The neurological presentations of childhood and adult mitochondrial disease: established syndromes and phenotypic variations

Mitochondrial disorders are caused by mutations of nuclear or mitochondrial DNA encoded genes involved in oxidative phosphorylation (OXPHOS). Mutations in these critical genes are associated with specific clinical syndromes with diverse presentations (DiMauro and Schon, 2003. NEJM 348, 2656; Hart et al., 2002. Mitochondrial Disorders in Neurology). Since mitochondria are present in many of our organs and play a key role in energy metabolism, mitochondrial encephalomyopathies often present as multisystem disorders which may manifest with neurologic, cardiac, endocrine, gastrointestinal, hepatic, renal and/or hematologic involvement (DiMauro and Bonilla, 1997. The Molecular and Genetic Basis of Neurological Disease; Vu et al., 2002. Neurol. Clin. N. Am. 20, 809). This chapter will address adult and childhood onset mitochondrial DNA encephalomyopathies, characteristic clinical presentations, as well as their molecular characterization.     

Basking in reflected glory: the election of president Obama and naming behaviour

The influence of the 2008 election of President Barack Obama on the naming of children born to African American mothers was investigated. Results indicated that children born after the election were given names that sounded more ‘African American’ than were children born before the election. In addition, African American mother’s Collective Self-Esteem scores were positively correlated with the ethnic sound of a child’s name. It was concluded that this difference in naming behaviour could be viewed through a social identity theory approach and might indicate a desire to ‘bask in the reflected glory’ of President Obama’s election.     

Environmental and genetic cues in the evolution of phenotypic polymorphism

Phenotypic polymorphism is a consequence of developmental plasticity, in which the trajectories of developing organisms diverge under the influence of cues. Environmental and genetic phenotype determination are the two main categories of polymorphic development. Even though both may evolve as a response to varied environments, they are traditionally regarded as fundamentally distinct phenomena. They can however be joined into a single framework that emphasizes the parallel roles of environmental and genetic cues in phenotype determination. First, from the point of view of immediate causation, it is common that phenotypic variants can be induced either by environmental or by allelic variation, and this is referred to as gene-environment interchangeability. Second, from the point of view of adaptation, genetic cues in the form of allelic variation at polymorphic loci can play similar roles as environmental cues in providing information to the developmental system about coming selective conditions. Both types of cues can help a developing organism to fit its phenotype to selective circumstances. This perspective of information in environmental and genetic cues can produce testable hypotheses about phenotype determination, and can thus increase our understanding of the evolution of phenotypic polymorphism.     

Effect of the freeze-drying process on the phenotypic diversity of Pseudomonas putida strains isolated from the interior of healthy roots of Sida hermaphrodita: Phenotype microarrays (PMs)

The objective of this study was to research the effect of the freeze-drying process on the metabolic changes of Pseudomonas putida strains (E41, E42, R85) isolated from the interior of Sida hermaphrodita roots with the use of the phenotypic microarrays (PM) technology.The proposed method of the freeze-drying process with inulin as component lycoprotectant demonstrated a high bacterial survival ratio (BSR) immediately after freeze-drying and storage after 12 months. While, after 360 days of freeze-drying BSR decreased to value of 74.38.Pseudomonas putida strains were assayed on microplates PM1-PM5, and PM9-PM13 testing 664 different substrates. However, no significant differences in the use of C substrates were observed either before or after the freeze drying process. An insignificant negative effect of the freeze-drying on the use of these substrates was observed. The utilization of N, P and S sources was low or showed no metabolic activity for most of the compounds after freeze-drying. The freeze-drying process increased the sensitivity of the bacteria to antibiotics and selected chemicals.In this study, the freeze-drying process decreased the metabolic activities of the tested strains and their resistance to antibiotics and chemicals.     

Responses to selection on genotypic or phenotypic values in the presence of genes with major effects

Summary Average genotypic responses were compared after selection for genotypic values and for phenotypic values on the basis of single-gene models and multigene models in simulated livestock populations. Single-gene models dealt with single gene control of the genetic differences between animals, while multigene models considered a collection of genes with various magnitudes of effects on a trait. In each case, selection lasted through discrete generations until the fixation of the gene frequencies occurred. Generations to reach fixation were used to compare various models, and the two criteria for selection, for their efficiency in selection. Implications of using these models versus using infinitesimal models for selection in practice are presented.     

Preliminary phenotypic characterization of newly isolated halophilic microorganisms by footprinting: a rapid metabolome analysis

The emerging need for rapid screening and identification methods for microbiological purposes necessitates the combined uses of high-tech instruments. In this work, electrospray ionization mass spectrometry was used to visualize the relation of ten newly isolated moderately halophilic microorganisms, to Halomonas salina DSMZ 5928 and Halomonas halophila DSMZ 4770. The method was based on the global analysis of the metabolites in culture media and is termed as metabolic footprinting. Since it was not possible to gain insight into the similarities solely based on the visual inspection of the chromatograms, principal component (PC) analysis was applied on the data. Three PCs alone were able to explain 99% of the information in the data set. The score plots revealed the relation of the new isolates to the two type strains whereas the loading plots gave important clues on the significant ions responsible for the observed clustering. Loading plots also indicated inversely correlated ions that give clues on differing metabolic pathways. The work described here offers a potentially useful way for preliminary rapid phenotypic characterization of new and closely related isolates and a method for screening of similar microorganisms for different and valuable secondary metabolites.     

Correlation of DNA methylation patterns to the phenotypic features of Tibetan elite alpinists in extreme hypoxia

High altitude is an extreme environment that imposes hypoxic pressure on physiological processes, and natives living at high altitudes are more adaptive in certain physiological processes. So far, epigenetic modifications under extreme changes in hypoxic pressures are relatively less understood. Here, we recruit 32 Tibetan elite alpinists (TEAs), who have successfully mounted Everest (8848 m) at least five times. Blood samples and physiological phenotypes of TEAs and 32 matched non-alpinist Tibetan volunteers (non-TEAs) are collected for analysis. Genome-wide DNA methylation analysis identifies 23,202 differentially methylated CpGs (P_adj < 0.05, |β| > 0.1) between the two groups. Some differentially methylated CpGs are in hypoxia-related genes such as PPP1R13L, MAP3K7CL, SEPTI-9, and CUL2. In addition, Gene ontology enrichment analysis reveals several inflammation-related pathways. Phenotypic analysis indicates that 12 phenotypes are significantly different between the two groups. In particular, TEAs exhibit higher blood oxygen saturation levels and lower neutrophil count, platelet count, and heart rate. For DNA methylation association analysis, we find that two CpGs (cg16687447, cg06947206) upstream of PTEN were associated with platelet count. In conclusion, extreme hypoxia exposure leads to epigenetic modifications and phenotypic alterations of TEA, providing us clues for exploring the molecular mechanism underlying changes under extreme hypoxia conditions.     

Beyond the phenotypic gambit: molecular behavioural ecology and the evolution of genetic architecture

Most studies of behaviour examine traits whose proximate causes include sensory input and neural decision-making, but conflict and collaboration in biological systems began long before brains or sensory systems evolved. Many behaviours result from non-neural mechanisms such as direct physical contact between recognition proteins or modifications of development that coincide with altered behaviour. These simple molecular mechanisms form the basis of important biological functions and can enact organismal interactions that are as subtle, strategic and interesting as any. The genetic changes that underlie divergent molecular behaviours are often targets of selection, indicating that their functional variation has important fitness consequences. These behaviours evolve by discrete units of quantifiable phenotypic effect (amino acid and regulatory mutations, often by successive mutations of the same gene), so the role of selection in shaping evolutionary change can be evaluated on the scale at which heritable phenotypic variation originates. We describe experimental strategies for finding genes that underlie biochemical and developmental alterations of behaviour, survey the existing literature highlighting cases where the simplicity of molecular behaviours has allowed insight to the evolutionary process and discuss the utility of a genetic knowledge of the sources and spectrum of phenotypic variation for a deeper understanding of how genetic and phenotypic architectures evolve.     

豚鼠气管平滑肌化学介质敏感性与体征表型的相关性

目的研究豚鼠体征表型与气管平滑肌化学介质敏感性的相关性。方法根据体征表型眼睛颜色、毛色、性别差异选取36只豚鼠,将动物按体征表型分为白色黑眼雌性组（WBEF）,白色黑眼雄性组（WBEM）,白色红眼雌性组（WREF）,白色红眼雄性组（WREM）,杂色黑眼雌性组（VBEF）,杂色黑眼雄性组（VBEM）,每组动物各6只。用旋割法制备离体豚鼠气管螺旋条,以组胺histamine（浴槽浓度2.0×10^-3g/L）和乙酰胆碱acetylcholine（浴槽浓度2.0×10^-4g/L）诱导气管螺旋条收缩,用BL420生物信号采集系统与张力传感器测定标本张力变化值,分析豚鼠眼睛颜色、毛色、性别与组胺、乙酰胆碱诱导的气管螺旋条收缩效应强弱的关系。数据采用SPSS 11.5软件在α=0.05的信度下进行单因素方差检验。结果豚鼠毛色与眼睛颜色表型其气管平滑肌化学介质敏感性差异有显著性（P〈0.05）,白色体征表型豚鼠的气管平滑肌化学介质敏感性较杂色表型高,红色眼睛表型较黑色眼睛表型高。性别表型对其介质敏感性差异不显著。结论毛色、眼睛颜色表型不同其豚鼠气管平滑肌化学介质敏感性差异显著,性别表型不同其介质敏感性差异不显著,平喘动物模型宜优先选择白色红眼表型豚鼠。     

Evolution and maintenance of the environmental component of the phenotypic variance: benefit of plastic traits under changing environments

How environmental variances in quantitative traits are influenced by variable environments is an important problem in evolutionary biology. In this study, the evolution and maintenance of phenotypic variance in a plastic trait under stabilizing selection are investigated. The mapping from genotypic value to phenotypic value of the quantitative trait is approximated by a linear reaction norm, with genotypic effects on its phenotypic mean and sensitivity to environment. The environmental deviation is assumed to be decomposed into environmental quality, which interacts with genotypic value, and residual developmental noise, which is independent of genotype. Environmental quality and the optimal phenotype of stabilizing selection are allowed to randomly fluctuate in both space and time, and individuals migrate equally before development and reproduction among different niches. Analyses show that phenotypic plasticity is adaptive within variable environments if correlations have become established between the optimal phenotype and environmental quality in space and/or time. The evolved plasticity increases with variances in optimal phenotypes and correlations between optimal phenotype and environmental quality; this further induces increases in mean fitness and the environmental variance in the trait. Under certain circumstances, however, the environmental variance may decrease with increase in variation in environmental quality.     

Phenological shifts in North American red squirrels: disentangling the roles of phenotypic plasticity and microevolution

Phenological shifts are the most widely reported ecological responses to climate change, but the requirements to distinguish their causes (i.e. phenotypic plasticity vs. microevolution) are rarely met. To do so, we analysed almost two decades of parturition data from a wild population of North American red squirrels (Tamiasciurus hudsonicus). Although an observed advance in parturition date during the first decade provided putative support for climate change‐driven microevolution, a closer look revealed a more complex pattern. Parturition date was heritable [h² = 0.14 (0.07–0.21 (HPD interval)] and under phenotypic selection [β = ?0.14 ± 0.06 (SE)] across the full study duration. However, the early advance reversed in the second decade. Further, selection did not act on the genetic contribution to variation in parturition date, and observed changes in predicted breeding values did not exceed those expected due to genetic drift. Instead, individuals responded plastically to environmental variation, and high food [white spruce (Picea glauca) seed] production in the first decade appears to have produced a plastic advance. In addition, there was little evidence of climate change affecting the advance, as there was neither a significant influence of spring temperature on parturition date or evidence of a change in spring temperatures across the study duration. Heritable traits not responding to selection in accordance with quantitative genetic predictions have long presented a puzzle to evolutionary ecologists. Our results on red squirrels provide empirical support for one potential solution: phenotypic selection arising from an environmental, as opposed to genetic, covariance between the phenotypic trait and annual fitness.     

New species and unexpected diversity of socially parasitic bees in the genus Inquilina Michener (Hymenoptera: Apoidea: Apidae)

Abstract  Allodapine bees present particular problems for taxonomy due to a high level of morphological conservatism in adults, even between genera. However, this tribe of bees also presents a unique opportunity to explore the evolution of social parasitism because of the comparatively large number of origins of socially parasitic species. Morphological differences presented here, along with DNA sequence data and molecular phylogenetic analyses, indicate a much larger number of Australian social parasite species in the genus Inquilina than previously anticipated, and suggest that the final number of socially parasitic species may be considerable. We describe five new species and present sequence data that will help elucidate the delineation of further new species. Inquilina provides a unique opportunity to study the evolution of social parasitism in social insects, but further studies will need to encompass both population genetic and phylogenetic approaches.     

Quantifying the phenotypic information in mRNA abundance

Quantifying the dependency between mRNA abundance and downstream cellular phenotypes is a fundamental open problem in biology. Advances in multimodal single‐cell measurement technologies provide an opportunity to apply new computational frameworks to dissect the contribution of individual genes and gene combinations to a given phenotype. Using an information theory approach, we analyzed multimodal data of the expression of 83 genes in the Ca²⁺ signaling network and the dynamic Ca²⁺ response in the same cell. We found that the overall expression levels of these 83 genes explain approximately 60% of Ca²⁺ signal entropy. The average contribution of each single gene was 17%, revealing a large degree of redundancy between genes. Using different heuristics, we estimated the dependency between the size of a gene set and its information content, revealing that on average, a set of 53 genes contains 54% of the information about Ca²⁺ signaling. Our results provide the first direct quantification of information content about complex cellular phenotype that exists in mRNA abundance measurements.     

Unravelling the evolution of complex reproductive traits with phenotypic engineering

The social dynamics surrounding courtship, mating and parental care are complex enough when just a single male and female are involved, but for species that employ multiple strategies for achieving fertilization success, the network of interactions among rivals, allies and suitors can be utterly complicated. Such is the case in the ocellated wrasse, Symphodus ocellatus, in which males adopt one of three mating strategies. The large, colourful “nesting males” court females, defend territories and care for fertilized eggs until they hatch. The smaller “satellite males” help the nesting males court females and guard against the third morph, the “sneaker males”, which sneak in when a nesting male is spawning with a female and surreptitiously release sperm. Sneaker males perform no courtship displays nor defend territories, so their reproductive investment is devoted entirely to sperm production. And these alternative male strategies work: 100% of nests contain some eggs fertilized by sneaker and satellite males, despite the fact that parental care is solely the responsibility of nesting males In this issue of Molecular Ecology, work to untangle the proximate mechanisms regulating the reproductive physiology of nesting males and their behaviour towards other males, which impacts the entire social network. Moreover, they describe how variation in neuroendocrine regulation can give rise to variation in reproductive traits, upon which sexual selection can act.     

Slow food and the politics of pork fat: Italian food and European identity

This paper explores the emergence of the Slow Food Movement, an international consumer movement dedicated to the protection of ‘endangered foods.’ The history of one of these ‘endangered foods’, lardo di Colonnata, provides the ethnographic window through which I examine Slow Food's cultural politics. The paper seeks to understand the politics of ‘slowness’ within current debates over European identity, critiques of neo-liberal models of rationality, and the significant ideological shift towards market-driven politics in advanced capitalist societies.     

Saving face: the emotional costs of the Asian immigrant family myth

Access to resources through ethnic group membership is often presumed to affect the intensity of ethnic identification. We examine this premise using survey data on three ethnic groups in Mauritius: Creoles, Hindus, and Muslims. Two key findings emerge from our research. First, access to material resources explains only a modest proportion of total variation in ethnic identification within each group. Second, the resources that affect ethnic identification differ significantly across groups. Access to political goods through group membership affects Hindu identification but is unrelated to ethnic identification among Creoles or Muslims. Conversely, access to economic goods affects Creole and Muslim identification but has no effect on Hindu identification. Explaining these group differences leads us beyond a basic means–ends instrumentalist model to identify conditions that likely mediate the relationship between individual interests and collective identification including the divisibility of economic goods relative to political goods in Mauritius.     

PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer

Small cell lung cancer(SCLC) is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy. However, the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear. Through comprehensive bioinformatic analyses, we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy. Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant. Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance. Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors. Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.