g<Emphasis FontCategory="NonProportional">raphite</Emphasis> - a Bioconductor package to convert pathway topology to gene network

Background  

Gene set analysis is moving towards considering pathway topology as a crucial feature. Pathway elements are complex entities such as protein complexes, gene family members and chemical compounds. The conversion of pathway topology to a gene/protein networks (where nodes are a simple element like a gene/protein) is a critical and challenging task that enables topology-based gene set analyses.     

Motif D of Viral RNA-Dependent RNA Polymerases Determines Efficiency and Fidelity of Nucleotide Addition

Fast, accurate nucleotide incorporation by polymerases facilitates expression and maintenance of genomes. Many polymerases use conformational dynamics of a conserved α helix to permit efficient nucleotide addition only when the correct nucleotide substrate is bound. This α helix is missing in structures of RNA-dependent RNA polymerases (RdRps) and RTs. Here, we use solution-state nuclear magnetic resonance to demonstrate that the conformation of conserved structural motif D of an RdRp is?linked to the nature (correct versus incorrect) of the bound nucleotide and the protonation state of a conserved, motif-D lysine. Structural data also reveal the inability of motif D to achieve its optimal conformation after incorporation of an incorrect nucleotide. Functional data are consistent with the conformational change of motif D becoming rate limiting during and after nucleotide misincorporation. We conclude that motif D of RdRps and, by inference, RTs is the functional equivalent to the fidelity helix of other polymerases.     

Protein conducting channels-mechanisms, structures and applications

In the past decade among the main developments in the field of bionanotechnology is the application of proteins in devices. Research focuses on the modification of enzyme systems by means of chemical and physical tools in order to achieve full control of their function and to employ them for specific tasks. Membrane protein channels are intriguing biological devices as they allow the recognition and passage of a variety of macromolecules through an otherwise impermeable lipid bilayer. Hence, membrane proteins can be used as sensory devices for detection or as molecular nanovalves to allow for the controlled release of molecules. Here, we discuss the structure and function of three different channel proteins that mediate the membrane passage of macromolecules using different mechanisms. These systems are described in a comparative manner and an overview is provided of the technological advances in employing these proteins in external (or human) controllable devices.     

Harmonine, a defence compound from the harlequin ladybird, inhibits mycobacterial growth and demonstrates multi-stage antimalarial activity

The harlequin ladybird beetle Harmonia axyridis has been introduced in many countries as a biological control agent, but has become an invasive species threatening the biodiversity of native ladybirds. Its invasive success has been attributed to its vigorous resistance against diverse pathogens. This study demonstrates that harmonine ((17R,9Z)-1,17-diaminooctadec-9-ene), which is present in H. axyridis haemolymph, displays broad-spectrum antimicrobial activity that includes human pathogens. Antibacterial activity is most pronounced against fast-growing mycobacteria and Mycobacterium tuberculosis, and the growth of both chloroquine-sensitive and -resistant Plasmodium falciparum strains is inhibited. Harmonine displays gametocytocidal activity, and inhibits the exflagellation of microgametocytes and zygote formation. In an Anopheles stephensi mosquito feeding model, harmonine displays transmission-blocking activity.     

Physiological implications of pair-bond status in greylag geese

In group-living vertebrates, reliable social allies play a decisive role in dealing with stressors. For example, support by social allies is known to dampen glucocorticoid responses. It remains unknown, however, how social embedding affects the sympatho-adrenergic axis as indicated by heart rate (HR) in non-human animals. We studied the relationships between HR, pair-bond status and distance from the pair-partner in twenty-five free-ranging greylag geese (Anser anser) in a natural social environment. In three individuals, we investigated HR responses following partner loss. Overall, we found a context- and sex-dependent difference in HR between paired and unpaired individuals, paired males having a lower HR during agonistic encounters, and unpaired females having a lower HR during resting. Also, in paired females HR increased with increasing distance from the partner. Our data suggest that HR is modulated by pair-bond status in greylag geese in a context- and sex-dependent manner, which may be representative for social vertebrates in general. Despite the low sample size, the present study indicates that proper social embedding may optimize an individual's physiological investment in the social domain. This reduces individual energy expenditure and may benefit health and reproductive success.     

Healing war wounds and perfuming exile: the use of vegetal,animal, and mineral products for perfumes,cosmetics, and skin healing among Sahrawi refugees of Western Sahara

Background

Over the past decade, there has been growing interest within ethnobiology in the knowledge and practices of migrating people. Within this, scholars have given relatively less attention to displaced people and refugees: to the loss, maintenance, and adaptation of refugees’ ethnobiological knowledge, and to its significance for refugees’ wellbeing. This study focuses on cosmetics and remedies used to heal skin afflictions that are traditionally used by Sahrawi refugees displaced in South Western Algerian refugee camps.

Methods

The research methods included a structured survey carried out with 37 refugee households, semi-structured interviews with 77 refugees, 24 retrospective interviews with refugees and other knowledgeable informants, and a voucher specimen collection of the plants and products cited.

Results

We recorded the use of 55 plant species, nine animal species, and six mineral products used within the three main use categories discussed in this paper: 1) Remedies for health issues that are typical of the desert environment where the Sahrawi once lived as nomads and now live as refugees (e.g. eye afflictions); 2) Remedies for wounds that are influenced by the Sahrawi’s recent history of guerrilla warfare; and 3) Cosmetics and products used for body care, decoration and perfuming (e.g. hair care, teeth cleansing, henna use) and for aromatizing the air inside of tents and which are widely used in everyday life and social practices.

Conclusions

We discuss the changes that have occurred in the patterns of use and procurement of these products with exile and sedentarization in refugee camps, and conclude that refugees are not simply passive recipients of national and international aid, but rather struggle to maintain and recover their traditional ethnobiological practices in exile. Finally, we suggest further research into the ethnobiological practices and knowledge of displaced populations.

Resumen

Sanando las heridas de guerra y perfumando el exilio: el uso de productos vegetales, animales y minerales con fines de perfumería, cosmética y curativos de la piel entre los refugiados saharauis del Sáhara Occidental.

Antecedentes

Durante la última década ha habido un creciente interés en los estudios etnobiológicos de los conocimientos y prácticas de las personas que migran. Dentro de esta tendencia, los estudiosos han prestado relativamente menor atención a las personas desplazadas y a los refugiados: a la pérdida, el mantenimiento y la adaptación de sus conocimientos etnobiológicos, y su importancia para el bienestar de los refugiados. Este estudio se centra en los cosméticos y remedios para curar problemas de la piel tradicionalmente utilizados por los refugiados saharauis en los campamentos de desplazados al sudoeste de Argelia.

Métodos

Los métodos de investigación que se utilizaron son: una encuesta estructurada con 37 familias de refugiados, entrevistas semi-estructuradas con 77 refugiados, 24 entrevistas retrospectivas con refugiados e informantes conocedores, y una colección de muestra de las plantas y productos citados.

Resultados

Se registró el uso de 55 especies vegetales, nueve especies animales, y seis productos minerales utilizados en tres principales categorías de usos: 1) Recursos contra los problemas de salud característicos del entorno desértico donde una vez vivieron los saharauis como nómadas y donde ahora viven como refugiados (por ejemplo problemas en los ojos); 2) Remedios para heridas que reflejan la historia reciente de guerra de guerrilla de los nómadas saharauis; y 3) Cosméticos y productos utilizados para el cuidado del cuerpo, decoración y perfumes (por ejemplo, atención al cabello, limpieza de dientes, uso del henna) y como aromatizantes del aire al interior de las tiendas, que son ampliamente utilizados en la vida y las prácticas sociales cotidianas de los refugiados.

Conclusiones

En la discusión, se analizan los cambios que se han producido en los patrones de uso y en la adquisición de estos productos durante el exilio. Llegamos a la conclusión de que los refugiados no son recipientes pasivos de la ayuda nacional e internacional, sino más bien luchan para mantener y recuperar sus prácticas tradicionales etnobiológicas en el exilio. Finalmente, sugerimos nuevas direcciones para la investigación de las prácticas y los conocimientos etnobiológicos de las poblaciones desplazadas.

     

A cross-sectional single-centre study on Pompe disease in 42 German patients: Molecular analysis of the GAA gene, manifestation and genotype-phenotype correlations

ABSTRACT: BACKGROUND: Pompe disease (Glycogen storage disease type II, GSD II, acid alpha-glucosidase deficiency, acid maltase deficiency, OMIM # 232300) is an autosomal-recessive lysosomal storage disorder due to a deficiency of acid alpha-glucosidase (GAA, acid maltase, EC 3.2.1.20, Swiss-Prot P10253). Clinical manifestations are dominated by progressive weakness of skeletal muscle throughout the clinical spectrum. In addition, the classic infantile form is characterised by hypertrophic cardiomyopathy. Methods: In a cross-sectional single-centre study we clinically assessed 3 patients with classic infantile Pompe disease and 39 patients with non-classic presentations, measured their acid alpha-glucosidase activities and analysed their GAA genes. Results: Classic infantile patients had nearly absent residual enzyme activities and a typical clinical course with hypertrophic cardiomyopathy until the beginning of therapy. The disease manifestations in non-classic patients were heterogeneous. There was a broad variability in the decline of locomotive and respiratory function. The age of onset ranged from birth to late adulthood and correlated with enzyme activities. Molecular analysis revealed as many as 33 different mutations, 14 of which are novel. All classic infantile patients had two severe mutations. The most common mutation in the non-classic group was c.-32-13T>G. It was associated with a milder course in this subgroup. Conclusion: Disease manifestation strongly correlates with the nature of the GAA mutations, while the variable progression in non-classic Pompe disease is likely to be explained by yet unknown modifying factors. This study provides the first comprehensive dataset on the clinical course and the mutational spectrum of Pompe disease in Germany.