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

Shock acceleration as origin of the radio relic in A521?

We present new high sensitivity observations of the radio relic in A521 carried out with the Giant Metrewave Radio Telescope at 327 MHz and with the Very Large Array at 4.9 and 8.5 GHz. We imaged the relic at these frequencies and carried out a detailed spectral analysis, based on the integrated radio spectrum between 235 MHz and 4.9 GHz, and on the spectral index image in the frequency range 327-610 MHz. To this aim we used the new GMRT observations and other proprietary as well as archival data. We also searched for a possible shock front co-located with the relic on a short archival Chandra X-ray observation of the cluster. The integrated spectrum of the relic is consistent with a single power law; the spectral index image shows a clear trend of steepening going from the outer portion of the relic toward the cluster centre. We discuss the origin of the source in the light of the theoretical models for the formation of cluster radio relics. Our results on the spectral properties of the relic are consistent with acceleration of relativistic electrons by a shock in the intracluster medium. This scenario is further supported by our finding of an X-ray surface brightness edge coincident with the outer border of the radio relic. This edge is likely a shock front.Comment: 13 pages, 12 figures, accepted for publication in A&

Data mining-based statistical analysis of biological data uncovers hidden significance: clustering Hashimoto’s thyroiditis patients based on the response of their PBMC with IL-2 and IFN-γ secretion to stimulation with Hsp60

The pathogenesis of Hashimoto’s thyroiditis includes autoimmunity involving thyroid antigens, autoantibodies, and possibly cytokines. It is unclear what role plays Hsp60, but our recent data indicate that it may contribute to pathogenesis as an autoantigen. Its role in the induction of cytokine production, pro- or anti-inflammatory, was not elucidated, except that we found that peripheral blood mononucleated cells (PBMC) from patients or from healthy controls did not respond with cytokine production upon stimulation by Hsp60 in vitro with patterns that would differentiate patients from controls with statistical significance. This “negative” outcome appeared when the data were pooled and analyzed with conventional statistical methods. We re-analyzed our data with non-conventional statistical methods based on data mining using the classification and regression tree learning algorithm and clustering methodology. The results indicate that by focusing on IFN-γ and IL-2 levels before and after Hsp60 stimulation of PBMC in each patient, it is possible to differentiate patients from controls. A major general conclusion is that when trying to identify disease markers such as levels of cytokines and Hsp60, reference to standards obtained from pooled data from many patients may be misleading. The chosen biomarker, e.g., production of IFN-γ and IL-2 by PBMC upon stimulation with Hsp60, must be assessed before and after stimulation and the results compared within each patient and analyzed with conventional and data mining statistical methods

Preferencias educativas de los estudiantes postgraduados ante los cambios del Espacio Europeo de Educación Superior

La implantación del Espacio Europeo de Educación Superior (EEES) ha provocado profundos cambios que atañen a nuevas concepciones del proceso de enseñanza-aprendizaje. En este contexto, la técnica del Análisis Conjunto (AC) fue aplicada a una muestra de 179 postgraduados pertenecientes al Curso de Adaptación Pedagógica (CAP) 2007-2008, de la Universidad de Granada (UGR), con la intención de determinar sus preferencias hacia los cambios impuestos por el EEES. Los resultados muestran cómo las preferencias formativas de los estudiantes se centran en la adquisición de competencias para el desarrollo de habilidades, la presencialidad de las clases y un enfoque tutorial mediante seguimiento académico

Understanding the Support Needs of Minority Women with Heart Disease

Background. Cardiovascular disease (CVD) affects minority women disproportionately. WomenHeart: The National Coalition for Women with Heart Disease sought to determine effective ways to support non-Caucasian women with CVD. We surveyed women of color living with CVD to understand their unique CVD-related support needs. Methods. 514 non-white women (100 Hispanic, 180 African American, 104 Asian, 107 Indigenous, 23 multiracial) with CVD from 46 states responded to a 55-question survey (online/telephone, English/Spanish) 8/28/15 through 9/11/15. Results. Among respondents not currently attending support groups, 80% were interested in attending support groups. Of WomenHeart services, respondents were most interested in online message boards. Among new services, respondents were most interested in a support group with a medical expert facilitator. Women with tachycardia wanted a support group with others with the same condition. Those with cardiomyopathy preferred to meet most frequently. Respondents most preferred a monthly support group with flexible membership. Community venues were the most popular location for support groups. Indigenous populations had the lowest CVD knowledge and self-efficacy levels, were most likely to prefer a support group with women of their own race, and wished to meet with their groups most frequently. Multiracial women were most likely to have never been told about clinical trials and were least interested in support groups. Hispanics had the least social support. Conclusions. Minority women with CVD indicated interest in support groups. They may benefit from referrals to tailored support group types, including online platforms facilitated by medical experts, and to cardiac rehabilitation and clinical trials

Double Barrel Nasal Trumpets to Prevent Upper Airway Obstruction after Nasal and Non-Nasal Surgery

Objectives. During anesthesia emergence, patients are extubated and the upper airway can become vulnerable to obstruction. Nasal trumpets can help prevent obstruction. However, we have found no manuscript describing how to place nasal trumpets after nasal surgery (septoplasties or septorhinoplasties), likely because (1) the lack of space with nasal splints in place and (2) surgeons may fear that removing the trumpets could displace the splints. The objective of this manuscript is to describe how to place nasal trumpets even with nasal splints in place. Materials and Methods. The authors describe techniques (Double Barrel Technique and Modified Double Barrel Technique) that were developed over three years ago and have been used in patients with obstructive sleep apnea (OSA) and other patients who had collapsible or narrow upper airways (i.e., morbidly obese patients). Results. The technique described in the manuscript provides a method for placing one long and one short nasal trumpet in a manner that helps prevent postoperative upper airway obstruction. The modified version describes a method for placing nasal trumpets even when there are nasal splints in place. Over one-hundred patients have had nasal trumpets placed without postoperative oxygen desaturations. Conclusions. The Double Barrel Technique allows for a safe emergence from anesthesia in patients predisposed to upper airway obstruction (such as in obstructive sleep apnea and morbidly obese patients). To our knowledge, the Modified Double Barrel Technique is the first description for the use of nasal trumpets in patients who had nasal surgery and who have nasal splints in place

A human CCT5 gene mutation causing distal neuropathy impairs hexadecamer assembly in an archaeal model

Chaperonins mediate protein folding in a cavity formed by multisubunit rings. The human CCT has eight non-identical subunits and the His147Arg mutation in one subunit, CCT5, causes neuropathy. Knowledge is scarce on the impact of this and other mutations upon the chaperone’s structure and functions. To make progress, experimental models must be developed. We used an archaeal mutant homolog and demonstrated that the His147Arg mutant has impaired oligomeric assembly, ATPase activity, and defective protein homeostasis functions. These results establish for the first time that a human chaperonin gene defect can be reproduced and studied at the molecular level with an archaeal homolog. The major advantage of the system, consisting of rings with eight identical subunits, is that it amplifies the effects of a mutation as compared with the human counterpart, in which just one subunit per ring is defective. Therefore, the slight deficit of a non-lethal mutation can be detected and characterized

The challenging riddle about the janus‐type role of hsp60 and related extracellular vesicles and miRNAs in carcinogenesis and the promises of its solution

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasmacell membrane, and extracellular vesicles (EVs). Consequently, non‐canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi‐faceted role of this chaperonin in human cancers, showing the contribution of intra‐ and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA‐mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti‐cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro‐ or anti‐tumor

Doxorubicin anti-tumor mechanisms include Hsp60 post-translational modifications leading to the Hsp60/p53 complex dissociation and instauration of replicative senescence

The chaperone Hsp60 is pro-carcinogenic in certain tumor types by interfering with apoptosis and with tumor cell death. In these tumors, it is not yet known whether doxorubicin anti-tumor effects include a blockage of the pro-carcinogenic action of Hsp60. We found a doxorubicin dose-dependent viability reduction in a human lung mucoepidermoid cell line that was paralleled by the appearance of cell senescence markers. Concomitantly, intracellular Hsp60 levels decreased while its acetylation levels increased. The data suggest that Hsp60 acetylation interferes with the formation of the Hsp60/p53 complex and/or promote its dissociation, both causing an increase in the levels of free p53, which can then activate the p53-dependent pathway toward cell senescence. On the other hand, acetylated Hsp60 is ubiquitinated and degraded and, thus, the anti-apoptotic effect of the chaperonin is abolished with subsequent tumor cell death. Our findings could help in the elucidation of the molecular mechanisms by which doxorubicin counteracts carcinogenesis and, consequently, it would open new roads for the development of cancer treatment protocols targeting Hsp60

Hsp60 Post-translational Modifications: Functional and Pathological Consequences

Hsp60 is a chaperone belonging to the Chaperonins of Group I and typically functions inside mitochondria in which, together with the co-chaperonin Hsp10, maintains protein homeostasis. In addition to this canonical role, Hsp60 plays many others beyond the mitochondria, for instance in the cytosol, plasma-cell membrane, extracellular space, and body fluids. These non-canonical functions include participation in inflammation, autoimmunity, carcinogenesis, cell replication, and other cellular events in health and disease. Thus, Hsp60 is a multifaceted molecule with a wide range of cellular and tissue locations and functions, which is noteworthy because there is only one hsp60 gene. The question is by what mechanism this protein can become multifaceted. Likely, one factor contributing to this diversity is post-translational modification (PTM). The amino acid sequence of Hsp60 contains many potential phosphorylation sites, and other PTMs are possible such as O-GlcNAcylation, nitration, acetylation, S-nitrosylation, citrullination, oxidation, and ubiquitination. The effect of some of these PTMs on Hsp60 functions have been examined, for instance phosphorylation has been implicated in sperm capacitation, docking of H2B and microtubule-associated proteins, mitochondrial dysfunction, tumor invasiveness, and delay or facilitation of apoptosis. Nitration was found to affect the stability of the mitochondrial permeability transition pore, to inhibit folding ability, and to perturb insulin secretion. Hyperacetylation was associated with mitochondrial failure; S-nitrosylation has an impact on mitochondrial stability and endothelial integrity; citrullination can be pro-apoptotic; oxidation has a role in the response to cellular injury and in cell migration; and ubiquitination regulates interaction with the ubiquitin-proteasome system. Future research ought to determine which PTM causes which variations in the Hsp60 molecular properties and functions, and which of them are pathogenic, causing chaperonopathies. This is an important topic considering the number of acquired Hsp60 chaperonopathies already cataloged, many of which are serious diseases without efficacious treatment