Reconciling west nile virus with the autophagic pathway

© 2015, Taylor & Francis Group, LLC. West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus responsible for recurrent outbreaks of meningitis and encephalitis. Several studies analyzing the interactions of this pathogen with the autophagic pathway have reported opposite results with evidence for and against the upregulation of autophagy in infected cells. In this regard, we have recently reported that minimal genetic changes (single amino acid substitutions) in nonstructural proteins of WNV can modify the ability of the virus to induce autophagic features such as LC3 modification and aggregation in infected cells. We think that these results could help explain some of the previously reported discrepancies. These findings could also aid in deciphering the interactions of this pathogen with the autophagic pathway at the molecular level aimed to develop feasible antiviral strategies to combat this pathogen, and other related flaviviruses.INIA (RTA2011-0036 and E-RTA2013-00013-C01) and the Comunidad Autónoma de Madrid PLATESA (P2013/ABI-2906)Peer Reviewe

BiblogTecarios: el poder de las conexiones y del crowdsourcing

BiblogTecarios (“blogging librarians”) was created with a clear objective: to offer its members the possibility of having a platform to publish their knowledge, concerns and opinions about their professional sector, that of Information and Documentation. Since its beginnings it has been clear that the purpose of the project was not intended to allow a few to publish each day, but rather that the more people participating in the project, the greater variety of topics could be discussed. Now that BiblogTecarios has 40 blogs, communication tools are essential for the proper functioning of the website, as well as the desire to work on a joint (collaborative and cooperative) project. Crowdsourcing, or the collective intelligence of its members, helped this project to grow; personal connections and collective work are the key pillars for its continued growth. BiblogTecarios connects people: it is crowdsourcing

Limited susceptibility of mice to Usutu virus (USUV) infection and induction of flavivirus cross-protective immunity

© 2015 Elsevier Inc. Flaviviruses are RNA viruses that constitute a worrisome threat to global human and animal health. In Europe, West Nile virus (WNV) outbreaks have dramatically increased in number and severity in recent years, with dozens of human and horse deaths and a high avian mortality across the continent. Besides WNV, the only clinically relevant mosquito-borne flavivirus detected so far in Europe has been the Usutu virus (USUV), which after being reported for the first time in Austria in 2001, quickly spread across Europe, causing a considerable number of bird deaths and neurological disorders in a few immunocompromised patients. Even though USUV infects multiple avian species that develop antibodies, there is little information about USUV susceptibility, pathogenicity and cross-reactive immunity. Here, the susceptibility of suckling and adult mice to USUV infection and the induction of cross-protective immunity against WNV challenge have been addressed.Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), PLATESA (P2013/ABI-2906) from the Comunidad Autónoma de Madrid, and by the Network of Animal Disease Infectiology and Research-European Union (NADIR-EU- 228394)Peer Reviewe

Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury

The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX2)/intracellular prostaglandin E2 (iPGE2)/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE2 in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE2/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naïve HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE2/EP receptor pathway. These results suggest that ABs, through iPGE2-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE2 also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE2/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injuryThis work was supported in part from grants from the Spanish Ministerio de Ciencia e Innovación, Spain (SAF2011-26838 and SAF2014-53218-R), Instituto de Salud Carlos III, Spain (PI15/02139) -Fondo Europeo de Desarrollo Regional, European-Union (FEDER)- and Comunidad Autónoma de Madrid, Spain -Programa de Actividades I+D en Biomedicina 2017- (B2017-BMD-3686). Coral Garcia-Pastor is recipient of a FPU fellowship from the University of Alcal

West Nile Virus Replication Requires Fatty Acid Synthesis but Is Independent on Phosphatidylinositol-4-Phosphate Lipids

West Nile virus (WNV) is a neurovirulent mosquito-borne flavivirus, which main natural hosts are birds but it also infects equines and humans, among other mammals. As in the case of other plus-stranded RNA viruses, WNV replication is associated to intracellular membrane rearrangements. Based on results obtained with a variety of viruses, different cellular processes have been shown to play important roles on these membrane rearrangements for efficient viral replication. As these processes are related to lipid metabolism, fatty acid synthesis, as well as generation of a specific lipid microenvironment enriched in phosphatidylinositol-4-phosphate (PI4P), has been associated to it in other viral models. In this study, intracellular membrane rearrangements following infection with a highly neurovirulent strain of WNV were addressed by means of electron and confocal microscopy. Infection of WNV, and specifically viral RNA replication, were dependent on fatty acid synthesis, as revealed by the inhibitory effect of cerulenin and C75, two pharmacological inhibitors of fatty acid synthase, a key enzyme of this process. However, WNV infection did not induce redistribution of PI4P lipids, and PI4P did not localize at viral replication complex. Even more, WNV multiplication was not inhibited by the use of the phosphatidylinositol-4-kinase inhibitor PIK93, while infection by the enterovirus Coxsackievirus B5 was reduced. Similar features were found when infection by other flavivirus, the Usutu virus (USUV), was analyzed. These features of WNV replication could help to design specific antiviral approaches against WNV and other related flaviviruses

Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury

The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX-2)/intracellular prostaglandin E-2 (iPGE(2))/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE(2) in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE(2)/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naive HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE(2)/EP receptor pathway. These results suggest that ABs, through iPGE(2)-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE(2) also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE(2)/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury.Ministerio de Ciencia e InnovaciónInstituto de Salud Carlos IIIComunidad Autónoma de Madri

Exploring the Risk of Suicide in Real Time on Spanish Twitter: Observational Study

Background:Social media is now a common context wherein people express their feelings in real time. These platforms are increasingly showing their potential to detect the mental health status of the population. Suicide prevention is a global health priority and efforts toward early detection are starting to develop, although there is a need for more robust research. Objective:We aimed to explore the emotional content of Twitter posts in Spanish and their relationships with severity of the risk of suicide at the time of writing the tweet. Methods:Tweets containing a specific lexicon relating to suicide were filtered through Twitter's public application programming interface. Expert psychologists were trained to independently evaluate these tweets. Each tweet was evaluated by 3 experts. Tweets were filtered by experts according to their relevance to the risk of suicide. In the tweets, the experts evaluated: (1) the severity of the general risk of suicide and the risk of suicide at the time of writing the tweet (2) the emotional valence and intensity of 5 basic emotions; (3) relevant personality traits; and (4) other relevant risk variables such as helplessness, desire to escape, perceived social support, and intensity of suicidal ideation. Correlation and multivariate analyses were performed. Results:Of 2509 tweets, 8.61% (n=216) were considered to indicate suicidality by most experts. Severity of the risk of suicide at the time was correlated with sadness (ρ=0.266; P<.001), joy (ρ=–0.234; P=.001), general risk (ρ=0.908; P<.001), and intensity of suicidal ideation (ρ=0.766; P<.001). The severity of risk at the time of the tweet was significantly higher in people who expressed feelings of defeat and rejection (P=.003), a desire to escape (P<.001), a lack of social support (P=.03), helplessness (P=.001), and daily recurrent thoughts (P=.007). In the multivariate analysis, the intensity of suicide ideation was a predictor for the severity of suicidal risk at the time (β=0.311; P=.001), as well as being a predictor for fear (β=–0.009; P=.01) and emotional valence (β=0.007; P=.009). The model explained 75% of the variance. Conclusions:These findings suggest that it is possible to identify emotional content and other risk factors in suicidal tweets with a Spanish sample. Emotional analysis and, in particular, the detection of emotional variations may be key for real-time suicide prevention through social media

Vertical preparation: a new technique for analogical and digital impressions

The BOPT technique (Biologically Oriented Preparation Technique) was proposed by Loi et al. (1) and has become a popular form of vertical preparation for complete crowns with promising results. In this procedure, the clinician can operate on the gingival tissue during preparation and modify its structure in thickness and height by adding modifications on the provisional restoration. However, one of the main challenges in this technique is the transference of information about the gingival tissue to the laboratory technician, who will place the margin of the restoration randomly in a space determined by two marks on the working cast.The technique proposed enables the accurate transmission of the exact point where the margin of the restoration needs to be placed. Furthermore, it facilitates the recording of conventional impression materials and intraoral scanners due to the compression of polytetrafluoroethylene (PTFE) tape into the sulcus, which allows to arrest bleeding or intracrevicular liquid and is easily registered irrespective of the method of impression used