Pedigree derived mutation rate across the entire mitochondrial genome of the Norfolk Island population.

Estimates of mutation rates for various regions of the human mitochondrial genome (mtGenome) vary widely, depending on whether they are inferred using a phylogenetic approach or obtained directly from pedigrees. Traditionally, only the control region, or small portions of the coding region have been targeted for analysis due to the cost and effort required to produce whole mtGenome Sanger profiles. Here, we report one of the first pedigree derived mutation rates for the entire human mtGenome. The entire mtGenome from 225 individuals originating from Norfolk Island was analysed to estimate the pedigree derived mutation rate and compared against published mutation rates. These individuals were from 45 maternal lineages spanning 345 generational events. Mutation rates for various portions of the mtGenome were calculated. Nine mutations (including two transitions and seven cases of heteroplasmy) were observed, resulting in a rate of 0.058 mutations/site/million years (95% CI 0.031-0.108). These mutation rates are approximately 16 times higher than estimates derived from phylogenetic analysis with heteroplasmy detected in 13 samples (n = 225, 5.8% individuals). Providing one of the first pedigree derived estimates for the entire mtGenome, this study provides a better understanding of human mtGenome evolution and has relevance to many research fields, including medicine, anthropology and forensics.

Safety and tolerability of Pau d' Arco (Tabebuia avellanedae) for primary dysmenorrhea: A single-arm, open-label trial on adults ages 18-45.

Objectives: To evaluate the safety and tolerability of encapsulated Tabebuia avellanedae in generally healthy women aged 18-45 with primary dysmenorrhea. Methods: A single arm, open-label trial was conducted in which 1050 mg/day of encapsulated Tabebuia avellanedae (Pau d'Arco) was administered to twelve healthy women aged 18-45 for eight weeks. The primary outcome was safety and tolerability as measured by standardized adverse events scales and serial collection of laboratory markers to assess general health, prothrombin times, and the presence or absence of anemia. Secondary outcomes included pain intensity, quality of life, and pain interference measured by the Visual Analog Scale (VAS), the Patient-Reported Outcomes Measurement Information System (PROMIS) 29 survey, and the PROMIS Visual Sexual Function and Satisfaction: Interfering Factors survey, respectively. Exploratory outcomes included serum concentration of high-sensitivity C-reactive protein as a marker of systemic inflammation. Results: Seventy-five percent of participants (n = 9/12) completed the study. Seventy-five percent of study participants (n = 9/12) reported an adverse event, most of which were characterized as mild, and none were determined to be a Food and Drug Administration (FDA) serious adverse event. Most laboratory markers stayed within normal limits throughout the study period with a few clinically mild abnormalities. There was a significant decrease in pain intensity compared to baseline after the first dose (p < .01), after 4 weeks of treatment (p < .01), and after 8 weeks of treatment (p < .01). Over the 8-week intervention period, pain interference, quality of life, and sexual function and satisfaction scores improved nonsignificantly and hs-CRP decreased nonsignificantly. Conclusions: Tabebuia avellanedae supplementation of 1050 mg/day dose for eight weeks in generally healthy women aged 18-45 with primary dysmenorrhea was generally safe, associated with moderate tolerability, and associated with significant improvements in pain intensity scores. Future studies examining the safety and efficacy of Tabebuia avellanedae on primary dysmenorrhea are warranted.

Foot shock facilitates reward seeking in an experience-dependent manner.

Animals organize reward seeking around aversive events. An abundance of research shows that foot shock, as well as a shock-associated cue, can elicit freezing and suppress reward seeking. Yet, there is evidence that experience can flip the effect of foot shock to facilitate reward seeking. Here we examined cue suppression, foot shock suppression and foot shock facilitation of reward seeking in a single behavioural setting. Male Long Evans rats received fear discrimination consisting of danger, uncertainty, and safety cues. Discrimination took place over a baseline of rewarded nose poking. With limited experience (1-2 sessions), all cues and foot shock suppressed reward seeking. With continued experience (10-16 sessions), suppression became specific to shock-associated cues, foot shock briefly suppressed, then facilitated reward seeking. Our results provide a means of assessing positive properties of foot shock, and may provide insight into maladaptive behaviour around aversive events.

Maternalism: a healthy alliance for recovery and transition in eating disorder services.

ACCESSIBLE SUMMARY: The therapeutic relationship is pivotal to mental health nursing, but very little is known about how it is experienced in adult eating disorder services. This paper reports on a research project that sought to discover how the therapeutic relationship is experienced between care workers and women with anorexia nervosa in an adult eating disorder service. Both care workers and women spoke of a relationship that had similarities to the mother-daughter relationship, that it felt therapeutic and that it was in keeping with a professional and compassionate nursing approach. These findings provide new insight. Maternalism is seen as a positive, nurturing and transient relationship that ensures the safety of the person and promotes recovery and transition to eventual independence. ABSTRACT: This paper reports on a UK interpretative phenomenological research study that aimed to explore the lived experience of the relationship between women with anorexia and their care workers in the context of a specialist eating disorder (ED) unit. Here, the concept of maternalism as a phenomenon occurring within the therapeutic relationship in specialist ED units is discussed. Consideration is given to the parallel roles of the health care worker whose duty it is to protect, preserve life and to promote health and that of a mother/guardian. Although seemingly simplistic, the comforting, soothing and nurturing techniques that are used by the workers to diffuse distress and help the person feel cared for have many similarities to 'mothering'. Hence, a maternalistic approach that provides a sense of security and nurturing can be a compassionate way to facilitate hope and a route out of their anorexia into recovery, in the same way that good parenting can facilitate maturation and independence.

A multi-tiered intervention to address behavioural and cognitive changes after diagnosis of primary brain tumour: a feasibility study.

PURPOSE: Untreated behavioural and cognitive changes after primary brain tumour (PBT) can result in challenging behaviours (CBs), with limited documentation on treatment approaches. This study explored the feasibility of employing a Behavioural Consultancy approach to manage CBs, targeting individuals with PBT, family and treating staff. METHODS: Participants were patients and families of two hospitals and health professionals from cancer/neurological services. A single-case experimental design piloted skill-based training and environmental changes in managing socio-behavioural impairments in a person with a low grade astrocytoma. A half-day workshop to train family members (n = 7) in compensatory strategy use to manage CBs after PBT was piloted. Finally, a 1-day workshop was provided to 43 health professionals in managing CBs after PBT. For both workshops, a pre-post impact evaluation was conducted employing a purpose-designed Strategies Use Measure. RESULTS: All three interventions demonstrated positive results. The single case showed a 71% decrease in the target behaviour (time spent talking) post-intervention. Some attrition to these gains was observed at two follow-up time points (3 and 5 months). Participants from both workshops demonstrated significant post-intervention increases in perceived knowledge of Strategy Use (family members z = 2.03, p < 0.05; health professionals z = 4.95, p < 0.00; Wilcoxon signed-rank test). CONCLUSIONS: These initial studies highlight the potential of employing an integrated multi-tiered intervention based on a Behavioural Consultancy model to manage CBs after PBT.

An angel on my shoulder: a study of relationships between women with anorexia and healthcare professionals.

Adults with anorexia are an under-researched group because the usual focus is on adolescents. The relationships that occur between healthcare professionals and adults with anorexia are often challenging, because they do not necessarily agree on the goals of treatment. The therapeutic relationship is widely recognized as crucial to care, even healing and restorative in its own right but problematic in this setting. This is a phenomenological study of how therapeutic relationships are negotiated and maintained in a day care service. Six women with anorexia nervosa and seven of their healthcare professionals were interviewed in the care setting to explore their lived experience of their relationships. Six important themes emerged from the interviews: the authenticity of the relationship, safety, the externalization of the eating disorder, recovery measured in kilos, the power of hope and optimism and the use and acceptance of maternalism in the care setting. Findings suggest that patients appreciated the safety and security of care, but some were using the service as respite rather than recovery. Patients saw goals and tasks related directly to weight gain as irrelevant to their main concerns, but engagement with people who provided a secure, nurturing and maternalistic context for safety and optimism was seen as supportive.

Mimulus is an emerging model system for the integration of ecological and genomic studies.

The plant genus Mimulus is rapidly emerging as a model system for studies of evolutionary and ecological functional genomics. Mimulus contains a wide array of phenotypic, ecological and genomic diversity. Numerous studies have proven the experimental tractability of Mimulus in laboratory and field studies. Genomic resources currently under development are making Mimulus an excellent system for determining the genetic and genomic basis of adaptation and speciation. Here, we introduce some of the phenotypic and genetic diversity in the genus Mimulus and highlight how direct genetic studies with Mimulus can address a wide spectrum of ecological and evolutionary questions. In addition, we present the genomic resources currently available for Mimulus and discuss future directions for research. The integration of ecology and genetics with bioinformatics and genome technology offers great promise for exploring the mechanistic basis of adaptive evolution and the genetics of speciation.

Methods for peak assignment in low-resolution multidimensional NMR cross-correlation relaxometry.

Several NMR protocols are presented for assigning peaks in complex T1-T2 spectra, including the effects of varying the spectrometer frequency and the CPMG pulsing rate. Extensions into a third dimension based on chemical-shift; diffusion- and field-cycled weighted T1-T2 cross-correlation methods are also explored as a means of peak assignment. We illustrate the power of these novel techniques with reference to simple aqueous sucrose solutions, but the methodology should be generally applicable.

Apoptosome dependent caspase-3 activation pathway is non-redundant and necessary for apoptosis in sympathetic neurons.

Although sympathetic neurons are a well-studied model for neuronal apoptosis, the role of the apoptosome in activating caspases in these neurons remains debated. We find that the ability of sympathetic neurons to undergo apoptosis in response to nerve growth factor (NGF) deprivation is completely dependent on having an intact apoptosome pathway. Genetic deletion of Apaf-1, caspase-9, or caspase-3 prevents apoptosis after NGF deprivation, and importantly, allows these neurons to recover and survive long-term following readdition of NGF. The inability of caspase-3 deficient sympathetic neurons to undergo apoptosis is particularly striking, as apoptosis in dermal fibroblasts and cortical neurons proceeds even in the absence of caspase-3. Our results show that in contrast to dermal fibroblasts and cortical neurons, sympathetic neurons express no detectable levels of caspase-7. The strict requirement for an intact apoptosome, coupled with a lack of effector caspase redundancy, provides sympathetic neurons with a markedly increased control over their apoptotic pathway.

Motional relativity and industrial NMR sensors.

We explore the implications of motional relativity in NMR and show that sample translation can be used to acquire NMR signals without the need for pulsed RF excitation or pulsed magnetic field gradients. Novel single-shot, on-line NMR acquisition protocols for samples being conveyed at high speed are discussed and preliminary results using a low-cost, on-line prototype NMR sensor are presented.

A low-field, low-cost Halbach magnet array for open-access NMR.

A working prototype of a novel low-cost Halbach-array-based NMR system is described. The new design provides open access to the sample relative to conventional NMR magnet designs and this facilitates the simultaneous use of multi-sensor techniques on the same sample, in which NMR/MRI can potentially be combined with other spectroscopies such as impedance spectroscopy, laser scattering and rheological experiments.

Microstructural effects on microbial survival: phase-separating dextran solutions.

Evolving microstructure in a model dextran solution is shown to exert a major influence on the survival of Escherichia coli K-12 frag 1 and Salmonella typhimurium LT2. The microstructure results from microscopic phase separation, which develops over several hours resulting in hardening of the solution into a glassy state. The microstructure is characterized by an array of physical methods including image analysis, electron spin resonance and bulk rheology, and it is shown that bacterial survival depends on the formation of microscopic. water-rich domains and not primarily on bulk water activity or hardness.

Effective particle-mediated vaccination against mouse melanoma by coadministration of plasmid DNA encoding Gp100 and granulocyte-macrophage colony-stimulating factor.

Particle-mediated gene delivery was used to immunize mice against melanoma. Mice were immunized with a plasmid cDNA coding for the human melanoma-associated antigen, gp100. Murine B16 melanoma, stably transfected with human gp100 expression plasmid, was used as a tumor model. Particle-mediated delivery of gp100 plasmid into the skin of naïve mice resulted in significant protection from a subsequent tumor challenge. Co-delivery of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) expression plasmid together with the gp100 plasmid consistently resulted in a greater level of protection from tumor challenge. The inclusion of the GM-CSF plasmid with the gp100 DNA vaccine allowed a reduction in the gp100 plasmid dose required for antitumor efficacy. Protection from tumor challenge was achieved with as little as 62.5 ng of gp100 DNA per vaccination. Tumor protection induced by the gp100 + GM-CSF gene combination was T cell mediated, because it was abrogated in vaccinated mice treated with anti-CD4 and anti-CD8 monoclonal antibodies. In addition, administration of the gp100 + GM-CSF DNA vaccine to mice bearing established 7-day tumors resulted in significant suppression of tumor growth. These results indicate that inclusion of GM-CSF DNA augments the efficacy of particle-mediated vaccination with gp100 DNA, and this form of combined gp100 + GM-CSF DNA vaccine warrants clinical evaluation in melanoma patients.

Analysis of the N gene hypersensitive response induced by a fluorescently tagged tobacco mosaic virus.

The hypersensitive response (HR) triggered on Nicotiana edwardsonii by tobacco mosaic virus was studied using a modified viral genome that directed expression of the green fluorescent protein. Inoculated plants were initially incubated at 32 degrees C to inhibit the N gene-mediated HR. Transfer to 20 degrees C initiated the HR, and fluorescent infection foci were monitored for early HR-associated events. Membrane damage, which preceded visible cell collapse by more than 3 h, was accompanied by a transient restriction of the xylem within infection sites. Following cell collapse and the rapid desiccation of tissue undergoing the HR, isolated, infected cells were detected at the margin of necrotic lesions. These virus-infected cells were able to reinitiate infection on transfer to 32 degrees C, however, if maintained at 20 degrees C they eventually died. The results indicate that the tobacco mosaic virus-induced HR is a two-phase process with an early stage culminating in rapid cell collapse and tissue desiccation followed by a more extended period during which the remaining infected cells are eliminated.

Surgery of amphibians.

This article is an introduction to common amphibian surgical techniques. No overwhelming obstacles preclude incorporating amphibian surgeries into the repertoire of veterinary clinicians. With the proper tools and reference materials and a little practice, the skills needed may be readily acquired.

Basic husbandry and clinical assessment of the amphibian patient.

The veterinarian presented with an amphibian patient must be prepared to assess both the animal's medical condition and its husbandry record; good health is inextricably linked to proper care and diet. This article provides the clinician with guidelines for maintaining amphibians in captivity, including information on climate control and lighting, housing and cage enrichment, and nutrition. The article also covers questions to ask when taking a history, methods of restraint, and practical advice on the equipment and techniques used to conduct a complete physical examination of the amphibian patient.

Microstructural characterization of starch systems by NMR relaxation and Q-space microscopy.

Nuclear magnetic resonance (NMR) relaxation and q-space diffusion measurements have been used to probe the microscopic water distribution in a variety of starch-based systems, including packed beds of native starch granules with varying water contents, starch gels, and freeze-dried starch gels. The q-space data for the granular beds is compared with a variety of theoretical models and conforms best to unbounded diffusion in a lower dimensional space. In contrast to some earlier reports, the data for the gelatinized samples are not anomalous and conform to simple unrestricted diffusion in a three-dimensional space. The paper concludes with a novel method for probing pore size distribution in freeze-dried starch gels by infusion of acetone.