Vesiculation and rafts in stomatocytic red cells

This thesis describes work on ATP-dependent endocytic vesiculation and sphingomyelin and cholesterol-rich lipid rafts in the membrane of normal red cells and those with 'hereditary stomatocytosis' (HSt) syndromes, a set of rare congenital human haemolytic anaemias which show a 'leak' to the univalent cations Na+ and K+ and in some cases the deficiency of a 32 kDa raft protein, 'stomatin'. The work explores the idea that the pathophysiology of these diseases may be secondary to an abnormality in cellular processes of vesiculation based on membrane rafts. It was found that an in vitro process of ATP-dependent vesiculation, which occurs in normal red cell membranes, was completely absent in two pedigrees with overhydrated HSt (OHSt), the most severe version of these diseases. Both this defect and the cation leak were corrected by the cross-linking reagent, dimethyl adipimidate. In eleven other HSt pedigrees with different variants of the stomatocytosis syndromes ATP-dependent endocytic vesiculation was present. It was determined that lipid rafts existed in the normal erythrocyte membrane and that stomatin was partially associated with the rafts. Rafts were found to exist in the OHSt membrane in spite of the lack of stomatin. The degree of raft association of various membrane proteins, was investigated and the proportion of raft associated actin was found to be significantly reduced in OHSt cells. It was found that in normal red cell membranes, the process of ATP- dependent vesiculation could be inhibited by incubating erythrocyte ghosts with an antibody to stomatin. The raft disrupters nystatin, filipin, digitonin, saponin and methyl-[beta]-cyclodextrin were also found to inhibit this process. Further work exploring the mechanism of ATP-dependent endocytosis was performed. This work is consistent with the suggestion that the basic defect in the leaky OHSt cell may lie in a raft-based process of endocytosis, which may involve the stomatin protein

Local and remote impacts of aerosol species on Indian summer monsoon rainfall in a GCM

The HadGEM2 AGCM is used to determine the most important anthropogenic aerosols in the Indian monsoon using experiments in which observed trends in individual aerosol species are imposed. Sulphur dioxide (SD) emissions are shown to impact rainfall more strongly than black carbon (BC) aerosols, causing reduced rainfall especially over northern India. Significant perturbations due to BC are not noted until its emissions are scaled up in a sensitivity test, resulting in rainfall increases over northern India due to the Elevated Heat Pump mechanism, enhancing convection during the pre-monsoon and bringing forward the monsoon onset. Secondly, the impact of anthropogenic aerosols is compared to that of increasing greenhouse-gas concentrations and observed sea-surface temperature (SST) warming. The tropospheric temperature gradient driving the monsoon shows weakening when forced by either SD or imposed SST trends. However the observed SST trend is dominated by warming in the deep tropics; when the component of SST trend related to aerosol emissions is removed, further warming is found in the extratropical northern hemisphere that tends to offset monsoon weakening. This suggests caution is needed when using SST forcing as a proxy for greenhouse warming. Finally, aerosol emissions are decomposed into those from the Indian region and those elsewhere, in pairs of experiments with SD and BC. Both local and remote aerosol emissions are found to lead to rainfall changes over India; for SD, remote aerosols contribute around 75% of the rainfall decrease over India, while for BC the remote forcing is even more dominant

Innovations in Practice: The Relationship Between Sleep Disturbances, Depression, and Interpersonal Functioning in Treatment for Adolescent Depression

Sleep disturbance is frequently comorbid with depression and sleep complaints are the most common residual symptoms after treatment among adolescents with depression. The present analyses investigated the effect of sleep disturbance in depressed adolescents treated with interpersonal psychotherapy for adolescents (IPT-A) versus treatment as usual (TAU) in school-based mental health clinics

Electroconvulsive therapy for negative symptoms in schizophrenia: a literature review from 2000 to 2021

Negative symptoms in schizophrenia remain a clinical challenge with small effect sizes and evidence for pharmacological or psychotherapeutic treatment approaches. Studies suggest that electroconvulsive therapy (ECT) holds some promise as a treatment option of often persistent negative symptoms with clinically meaningful effects. This review summarizes the existing evidence on the efficacy of ECT on negative symptoms in patients with schizophrenia. Thirty-five publications were included in this literature review comprising 21 studies, two meta-analyses, eight reviews and four case reports. Conclusions should be interpreted cautiously, given the small number and methodological shortcomings of the included publications with a variation of study designs and missing standardized protocols. Implications for future research and practice are critically discussed. Recommendations are given to provide more evidence that will meet the clinical challenge of reducing the negative symptoms in schizophrenia. Study designs that focus explicitly on negative symptoms and assess patients over longer follow up periods could be helpful. Future research should include control groups, and possibly establish international multicentered studies to get a sufficient study population. Findings suggest that patients with schizophrenia resistant to pharmacological treatment might benefit from ECT. A risk and benefit assessment speaks in favour of the ECT treatment. Future practice of ECT should include a combination treatment with antipsychotics. Whereas the use of anaesthetics and electrode placement does not seem to play a role, the recommendation regarding frequency of ECT treatments is currently three times a week, For the assessment of negative symptoms the assessment tool should be chosen carefully

‘Chaucer’s World’ study days in Oxford for post-16 students: enhancing learning and encouraging wonder

This collaborative essay, structured as a collection of tales akin to Chaucer’s, provides a multiperspectival reflection on enhancement study days, entitled ‘Chaucer’s World’, co-organised by the University of Oxford, the Ashmolean Museum, the Bodleian Library, and secondary schools from the area. The event is aimed at UK secondary school students in their final two years of study, and is intended not only to help students with their preparation for the A-Level English Literature exam but also to instil in them appreciation for Chaucer’s works, as well as for medieval literature and culture in general

ACES: Analysis of Conservation with an Extensive list of Species

MOTIVATION: An abundance of new reference genomes is becoming available through large-scale sequencing efforts. While the reference FASTA for each genome is available, there is currently no automated mechanism to query a specific sequence across all new reference genomes. RESULTS: We developed ACES (Analysis of Conservation with an Extensive list of Species) as a computational workflow to query specific sequences of interest (e.g., enhancers, promoters, exons) against reference genomes with an available reference FASTA. This automated workflow generates BLAST hits against each of the reference genomes, a multiple sequence alignment file, a graphical fragment assembly file, and a phylogenetic tree file. These data files can then be used by the researcher in several ways to provide key insights into conservation of the query sequence. AVAILABILITY: ACES is available at https://github.com/TNTurnerLab/ACES. SUPPLEMENTARY INFORMATION: Supplementary Figure 1 is available online in Bioinformatics

Mediators of Interpersonal Psychotherapy for Depressed Adolescents On Outcomes in Latinos: The Role of Peer and Family Interpersonal Functioning

Peer and family interpersonal functioning were examined as mediators of the impact of Interpersonal Psychotherapy for Depressed Adolescents (IPT-A; Mufson, Dorta, Moreau, & Weissman, 2004) on depression and suicidal ideation among Latino youth. Only youth self-identifying as Latino (n = 50) were included in the analyses. The majority were female (86%) with a mean age of 14.58 (SD = 1.91). The current sample was drawn from the intent to treat sample of a clinical trial examining the effectiveness of IPT-A as compared with treatment as usual (TAU; Mufson, Dorta, Wickramaratne et al., 2004). Youth were randomly assigned to receive IPT-A or TAU delivered by school-based mental health clinicians. Assessments, completed at baseline and at Weeks 4, 8, and 12 (or at early termination), included self-report measures of depression and interpersonal functioning as well as clinician-Administered measures of depression. Multilevel modeling indicated that IPT-A led to greater improvement in interpersonal functioning with family and peers. Improved family and peer interpersonal functioning emerged as significant partial mediators of the relationship between IPT-A and depression. Only improved family interpersonal functioning emerged as a significant partial mediator of the relationship between IPT-A and suicidal ideation. However, this indirect effect was small, suggesting that most of the benefit of IPT-A for suicidal ideation appears to proceed through a pathway other than family interpersonal functioning. These results suggest that the impact of IPT-A on depressive symptoms is partially mediated by family and peer interpersonal functioning and contributes to our understanding of the mechanisms of IPT-A

Talking about death and dying: Findings from deliberative discussion groups with members of the public

Talking about death and dying is promoted in UK health policy and practice, from a perception that to do so encourages people to plan for their end of life and so increase their likelihood of experiencing a good death. This encouragement occurs alongside a belief that members of the public are reluctant to talk about death, although surveys suggest this is not the case. This paper describes findings from a research study in which people participated in deliberative discussion groups during which they talked about a range of topics related to death, including talking about death, the good death, choice and planning and compassionate communities. Here we report what they had to say in relation to talking about death and dying. We identified three themes: 1. The difference between talking about death as an abstract concept and confronting the certainty of death, 2. how death and dying presents issues for planning and responsibility, and 3. approaches to normalising death within society. For our participants, planning was considered most appropriate in relation to wills and funerals, while dying was considered too unpredictable to be easy to plan for; they had complex ideas about the value of talking about death and dying

Chronic amphetamine enhances visual input to and suppresses visual output from the superior colliculus in withdrawal

Heightened distractibility is a core symptom of Attention Deficit Hyperactivity Disorder (ADHD). Effective treatment is normally with chronic orally administered psychostimulants including amphetamine.Treatment prevents worsening of symptoms but the site of therapeutic processes, and their nature, is unknown. Mounting evidence suggests that the superior colliculus (SC) is a key substrate in distractibility and a therapeutic target, so we assessed whether therapeutically-relevant changes are induced in this structure by chronic oral amphetamine. We hypothesized that amphetamine would alter visual responses and morphological measures. Six-week old healthy male rats were treated with oral amphetamine (2, 5 or 10 mg/kg) or a vehicle for one month after which local field potential and multiunit recordings were made from the superficial layers of the SC in response to whole-field light flashes in withdrawal. Rapid Golgi staining was also used to assess dendritic spines, and synaptophysin staining was used to assess synaptic integrity. Chronic amphetamine increased local field potential responses at higher doses, and increased synaptophysin expression, suggesting enhanced visual input involving presynaptic remodelling. No comparable increases in multiunit activity were found suggesting a mphetamine suppresses collicular output activity, counterbalancing the increased input. We also report,for the first time, five different dendritic spine types in the superficial layers and show these to be unaffected by amphetamine, indicating that suppression does not involve gross postsynaptic structural alterations. In conclusion, we suggest that amphetamine produces changes at the collicular level that potentially stabilise the structure and may prevent the worsening of symptoms in disorders like ADHD

‘It’s Not Like in the Films’: Bereaved People’s Experiences of the Deathbed Vigil

This paper explores how people enact and experience the deathbed vigil when someone close to them is dying. It draws on qualitative interviews with 34 bereaved people carried out as part of a wider study exploring public perceptions of death and dying. Participants were aware of the expectation that they would attend the deathbed and did their best to do so. Findings are reported using four themes: gathering, enacting the deathbed vigil, experiencing the deathbed vigil and moment of death. Participants’ experiences varied. Some families kept vigil as a group, while others established a shift system or waited alone. Activities at the bedside included reading to the dying person, talking amongst themselves, sharing memories, saying goodbye. The covid-19 pandemic highlighted families’ wish to accompany their dying relatives