Myelin pathology: Involvement of molecular chaperones and the promise of chaperonotherapy

The process of axon myelination involves various proteins including molecular chaperones. Myelin alteration is a common feature in neurological diseases due to structural and functional abnormalities of one or more myelin proteins. Genetic proteinopathies may occur either in the presence of a normal chaperoning system, which is unable to assist the defective myelin protein in its folding and migration, or due to mutations in chaperone genes, leading to functional defects in assisting myelin maturation/migration. The latter are a subgroup of genetic chaperonopathies causing demyelination. In this brief review, we describe some paradigmatic examples pertaining to the chaperonins Hsp60 (HSPD1, or HSP60, or Cpn60) and CCT (chaperonin-containing TCP-1). Our aim is to make scientists and physicians aware of the possibility and advantages of classifying patients depending on the presence or absence of a chaperonopathy. In turn, this subclassification will allow the development of novel therapeutic strategies (chaperonotherapy) by using molecular chaperones as agents or targets for treatment

Pure silica nanoparticles for liposome/lipase system encapsulation: Application in biodiesel production

In this work we report the synthesis of organic inorganic solid with spherical morphology where enzyme, as active compounds, is encapsulated. The organic phase of nanospheres is composed of l-phosphatidylcholine, as liposome, and lipase from Rhizomucor miehei, as enzyme. The organic phase is covered with porous inorganic silica shell that could stabilize the internal liposomal phase and, consequently, isolate and protect the bioactive molecules. The liposome and silica amount used during the immobilization procedure have been optimized in order to obtain active and stable heterogeneous biocatalyst. Hybrid-nanospheres containing the enzyme were used to catalyze the transesterification reaction of triolein with methanol to methyl esters, typical biodiesel mixture compounds. The encapsulated enzyme retains its activity after 5 reaction cycles. The total productivity of the best catalyst obtained is higher than that of the free enzyme.The authors, A.C. and U.D., thank the Spanish MICINN (Consolider Ingenio 2010-MULTICAT (CSD2009-00050) and MAT2011-29020-C02-01) for their financial support.Macario, A.; Verri, F.; Díaz Morales, UM.; Corma Canós, A.; Giordano, G. (2013). Pure silica nanoparticles for liposome/lipase system encapsulation: Application in biodiesel production. Catalysis Today. 204:148-155. doi:10.1016/j.cattod.2012.07.014S14815520

SARS-CoV-2 in patients with cancer: possible role of mimicry of human molecules by viral proteins and the resulting anti-cancer immunity

A few reports suggest that molecular mimicry can have a role in determining the more severe and deadly forms of COVID-19, inducing endothelial damage, disseminated intravascular coagulation, and multiorgan failure. Heat shock proteins/molecular chaperones can be involved in these molecular mimicry phenomena. However, tumor cells can display on their surface heat shock proteins/molecular chaperones that are mimicked by SARS-CoV-2 molecules (including the Spike protein), similarly to what happens in other bacterial or viral infections. Since molecular mimicry between SARS-CoV-2 and tumoral proteins can elicit an immune reaction in which antibodies or cytotoxic cells produced against the virus cross-react with the tumor cells, we want to prompt clinical studies to evaluate the impact of SARS-CoV-2 infection on prognosis and follow up of various forms of tumors. These topics, including a brief historical overview, are discussed in this paper

Does sars-cov-2 trigger stress-induced autoimmunity by molecular mimicry? A hypothesis

Viruses can generate molecular mimicry phenomena within their hosts. Why should severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these? Information in this short review suggests that it might be so and, thus, encourages research aiming at testing this possibility. We propose, as a working hypothesis, that the virus induces antibodies and that some of them crossreact with host’s antigens, thus eliciting autoimmune phenomena with devasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests, this could drive researchers to find effective treatments against the virus

A Network of Text, Data and People for the Earth System Sciences

Earth System Science is an outstanding example of a field of research which yields important results especially when conducted in multidisciplinary and global cooperation. The International Polar Year and its expected legacy are used as an example to illustrate this assertion and the financial and intellectual expense invested. It follows that any effort to make more out of the globally distributed – if not fragmented – results and to network the knowledge gained would be valuable indeed. An experimental implementation of such a system, connecting journal articles to datasets, expeditions and researchers involved, is introduced. Some developments necessary to implement comparable and more powerful systems on a global scale are discussed

Male phenotypic diversity experienced during ontogeny mediates female mate choice in guppies

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.Early social experience can be important in shaping female mate choice. Previous work has shown that females adjust their decisions based on the distribution of male sexual trait values encountered during development. However, other phenotypic features could be important in the formation of mate preferences if, for example, they provide additional information about the males available. Here, we examined how the level of overall phenotypic variance (independent of trait values) experienced during ontogeny, mediated female choice in guppies, Poecilia reticulata. Developing females were reared with males either all different in colouration or all similar in colouration or with adult females representing high variance, low variance and no experience of male variance respectively. We found that females were more sexually responsive when reared with females only than in either of the male treatments. When reared with males, responsiveness was greater in the low-variance compared to the high variance treatment. Moreover, females had stronger sexual preferences following rearing in the high variance compared to the low variance condition. In turn, males switched mating tactics, increasing the rate of coerced copulation attempts when facing choosier females, possibly to balance the loss in mating opportunities. Taken together, these results demonstrate the adaptive plasticity of female mating decisions and the dynamic selection pressures they might impose on the evolution of male sexual traits, potentially contributing to the maintenance of the extreme polymorphism found in male colour patterns.This work was supported by the University of Exeter through an Exeter Graduate Fellow studentship

The chaperone system in cancer therapies: Hsp90

: The chaperone system (CS) of an organism is composed of molecular chaperones, chaperone co-factors, co-chaperones, and chaperone receptors and interactors. It is present throughout the body but with distinctive features for each cell and tissue type. Previous studies pertaining to the CS of the salivary glands have determined the quantitative and distribution patterns for several members, the chaperones, in normal and diseased glands, focusing on tumors. Chaperones are cytoprotective, but can also be etiopathogenic agents causing diseases, the chaperonopathies. Some chaperones such as Hsp90 potentiate tumor growth, proliferation, and metastasization. Quantitative data available on this chaperone in salivary gland tissue with inflammation, and benign and malignant tumors suggest that assessing tissue Hsp90 levels and distribution patterns is useful for differential diagnosis-prognostication, and patient follow up. This, in turn, will reveal clues for developing specific treatment centered on the chaperone, for instance by inhibiting its pro-carcinogenic functions (negative chaperonotherapy). Here, we review data on the carcinogenic mechanisms of Hsp90 and their inhibitors. Hsp90 is the master regulator of the PI3K-Akt-NF-kB axis that promotes tumor cell proliferation and metastasization. We discuss pathways and interactions involving these molecular complexes in tumorigenesis and review Hsp90 inhibitors that have been tested in search of an efficacious anti-cancer agent. This targeted therapy deserves extensive investigation in view of its theoretical potential and some positive practical results and considering the need of novel treatments for tumors of the salivary glands as well as other tissues

CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma

CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study, we analyzed a series of KAs and SCCs by immunohistochemistry for CD1a and Hsp60. Our results show that the levels of both are significantly lower in KA than in SCC and support the hypothesis that KA may evolve towards SCC if there is a failure of the local modulation of the antitumor immune response. The data also show that immunohistochemistry for CD1a and Hsp60 can be of help in differential diagnosis between KAs and well-differentiated forms of SCC

KAPALIGIRANG PAMPAGKATUTO, KLIMANG PANGKLASRUM AT PERFROMANS SA FILIPINO NG MGA MAG-AARAL SA GRADO 11

Ang pag-aaral na ito ay naglalayong alamin ang kapaligirang pampagkatuto, klimang pangklasrum at performans sa Filipino ng mga mag-aaral sa grado labing-isa (11) ng Mataas na Paaralang Nasyonal ng Ajuy. Ito rin ay naglayong matukoy kung mayroong makabuluhang pagkakaiba sa kapaligirang pampagkatuto at klimang pangklasrum at kung mayroon bang makabuluhang kaugnayan sa performans sa Filipino. Ang mga kinakailangang datos ay tinipon sa pamamagitan ng pagbigay ng talatanungan sa kapaligirang pampagkatuto, klimang pangklasrum at pagsusulit sa performans sa Filipino. Isandaan na nagmula sa Mataas na Paaralang Nasyonal ng Ajuy ang naging kalahok sa pagaaral na ito. Sila ay pinili gamit ang stratified quota random sampling. Ang mga datos ay sinuri sa larangan ng computerprocessed statistics, percentage mean, frequency count, standard deviation, One Way ANOVA (Analysis of Variance), t-test at Pearson’ r. Ang alpha level ay nakaset sa .05 sa lahat ng inferensyal na pagsusulit. Ang mga natuklasan ay nagpakita na may “kaaya-aya” na antas ang kapaligirang pampagkatuto at may “kaaya-aya” na antas ang klimang pangklasrum. Napag-alaman din na mayroon silang “katamtamang” performans sa Filipino. Nakita rin sa pananaliksik na ito na “walang makabuluhang kaugnayan” ang performans sa Filipino sa antas ng kapaligirang pampagkatuto at antas ng klimang pangklasrum. Napag-alaman din na “walang makabuluhang pagkakaiba” ang kapaligirang pampagkatuto sa performans sa Filipino. “Wala ring makabuluhang pagkakaiba” ang klimang pangklasrum ng mga mag-aaral sa Filipino sa performans sa Filipino. Napag-alaman din na “walang makabuluhang kaugnayan” ang kapaligirang pampagkatuto sa klimang pangklasrum maging ang kapaligirang ampagkatuto sa performans sa Filipino gayundin ang klimang pangklasrum at performans sa Filipin