The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.

The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted

Adherence to Tuberculosis Therapy among Patients Receiving Home-Based Directly Observed Treatment: Evidence from the United Republic of Tanzania.

\ud \ud Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions

Kainate induced theta-frequency oscillatory network activity in the medial septum/diagonal band complex

The medial septum/diagonal band complex (MS/DB) forms part of the septo-hippocampal feedback loop and is thought to have a major functional role in the generation and/or maintenance of the hippocampal theta rhythm in vivo (4 * 15 Hz). Several different mechanistic scenarios may underlie the generation of a theta-frequency EEG pattern, amongst them (1) an external pacemaker-type input (2) theta activity being an emergent property of the septo-hippocampal feedback loop and (3) theta arising in the synaptic network of the MS/DB itself. This investigation tested the latter scenario by using an in vitro slice preparation of the (deafferented) MS/DB. Longitudinal slices (0.45 mm) from 21 day old rats were maintained at 32 deg C in an interface recording chamber perfused with oxygenated ACSF. Following the bath application of the AMPA/kainate receptor agonist kainate (25 *100 nM), extracellular recordings, using ACSF-filled micropipettes, showed rhythmic population activity with a mean peak frequency of ~6 Hz which was most prominent along the midline of the MS/DB. The higher concentrations of kainate were accompanied by corresponding increases in spectral power (amplitude). Subsequently, intracellular recordings were obtained with QX-314 containing electrodes to prevent spiking-activity, and thus allowing IPSPs to be recorded at depolarised membrane potentials. These recordings revealed the presence of rhythmic IPSPs (~6 Hz) in the class of fast-firing cells of oscillating MS/DB slices, presumably arising in the mutually connected interneuronal network of the MS/DB and pacing the oscillation. Moreover, these findings clearly demonstrate that the intrinsic circuitry of the isolated MS/DB complex is sufficient to generate rhythmic theta frequency activity

Theta oscillations in the rat MS/DB complex in vitro: a locally generated, inhibition-based brain rhythm

The medial septum/diagonal band (MS/DB) complex, which forms part of the septohippocampal feedback loop, is thought to be critical for the generation and/or maintenance of the hippocampal theta rhythm (4-15 Hz) in vivo. Previously we demonstrated the presence of theta frequency rhythmic activity, within an in vitro slice preparation of the MS/DB, following application of the AMPA/kainate receptor agonist kainate (25–100 nM). Here we further investigate this rhythmic activity, in particular the effects of GABAA receptor mediated inhibition, on kainate induced theta activity in the MS/DB, using bath application of bicuculline. Longitudinal slices of the MS/DB (450 μm), from 21 day old rats, were maintained at 32°C in an interface recording chamber perfused with oxygenated ACSF. Following the bath application of kainate at 100 nM to the MS/DB, extracellular recordings of neuronal population activity, using ACSF-filled micropipettes, revealed rhythmic theta frequency activity. Bicuculline was then applied to the recording chamber and subsequent changes to the kainate induced activity were recorded at 30 and 60 minutes there after. Application of 10 µM bicuculline produced a significant reduction (P< 0.05, Student's T test) in the activity recorded at theta frequency (spectral integral in 4-15 Hz range) and in peak amplitude within 60 minutes of application (n=6). These results indicate a pivotal role for inhibitory transmission in pacing and maintaining the rhythmic activity that is observed in the MS/DB slice preparation following kainate induced theta frequency oscillations. SPONSOR: British Neuroscience Association

Kainate induced theta-frequency oscillatory network activity in the medial septum/diagonal band complex

The medial septum/diagonal band complex (MS/DB) forms part of the septo-hippocampal feedback loop and is thought to have a major functional role in the generation and/or maintenance of the hippocampal theta rhythm in vivo (4 * 15 Hz). Several different mechanistic scenarios may underlie the generation of a theta-frequency EEG pattern, amongst them (1) an external pacemaker-type input (2) theta activity being an emergent property of the septo-hippocampal feedback loop and (3) theta arising in the synaptic network of the MS/DB itself. This investigation tested the latter scenario by using an in vitro slice preparation of the (deafferented) MS/DB. Longitudinal slices (0.45 mm) from 21 day old rats were maintained at 32 deg C in an interface recording chamber perfused with oxygenated ACSF. Following the bath application of the AMPA/kainate receptor agonist kainate (25 *100 nM), extracellular recordings, using ACSF-filled micropipettes, showed rhythmic population activity with a mean peak frequency of ~6 Hz which was most prominent along the midline of the MS/DB. The higher concentrations of kainate were accompanied by corresponding increases in spectral power (amplitude). Subsequently, intracellular recordings were obtained with QX-314 containing electrodes to prevent spiking-activity, and thus allowing IPSPs to be recorded at depolarised membrane potentials. These recordings revealed the presence of rhythmic IPSPs (~6 Hz) in the class of fast-firing cells of oscillating MS/DB slices, presumably arising in the mutually connected interneuronal network of the MS/DB and pacing the oscillation. Moreover, these findings clearly demonstrate that the intrinsic circuitry of the isolated MS/DB complex is sufficient to generate rhythmic theta frequency activity

Testing the cognitive-behavioural maintenance models across DSM-5 bulimic-type eating disorder diagnostic groups: A multi-centre study

The original cognitive-behavioural (CB) model of bulimia nervosa, which provided the basis for the widely used CB therapy, proposed that specific dysfunctional cognitions and behaviours maintain the disorder. However, amongst treatment completers, only 40–50 % have a full and lasting response. The enhanced CB model (CB-E), upon which the enhanced version of the CB treatment was based, extended the original approach by including four additional maintenance factors. This study evaluated and compared both CB models in a large clinical treatment seeking sample (N = 679), applying both DSM-IV and DSM-5 criteria for bulimic-type eating disorders. Application of the DSM-5 criteria reduced the number of cases of DSM-IV bulimic-type eating disorders not otherwise specified to 29.6 %. Structural equation modelling analysis indicated that (a) although both models provided a good fit to the data, the CB-E model accounted for a greater proportion of variance in eating-disordered behaviours than the original one, (b) interpersonal problems, clinical perfectionism and low self-esteem were indirectly associated with dietary restraint through over-evaluation of shape and weight, (c) interpersonal problems and mood intolerance were directly linked to binge eating, whereas restraint only indirectly affected binge eating through mood intolerance, suggesting that factors other than restraint may play a more critical role in the maintenance of binge eating. In terms of strength of the associations, differences across DSM-5 bulimic-type eating disorder diagnostic groups were not observed. The results are discussed with reference to theory and research, including neurobiological findings and recent hypotheses