48 research outputs found

    An exploration into the client at the heart of therapy : a qualitative perspective

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    Over 50 years ago Eysenck challenged the existing base of research into psychotherapy. Since that time, a large number of investigations have been conducted to verify the efficacy of therapy. Recently however, an increasing number of studies have cast new doubts on this research base. Instead of therapy being a function of the therapist, it is now becoming ever more apparent that the client plays a prime role in the therapeutic process. The qualitative studies presented in this paper provide some examples of research that demonstrates that clients are actively involved in their therapy, even making counselling work despite their counsellor. These studies suggest that clients may not experience therapy as beneficially as traditional outcome studies indicate. This raises a new challenge to researchers to more fully explore the client's experience of therapy, a challenge to which qualitative methods of inquiry would appear well suited

    <i>orsai</i>, the Drosophila homolog of human ETFRF1, links lipid catabolism to growth control

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    BACKGROUND: Lipid homeostasis is an evolutionarily conserved process that is crucial for energy production, storage and consumption. Drosophila larvae feed continuously to achieve the roughly 200-fold increase in size and accumulate sufficient reserves to provide all energy and nutrients necessary for the development of the adult fly. The mechanisms controlling this metabolic program are poorly understood. RESULTS: Herein we identified a highly conserved gene, orsai (osi), as a key player in lipid metabolism in Drosophila. Lack of osi function in the larval fat body, the regulatory hub of lipid homeostasis, reduces lipid reserves and energy output, evidenced by decreased ATP production and increased ROS levels. Metabolic defects due to reduced Orsai (Osi) in time trigger defective food-seeking behavior and lethality. Further, we demonstrate that downregulation of Lipase 3, a fat body-specific lipase involved in lipid catabolism in response to starvation, rescues the reduced lipid droplet size associated with defective orsai. Finally, we show that osi-related phenotypes are rescued through the expression of its human ortholog ETFRF1/LYRm5, known to modulate the entry of β-oxidation products into the electron transport chain; moreover, knocking down electron transport flavoproteins EtfQ0 and walrus/ETFA rescues osi-related phenotypes, further supporting this mode of action. CONCLUSIONS: These findings suggest that Osi may act in concert with the ETF complex to coordinate lipid homeostasis in the fat body in response to stage-specific demands, supporting cellular functions that in turn result in an adaptive behavioral response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-022-01417-w

    Transcriptional responses of ecologically diverse drosophila species to larval diets differing in relative sugar and protein ratios

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    We utilized three ecologically diverse Drosophila species to explore the influence of ecological adaptation on transcriptomic responses to isocaloric diets differing in their relative proportions of protein to sugar. Drosophila melanogaster, a cosmopolitan species that breeds in decaying fruit, exemplifies individuals long exposed to a Western diet higher in sugar, while the natural diet of the cactophilic D. mojavensis, is much lower in carbohydrates. Drosophila arizonae, the sister species of D. mojavensis, is largely cactophilic, but also utilizes rotting fruits that are higher in sugars than cacti. We exposed third instar larvae for 24 hours to diets either (1) high in protein relative to sugar, (2) diets with equal amounts of protein and sugar, and (3) diets low in protein but high in sugar. As we predicted, based upon earlier interspecific studies of development and metabolism, the most extreme differences in gene expression under different dietary conditions were found in D. mojavensis followed by D. arizonae. No differential expression among diets was observed for D. melanogaster, a species that survives well under all three conditions, with little impact on its metabolism. We suggest that these three species together provide a model to examine individual and population differences in vulnerability to lifestyle-associated health problems such as metabolic syndrome and diabetes

    Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis

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    <p>Abstract</p> <p>Background</p> <p><it>TARDBP </it>mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between <it>TARDBP </it>mutations and Chinese patients with ALS.</p> <p>Methods</p> <p>71 SALS patients and 5 FALS families with non-<it>SOD1 </it>mutations were screened for <it>TARDBP </it>mutations via direct sequencing.</p> <p>Results</p> <p>A novel heterozygous variation, Ser292Asn (875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c).</p> <p>Conclusions</p> <p>The present data have extended the spectrum of <it>TARDBP </it>mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.</p

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    The thermolabile variant of 5,10-methylenetetrahydrofolate reductase is a possible risk factor for amyotrophic lateral sclerosis

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    Abstract Hyperhomocysteinemia is a risk factor for neurodegeneration, and binding of copper by homocysteine is a putative underlying mechanism. As mutations of the copper-dependent superoxide dismutase are observed in familial ALS, we tested whether genetic variants with influence on homocysteine metabolism are associated with ALS. We compared the frequency of seven variants of genes involved in homocysteine metabolism in 162 patients with sporadic ALS and 162 controls who did not significantly differ in age (t = 1.27, p = 0.205) and gender (χ(2) = 2.48, p = 0.115) using binary regression analysis. Results showed that the variant MTHFR c.677C>T was significantly associated with ALS, i.e. the T-allele was more frequent among patients. Explorative regression analysis revealed that MTHFR c.677C>T was not associated with spinal ALS, but with bulbar onset: CC/CT/TT in patients 0.33/0.51/0.16 versus 0.50/0.44/0.06 in controls; Wald = 5.73, p = 0.017. In addition, DHFR c.594+59del19bp was not associated with spinal, but with bulbar onset: del,del/del,ins/ins,ins in patients 0.16/0.67/0.18 versus 0.11/0.52/0.37 in controls; Wald = 5.02, p = 0.025. The other variants did not show significant associations. In summary, the variants MTHFR c.677C>T and DHFR c.594+59del19bp are involved in homocysteine metabolism. Homocysteine is neurotoxic and binds copper. Thus, the individual variability of homocysteine metabolism, e.g. due to genetic variants, may contribute to the vulnerability of ALS

    A Tritium Diagnostic and Trap for JUDITH - First Results in Disruption Simulation Experiments with Neutron Irradiated Beryllium During Cyclic Electron Beam Testing

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    In the present study, the effect of disruptions on beryllium has been studied. Disruptions are simulated in the electron beam facility JUDITH by high energetic pulses of up to 250 Mj/m(2). Under these loads, the beryllium surface may roughen combined with the forming of cracks. During the experiments, a special problem arises from the fact that during the neutron irradiation beryllium transmutes to tritium. This tritium is bound in the beryllium matrix, but during the heating of the samples, the tritium may be set free and through the vacuum pump it maybe released to the environment. In order to avoid and to quantify this release of tritium. a special tritium trap has been constructed. In this tritium trap the gas is pumped by means of a metal bellows pump through a catalyst tube filled with copper oxide. At a temperature of 300 degrees C, the tritium is oxidized to HTO. This HTO is lead through gas washing bottles filled with water. Here approximately 98% of the released tritium is caught. The temperatures in the process are controlled by thermocouples, and the tritium content is controlled by a tritium gas monitor and in addition with a liquid scintillation counter (LSQ. (C) 2008 Elsevier B.V. All rights reserved
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