Models and mechanisms of repeat expansion disorders: a worm’s eye view

The inappropriate genetic expansion of various repetitive DNA sequences underlies over 20 distinct inherited diseases. The genetic context of these repeats in exons, introns and untranslated regions has played a major role in thinking about the mechanisms by which various repeat expansions might cause disease. Repeat expansions in exons are thought to give rise to expanded toxic protein repeats (i.e. polyQ). Repeat expansions in introns and UTRs (i.e. FXTAS) are thought to produce aberrant repeat-bearing RNAs that interact with and sequester a wide variety of essential proteins, resulting in cellular toxicity. However, a new phenomenon termed ‘repeat-associated nonAUG dependent (RAN) translation’ paints a new and unifying picture of how distinct repeat expansion-bearing RNAs might act as substrates for this noncanonical form of translation, leading to the production of a wide range of repeat sequence-specific-encoded toxic proteins. Here, we review how the model system Caenorhabditis elegans has been utilized to model many repeat disorders and discuss how RAN translation could be a previously unappreciated contributor to the toxicity associated with these different models.     

The structure of the Golgi apparatus: a sperm’s eye view in principal epithelial cells of the rat epididymis

 The Golgi apparatus of epididymal principal cells shares many structural features with other cell types. Saccular regions are arranged in a cis-Golgi network, eight flattened saccules, and several trans-Golgi networks (TGNs). Dilated tubules form intersaccular connecting regions which joint together saccules at the same or different levels between adjacent stacks. Wells exist as large perforations in register with the four cis-most saccules and serve as areas of vesicular interactions. TGNs are variable and can appear to peel off the stack or to be detached from it in the form of an anastomotic tubular network with pale dilated areas corresponding to prosecretory granules connected by short narrow bridges. Elongated or discoid dilated cisternae of endoplasmic reticulum (ER) (sparsely granulated) lie over the cis face of the stack, from which they are separated by an intermediate compartment filled with vesicles and tubules. The ER is also closely juxtaposed to the TGNs and the eighth saccule but interconnections are never seen between them. Vesicles of the COP variety reside at all levels of the stack and appear to bud off the cis-located ER and the edges of the saccules, while clathrin-coated vesicles appear mainly on the trans face of the stack and next to lysosomes. In the supranuclear cytoplasm, clusters of vesicles and tubules, at times budding off enveloping ER, appear to radiate toward the Golgi stacks where they fuse with cis Golgi elements. Taken together, these observations suggest dynamic functions and interactions for the various Golgi elements, associated vesicles, ER, and vesicular tubular clusters. Accepted: 29 January 1998     

Fungal culture of musculoskeletal tissue: what’s the point?

There have not been any studies that review the prevalence of fungal isolates using selective media from samples of banked musculoskeletal tissue retrieved from living and cadaveric donors. A total of 2,036 swab and 2,621 biopsy samples of musculoskeletal tissue from tissue banks were received from the 1st August 2008 till 31st December 2010. Routine culture for fungi using selective media with a prolonged incubation period failed to demonstrate a greater prevalence of fungal isolates than by using non-selective culture media alone. Using selective culture fungi were recovered from only two Sabouraud agar plates (0.1%) but not from non-selective media. During the same period fungi were isolated from three graft samples cultured in non-selective broth media only (0.1%). There was no correlation of fungal isolates from selective or non-selective media inoculated at the same time nor from multiple graft samples collected from the same donor supporting the possibility of an exogenous source for fungal isolates rather than an endogenous source.     

A specialist’s audit of aggregated occurrence records: An ‘aggregator’s’ perspective

A recent ZooKeys’ paper (Mesibov, 2013: http://www.pensoft.net/journal_home_page.php?journal_id=1&page=article&SESID=df7bcb35b02603283dcb83ee0e0af0c9&type=show&article_id=5111) has highlighted data quality issues in aggregated data sets, but did not provide a realistic way to address these issues. This paper provides an aggregator’s perspective including ways that the whole community can help to address data quality issues. The establishment of GBIF and national nodes (national aggregators) such as the Atlas of Living Australia (ALA) have integrated and exposed a huge diversity of biological observations along with many associated issues. Much of the admirable work by Mesibov (2013) was enabled by having the data exposed.Data quality, one of the highest priorities for GBIF, the national nodes and other aggregators, depends on both automatic methods and community experts to detect and correct data issues. Not all issues can however be automatically detected or corrected, so community assistance is needed to help improve the quality of exposed biological data. We do need to improve the infrastructure and associated processes to more easily identify data issues and document all changes to ensure a full record is permanently and publicly available.     

An amicable separation: Chick’s way of doing EMT

Epithelial to mesenchymal transition (EMT) is a morphogenetic process in which cells lose their

epithelial characteristics and gain mesenchymal properties, and is fundamental for many tissue

remodeling events in developmental and pathological conditions. Although general cell biology of

EMT has been well-described, how it is executed in diverse biological settings depends largely on

individual context, and as a consequence, regulatory points for each EMT may vary. Here we discuss

developmental and cellular events involved in chick gastrulation EMT. Regulated disruption of

epithelial cell/basement membrane (BM) interaction is a critical early step. This takes place after

molecular specification of mesoderm cell fate, but before the disruption of tight junctions. The

epithelial cell/BM interaction is mediated by small GTPase RhoA and through the regulation of basal

microtubule dynamics. We propose that EMT is not regulated as a single morphogenetic event.

Components of EMT in different settings may share similar regulatory mechanisms, but the sequence

of their execution and critical regulatory points vary for each EMT.     

India’s Biological Diversity Act 2002: An act for the new millenium

Journal of Biosciences -     

Are parents’ working patterns associated with their child’s sleep? An analysis of dualparent families in Australia

Insufficient sleep in children predicts emotional and behavioral problems, poorer school performance, and health problems. Child sleep durations have declined in recent decades, suggesting a need to identify and understand predictors of short sleep. The present study investigated whether aspects of parental employment (i.e. parental work hours, and non-standard work hours) were associated with sleep in children. Data collected from 2477 children aged 6-7 years as part of the Longitudinal Study of Australian Children were used in this paper. Child sleep duration, bedtimes, and wake times were determined from parent self-report using time-use diaries. Parents completed a survey assessing their work patterns as well as a range of other demographic and social factors. The results indicated that long mother work hours were associated with later bedtimes and increased odds of <9.5 h sleep in children. Long father work hours were associated with earlier waketimes, earlier bedtimes, and reduced odds of long sleep. Non-standard work hours were associated with longer sleep and earlier bedtimes. The present results indicate the need to develop strategies to limit any adverse effects of parental work on child sleep, perhaps by promoting earlier and regular bedtimes. These findings warrant further investigation given the importance of sleep in healthy child development.

     

Lipid Integration in Neurodegeneration: An Overview of Alzheimer’s Disease

Various types of lipids and their metabolic products associated with the biological membrane play a crucial role in signal transduction, modulation, and activation of receptors and as precursors of bioactive lipid mediators. Dysfunction in the lipid homeostasis in the brain could be a risk factor for the many types of neurodegenerative disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. These neurodegenerative disorders are marked by extensive neuronal apoptosis, gliosis, and alteration in the differentiation, proliferation, and development of neurons. Sphingomyelin, a constituent of plasma membrane, as well as its primary metabolite ceramide acts as a potential lipid second messenger molecule linked with the modulation of various cellular signaling pathways. Excessive production of reactive oxygen species associated with enhanced oxidative stress has been implicated with these molecules and involved in the regulation of a variety of different neurodegenerative and neuroinflammatory disorders. Studies have shown that alterations in the levels of plasma lipid/cholesterol concentration may result to neurodegenerative diseases. Alteration in the levels of inflammatory cytokines and mediators in the brain has also been found to be implicated in the pathophysiology of neurodegenerative diseases. Although several mechanisms involved in neuronal apoptosis have been described, the molecular mechanisms underlying the correlation between lipid metabolism and the neurological deficits are not clearly understood. In the present review, an attempt has been made to provide detailed information about the association of lipids in neurodegeneration especially in Alzheimer’s disease.     

Angola’s central scarp forests: patterns of bird diversity and conservation threats

Despite Angola’s central scarp forests being recognised as a critical global priority for bird conservation, fine-scale information on threatened bird distributions and patterns of bird diversity are lacking. These data are essential to identify sites within the Western Angola Endemic Bird Area that should be targeted for conservation. First endemic and near-endemic species and subspecies, and species with isolated populations along the Angolan scarp were identified to highlight taxa of greatest priority for conservation and for use in studying the evolutionary origins of the region. Thereafter survey data collected during 2005 from 13 forest sites along the central scarp was analysed. These data show that there are three distinct bird communities across the width of the escarpment, each associated with a distinctive forest type. Of note is the finding that threatened and Near Threatened endemic species occur almost exclusively in the dry forests adjacent to the main escarpment, rather than in the moistest forests found on the main escarpment, which instead are richer in Congo Basin forest birds. Based on these data, summaries of ranges, populations and conservation threats are given for the seven most threatened bird species. Attention is drawn to threats to the habitats of greatest importance to these species. A conservation area network should be established that encompasses the full spectrum of bird diversity described, to ensure survival of current unique taxa and the future evolutionary potential of the area.     

BioBanking: an environmental scientist’s view of the role of biodiversity banking offsets in conservation

Offsets, first formalised in the United States of America in the 1970s for wetland mitigation, are now widely used globally with the aim to mitigate loss of biodiversity due to development. Embracing biodiversity offsets is one method of governments to meet their commitments under the Millennium Development Goals and the Convention on Biological Diversity. Resource extraction companies see them as a method of gaining access to land, while the community may perceive them as a way of enhancing environmental outcomes. In New South Wales, Australia, BioBanking legislation was introduced in late 2006 with the aim of ‘no net loss’ of biodiversity associated with development, particularly expanding urban and coastal development. The strengths of the legislation are that it aims to enhance threatened species conservation, and raise the profile of conservation of threatened species and habitats. Weaknesses include (1) the narrowness of the definition of biodiversity; (2) the concepts are based on a flawed logic and immature, imprecise and complex science which results in difficulties in determining biodiversity values; (3) likely problems with management and compliance; and (4) an overall lack of resources for implementation and long-term monitoring. It is concluded that the legislation is a concerted effort to deal with biodiversity loss, however, stakeholders have concerns with the process, and it is unworkable with the complexity of such ecosystems (compared for example to carbon credit trading), and underdeveloped disciplines such as restoration biology and ecology. Despite these criticisms, there is a need for all stakeholders to work to improve the outcomes.     

A new method of quantitative determination of contamination of baker’s yeast by wild yeasts or by dissociation forms of the production culture

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Different perspectives in understanding muscle functions in Parkinson’s disease through surface electromyography: Exploring multiple activation patterns

Gait disorders are one of the cardinal features of Parkinson’s Disease (PD) and might be affected by a modified pattern of motor unit activation. This work explores how PD affects the lower limb muscle control and how muscle activity contributes to gait impairment. Using clinical gait analysis data, the onset and the offset of the surface electromyographic (sEMG) signal of four lower limb muscles were determined in 18 people with PD and compared with 10 heathy controls. Different motor patterns were identified in both the populations through a statistical detector algorithm and described in terms of linear envelope, local maxima activation magnitude and occurrence, co-contractions, and bursts duration. Statistical analysis was performed using statistical parametric mapping for the sEMG envelope and linear mixed effects models for the sEMG parameters. An equivalent number of sEMG patterns was detected in PD with respect to controls. Significant differences were highlighted between the two cohorts within the same activation modality. Plantarflexors muscles activation was delayed on time and had different durations and activations peaks, while Biceps Femoris revealed a higher local maximum. These results suggested that functional tibiotarsus joint reeducation coupled with postural rehabilitation might be beneficial for people with PD.     

Bicarbonate transport inhibitor SITS modulates pH homeostasis triggering apoptosis of Dalton’s lymphoma: implication of novel molecular mechanisms

Bicarbonate transporter (BCT) plays a crucial role in maintaining pH homeostasis of tumor cells by import of \({\text{HCO}}_{3}^{ - } .\) This helps the tumor cells in manifesting extracellular tumor acidosis, accompanied by a relative intracellular alkalinization, which in turn promotes tumor progression. Therefore, blocking BCT-mediated \({\text{HCO}}_{3}^{ - }\) transport is envisaged as a promising anticancer therapeutic approach. Thus, using a murine model of a T cell lymphoma, designated as Dalton’s lymphoma (DL), in the present in vitro investigation the antitumor consequences of blocking BCT function by its inhibitor 4-acetamido-4-isothiocyanostilbene-2,2-disulfonate (SITS) were explored. Treatment of DL cells with SITS resulted in an increase in the extracellular pH, associated with a decline in DL cell survival and augmented induction of apoptosis. BCT inhibition also elevated the expression of cytochrome c, caspase-9, caspase-3, Bax, reactive oxygen species, and nitric oxide along with inhibition of HSP-70 and Bcl2, which regulate tumor cell survival and apoptosis. SITS-treated DL cells displayed upregulated production of IFN-γ and IL-6 along with a decline of IL-10. Treatment of DL cells with SITS also inhibited the expression of fatty acid synthase, which is crucial for membrane biogenesis in neoplastic cells. The expression of lactate transporter MCT-1 and multidrug resistance regulating protein MRP-1 got inhibited along with hampered uptake of glucose and lactate production in SITS-treated DL cells. Thus, the declined tumor cell survival following inhibition of BCT could be the consequence of interplay of several inter-connected regulatory molecular events. The outcome of this study indicates the potential of BCT inhibition as a novel therapeutic approach for treatment of hematological malignancies.     

Ecology of Children’s Growth: An Example from Transitional Populations of the Brazilian Amazon

The intense environmental and social changes taking place in Amazonia make this a key area for health studies of populations transitioning to a cosmopolitan lifestyle and market economy. Caboclos are among those populations. They comprise the majority of rural Brazilian Amazon peoples. At present there is limited information about their patterns of growth and health. In this paper, anthropometric data on Caboclo children from three groups living in different environments are presented and discussed within a bioanthropological framework. Caxiuanã, Aracampina, and Santana have a combined population of 1,069 people. Caxiuanã relies more on subsistence activities for survival and Santana more on commerce, while Aracampina uses both subsistence strategies. Compared to US children, Caboclo are generally shorter and lighter in all age groups. However, their weight-for-height is above the 50th percentile. In relation to skinfolds, age groups 0–2, 6–8, and 9–11 years present statistically significant differences among the three communities. Caxiuanã children have the smallest and Aracampina children have the largest skinfolds. While seasonal and environmental differences may account for some of the observed variation in growth and fatness patterns, socioeconomic factors also play a key role in the trends observed. Thus, an ecological model provides the best framework for explaining these findings. Caxiuanã children are small and thin as a result of their combined poor environment and limited access to cash, western goods, and health care. Aracampina and Santana’s fuller access to such socioeconomic influences and richer ecology results in taller and fatter children. Understanding similar interactions between ecology and social factors will be fundamental to developing sustainable health initiatives among rural Amazonian populations.     

The rebound effect through industrial ecology’s eyes: a review of LCA-based studies

Purpose

Industrial ecology academics have embraced with great interest the rebound effect principle operationalised within energy economics. By pursuing more comprehensive assessments, they applied tools such as life cycle assessment (LCA) to appraise the environmental consequences of the rebound effect. As a result, the mainstream rebound mechanism was broadened and a diversity of (sometimes inconsistent) definitions and approaches unveiled. To depict the state of play, a comprehensive literature review is needed.

Methods

A literature review has been carried out by targeting scientific documents relevant for the integration of the rebound effect into LCA-based studies. The search was conducted using two approaches: (1) via online catalogues using a defined search criterion and (2) via cross-citation analysis from the documents identified through the first approach.

Results and discussion

By analysing a total of 42 works yielded during our review, it was possible to bring together the various advantages of the life cycle perspective, as well as to identify the main inconsistencies and uninformed claims present in literature. Concretely, three main advantages have been identified and are discussed: (1) the representation of the rebound effect as a multi-dimensional, life cycle estimate, (2) the improvement of the technology explicitness and (3) the broadening of the consumption and production factors leading to the rebound effect. Also, inconsistencies on the definition and classification of the rebound effect have been found among studies.

Conclusions

The review contributes a number of valuable insights to understand how the rebound effect has been treated within the industrial ecology and LCA fields. For instance, the conceptual and methodological refinements introduced by these fields represent a step forward from traditional viewpoints, making the study of the rebound effect more comprehensive and meaningful for environmental assessment and policy making. However, the broadened scope of this new approach unveiled some conceptual inconsistencies, which calls for a common framework. This framework would help the LCA community to consistently integrate the rebound effect as well as to create a common language with other disciplines, favouring learning and co-evolution. We believe that our findings can serve as a starting point in order to delineate such a common framework.     

‘An island of socialism in a capitalist country’: Postsocialist Russian science and the culture of the state

Through a comparison of privatization programs in two physics institutes, this article explores the ways in which scientists in the Siberian science city of Akademgorodok adapted to the low levels of state funding available to them in the 1990s. Scientists transformed structures that were available under socialism into hybrid state-private ventures. Rather than ‘freeing’ Russian science from its former dependence on the state, however, these changes have reconfigured, and in some cases even strengthened, the relationship between state power and the production of knowledge. Seeing ‘the state’ as it is constituted in Russian scientists' discourse challenges Western models of the autonomy of science.