Rabies in primates: are aggressive pet lemurs a risk to humans?

Non-human primates harbor zoonotic pathogens including the rabies virus (Rabies lyssavirus). Though the chances of rabies transmission from primates is low, guidelines currently recommend a post-exposure prophylaxis for unvaccinated persons. In Madagascar, lemurs have been described as carriers of the rabies virus, but a discussion about the risk of rabies transmission to humans from lemurs, particularly in the context of in-country ownership of lemurs, has not been studied. We use qualitative and quantitative data collected from household surveys (n = 271 interviewees who had seen a pet lemur across 1 2 urban towns), web-based surveys (n = 229), and the literature (publications using data collected by the Institute Pasteur of Madagascar over the last century) to examine the context in which the rabies virus could be transmitted from lemurs to humans. Though only a few wild and pet lemurs in Madagascar have tested positive for rabies, post-exposure treatment is sometimes also sought out following aggressive incidents with lemurs. Many interviewees (22 ± 6%, mean ± 95% confidence interval CI) across 1 2 towns indicated that pet lemurs they had seen, had a history of aggression. Some lemur owners appear to be aware that their pets could transmit the rabies virus and seek veterinary care to prevent this. The public health burden of rabies is relatively low in Madagascar and despite some anecdotes in the literature, it appears that lemurs are rarely the source of rabies when humans become infected. However, this case study highlights the lack of data and publications regarding the public health implications of human-lemur contact in Madagascar. RÉSUMÉLes primates non-humains hébergent des pathogènes zoonotiques incluant le virus de la rage (Rabies lyssavirus). Bien que les risques de transmission de la rage par les primates soient faibles, les lignes directrices recommandent actuellement une prophylaxie post-exposition pour les personnes non vaccinées. À Madagascar, les lémuriens ont été décrits comme porteurs du virus de la rage, mais une discussion sur le risque de transmission de la rage à l'Homme par les lémuriens, en particulier dans le contexte de la propriété locale des lémuriens, n'a pas été étudiée. Nous utilisons des données qualitatives et quantitatives collectées à partir d'enquêtes auprès des foyers (n = 271 interviewés ayant vu un lémurien dans 1 2 villes), des enquêtes en ligne (n = 229) et de la littérature (publications utilisant des données collectées par l' Institut Pasteur de Madagascar au cours du siècle dernier) pour examiner le contexte dans lequel le virus de la rage pourrait être transmis par les lémuriens aux humains. Bien que seuls quelques lémuriens sauvages et animaux de compagnie à Madagascar aient été testés positifs à la rage, un traitement post-exposition est parfois également recherché suite à des agressions par des lémuriens. De nombreuses personnes interrogées (22 ± 6%, moyenne ± Intervalle de confiance IC à 95%) dans 1 2 villes ont indiqué que les animaux de compagnie qu' ils avaient vus avaient des antécédents d'agression. Quelques propriétaires de lémuriens semblent être conscients que leurs animaux de compagnie peuvent transmettre le virus de la rage et demander des soins vétérinaires pour éviter cela. La rage constitue une charge relativement faible pour la santé publique à Madagascar et malgré quelques anecdotes dans la littérature, il semble que les lémuriens soient rarement la source de la rage lorsque les humains sont infectés. Cependant, cette étude de cas souligne le manque de données et de publications concernant les implications / conséquences du contact entre humains et lémuriens sur la santé publique à Madagascar

Trade of parrots in urban areas of Madagascar

The live capture of parrots is causing increasing concern across Africa. In Madagascar, home to three species of parrot (Coracopsis nigra, C. vasa, Agapornis canus), no study has examined how these species are being extracted from the wild and traded. In this study, we examined the procurement, length of ownership, and the end of ownership of pet parrots. Data were collected via household surveys (n = 440 interviews in 9 towns), market visits (nd = 1 7 markets in 6 towns), and opportunistic data collection methods in urban, Malagasy towns. Most Coracopsis spp. are purchased (59%) or captured directly by the owner from the wild (22%), although we were unable to determine how A. canus was procured. Survey respondents reported purchasing Coracopsis spp. for the price of USD 5.36 ± 3.20. The average Coracopsis spp. was kept in captivity for 3.1 7 ± 2.51 years. No survey respondents provided information on the purchase price or length of ownership for A. canus. Ownership ended primarily when Coracopsis spp. escaped/flew away (36%) or died of unknown causes (21%). A. canus also flew away, although this was only reported in one instance. In-country demand appears to be met by a trade network of both informal and formal actors. It is unclear whether current protections for Madagascar’s parrots, as far as the domestic market is concerned, are sufficient to ensure sustainable extraction of live individuals

Regional N-Glycan and Lipid Analysis from Tissues Using MALDI-Mass Spectrometry Imaging

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix. For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020)

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003

Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease.</p

Self-Guided Psychological Treatment for Depressive Symptoms: A Meta-Analysis

Background: A number of trials have examined the effects of self-guided psychological intervention, without any contact between the participants and a therapist or coach. The results and sizes of these trials have been mixed. This is the first quantitative meta-analysis, aimed at organizing and evaluating the literature, and estimating effect size. Method: We conducted systematic literature searches in PubMed, PsycINFO and Embase up to January 2010, and identified additional studies through earlier meta-analyses, and the references of included studies. We identified seven randomized controlled trials that met our inclusion criteria, with a total of 1,362 respondents. The overall quality of the studies was high. A post-hoc power calculation showed that the studies had sufficient statistical power to detect an effect size of d = 0.19. Results: The overall mean effect size indicating the difference between self-guided psychological treatment and control groups at post-test was d = 0.28 (pless than0.001), which corresponds to a NNT of 6.41. At 4 to 12 months follow-up the effect size was d = 0.23. There was no indication for significant publication bias. Conclusions: We found evidence that self-guided psychological treatment has a small but significant effect on participants with increased levels of depressive symptomatology.Original Publication:Pim Cuijpers, Tara Donker, Robert Johansson, David C. Mohr, Annemieke van Straten and Gerhard Andersson, Self-Guided Psychological Treatment for Depressive Symptoms: A Meta-Analysis, 2011, PLoS ONE, (6), 6.http://dx.doi.org/10.1371/journal.pone.0021274Copyright: Public Library of Science (PLoS)http://www.plos.org

Challenges for automatically extracting molecular interactions from full-text articles

<p>Abstract</p> <p>Background</p> <p>The increasing availability of full-text biomedical articles will allow more biomedical knowledge to be extracted automatically with greater reliability. However, most Information Retrieval (IR) and Extraction (IE) tools currently process only abstracts. The lack of corpora has limited the development of tools that are capable of exploiting the knowledge in full-text articles. As a result, there has been little investigation into the advantages of full-text document structure, and the challenges developers will face in processing full-text articles.</p> <p>Results</p> <p>We manually annotated passages from full-text articles that describe interactions summarised in a Molecular Interaction Map (MIM). Our corpus tracks the process of identifying facts to form the MIM summaries and captures any factual dependencies that must be resolved to extract the fact completely. For example, a fact in the results section may require a synonym defined in the introduction. The passages are also annotated with negated and coreference expressions that must be resolved.</p> <p>We describe the guidelines for identifying relevant passages and possible dependencies. The corpus includes 2162 sentences from 78 full-text articles. Our corpus analysis demonstrates the necessity of full-text processing; identifies the article sections where interactions are most commonly stated; and quantifies the proportion of interaction statements requiring coherent dependencies. Further, it allows us to report on the relative importance of identifying synonyms and resolving negated expressions. We also experiment with an oracle sentence retrieval system using the corpus as a gold-standard evaluation set.</p> <p>Conclusion</p> <p>We introduce the MIM corpus, a unique resource that maps interaction facts in a MIM to annotated passages within full-text articles. It is an invaluable case study providing guidance to developers of biomedical IR and IE systems, and can be used as a gold-standard evaluation set for full-text IR tasks.</p