No mutations detected in the INSR gene in a chromosome 19p13 linked migraine pedigree

The aim of this study was to investigate through direct sequencing the insulin receptor (INSR) gene in DNA samples from a migraine affected family previously showing linkage to chromosome 19p13 in an attempt to detect disease associated mutations. Migraine is a common debilitating disorder with a significant genetic component. At present, the number and type of genes involved in the common forms of migraine are not clear. The INSR gene on chromosome 19p13.3-13.2 is a gene of interest since a number of single nucleotide polymorphisms (SNPs) located within the gene have been implicated in migraine with (MA) and without aura (MO). Six DNA samples obtained from non-founding migraine affected members of migraine family 1 (MF1) were used in this study. Genomic DNA was sequenced for the INSR gene in exons 1-22 and the promoter region. In the six migraine family member samples, previously reported SNPs were detected within two exonic DNA coding regions of the INSR gene. These SNPs, in exons 13 and 17, do not alter the normal INSR polypeptide sequence. In addition, intron 7 also revealed a DNA base sequence variation. For the 5' untranslated promoter region of the gene, no mutations or polymorphisms were detected. In conclusion, this study detected no INSR mutations in affected members of a chromosome 19 linked migraine pedigree. Hence, migraine linkage to this chromosomal region may involve other candidate genes.

Child complainants and the court process in Australia

In recent years, it has been recognised that child complainants in the criminal justice system can experience difficulties over and above those of other complainants and that children can experience the court process as extremely traumatising. This can be exacerbated if children are complainants in child sexual offence matters and if they have to give evidence against a family member. This paper has three primary aims. First, it outlines the major factors that contribute to making court processes harrowing for child complainants. Second, it outlines some of the main initiatives that have been introduced to address these factors. Finally, it weighs up the evidence about initiatives designed to assist child complainants and concludes that such initiatives have had only limited practical impact for child complainants in the criminal justice system. The limited impact is attributed to the need to balance the rights of the accused with consideration for the complainant, a failure to translate legislative changes into practice, the impact of judicial discretion and/or a focus on protecting child complainants at the expense of increasing convictions.

Efficient silencing of endogenous microRNAs using artificial microRNAs in Arabidopsis thaliana

We report here that the expression of endogenous microRNAs (miRNAs) can be efficiently silenced in Arabidopsis thaliana (Arabidopsis) using artificial miRNA (amiRNA) technology. We demonstrate that an amiRNA designed to target a mature miRNA directs silencing against all miRNA family members, whereas an amiRNA designed to target the stem-loop region of a miRNA precursor transcript directs silencing against only the individual family member targeted. Furthermore, our results indicate that amiRNAs targeting both the mature miRNA and stem-loop sequence direct RNA silencing through cleavage of the miRNA precursor transcript, which presumably occurs in the nucleus of a plant cell during the initial stages of miRNA biogenesis. This suggests that small RNA (sRNA)-guided RNA cleavage in plants occurs not only in the cytoplasm, but also in the nucleus. Many plant miRNA gene families have been identified via sequencing and bioinformatic analysis, but, to date, only a small tranche of these have been functionally characterized due to a lack of effective forward or reverse genetic tools. Our findings therefore provide a new and powerful reverse-genetic tool for the analysis of miRNA function in plants. © The Author 2010. Published by the Molecular Plant Shanghai Editorial Office in association with Oxford University Press on behalf of CSPP and IPPE, SIBS, CAS.

An exploratory study of grief and health-related quality of life for caregivers of people with dementia

The aim of this qualitative study was to explore key positive and negative factors that impact on grief resolution and health outcomes of caregivers who were caring, or had cared, for a family member with dementia who had died. The study was a scoping study and involved face-to-face interviews with these family caregivers (N ¼ 13). Results indicated a complex interaction of issues (many unique to dementia caregiving) which in different combinations acted as protective or risk factors for caregiver outcomes. Interaction of individual characteristics, role appraisal, value of intrinsic and extrinsic resources, and experiences with health professionals during the caregiving period and around the death of their relative were shown to have the most influence on caregiver outcomes. Psychological resilience and satisfaction with caregiving were protective against negative outcomes while unresolved grief was a risk factor. These findings highlight the potential benefits of multicomponent, holistic dementia caregiver interventions.

Actinidia DRM1 : an intrinsically disordered protein whose mRNA expression is inversely correlated with spring budbreak in Kiwifruit

Intrinsically disordered proteins (IDPs) are a relatively recently defined class of proteins which, under native conditions, lack a unique tertiary structure whilst maintaining essential biological functions. Functional classification of IDPs have implicated such proteins as being involved in various physiological processes including transcription and translation regulation, signal transduction and protein modification. Actinidia DRM1 (Ade DORMANCY ASSOCIATED GENE 1), represents a robust dormancy marker whose mRNA transcript expression exhibits a strong inverse correlation with the onset of growth following periods of physiological dormancy. Bioinformatic analyses suggest that DRM1 is plant specific and highly conserved at both the nucleotide and protein levels. It is predicted to be an intrinsically disordered protein with two distinct highly conserved domains. Several Actinidia DRM1 homologues, which align into two distinct Actinidia-specific families, Type I and Type II, have been identified. No candidates for the Arabidopsis DRM1-Homologue (AtDRM2) an additional family member, has been identified in Actinidia.

Eldercare demands, mental health, and work performance : the moderating role of satisfaction with eldercare tasks

Due to demographic changes, a growing number of employees provide in-home care to an elderly family member. Previous research suggested a negative relationship between employees' eldercare demands and their work performance. However, the empirical nature of this relationship and its boundary conditions and mediating mechanisms have been neglected. The goal of this multisource study was to examine a mediated-moderation model of eldercare demands, mental health, and work performance. Drawing on the theory of conservation of resources (Hobfoll, 1989), it was expected that employees' satisfaction with eldercare tasks would buffer the negative relationship between eldercare demands and work performance, and that mental health would mediate this moderating effect. Data were collected from 165 employees providing in-home eldercare, as well as from one colleague and one family member of each employee. Results of mediated-moderation analyses supported the hypothesized model. The findings suggest that interventions that aim to increase employees' satisfaction with eldercare tasks may help protect employees from the negative effects of high eldercare demands on mental health and, subsequently, on work performance.

A methodological exploration to determine transportation disadvantage variables: the partial least square approach

Determining the key variables of transportation disadvantage remains a great challenge as the variables are commonly selected using ad-hoc techniques. In order to identify the variables, this research develops a transportation disadvantage framework by manipulating the capability approach. Developed framework is statistically analysed using partial least square-based software to determine the framework fitness. The statistical analysis identifies mobility and socioeconomic variables that significantly influence transportation disadvantage. The research reveals the key socioeconomic variables for transportation disadvantage in the case of Brisbane, Australia as household structure, presence of dependent family member, vehicle ownership, and driving licence possession.

Urban Aboriginal and Torres Strait Islander children's exposure to stressful events : a cross sectional study

Objectives To determine the frequency and types of stressful events experienced by urban Aboriginal and Torres Strait Islander children, and to explore the relationship between these experiences and the children’s physical health and parental concerns about their behaviour and learning ability. Design, setting and participants Cross-sectional study of Aboriginal and Torres Strait Islander children aged ≤ 14 years presenting to an urban Indigenous primary health care service in Brisbane for annual child health checks between March 2007 and March 2010. Main outcome measures Parental or carer report of stressful events ever occurring in the family that may have affected the child. Results Of 344 participating children, 175 (51%) had experienced at least one stressful event. Reported events included the death of a family member or close friend (40; 23%), parental divorce or separation (28; 16%), witness to violence or abuse (20; 11%), or incarceration of a family member (7; 4%). These children were more likely to have parents or carers concerned about their behaviour (P < 0.001) and to have a history of ear (P < 0.001) or skin (P = 0.003) infections. Conclusions Children who had experienced stressful events had poorer physical health and more parental concern about behavioural issues than those who had not. Parental disclosure in the primary health care setting of stressful events that have affected the child necessitates appropriate medical, psychological or social interventions to ameliorate both the immediate and potential lifelong negative impact. However, treating the impact of stressful events is insufficient without dealing with the broader political and societal issues that result in a clustering of stressful events in the Aboriginal and Torres Strait Islander population.

Pressure placed on paediatric haematopoietic stem cell donors: Views from health professionals

Aim Paediatric haematopoietic stem cell donors undergo non-therapeutic procedures and endure known and unknown physical and psychosocial risks for the benefit of a family member. One ethical concern is the risk they may be pressured by parents or health professionals to act as a donor. This paper adds to what is known about this topic by presenting the views of health professionals. Methods This qualitative study involved semi-structured interviews with 14 health professionals in Australasia experienced in dealing with paediatric donors. Transcripts were analysed using established qualitative methodologies. Results Health professionals considered that some paediatric donors experience pressure to donate. Situations were identified that were likely to increase the risk of pressure being placed on donors and views were expressed about the ethical ‘appropriateness’ of these practices within the family setting. Conclusions Children may be subject to pressure from family and health professionals to be tested and act as donors, Therefore, our ethical obligation to these children extends to implementing donor focused processes – including independent health professionals and the appointment of a donor advocate – to assist in detecting and addressing instances of inappropriate pressure being placed on a child.

Short-rib polydactyly and jeune syndromes are caused by mutations in WDR60

Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis.

Medication adherence of individuals with a first episode of psychosis

Objective To determine rates of adherence to antipsychotic medication in first episode patients and the correlates of adherence in this group. Method Subjects were the first 200 admissions to an Early Psychosis Program. Adherence was determined on a three-point scale. Symptoms, medication side-effects, quality of life, substance use and family involvement were examined longitudinally. Results In their first year in the program 39% were non-adherent, 20% inadequately adherent, and 41% adherent. Non-adherent patients demonstrated more positive symptoms, more relapses, more alcohol and cannabis use, reduced insight, and poorer quality of life. They were younger, had an earlier age of onset and less likely to have a family member involved in treatment. Conclusion Results for this group are similar to those reported in the literature. Correlates are often the consequence of non-adherence. Non-compliance has to be anticipated and relationships maintained with patients and families to intervene as soon as possible to minimize the consequence of non-compliance.

Inscription on the Holocaust memorial, Mahnmal am Opernplatz; Hannover, Germany.

Gottschalk family member names engraved on the memorial to the Jews of Hannover who perished in the Holocaust; Elizabeth Gottschalk nee Steinfeld, Henriette Gottschalk nee Rothschild, Jeanette Gottschalk (relationship unknown), and Karl Gottschalk.

Eldercare demands, strain, and work engagement: The moderating role of perceived organizational support

Demographic changes give rise to an increasing number of middle-aged employees providing home-based care to an elderly family member. However, the potentially important role of employees' perceptions of organizational support for eldercare has so far not been investigated. The goal of this study was to examine a stressor–strain–outcome model (Koeske & Koeske, 1993) of eldercare strain as a mediator of the relationship between eldercare demands and caregivers' work engagement. Perceived organizational eldercare support was expected to attenuate the positive relationship between eldercare demands and eldercare strain and to buffer the negative relationship between eldercare strain and work engagement. Results of mediation and moderated mediation analyses with data collected from 147 employees providing eldercare supported the hypotheses. The findings suggest that perceived organizational eldercare support is especially beneficial for employees' work engagement when eldercare demands and strain are high.

Novel TBK1 truncating mutation in a familial amyotrophic lateral sclerosis patient of Chinese origin

Missense and frameshift mutations in TRAF family member-associated NF-kappa-B activator (TANK)-binding kinase 1 (TBK1) have been reported in European sporadic and familial amyotrophic lateral sclerosis (ALS) cohorts. To assess the role of TBK1 in ALS patient cohorts of wider ancestry, we have analyzed whole-exome sequence data from an Australian cohort of familial ALS (FALS) patients and controls. We identified a novel TBK1 deletion (c.1197delC) in a FALS patient of Chinese origin. This frameshift mutation (p.L399fs) likely results in a truncated protein that lacks functional domains required for adapter protein binding, as well as protein activation and structural integrity. No novel or reported TBK1 mutations were identified in FALS patients of European ancestry. This is the first report of a TBK1 mutation in an ALS patient of Asian origin and indicates that sequence variations in TBK1 are a rare cause of FALS in Australia. © 2015 Elsevier Inc.

Characterization of LRRTM and NGR gene families: Expression and functions

Some leucine-rich repeat (LRR) -containing membrane proteins are known regulators of neuronal growth and synapse formation. In this work I characterize two gene families encoding neuronal LRR membrane proteins, namely the LRRTM (leucine-rich repeat, transmembrane neuronal) and NGR (Nogo-66 receptor) families. I studied LRRTM and NGR family member's mRNA tissue distribution by RT-PCR and by in situ hybridization. Subcellular localization of LRRTM1 protein was studied in neurons and in non-neuronal cells. I discovered that LRRTM and NGR family mRNAs are predominantly expressed in the nervous system, and that each gene possesses a specific expression pattern. I also established that LRRTM and NGR family mRNAs are expressed by neurons, and not by glial cells. Within neurons, LRRTM1 protein is not transported to the plasma membrane; rather it localizes to endoplasmic reticulum. Nogo-A (RTN4), MAG, and OMgp are myelin-associated proteins that bind to NgR1 to limit axonal regeneration after central nervous system injury. To better understand the functions of NgR2 and NgR3, and to explore the possible redundancy in the signaling of myelin inhibitors of neurite growth, I mapped the interactions between NgR family and the known and candidate NgR1 ligands. I identified high-affinity interactions between RTN2-66, RTN3-66 and NgR1. I also demonstrate that Rtn3 mRNA is expressed in the same glial cell population of mouse spinal cord white matter as Nogo-A mRNA, and thus it could have a role in myelin inhibition of axonal growth. To understand how NgR1 interacts with multiple structurally divergent ligands, I aimed first to map in more detail the nature of Nogo-A:NgR1 interactions, and then to systematically map the binding sites of multiple myelin ligands in NgR1 by using a library of NgR1 expression constructs encoding proteins with one or multiple surface residues mutated to alanine. My analysis of the Nogo-A:NgR1 -interactions revealed a novel interaction site between the proteins, suggesting a trivalent Nogo-A:NgR1-interaction. Our analysis also defined a central binding region on the concave side of NgR1's LRR domain that is required for the binding of all known ligands, and a surrounding region critical for binding MAG and OMgp. To better understand the biological role of LRRTMs, I generated Lrrtm1 and Lrrtm3 knock out mice. I show here that reporter genes expressed from the targeted loci can be used for maping the neuronal connections of Lrrtm1 and Lrrtm3 expressing neurons in finer detail. With regard to LRRTM1's role in humans, we found a strong association between a 70 kb-spanning haplotype in the proposed promoter region of LRRTM1 gene and two possibly related phenotypes: left-handedness and schizophrenia. Interestingly, the responsible haplotype was linked to phenotypic variability only when paternally inherited. In summary, I identified two families of neuronal receptor-like proteins, and mapped their expression and certain protein-protein interactions. The identification of a central binding region in NgR1 shared by multiple ligands may facilitate the design and development of small molecule therapeutics blocking binding of all NgR1 ligands. Additionally, the genetic association data suggests that allelic variation upstream of LRRTM1 may play a role in the development of left-right brain asymmetry in humans. Lrrtm1 and Lrrtm3 knock out mice developed as a part of this study will likely be useful for schizophrenia and Alzheimer s disease research.