Maternal age effects on fecundity and offspring egg-to-adult viability are not affected by mitochondrial haplotype

Ecology and Evolution published by John Wiley & Sons Ltd. While numerous studies have demonstrated that mitochondrial genetic variation can shape organismal phenotype, the level of contribution the mitochondrial genotype makes to life-history phenotype across the life course remains unknown. Furthermore, a clear technical bias has emerged in studies of mitochondrial effects on reproduction, with many studies conducted on males, but few on females. Here, we apply a classic prediction of the evolutionary theory of aging to the mitochondrial genome, predicting the declining force of natural selection with age will have facilitated the accumulation of mtDNA mutations that confer late-life effects on female reproductive performance. This should lead to increased levels of mitochondrial genetic variation on reproduction at later-life stages. We tested this hypothesis using thirteen strains of Drosophila melanogaster that each possessed a different mitochondrial haplotype in an otherwise standard nuclear genetic background. We measured fecundity and egg-to-adult viability of females over five different age classes ranging from early to late life and quantified the survival of females throughout this time period. We found no significant variation across mitochondrial haplotypes for the reproductive traits, and no mitochondrial effect on the slope of decline in these traits with increasing age. However, we observed that flies that died earlier in the experiment experienced steeper declines in the reproductive traits prior to death, and we also identified maternal and grandparental age effects on the measured traits. These results suggest the mitochondrial variation does not make a key contribution to shaping the reproductive performance of females

Branching on multi-aggregated variables

open5siopenGamrath, Gerald; Melchiori, Anna; Berthold, Timo; Gleixner, Ambros M.; Salvagnin, DomenicoGamrath, Gerald; Melchiori, Anna; Berthold, Timo; Gleixner, Ambros M.; Salvagnin, Domenic

Saw-tooth cardiomyopathy

We present an unusual case of cardiomyopathy in a two month old male infant with a grade-I systolic murmur. Echocardiographic examination disclosed left ventricular (LV), dysplasia with saw-tooth like inwards myocardial projections extending from the lateral walls towards the LV cavity. There was mild LV systolic dysfunction with apical hypokinesia. Cardiovascular magnetic resonance demonstrated in detail these cross bridging muscular projections originating from the inferior interventricular septum and lateral LV wall, along with areas of hypokinesis at the LV septum and apex in a noncoronary distribution, without any late gadolinium enhancement. We have termed this condition saw-tooth cardiomyopathy because of the very characteristic appearance

Assessment of potential cardiotoxic side effects of mitoxantrone in patients with multiple sclerosis

Previous studies showed that mitoxantrone can reduce disability progression in patients with multiple sclerosis (MS). There is, however, concern that it may cause irreversible cardiomyopathy with reduced left ventricular (LV) ejection fraction (EF) and congestive heart failure. The aim of this prospective study was to investigate cardiac side effects of mitoxantrone by repetitive cardiac monitoring in MS patients. The treatment protocol called for ten courses of a combined mitoxantrone (10 mg/m(2) body surface) and methylprednisolone therapy. Before each course, a transthoracic echocardiogram was performed to determine the LV end-diastolic diameter, the end-systolic diameter and the fractional shortening; the LV-EF was calculated. Seventy-three patients participated (32 males; age 48 +/- 12 years, range 20-75 years; 25 with primary progressive, 47 with secondary progressive and 1 with relapsing-remitting MS) who received at least four courses of mitoxantrone. Three of the 73 patients were excluded during the study (2 patients discontinued therapy; 1 patient with a previous history of ischemic heart disease developed atrial fibrillation after the second course of mitoxantrone). The mean cumulative dose of mitoxantrone was 114.0 +/- 33.8 mg. The mean follow-up time was 23.4 months (range 10-57 months). So far, there has been no significant change in any of the determined parameters (end-diastolic diameter, end-systolic diameter, fractional shortening, EF) over time during all follow-up investigations. Mitoxantrone did not cause signs of congestive heart failure in any of the patients. Further cardiac monitoring is, however, needed to determine the safety of mitoxantrone after longer follow-up times and at higher cumulative doses. Copyright (C) 2005 S. Karger AG, Basel

Older adults experiences of rehabilitation in acute health care

Rehabilitation is a key component of nursing and allied healthcare professionals’ roles in most health and social care settings. This paper reports on stage 2 of an action research project to ascertain older adult's experience of rehabilitation. Twenty postdischarge interviews were conducted and the interview transcripts were analysed using thematic content analysis. All older adults discharged from an acute older acute rehabilitation ward to their own homes in the community were eligible to participate. The only exclusion criterion was older adults who were thought to be unable to give consent to participate by the nurse in charge and the researcher. Whilst 92 older adults were eligible to participate in this research study, only 20 were interviewed. The findings from this study suggest that older adults valued communication with health professionals but were aware of their time constraints that hindered communication. This study suggests that both nurses and allied health professionals are not actively providing rehabilitative services to promote health and well-being, which contradicts the focus of active ageing. Furthermore, there was evidence of unmet needs on discharge, and older adults unable to recall the professions that were involved in their interventions and the rationale for therapy input. It is suggested that further research is needed to explore the effectiveness of allied health rehabilitation in the acute setting. This study highlights the need for further research into older adults’ perceptions of the rehabilitation process in the acute setting

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

The synergistic effect of chlorotoxin-mApoE in boosting drug-loaded liposomes across the BBB

We designed liposomes dually functionalized with ApoE-derived peptide (mApoE) and chlorotoxin (ClTx) to improve their blood-brain barrier (BBB) crossing. Our results demonstrated the synergistic activity of ClTx-mApoE in boosting doxorubicin-loaded liposomes across the BBB, keeping the anti-tumour activity of the drug loaded: mApoE acts promoting cellular uptake, while ClTx promotes exocytosis of liposomes

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio