On the identity of broad-shelled mussels (Mollusca, Bivalvia, Mytilus) from the Dutch delta region

Late Quaternary (Eemian) deposits of the Netherlands contain shells that resemble those of living Mytilus galloprovincialis. Similar broad-shelled mytilids also occur in estuaries of the southwestern Netherlands together with slender individuals typical of M. edulis. We sampled living mussels along a depth gradient in the Oosterschelde to a) investigate whether a relation exists between shell shape and depth, b) test if the broad-shelled specimens might represent M. galloprovincialis (or a hybrid with M. edulis) and c) assess by inference if the Quaternary specimens might be attributed to M. galloprovincialis as well. In order to do so, we compared genetic (length polymorphism of Me 15/16, COIII sequences and AFLPs) and shell-morphological characteristics (juvenile L/W ratios and so-called Verduin parameters) of the same specimens. The obtained dataset indicates that all studied mussels from the Oosterschelde should be attributed to M. edulis, including those with broad shell outlines. No correlation of shell-morphology and depth-distribution was found. The worn and generally damaged state of the Eemian specimens precluded measurement of the Verduin parameters, while juvenile L/W ratios turned out not to be diagnostic. Therefore the shell characters examined in this study are insufficient to demonstrate the possible presence of M. galloprovincialis shells in Quaternary deposits of the Netherlands

Renewed diversification following Miocene landscape turnover in a Neotropical butterfly radiation

International audienceAim: The landscape of the Neotropical region has undergone dynamic evolution throughout the Miocene, with the extensive Pebas wetland occupying western Amazonia between 23 and c. 10 Ma and the continuous uplift of the Andes mountains. The complex interaction between the Andes and Amazonia probably influenced the trajectory of Neotropical biodiversity, but evidence from time‐calibrated phylogenies of groups that diversified during this period is lacking. We investigate the role of these landscape transformations in the dynamics of diversification in the Neotropical region using a 26‐Myr‐old endemic butterfly radiation.Location: Neotropics.Time period: Oligocene to present.Major taxa studied: Ithomiini butterflies.Methods: We generated one of the most comprehensive time‐calibrated molecular phylogenies of a large clade of Neotropical insects, the butterfly tribe Ithomiini, comprising 340 species (87% of extant species) and spanning 26 Myr of diversification. We applied a large array of birth–death models and historical biogeography estimations to assess the dynamics of diversification and biotic interchanges, especially at the Amazonia–Andes interface.Results: Our results suggest that the Amazonian Pebas wetland system played a major role in the timing and geography of diversification of Ithomiini, by constraining dispersal and diversification in the Amazon basin until c. 10 Ma. During the Pebas wetland period, Ithomiini diversification mostly took place in the Andes, where terrestrial habitats were not affected. An explosion of interchanges with Amazonia and with the Northern Andes accompanied the demise of the Pebas system (11–8 Ma) and was followed by local diversification in those areas, which led to a substantial renewal of diversification.Main conclusions: Many studies on Neotropical diversity have focused only on the Andes, whereas we show that it is the waxing and waning of the Pebas mega‐wetland, interacting with Andean uplift, that determined the timing and patterns of regional interchanges and diversification in Ithomiini

On the identity of broad-shelled mussels (Mollusca, Bivalvia, Mytilus) from the Dutch delta region

Late Quaternary (Eemian) deposits of the Netherlands contain shells that resemble those of living Mytilus galloprovincialis. Similar broad-shelled mytilids also occur in estuaries of the southwestern Netherlands together with slender individuals typical of M. edulis. We sampled living mussels along a depth gradient in the Oosterschelde to a) investigate whether a relation exists between shell shape and depth, b) test if the broadshelled specimens might represent M. galloprovincialis (or a hybrid with M. edulis) and c) assess by inference if the Quaternary specimens might be attributed to M. galloprovincialis as well. In order to do so, we compared genetic (length polymorphism of Me 15/16, COIII sequences and AFLPs) and shellmorphological characteristics (juvenile L/W ratios and socalled Verduin parameters) of the same specimens. The obtained dataset indicates that all studied mussels from the Oosterschelde should be attributed to M. edulis, including those with broad shell outlines. No correlation of shell-morphology and depth-distribution was found. The worn and generally damaged state of the Eemian specimens precluded measurement of the Verduin parameters, while juvenile L/W ratios turned out not to be diagnostic. Therefore the shell characters examined in this study are insufficient to demonstrate the possible presence of M. galloprovincialis shells in Quaternary deposits of the Netherlands.

Mucosal vaccination with a live recombinant rhinovirus followed by intradermal DNA administration elicits potent and protective HIV-specific immune responses

Published: 17 November 2016Mucosal immunity is deemed crucial to control sexual transmission of human immunodeficiency virus (HIV). Herein we report the efficacy of a mucosal HIV vaccine strategy comprising intranasal (IN) vaccination with a cocktail of live recombinant human rhinoviruses (HRVs) encoding overlapping fragments of HIV Gag and full length Tat (rHRV-Gag/Tat) followed by intradermal (ID) vaccination with DNA vaccines encoding HIV Gag and Tat (pVAX-Gag-Tat). This heterologous prime-boost strategy will be referred to hereafter as rHRV-DNA. As a control, IN vaccination with wild type (wt)-HRV-A1 followed by a single ID dose of pVAX (wt-HRV-A1/pVAX vaccination) was included. rHRV-DNA vaccination elicited superior multi-functional CD8(+)T cell responses in lymphocytes harvested from mesenteric lymph nodes and spleens, and higher titres of Tat-specific antibodies in blood and vaginal lavages, and reduced the viral load more effectively after challenge with EcoHIV, a murine HIV challenge model, in peritoneal macrophages, splenocytes and blood compared compared with wt-HRV-A1/pVAX vaccination or administration of 3 ID doses of pVAX-Gag-Tat (3X pVAX-Gag-Tat vaccination). These data provide the first evidence that a rHRV-DNA vaccination regimen can induce HIV-specific immune responses in the gut, vaginal mucosa and systemically, and supports further testing of this regimen in the development of an effective mucosally-targeted HIV-1 vaccine.Khamis Tomusange, Danushka Wijesundara, Jason Gummow, Steve Wesselingh, Andreas Suhrbier, Eric J. Gowans, Branka Grubor-Bau

A Late Miocene methane-seep fauna from Kalimantan, Indonesia

This item is freely available online and the full text is attached. http://seep.paleo.pan.pl/AHS_5.htm

Prolonged wait time prior to entry to home care packages increases the risk of mortality and transition to permanent residential aged care services: findings from the Registry of Older South Australians (ROSA)

BACKGROUND:Older Australians prefer to live in their own homes for longer and reforms have attempted to increase the volume of home care packages (HCPs) accordingly but there remains a queue with the longer-term consequences unclear. OBJECTIVES:This study aims to characterise older Australians according to their wait times for a home care package (HCP), evaluate the association between wait time and mortality and evaluate the association between wait time and transition to permanent residential aged care services after HCP. DESIGN:A retrospective cohort study using data from the National Historical cohort (2003-2014) of the Registry of Older South Australians (ROSA) was conducted. SETTING:Home based aged care services, national cohort. METHODS:Wait time was estimated from approval date to date of receiving a HCP. Descriptive, survival estimates (95% confidence intervals (CIs)), and multivariable survival analyses (Cox-regression) were conducted to evaluate the risk of mortality and transition to permanent residential aged care services by quartiles of wait time for HCP. RESULTS:The cohort was followed for 4.0 years (interquartile range IQR (1.8-7.2)) and 38% were alive at the end of the study period with a median wait time for HCP of 62 (21-187) days. From 178,924 older people who received a HCP during the study period (2003-2013), 33.2% people received HCP within 30 days, 74.3% within 6 months and 25.7% after 6 months. The effect of wait time on risk of mortality was time-dependent, with longer wait times associated with higher mortality in the longer term. Compared to people who waited ≤30 days for a HCP, individuals who waited more than 6 months had an almost 20% excess risk of death (adjusted hazard ratio (aHR), 95%CI = (1.18, 1.16-1.21)) 2 years after entry into a HCP. Those who waited more than 6 months also had a 10% (1.10, 1.06-1.13) higher risk of transition to permanent residential aged care services after two years. CONCLUSION:Prolonged wait times for HCP is associated with a higher risk of long-term mortality as well as transition to permanent residential aged care. It remains to be seen if a shortening of this wait time translates into better health outcomes.Renuka Visvanathan, A. T. Amare, S. Wesselingh, R. Hearn, S. McKechnie, J. Mussared, M. C. Inaci

Complexity of the microglial activation pathways that drive innate host responses during lethal alphavirus encephalitis in mice

Microglia express multiple TLRs (Toll-like receptors) and provide important host defence against viruses that invade the CNS (central nervous system). Although prior studies show these cells become activated during experimental alphavirus encephalitis in mice to generate cytokines and chemokines that influence virus replication, tissue inflammation and neuronal survival, the specific PRRs (pattern recognition receptors) and signalling intermediates controlling microglial activation in this setting remain unknown. To investigate these questions directly in vivo, mice ablated of specific TLR signalling molecules were challenged with NSV (neuroadapted Sindbis virus) and CNS viral titres, inflammatory responses and clinical outcomes followed over time. To approach this problem specifically in microglia, the effects of NSV on primary cells derived from the brains of wild-type and mutant animals were characterized in vitro. From the standpoint of the virus, microglial activation required viral uncoating and an intact viral genome; inactivated virus particles did not elicit measurable microglial responses. At the level of the target cell, NSV triggered multiple PRRs in microglia to produce a broad range of inflammatory mediators via non-overlapping signalling pathways. In vivo, disease survival was surprisingly independent of TLR-driven responses, but still required production of type-I IFN (interferon) to control CNS virus replication. Interestingly, the ER (endoplasmic reticulum) protein UNC93b1 facilitated host survival independent of its known effects on endosomal TLR signalling. Taken together, these data show that alphaviruses activate microglia via multiple PRRs, highlighting the complexity of the signalling networks by which CNS host responses are elicited by these infections

Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source

<p>Abstract</p> <p>Background</p> <p>The Sydney blood bank cohort (SBBC) of long-term survivors consists of multiple individuals infected with attenuated, <it>nef</it>-deleted variants of human immunodeficiency virus type 1 (HIV-1) acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP) as well as long-term nonprogressors (LTNP). Convergent evolution of <it>nef </it>sequences in SBBC SP and LTNP indicates the <it>in vivo </it>pathogenicity of HIV-1 in SBBC members is dictated by factors other than <it>nef</it>. To better understand mechanisms underlying the pathogenicity of <it>nef</it>-deleted HIV-1, we examined the phenotype and <it>env </it>sequence diversity of sequentially isolated viruses (n = 2) from 3 SBBC members.</p> <p>Results</p> <p>The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-1 infection (subjects D36 and C98, respectively) and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection (subject C18). Both isolates from D36 were R5X4 phenotype and, compared to control HIV-1 strains, replicated to low levels in peripheral blood mononuclear cells (PBMC). In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of <it>env </it>by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter-patient <it>env </it>evolution.</p> <p>Conclusion</p> <p>Independent evolution of <it>env </it>despite convergent evolution of <it>nef </it>may contribute to the <it>in vivo </it>pathogenicity of <it>nef</it>-deleted HIV-1 in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity.</p

Increase in DNA vaccine efficacy by virosome delivery and co-expression of a cytolytic protein

The potential of DNA vaccines has not been realised due to suboptimal delivery, poor antigen expression and the lack of localised inflammation, essential for antigen presentation and an effective immune response to the immunogen. Initially, we examined the delivery of a DNA vaccine encoding a model antigen, luciferase (LUC), to the respiratory tract of mice by encapsulation in a virosome. Virosomes that incorporated influenza virus haemagglutinin effectively delivered DNA to cells in the mouse respiratory tract and resulted in antigen expression and systemic and mucosal immune responses to the immunogen after an intranasal (IN) prime/intradermal (ID) boost regimen, whereas a multidose ID regimen only generated systemic immunity. We also examined systemic immune responses to LUC after ID vaccination with a DNA vaccine, which also encoded one of the several cytolytic or toxic proteins. Although the herpes simplex virus thymidine kinase, in the presence of the prodrug, ganciclovir, resulted in cell death, this failed to increase the humoral or cell-mediated immune responses. In contrast, the co-expression of LUC with the rotavirus non-structural protein 4 (NSP4) protein or a mutant form of mouse perforin, proteins which are directly cytolytic, resulted in increased LUC-specific humoral and cell-mediated immunity. On the other hand, co-expression of LUC with diphtheria toxin subunit A or overexpression of perforin or NSP4 resulted in a lower level of immunity. In summary, the efficacy of DNA vaccines can be improved by targeted IN delivery of DNA or by the induction of cell death in vaccine-targeted cells after ID delivery.Tessa Gargett, Branka Grubor-Bauk, Darren Miller, Tamsin Garrod, Stanley Yu, Steve Wesselingh, Andreas Suhrbier, and Eric J Gowan

The risk of fall-related hospitalisations at entry into permanent residential aged care

Background: Entering permanent residential aged care (PRAC) is a vulnerable time for individuals. While falls risk assessment tools exist, these have not leveraged routinely collected and integrated information from the Australian aged and health care sectors. Our study examined individual, system, medication, and health care related factors at PRAC entry that are predictors of fall-related hospitalisations and developed a risk assessment tool using integrated aged and health care data. Methods: A retrospective cohort study was conducted on N=32,316 individuals ≥65 years old who entered a PRAC facility (01/01/2009-31/12/2016). Fall-related hospitalisations within 90 or 365days were the outcomes of interest. Individual, system, medication, and health care-related factors were examined as predictors. Risk prediction models were developed using elastic nets penalised regression and Fine and Gray models. Area under the receiver operating characteristics curve (AUC) assessed model discrimination. Results: 64.2% (N =20,757) of the cohort were women and the median age was 85 years old (interquartile range 80-89). After PRAC entry, 3.7% (N =1209) had a fall-related hospitalisation within 90days and 9.8% (N =3156) within 365days. Twenty variables contributed to fall-related hospitalisation prediction within 90days and the strongest predictors included fracture history (sub-distribution hazard ratio (sHR)=1.87, 95% confdence interval (CI) 1.63-2.15), falls history (sHR=1.41, 95%CI 1.21-2.15), and dementia (sHR=1.39, 95%CI 1.22-1.57). Twenty-seven predictors of fallrelated hospitalisation within 365days were identifed, the strongest predictors included dementia (sHR=1.36, 95%CI 1.24-1.50), history of falls (sHR=1.30, 95%CI 1.20-1.42) and fractures (sHR=1.28, 95%CI 1.15-1.41). The risk prediction models had an AUC of 0.71 (95%CI 0.68-0.74) for fall-related hospitalisations within 90days and 0.64 (95%CI 0.62-0.67) for within 365days. Conclusion: Routinely collected aged and health care data, when integrated at a clear point of action such as entry into PRAC, can identify residents at risk of fall-related hospitalisations, providing an opportunity for better targeting risk mitigation strategies.Maria C. Inacio, Max Moldovan, Craig Whitehead, Janet K. Sluggett, Maria Crotty, Megan Corlis, Renuka Visvanathan, Steve Wesselingh, and Gillian E. Caughe