Protein folding and quinary interactions: creating cellular organisation through functional disorder

The marginal stability of globular proteins in the cell is determined by the balance between excluded volume effect and soft interactions. Quinary interactions are a type of soft interactions involved in intracellular organisation and known to have stabilising or destabilising effects on globular proteins. Recent studies suggest that globular proteins have structural flexibility, exhibiting more than one functional state. Here, we propose that the quinary-induced destabilisation can be sufficient to produce functional partially unfolded states of globular proteins. The biological relevance of this mechanism is explored, involving intracellular phase separation and regulatory stress response mechanisms.The authors thank Hernani Geros for useful comments on the manuscript and Michael Smith for language advices. In addition, JCM and SR acknowledge the Foundation for Science and Technology, FCT- Portugal, for financial support through the Centre of Chemistry of the University of Minho (CQ-UM) (projects UID/QUI/00686/2013 and UID/QUI/00686/2016). SE acknowledges funding from the Cluster of Excellence RESOLV (EXC 1069) funded by the German Research Foundation (DFG) and the Human Frontier Science Program Organization Research Grant (Project: RGP0022/2017)

Identification of candidate pelagic marine protected areas through a seabird seasonal-, multispecific- and extinction risk-based approach

With increasing pressure on the oceans from environmental change, there has been a global call for improved protection of marine ecosystems through the implementation of marine protected areas (MPAs). Here, we used species distribution modelling (SDM) of tracking data from 14 seabird species to identify key marine areas in the southwest Atlantic Ocean, valuing areas based on seabird species occurrence, seasonality and extinction risk. We also compared overlaps between the outputs generated by the SDM and layers representing important human threats (fishing intensity, ship density, plastic and oil pollution, ocean acidification), and calculated loss in conservation value using fishing and ship density as cost layers. The key marine areas were located on the southern Patagonian Shelf, overlapping extensively with areas of high fishing activity, and did not change seasonally, while seasonal areas were located off south and southeast Brazil and overlapped with areas of high plastic pollution and ocean acidification. Non-seasonal key areas were located off northeast Brazil on an area of high biodiversity, and with relatively low human impacts. We found support for the use of seasonal areas depending on the seabird assemblage used, because there was a loss in conservation value for the seasonal compared to the non-seasonal approach when using ‘cost’ layers. Our approach, accounting for seasonal changes in seabird assemblages and their risk of extinction, identified additional candidate areas for incorporation in the network of pelagic MPAs

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

A study on trypsin, Aspergillus flavus and Bacillus sp. protease inhibitory activity in Cassia tora (L.) syn Senna tora (L.) Roxb. seed extract

<p>Abstract</p> <p>Background</p> <p>Proteases play an important role in virulence of many human, plant and insect pathogens. The proteinaceous protease inhibitors of plant origin have been reported widely from many plant species. The inhibitors may potentially be used for multiple therapeutic applications in viral, bacterial, fungal diseases and physiological disorders. In traditional Indian medicine system, <it>Cassia tora </it>(<it>Senna tora</it>) is reportedly effective in treatment of skin and gastrointestinal disorders. The present study explores the protease inhibitory activity of the above plant seeds against trypsin, <it>Aspergillus flavus </it>and <it>Bacillus </it>sp. proteases.</p> <p>Methods</p> <p>The crushed seeds of <it>Cassia tora </it>were washed thoroughly with acetone and hexane for depigmentation and defatting. The proteins were fractionated by ammonium sulphate (0-30, 30-60, 60-90%) followed by dialysis and size exclusion chromatography (SEC). The inhibitory potential of crude seed extract and most active dialyzed fraction against trypsin and proteases was established by spot test using unprocessed x-ray film and casein digestion methods, respectively. Electrophoretic analysis of most active fraction (30-60%) and SEC elutes were carried employing Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Gelatin SDS-PAGE. Inhibition of fungal spore germination was studied in the presence of dialyzed active inhibitor fraction. Standard deviation (SD) and ANOVA were employed as statistical tools.</p> <p>Results</p> <p>The crude seeds' extract displayed strong antitryptic, bacterial and fungal protease inhibitory activity on x-ray film. The seed protein fraction 30-60% was found most active for trypsin inhibition in caseinolytic assay (P < 0.001). The inhibition of caseinolytic activity of the proteases increased with increasing ratio of seed extract. The residual activity of trypsin, <it>Aspergillus flavus </it>and <it>Bacillus </it>sp. proteases remained only 4, 7 and 3.1%, respectively when proteases were incubated with 3 mg ml^-1seed protein extract for 60 min. The inhibitory activity was evident in gelatin SDS-PAGE where a major band (~17-19 kD) of protease inhibitor (PI) was detected in dialyzed and SEC elute. The conidial germination of <it>Aspergillus flavus </it>was moderately inhibited (30%) by the dialyzed seed extract.</p> <p>Conclusions</p> <p><it>Cassia tora </it>seed extract has strong protease inhibitory activity against trypsin, <it>Aspergillus flavus </it>and <it>Bacillus </it>sp. proteases. The inhibitor in <it>Cassia tora </it>may attenuate microbial proteases and also might be used as phytoprotecting agent.</p

Partnership and Capacity Building of Local Governance

Partnership is about sharing of power, responsibility and achievements. According to the World Bank Public Private Partnership (PPP) promoting group, ―partnership refer to informal and shortterm engagements of non-governmental organizations, the private sector and/or government agencies that join forces for a shared objective; to more formal, but still short-term private sector engagements for the provision of specific services, for example, annual outsourcing arrangements for janitorial services for a school or operations of the school cafeteria; to more complex contractual arrangements, such as build, operate, transfer regimes, where the private sector takes on considerable risk and remains engaged long term; or to full privatizations‖ (World Bank Group 2014, 29).© Springer Nature Switzerland AG 2020. This is a post-peer-review, pre-copyedit version of an article published in Partnerships for the Goals. Encyclopedia of the UN Sustainable Development Goals. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-319-71067-9_21-1.fi=vertaisarvioitu|en=peerReviewed

Myc Prevents Apoptosis and Enhances Endoreduplication Induced by Paclitaxel

BACKGROUND: The role of the MYC oncogene in the apoptotic pathways is not fully understood. MYC has been reported to protect cells from apoptosis activation but also to sensitize cells to apoptotic stimuli. We have previously demonstrated that the down-regulation of Myc protein activates apoptosis in melanoma cells and increases the susceptibility of cells to various antitumoral treatments. Beyond the well-known role in the G1-->S transition, MYC is also involved in the G2-M cell cycle phases regulation. METHODOLOGY/PRINCIPAL FINDINGS: In this study we have investigated how MYC could influence cell survival signalling during G2 and M phases. We used the microtubules damaging agent paclitaxel (PTX), to arrest the cells in the M phase, in a p53 mutated melanoma cell line with modulated Myc level and activity. An overexpression of Myc protein is able to increase endoreduplication favoring the survival of cells exposed to antimitotic poisoning. The PTX-induced endoreduplication is associated in Myc overexpressing cells with a reduced expression of MAD2, essential component of the molecular core of the spindle assembly checkpoint (SAC), indicating an impairment of this checkpoint. In addition, for the first time we have localized Myc protein at the spindle poles (centrosomes) during pro-metaphase in different cell lines. CONCLUSIONS: The presence of Myc at the poles during the prometaphase could be necessary for the Myc-mediated attenuation of the SAC and the subsequent induction of endoreduplication. In addition, our data strongly suggest that the use of taxane in antitumor therapeutic strategies should be rationally based on the molecular profile of the individual tumor by specifically analyzing Myc expression levels

An Atlas for Schistosoma mansoni Organs and Life-Cycle Stages Using Cell Type-Specific Markers and Confocal Microscopy

Schistosomiasis (bilharzia) is a tropical disease caused by trematode parasites (Schistosoma) that affects hundreds of millions of people in the developing world. Currently only a single drug (praziquantel) is available to treat this disease, highlighting the importance of developing new techniques to study Schistosoma. While molecular advances, including RNA interference and the availability of complete genome sequences for two Schistosoma species, will help to revolutionize studies of these animals, an array of tools for visualizing the consequences of experimental perturbations on tissue integrity and development needs to be made widely available. To this end, we screened a battery of commercially available stains, antibodies and fluorescently labeled lectins, many of which have not been described previously for analyzing schistosomes, for their ability to label various cell and tissue types in the cercarial stage of S. mansoni. This analysis uncovered more than 20 new markers that label most cercarial tissues, including the tegument, the musculature, the protonephridia, the secretory system and the nervous system. Using these markers we present a high-resolution visual depiction of cercarial anatomy. Examining the effectiveness of a subset of these markers in S. mansoni adults and miracidia, we demonstrate the value of these tools for labeling tissues in a variety of life-cycle stages. The methodologies described here will facilitate functional analyses aimed at understanding fundamental biological processes in these parasites

When Music and Long-Term Memory Interact: Effects of Musical Expertise on Functional and Structural Plasticity in the Hippocampus

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus

Testing and Assessment in an International Context: Cross- and Multi-cultural Issues

Globalisation, increase of migration flows, and the concurrent worldwide competitiveness impose rethinking of testing and assessment procedures and practices in an international and multicultural context. This chapter reviews the methodological and practical implications for psychological assessment in the field of career guidance. The methodological implications are numerous and several aspects have to be considered, such as cross-cultural equivalence or construct, method, and item bias. Moreover, the construct of culture by itself is difficult to define and difficult to measure. In order to provide non-discriminatory assessment, counsellors should develop their clinical cross-cultural competencies, develop more specific intervention strategies, and respect cultural differences. Several suggestions are given concerning translation and adaptation of psychological instruments, developing culture specific measures, and the use of these instruments. More research in this field should use mixed methods, multi-centric designs, and consider emic and etic psychological variables. A multidisciplinary approach might also allow identifying culture specific and ecological meaningful constructs. Non-discriminatory assessment implies considering the influence and interaction of personal characteristics and environmental factors