Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

The effectiveness of psychosocial interventions for cognitive dysfunction in cancer patients who have received chemotherapy : a systematic review

Background: Chemotherapy-related cognitive dysfunction (CRCD) refers to problems with memory,attention span, or concentration, experienced by patients with cancer who have had chemotherapy. CRCD can have a significant negative effect on a patient’s quality of life. The exact cause of CRCD is unknown but is presumed to be multifactorial. Objective: To conduct a systematic review of the effectiveness of psychosocial interventions designed to treat CRCD. Methods: Participants of interest to the review were over 18 years of age, diagnosed with cancer, and receiving chemotherapy or had received chemotherapy in the past. Interventions of interest were methods to improve cognitive function. Included study designs were randomized controlled trials, quasi-experimental trials, and quantitative observational studies. The primary outcome of interest was level of cognitive function. A three-step search strategy was utilized to identify studies published from 1985 to 2011 from a wide range of databases. Joanna Briggs Institute systematic review methods were used but findings were analyzed using the Cochrane Collaboration Review Manager 5.1 program.Weightedmean differences with 95% confidence intervals were calculated from the continuous data. Results: Searching identified 3,109 potentially relevant articles and 120 full-text articles were retrieved. Two further papers were sourced from reference lists of retrieved articles. From 122 papers, six were suitable for critical appraisal and six were included in the analysis. Meta-analysis was conducted on two cognitive behavioral therapy (CBT) trials for the outcome of inability to concentrate. Significant effect was seen for one CBT intervention at 20 weeks (p = .004). Significant effect from CBT on quality of life was seen at 6-month follow-up (p < .05). Conclusions: Despite some evidence of an effect, there is insufficient evidence at this stage to strongly recommend any of the interventions to assist in decreasing the effects of CRCD, except in terms of improving quality of life.

Long-term follow-up of flexor digitorum longus transfer and calcaneal osteotomy for stage II posterior tibial tendon dysfunction

Flexor digitorum longus transfer and medial displacement alcaneal osteotomy is a wellrecognised form of treatment or stage II posterior tibial tendon dysfunction. Although excellent short- and medium-term results have been reported, the long-term outcome is unknown. We reviewed the clinical outcome of 31 patients with a symptomatic flexible flatfoot deformity who underwent this procedure between 1994 and 1996. There were 21 women and ten men with a mean age of 54.3 years (42 to 70). The mean follow-up was 15.2 years (11.4 to 16.5). All scores improved significantly (p < 0.001). The mean American Orthopedic Foot and Ankle Society (AOFAS) score improved from 48.4 pre-operatively to 90.3 (54 to 100) at the final follow-up. The mean pain component improved from 12.3 to 35.2 (20 to 40). The mean function score improved from 35.2 to 45.6 (30 to 50). The mean visual analogue score for pain improved from 7.3 to 1.3 (0 to 6). The mean Short Form-36 physical component score was 40.6 (SD 8.9), and this showed a significant correlation with the mean AOFAS score (r = 0.68, p = 0.005). A total of 27 patients (87%) were pain free and functioning well at the final follow-up. We believe that flexor digitorum longus transfer and calcaneal osteotomy provides long-term pain relief and satisfactory function in the treatment of stage II posterior tibial tendon dysfunction.

Smell and taste dysfunction following minor stroke: A case report

Smell (olfactory) and taste (gustatory) are key senses in the regulation of nourishment and individual safety. Olfactory and gustatory dysfunctions have been infrequently reported together in patients following stroke (Landis et al., 2006; Leopold et al., 2006). This case report details two patients who experienced smell and taste dysfunction following minor stroke events. Symptoms reported included hyposmia (diminished sense of smell) and anosmia (complete loss of smell), and dysgeusia (distorted taste). Patients' sense of smell and taste were assessed in an ambulatory care stroke prevention clinic eight months following their strokes. Patient A presented with minor stroke due to a lesion in the anterior circulation, patient B with a lesion in the posterior circulation. Both patients reported intense olfactory and gustatory dysfunction immediately following their strokes. Examination revealed a general inability to detect subtle odours and the ability to identify only 'sweet' tastes for both patients. In addition, both patients reported heavily salting or sweetening their food to mask the distorted and unpleasant taste, which also impacted comorbid conditions such as hypertension and diabetes. Patients and their spouses reported a decrease in their appreciation of family-related activities due to the patients' olfactory and gustatory dysfunction. Patients reported weight loss, lack of energy and strength, likely due to poor nutrition. Olfactory and gustatory dysfunctions are potentially deleterious outcomes following minor stroke and should be assessed by health care professionals prior to patient discharge. Assistance may be required to promote the health and well-being of patients and their carers if smell and taste are impacted by the stroke event.

A mitochondrial genome phylogeny of owlet moths (Lepidoptera: Noctuoidea), and examination of the utility of mitochondrial genomes for lepidopteran phylogenetics

A phylogenetic hypothesis for the lepidopteran superfamily Noctuoidea was inferred based on the complete mitochondrial (mt) genomes of 12 species (six newly sequenced). The monophyly of each noctuoid family in the latest classification was well supported. Novel and robust relationships were recovered at the family level, in contrast to previous analyses using nuclear genes. Erebidae was recovered as sister to (Nolidae+(Euteliidae+Noctuidae)), while Notodontidae was sister to all these taxa (the putatively basalmost lineage Oenosandridae was not included). In order to improve phylogenetic resolution using mt genomes, various analytical approaches were tested: Bayesian inference (BI) vs. maximum likelihood (ML), excluding vs. including RNA genes (rRNA or tRNA), and Gblocks treatment. The evolutionary signal within mt genomes had low sensitivity to analytical changes. Inference methods had the most significant influence. Inclusion of tRNAs positively increased the congruence of topologies, while inclusion of rRNAs resulted in a range of phylogenetic relationships varying depending on other analytical factors. The two Gblocks parameter settings had opposite effects on nodal support between the two inference methods. The relaxed parameter (GBRA) resulted in higher support values in BI analyses, while the strict parameter (GBDH) resulted in higher support values in ML analyses.

The first mitochondrial genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997 (Diptera: Sciomyzoidea: Sepsidae), with mitochondrial genome phylogeny of cyclorrhapha

Sepsid flies (Diptera: Sepsidae) are important model insects for sexual selection research. In order to develop mitochondrial (mt) genome data for this significant group, we sequenced the first complete mt genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997. The circular 15,878 bp mt genome is typical of Diptera, containing all 37 genes usually present in bilaterian animals. We discovered inaccurate annotations of fly mt genomes previously deposited on GenBank and thus re-annotated all published mt genomes of Cyclorrhapha. These re-annotations were based on comparative analysis of homologous genes, and provide a statistical analysis of start and stop codon positions. We further detected two 18 bp of conserved intergenic sequences from tRNAGlu-tRNAPhe and ND1-tRNASer(UCN) across Cyclorrhapha, which are the mtTERM binding site motifs. Additionally, we compared automated annotation software MITOS with hand annotation method. Phylogenetic trees based on the mt genome data from Cyclorrhapha were inferred by Maximum-likelihood and Bayesian methods, strongly supported a close relationship between Sepsidae and the Tephritoidea.

The evolutionary history of termites as inferred from 66 mitochondrial genomes

Termites have colonized many habitats and are among the most abundant animals in tropical ecosystems, which they modify considerably through their actions. The timing of their rise in abundance and of the dispersal events that gave rise to modern termite lineages is not well understood. To shed light on termite origins and diversification, we sequenced the mitochondrial genome of 48 termite species and combined them with 18 previously sequenced termite mitochondrial genomes for phylogenetic and molecular clock analyses using multiple fossil calibrations. The 66 genomes represent most major clades of termites. Unlike previous phylogenetic studies based on fewer molecular data, our phylogenetic tree is fully resolved for the lower termites. The phylogenetic positions of Macrotermitinae and Apicotermitinae are also resolved as the basal groups in the higher termites, but in the crown termitid groups, including Termitinae + Syntermitinae + Nasutitermitinae + Cubitermitinae, the position of some nodes remains uncertain. Our molecular clock tree indicates that the lineages leading to termites and Cryptocercus roaches diverged 170 Ma (153-196 Ma 95% confidence interval [CI]), that modern Termitidae arose 54 Ma (46-66 Ma 95% CI), and that the crown termitid group arose 40 Ma (35-49 Ma 95% CI). This indicates that the distribution of basal termite clades was influenced by the final stages of the breakup of Pangaea. Our inference of ancestral geographic ranges shows that the Termitidae, which includes more than 75% of extant termite species, most likely originated in Africa or Asia, and acquired their pantropical distribution after a series of dispersal and subsequent diversification events.

Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins

Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.

Defective co-creation: Developing a typology of consumer dysfunction in professional services

Purpose This study aims to explore the scope of consumers’ defective co-creation behaviour in professional service encounters. One of the founding premises of service-dominant logic (Vargo and Lusch, 2004, 2008) is that consumers co-create the value they derive from service encounters. In practice, however, dysfunctional consumer behaviour can obstruct value co-creation. Extant research has not yet investigated consumers’ defective co-creation behaviour in highly relational services, such as professional services, that are heavily reliant on co-creation. Design/methodology/approach To investigate defective co-creation in professional services, 164 critical incidents were collected from 38 health-care and financial service providers using the critical incident technique within semi-structured, in-depth interviews. Thematic coding was used to identify emergent themes and patterns of consumer behaviour. Findings Thematic coding resulted in a comprehensive typology of consumers’ defective co-creation behaviour that both confirms the prevalence of previously identified dysfunctional behaviours (e.g. verbal abuse and physical aggression) and identifies two new forms of consumer misbehaviour: underparticipation and overparticipation. Further, these behaviours can vary, escalate and co-occur during service encounters. Originality/value Both underparticipation and overparticipation are newly identified forms of defective co-creation that need to be examined within the broader framework of service-dominant logic (SDL).

Mitochondrial DNA sequence analysis from multiple gene fragments reveals genetic heterogeneity of Crassostrea ariakensis in East Asia

The native Asian oyster, Crassostrea ariakensis is one of the most common and important Crassostrea species that occur naturally along the coast of East Asia. Molecular species diagnosis is a prerequisite for population genetic analysis of wild oyster populations because oyster species cannot be discriminated reliably using external morphological characters alone due to character ambiguity. To date there have been few phylogeographic studies of natural edible oyster populations in East Asia, in particular this is true of the common species in Korea C. ariakensis. We therefore assessed the levels and patterns of molecular genetic variation in East Asian wild populations of C. ariakensis from Korea, Japan, and China using DNA sequence analysis of five concatenated mtDNA regions namely; 16S rRNA, cytochrome oxidase I, cytochrome oxidase II, cytochrome oxidase III, and cytochrome b. Two divergent C. ariakensis clades were identified between southern China and remaining sites from the northern region. In addition, hierarchical AMOVA and pairwise UST analyses showed that genetic diversity was discontinuous among wild populations of C. ariakensis in East Asia. Biogeographical and historical sea level changes are discussed as potential factors that may have influenced the genetic heterogeneity of wild C. ariakensis stocks across this region.

Impulsivity-related cognition in alcohol dependence: Is it moderated by DRD2/ANKK1 gene status and executive dysfunction?

Perceived impaired control over alcohol use is a key cognitive construct in alcohol dependence that has been related prospectively to treatment outcome and may mediate the risk for problem drinking conveyed by impulsivity in non-dependent drinkers. The aim of the current study was to investigate whether perceived impaired control may mediate the association between impulsivity-related measures (derived from the Short-form Eysenck Personality Questionnaire-Revised) and alcohol-dependence severity in alcohol-dependent drinkers. Furthermore, the extent to which this hypothesized relationship was moderated by genetic risk (Taq1A polymorphism in the DRD2/ANKK1 gene cluster) and verbal fluency as an indicator of executive cognitive ability (Controlled Oral Word Association Test) was also examined. A sample of 143 alcohol-dependent inpatients provided an extensive clinical history of their alcohol use, gave 10ml of blood for DNA analysis, and completed self-report measures relating to impulsivity, impaired control and severity of dependence. As hypothesized, perceived impaired control (partially) mediated the association between impulsivity-related measures and alcohol-dependence severity. This relationship was not moderated by the DRD2/ANKK1 polymorphism or verbal fluency. These results suggest that, in alcohol dependence, perceived impaired control is a cognitive mediator of impulsivity-related constructs that may be unaffected by DRD2/ANKK1 and neurocognitive processes underlying the retrieval of verbal information

Childhood sexual abuse and adult sexual dysfunction: Response to commentary by Rind and Tromovitch (2007)

Rind and Tromovitch (2007) raised four concerns relating to our article (Najman, Dunne, Purdie, Boyle, & Coxeter, 2005. Archives of Sexual Behavior, 34, 517-526.) which suggested a causal association between childhood sexual abuse (CSA) and adult sexual dysfunction. We consider each of these concerns: magnitude of effect, cause and effect, confounding, and measurement error. We suggest that, while the concerns they raise represent legitimate reservations about the validity of our findings, on balance the available evidence indicates an association between CSA and sexual dysfunction that is of "moderate" magnitude, probably causal, and unlikely to be a consequence of confounding or measurement error.

Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line

This study aimed to investigate the effects of arsenic trioxide (As2O3) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 μmol/L As2O3in vitro, and the primary APL cells were treated with 2.0 μmol/L As2O3in vitro and 0.16 mg kg-1 d-1 As2O3in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As2O3 use, but the mutation spots were remarkably increased after As2O3 treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: rNB4-As2O3=0.973818, and rAPL-As2O3=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As2O3 aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As2O3 in APL treatment.

Exocrine pancreatic dysfunction in malnourished Australian Aboriginal children

Pancreatic exocrine dysfunction has been frequently recorded in protein-energy malnutrition in underdeveloped countries. In addition, the pancreas requires optimal nutrition for enzyme synthesis and potentially correctable pancreatic enzyme insufficiency may play a role in the continuation of protein-energy malnutrition. This problem has not been previously evaluated in Australian Aborigines. We have applied a screening test for pancreatic dysfunction (human immunoreactive trypsinogen [IRT] assay) to the study of 398 infants (6-36 months) admitted to the Alice Springs Hospital over a 20-month period. All infants were assessed by anthropometric measures and were assigned to to three nutritional groups (normal, moderate or severely malnourished) and two growth groups (stunted or not stunted). Of the 198 infants who had at least a single serum cationic trypsinogen measurement taken, normal values for serum IRT (with confidence limits) were obtained from 57 children, who were normally nourished. IRT levels were significantly correlated with the degree of underweight but there was no correlation with the degree of stunting or age. Mean IRT levels for the moderate and severely underweight groups were significantly greater than the mean for the normal group (P < 0.01). Seventeen children (8.6%) had trypsinogen levels in excess of the 95th percentile for the normally nourished group, reflecting acinar cell damage or ductal obstruction. We conclude that pancreatic dysfunction may be a common and important overlooked factor contributing to ongoing malnutrition and diseases in malnourished Australian Aboriginal children.