Critical role of extracellular vesicles in modulating the cellular effects of cytokines

Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time.     

Comprehensive list by habitat of algae of Utah, USA.

A list of the algal species that have been reported from the state of Utah is presented. Also listed are the habitats from which these algae were collected. A total of nearly 1,900 taxa have been identified to the species level or below. Diatoms comprise the largest group, with nearly 1,000 taxa, followed by the green algae with over 550 taxa.     

基于科学思维的英语文学教学:跨学科的视角

本文阐述基于科学思维过程的英语文学教学策略,即英语文学作品以综合课程的形式应用于教学实践活动.其要点是从优秀文学作品中选取需要解决问题的情境,从跨学科的视角来审视作品中的矛盾和冲突.教师们通过分析这些问题情境教给学生科学的思维方法.其教学策略的重点在于提出问题和做出决策.这些用于跨学科教学策略的文学作品是关注真实世界的起点.生活中面临的两难问题通过基于科学思维的文学教学而获得理性的解释或合理的解决.     

A mechanistic principle for proton pumping by cytochrome c oxidase

In aerobic organisms, cellular respiration involves electron transfer to oxygen through a series of membrane-bound protein complexes. The process maintains a transmembrane electrochemical proton gradient that is used, for example, in the synthesis of ATP. In mitochondria and many bacteria, the last enzyme complex in the electron transfer chain is cytochrome c oxidase (CytcO), which catalyses the four-electron reduction of O2 to H2O using electrons delivered by a water-soluble donor, cytochrome c. The electron transfer through CytcO, accompanied by proton uptake to form H2O drives the physical movement (pumping) of four protons across the membrane per reduced O2. So far, the molecular mechanism of such proton pumping driven by electron transfer has not been determined in any biological system. Here we show that proton pumping in CytcO is mechanistically coupled to proton transfer to O2 at the catalytic site, rather than to internal electron transfer. This scenario suggests a principle by which redox-driven proton pumps might operate and puts considerable constraints on possible molecular mechanisms by which CytcO translocates protons.     

Transverse and longitudinal variation in woody riparian vegetation along a montane river

This study explores how the relationship between flow and riparian vegetation varies along a montane river. We mapped occurrence of woody riparian plant communities along 58 km of the San Miguel River in southwestern Colorado. We determined the recurrence interval of inundation for each plant community by combining step-backwater hydraulic modeling at 4 representative reaches with Log-Pearson analysis of 4 stream gaging stations. Finally, we mapped bottomland surficial geology and used a Geographic Information System to overlay the coverages of geology and vegetation. Plant communities were distinctly arrayed along the hydrologic gradient. The Salix exigua Nuttall (sandbar willow) community occurred mostly on surfaces with a recurrence interval of inundation shorter than 2.2 years; the Betula occidentalis Hooker (river birch) community peaked on sites with recurrence intervals of inundation between 2.2 and 4.6 years. The hydrologic position occupied by communities dominated by Populus angustifolia James (narrowleaf cottonwood) was strongly related to age of trees and species composition of understory shrubs. The fraction of riparian vegetation on surfaces historically inundated by the river decreased in the upstream direction from almost 100% near Uravan to <50% along the South Fork of the San Miguel River. In upstream reaches much of the physical disturbance necessary to maintain riparian vegetation is provided by valley-side processes including debris flows, floods from minor tributaries, landslides, and beaver activity. Where valley-side processes are important, prediction of riparian vegetation change based on alterations of river flow will be incomplete.     

Extracellular vesicles regulate the human osteoclastogenesis: divergent roles in discrete inflammatory arthropathies

Objective

Extracellular vesicles (EVs) are subcellular signalosomes. Although characteristic EV production is associated with numerous physiological and pathological conditions, the effect of blood-derived EVs on bone homeostasis is unknown. Herein we evaluated the role of circulating EVs on human osteoclastogenesis.

Methods

Blood samples from healthy volunteers, rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients were collected. Size-based EV sub-fractions were isolated by gravity-driven filtration and differential centrifugation. To investigate the properties of EV samples, resistive pulse sensing technique, transmission electron microscopy, flow cytometry and western blot were performed. CD14⁺ monocytes were separated from PBMCs, and stimulated with recombinant human M-CSF, RANKL and blood-derived EV sub-fractions. After 7 days, the cells were fixed and stained for tartrate-resistant acid phosphatase and counted.

Results

EVs isolated by size-based sub-fractions were characterized as either microvesicles or exosomes (EXO). Healthy (n = 11) and RA-derived (n = 12) EXOs profoundly inhibited osteoclast differentiation (70%, p < 0.01; 65%, p < 0.01, respectively). In contrast, PsA-derived (n = 10) EXOs had a stimulatory effect (75%, p < 0.05). In cross-treatment experiments where EXOs and CD14⁺ cells were interchanged between the three groups, only healthy (n = 5) and RA (n = 5)-derived EXOs inhibited (p < 0.01, respectively) the generation of osteoclasts in all groups, whereas PsA (n = 7)-derived EXOs were unable to mediate this effect.

Conclusions

Our data suggest that blood-derived EXOs are novel regulators of the human osteoclastogenesis and may offer discrete effector function in distinct inflammatory arthropathies.

     

New species of Australian arid zone chelonine wasps from the genera Phanerotoma and Ascogaster (Hymenoptera: Braconidae) informed by the ‘Bush Blitz’ surveys of national reserves

Here we focus on the poorly studied braconid wasp subfamily Cheloninae for the arid zone of the Australian continent, using material, in part, resulting from comprehensive surveys of three arid zone reserves. The Bush Blitz programme is a multi-institutional project with the aim of documenting the diversity of the flora and fauna in Australia’s National Reserve System, with describing new species being a key focus of the programme. In total, 11 species from the genera Ascogaster and Phanerotoma are treated, with species’ delimitation based on both molecular and morphological data. Two species are redescribed (Phanerotoma behriae Zettel, 1988a and P. decticauda Zettel, 1988a) and nine species are described as new (Ascogaster brevivena sp. nov., A. ferruginegaster sp. nov., A. prolixogaster sp. nov., A. rubriscapa sp. nov., Phanerotoma bonbonensis sp. nov., P. bushblitz sp. nov., P. lutea sp. nov., P. nigriscapulata sp. nov. and P. witchelinaensis sp. nov.). Keys to the arid zone species of these two genera are provided, along with a species richness estimation of Australian chelonine wasps.     

Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved?in both?prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy.