The phylogeny of halichondrid demosponges: past and present re-visited with DNA-barcoding data

Halichondrid sponges play a pivotal role in the classification of demosponges as changes in their classification has had direct consequences for the classification of Demospongiae. Historically, the systematics of halichondrids has been unstable. During the 1950s, the order was divided into two subclasses, which were based on empirical and assumed reproductive data. Subsequent morphological and biochemical analyses postulated the re-merging of halichondrid families, but recent molecular data indicate their polyphyly. Here we review the classification history of halichondrid taxa, compare it with the current and predominantly ribosomal molecular data, and support the new phylogenetic hypotheses with mitochondrial data from DNA barcoding.     

Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial

Background

Asthma guidelines suggest that therapy can be reduced once asthma is controlled. Despite these recommendations, asthmatic patients are seldom stepped down in clinical practice, and questions remain about when and how to reduce asthma therapy. The purpose of the present study was to evaluate lung function and asthma control in patients who were stepped down from the highest recommended dose of inhaled corticosteroid/long acting β₂ agonist combination therapy.

Methods

This was a prospective, randomised, controlled, two-arm parallel group study. Asthmatic patients who were fully controlled with a high daily dose (1000/100 μg) of fluticasone/salmeterol were randomly assigned to 6 months of open-label treatment with either 500/100 μg fluticasone/salmeterol Diskus daily or 400/24 μg extrafine beclomethasone/formoterol pMDI daily. The primary outcome was the change in morning peak expiratory flow (PEF) values between baseline and the end of treatment. The secondary outcomes included asthma control and exacerbation frequency.

Results

Four hundred twenty-two patients were included in the analysis. The PEF values remained above 95% of the predicted values throughout the study. The end-study morning PEF rates showed equivalence between the groups (difference between means, 2.49 L/min; 95% CI, -13.43 to 18.42). No changes from baseline were detected in PEF and forced expiratory volume in 1 second measured at the clinics, in the symptom scores or in the use of rescue medication. Asthma control was maintained in 95.2% of the patients at 6 months. No significant differences between the groups were detected in any other parameter, including exacerbation frequency and adverse events.

Conclusions

Stepping down patients whose asthma is controlled with the highest recommended dose of fluticasone/salmeterol to either 500/100 μg fluticasone/salmeterol daily or 400/24 μg extra-fine beclomethasone/formoterol daily provides comparable maintenance of lung function and asthma control.

Trial registration

clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00497237","term_id":"NCT00497237"}}NCT00497237     

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.     

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.     

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.

     

The empowerment of translational research: lessons from laminopathies

The need for a collaborative approach to complex inherited diseases collectively referred to as laminopathies, encouraged Italian researchers, geneticists, physicians and patients to join in the Italian Network for Laminopathies, in 2009. Here, we highlight the advantages and added value of such a multidisciplinary effort to understand pathogenesis, clinical aspects and try to find a cure for Emery-Dreifuss muscular dystrophy, Mandibuloacral dysplasia, Hutchinson-Gilford Progeria and forms of lamin-linked cardiomyopathy, neuropathy and lipodystrophy.     

Reorienting the Fab Domains of Trastuzumab Results in Potent HER2 Activators

The structure of the Fab region of antibodies is critical to their function. By introducing single cysteine substitutions into various positions of the heavy and light chains of the Fab region of trastuzumab, a potent antagonist of HER2, and using thiol chemistry to link the different Fabs together, we produced a variety of monospecific F(ab′)₂-like molecules with activities spanning from activation to inhibition of breast tumor cell growth. These isomers (or bis-Fabs) of trastuzumab, with varying relative spatial arrangements between the Fv-regions, were able to either promote or inhibit cell-signaling activities through the PI3K/AKT and MAPK pathways. A quantitative phosphorylation mapping of HER2 indicated that the agonistic isomers produced a distinct phosphorylation pattern associated with activation. This study suggests that antibody geometric isomers, found both in nature and during synthetic antibody development, can have profoundly different biological activities independent of their affinities for their target molecules.     

Characterization of HLA class II/peptide-TCR interactions of the immunodominant T cell epitope in Art v 1, the major mugwort pollen allergen

More than 95% of mugwort pollen-allergic individuals are sensitized to Art v 1, the major allergen in mugwort pollen. Interestingly, the CD4 T cell response to Art v 1 involves only one single immunodominant peptide, Art v 1(25-36) (KCIEWEKAQHGA), and is highly associated with the expression of HLA-DR1. Therefore, we investigated the molecular basis of this unusual immunodominance among allergens. Using artificial APC expressing exclusively HLA-DRB1*0101 and HLA-DRA*0101, we formally showed that DR1 acts as restriction element for Art v 1(25-36)-specific T cell responses. Further assessment of binding of Art v 1(25-36) to artificial HLA-DR molecules revealed that its affinity was high for HLA-DR1. Amino acid I27 was identified as anchor residue interacting with DR molecules in pocket P1. Additionally, Art v 1(25-36) bound with high affinity to HLA-DRB1*0301 and *0401, moderately to HLA-DRB1*1301 and HLA-DRB5*0101, and weakly to HLA-DRB1*1101 and *1501. T cell activation was also inducible by Art v 1(25-36)-loaded, APC-expressing HLA molecules other than DR1, indicating degeneracy of peptide binding and promiscuity of TCR recognition. Specific binding of HLA-DRB1*0101 tetramers containing Art v 1(19-36) allowed the identification of Art v 1(25-36)-specific T cells by flow cytometry. In summary, the immunodominance of Art v 1(25-36) relies on its affinity to DR1, but is not dictated by it. Future investigations at the molecular HLA/peptide/TCR and cellular level using mugwort pollen allergy as a disease model may allow new insights into tolerance and pathomechanisms operative in type I allergy, which may instigate new, T cell-directed strategies in specific immunotherapy.     

Administration of PLP139-151 primes T cells distinct from those spontaneously responsive in vitro to this antigen

We examined the TCR repertoire used by naive SJL mice in their in vitro spontaneous response to proteolipid protein (PLP) 139-151 by Vbeta-Jbeta spectratyping and compared it to that used after immunization with the peptide. T cells from immunized mice use the public rearrangement Vbeta10-Jbeta1.1, but naive mice do not; in contrast, TCR CDR3-beta rearrangements of Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 consistently are associated with the spontaneous response. T cells involved in spontaneous and induced responses can each recognize PLP(139-151) presented in vivo, but its s.c. administration has different consequences for the two repertoires. Four days after immunization, T cells associated with spontaneous responsiveness appear in the draining lymph nodes but disappear by day 10 and never appear elsewhere. Simultaneously, Vbeta10-Jbeta1.1 T cells are likewise activated in the lymph nodes by day 4 and spread to the spleen by day 10. Eight- to 10-wk-old naive mice use a narrower repertoire of TCRs than do immunized age-matched mice. Induced Vbeta10-Jbeta1.1 T cells home to the CNS during experimental autoimmune encephalomyelitis, whereas we failed to detect Vbeta18-Jbeta1.2 and Vbeta19-Jbeta1.2 TCR rearrangements in the CNS. Thus, we observe that administration of PLP(139-151) primes a T cell repertoire distinct from the one responsible for spontaneous responsiveness. This "immunized" repertoire substitutes for the naive one and becomes dominant at the time of disease onset.