and genomic imprinting coevolved with parental conflict over resource distribution to mammalian offspring. The imprinted genes IGF2 and IGF2R code for the growth promoter insulin-like growth factor 2 (IGF2) and its inhibitor, mannose 6-phosphate (M6P)/IGF2 receptor (IGF2R), respectively. M6P/IGF2R of birds and fish do not recognize IGF2.

Unique topographic distribution of greyhound nonsuppurative meningoencephalitis.

Greyhound nonsuppurative meningoencephalitis is an idiopathic breed-associated fatal meningoencephalitis with lesions usually occurring within the rostral cerebrum. This disorder can only be confirmed by postmortem examination, with a diagnosis based upon the unique topography of inflammatory lesions. Our purpose was to describe the magnetic resonance (MR) imaging features of this disease.

Insulin-like growth factor-2 regulates early neural and cardiovascular system development in zebrafish embryos.

The insulin-like growth factor (IGF) family is essential for normal embryonic growth and development and it is highly conserved through vertebrate evolution. However, the roles that the individual members of the IGF family play in embryonic development have not been fully elucidated. This study focuses on the role of IGF-2 in zebrafish embryonic development.

Regulation of expression of zebrafish (Danio rerio) insulin-like growth factor 2 receptor: implications for evolution at the IGF2R locus.

The insulin-like growth factor 2 receptor (IGF2R) is an unusual multifunctional receptor that interacts with a diverse variety of ligands. While the receptor has been well-characterized in mammals, little is known of its biology in other vertebrates. In this report, we characterize the expression of the zebrafish (Danio rerio) ortholog of the IGF2R gene.

Imprinted expression of the canine IGF2R, in the absence of an anti-sense transcript or promoter methylation.

Imprinted genes are epigenetically modified in a parent of origin-dependent manner, and as a consequence, are differentially expressed. Although the evolution of genomic imprinting is a subject of intense debate, imprinted genes have been studied primarily in mice and humans and in a small number of marsupial mammals. Comparative studies involving rodents and primates are of limited value, as they belong to the same superordinal group of eutherian mammals (Euarchontoglires).

Circulating insulin-like growth factors and related binding proteins are selectively altered in amyotrophic lateral sclerosis and multiple sclerosis.

Objective: To provide a detailed profile of the peripheral IGF system in the neurological conditions; amyotrophic lateral sclerosis (ALS), post polio syndrome (PPS) and multiple sclerosis (MS). To determine whether subsets of patients within the disease groups could be identified in whom one or more components of the IGF regulatory system are altered compared to healthy control subjects matched for age, sex and BMI.

Design: Three cohorts of patients were recruited, 28 with ALS, 18 with PPS and 23 with MS.

Callipyge mutation affects gene expression in cis: a potential role for chromatin structure.

Muscular hypertrophy in callipyge sheep results from a single nucleotide substitution located in the genomic interval between the imprinted Delta, Drosophila, Homolog-like 1 (DLK1) and Maternally Expressed Gene 3 (MEG3). The mechanism linking the mutation to muscle hypertrophy is unclear but involves DLK1 overexpression. The mutation is contained within CLPG1 transcripts produced from this region.

Mannose 6-phosphate receptors in an ancient vertebrate, zebrafish.

The endosome/lysosome system plays key roles in embryonic development, but difficulties posed by inaccessible mammalian embryos have hampered detailed studies. The accessible, transparent embryos of Danio rerio, together with the genetic and experimental approaches possible with this organism, provide many advantages over rodents. In mammals, mannose 6-phosphate receptors (MPRs) target acid hydrolases to endosomes and lysosomes, but nothing is known of acid hydrolase targeting in zebrafish.

Abnormal postnatal maintenance of elevated DLK1 transcript levels in callipyge sheep.

The underlying mechanism of the callipyge muscular hypertrophy phenotype in sheep (Ovis aries) is not presently understood. This phenotype, characterized by increased glycolytic type II muscle proportion and cell size accompanied by decreased adiposity, is not visibly detectable until approximately three to eight weeks after birth. The muscular hypertrophy results from a single nucleotide change located at the telomeric end of ovine Chromosome 18, in the region between the imprinted MATERNALLY EXPRESSED GENE 3 (MEG3) and DELTA, DROSOPHILA, HOMOLOG-LIKE 1 (DLK1) genes.

Insulin-like growth factor (IGF) signalling is required for early dorso-anterior development of the zebrafish embryo.

The insulin-like growth factor (IGF) signalling pathway has been highly conserved in animal evolution and, in mammals and Xenopus, plays a key role in embryonic growth and development, with the IGF-1 receptor (IGF-1R) being a crucial regulator of the signalling cascade. Here we report the first functional role for the IGF pathway in zebrafish. Expression of mRNA coding for a dominant negative IGF-1R resulted in embryos that were small in size compared to controls and had disrupted head and CNS development.

Phylogenetic footprint analysis of IGF2 in extant mammals.

Genomic imprinting results in monoallelic gene transcription that is directed by cis-acting regulatory elements epigenetically marked in a parent-of-origin-dependent manner. We performed phylogenetic sequence and epigenetic comparisons of IGF2 between the nonimprinted platypus (Ornithorhynchus anatinus) and imprinted opossum (Didelphis virginiana), mouse (Mus musculus), and human (Homo sapiens) to determine if their divergent imprint status would reflect differences in the conservation of genomic elements important in the regulation of imprinting. We report herein that IGF2 imprinting does not correlate evolutionarily with differential intragenic methylation, nor is it associated with motif 13, a reported IGF2-specific "imprint signature" located in the coding region.

The child maltreatment log: a computer-based program for describing research samples.

The Child Maltreatment Log (CML) is a computer-based program designed to record information about children's maltreatment experiences and associated life events. Addressing concerns posed by scientific panels and grant review panels, the CML was designed to improve upon existing instruments to facilitate collaboration among researchers interested in maltreatment. The CML encourages researchers to collect information from multiple sources and informants concerning children's maltreatment experiences.

Tissue-specific inactivation of murine M6P/IGF2R.

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) encodes a multifunctional protein involved in lysosomal enzyme trafficking, fetal organogenesis, tumor suppression, and T cell- mediated immunity. M6P/IGF2R is an imprinted gene in mice with expression only from the maternal allele. Complete knockout of this gene causes neonatal lethality, thus preventing analysis of its multifunctional role postnatally.