AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.Peer reviewedProo

Orientation Sensitivity at Different Stages of Object Processing: Evidence from Repetition Priming and Naming

An ongoing debate in the object recognition literature centers on whether the shape representations used in recognition are coded in an orientation-dependent or orientation-invariant manner. In this study, we asked whether the nature of the object representation (orientation-dependent vs orientation-invariant) depends on the information-processing stages tapped by the task

ENSO Atmospheric Teleconnections and Their Response to Greenhouse Gas Forcing

This is the final version of the article. Available from AGU via the DOI in this record.El Niño and Southern Oscillation (ENSO) is the most prominent year-to-year climate fluctuation on Earth, alternating between anomalously warm (El Niño) and cold (La Niña) sea surface temperature (SST) conditions in the tropical Pacific. ENSO exerts its impacts on remote regions of the globe through atmospheric teleconnections, affecting extreme weather events worldwide. However, these teleconnections are inherently nonlinear and sensitive to ENSO SST anomaly patterns and amplitudes. In addition, teleconnections are modulated by variability in the oceanic and atmopsheric mean state outside the tropics and by land and sea ice extent. The character of ENSO as well as the ocean mean state have changed since the 1990s, which might be due to either natural variability or anthropogenic forcing, or their combined influences. This has resulted in changes in ENSO atmospheric teleconnections in terms of precipitation and temperature in various parts of the globe. In addition, changes in ENSO teleconnection patterns have affected their predictability and the statistics of extreme events. However, the short observational record does not allow us to clearly distinguish which changes are robust and which are not. Climate models suggest that ENSO teleconnections will change because the mean atmospheric circulation will change due to anthropogenic forcing in the 21st century, which is independent of whether ENSO properties change or not. However, future ENSO teleconnection changes do not currently show strong intermodel agreement from region to region, highlighting the importance of identifying factors that affect uncertainty in future model projections.S. W. Y. is supported by the KoreaMeteorological Administration Researchand Development Program under grant KMIPA2015-2112. Wenju Cai is supported by Earth System and Climate Change Hub of the Australia National Environmental Science Programme, and Centre for Southern Hemisphere Oceans Research, an international collaboration between CSIRO and Qingdao National Laboratory for Marine Sciences and Technology. B. Dewitte acknowledges supports from FONDECYT(1151185) and from LEFE-GMMC. Dietmar Dommenget is supported by ARC Centre of Excellence for Climate System Science (CE110001028)

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients

A genome-wide investigation of the effect of farming and human-mediated introduction on the ubiquitous seaweed Undaria pinnatifida

International audienceHuman activity is an important driver of ecological and evolutionary change on our planet. In particular, domestication and biological introductions have important and long-lasting effects on species’ genomic architecture and diversity. However, genome-wide analysis of independent domestication and introduction events within a single species has not previously been performed. The Pacific kelp Undaria pinnatifida provides such an opportunity because it has been cultivated in its native range in Northeast Asia but also introduced to four other continents in the past 50 years. Here we present the results of a genome-wide analysis of natural, cultivated and introduced populations of U. pinnatifida to elucidate human-driven evolutionary change. We demonstrate that these three categories of origin can be distinguished at the genome level, reflecting the combined influence of neutral (demography and migration) and non-neutral (selection) processes