During combined anti-retroviral treatment, a latent HIV reservoir persists within resting memory CD4 T cells that initiates viral recrudescence upon treatment interruption. Strategies for HIV-1 cure ...have largely focused on latency reversing agents (LRAs) capable of reactivating and eliminating this viral reservoir. Previously investigated LRAs have largely failed to achieve a robust latency reversal sufficient for reduction of latent HIV pool or the potential of virus-free remission in the absence of treatment.
We utilize a polyvalent virus-like particle (VLP) formulation called Activator Vector (ACT-VEC) to ‘shock’ provirus into transcriptional activity. Ex vivo co-culture experiments were used to evaluate the efficacy of ACT-VEC in relation to other LRAs in individuals diagnosed and treated during the acute stage of infection. IFN-γ ELISpot, qRT-PCR and Illumina MiSeq were used to evaluate antigenicity, latency reversal, and diversity of induced virus respectively.
Using samples from HIV+ patients diagnosed and treated at acute/early infection, we demonstrate that ACT-VEC can reverse latency in HIV infected CD4 T cells to a greater extent than other major recall antigens as stimuli or even mitogens such as PMA/Iono. Furthermore, ACT-VEC activates more latent HIV-1 than clinically tested HDAC inhibitors or protein kinase C agonists.
Taken together, these results show that ACT-VEC can induce HIV reactivation from latently infected CD4 T cells collected from participants on first line combined antiretroviral therapy for at least two years after being diagnosed and treated at acute/early stage of infection. These findings could provide guidance to possible targeted cure strategies and treatments.
NIH and CIHR
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Describing how population‐level survival rates are influenced by environmental change becomes necessary during recovery planning to identify threats that should be the focus for future remediation ...efforts. However, the ways in which data are analyzed have the potential to change our ecological understanding and thus subsequent recommendations for remedial actions to address threats. In regression, distributional assumptions underlying short time series of survival estimates cannot be investigated a priori and data likely contain points that do not follow the general trend (outliers) as well as contain additional variation relative to an assumed distribution (overdispersion). Using juvenile survival data from three endangered Atlantic salmon Salmo salar L. populations in response to hydrological variation, four distributions for the response were compared using lognormal and generalized linear models (GLM). The influence of outliers as well as overdispersion was investigated by comparing conclusions from robust regressions with these lognormal models and GLMs. The analyses strongly supported the use of a lognormal distribution for survival estimates (i.e., modeling the instantaneous rate of mortality as the response) and would have led to ambiguity in the identification of significant hydrological predictors as well as low overall confidence in the predicted relationships if only GLMs had been considered. However, using robust regression to evaluate the effect of additional variation and outliers in the data relative to regression assumptions resulted in a better understanding of relationships between hydrological variables and survival that could be used for population‐specific recovery planning. This manuscript highlights how a systematic analysis that explicitly considers what monitoring data represent and where variation is likely to come from is required in order to draw meaningful conclusions when analyzing changes in survival relative to environmental variation to aid in recovery planning.
We demonstrate how outliers and overdispersion relative to regression assumptions can influence our ecological understanding of survival relative to environmental change, and how Robust Regression can be used to more effectively describe such relationships. This has direct implications on recovery planning for species in decline given that understanding survival‐environmental relationships is a prerequisite for recovery planning.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The eastern Cape Breton (ECB) designable unit (DU) of Atlantic Salmon Salmo salar comprises populations in 46 or more rivers in the eastern portion of Cape Breton Island, Nova Scotia, Canada. In ...2010, the Committee on the Status of Endangered Wildlife in Canada classified the ECB DU as endangered. In support of recovery planning processes, we developed an integrated, statistical, life history-based model for evaluating the dynamics of populations belonging to this DU. Using maximum likelihood, the model was fitted to recreational fishery catch and effort data, fish counts by divers, intermittent mark–recapture data, and sparse age composition data for two populations in the DU. The model output included estimates of maximum lifetime reproductive rate () and equilibrium population size—parameters that are important for determining extinction risk. The for the Middle River population (2.82 spawners/spawner) was double that of the Baddeck River population (1.39 spawners/spawner). These values would be considered low for Atlantic Salmon populations in general but are higher than those of populations in a neighboring endangered DU to the south. Slightly negative trends in recruitment deviates may indicate declining productivity in the two ECB populations; based on equilibrium analyses, neither population is expected to achieve the proposed recovery targets without an increase in productivity, survival, or both. Atlantic Salmon populations and habitat characteristics in ECB exhibit considerable diversity. Therefore, the dynamics of the Middle River and Baddeck River populations are unlikely to be representative of all populations in the ECB DU. Based on recent trends in recreational fishery catches, these two populations are likely among the healthier populations within the DU. Received July 8, 2014; accepted December 17, 2014
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We examined relationships between abundance and habitat use in three age classes of juvenile Atlantic salmon (
Salmo salar
) in the Stewiacke River, Nova Scotia, Canada. Using stream gradient as a ...proxy for habitat quality, we used a double half normal function, modified to include density dependence, to model the relationship between habitat quality and fish density. We found that density was asymmetrically distributed around a similar optimum gradient for all three age classes regardless of abundance. Habitat use was highly density-dependent for age-0 and age-1 juveniles, but not for age-2+ salmon. As abundance of age-0 and age-1 salmon increased, their relative density decreased in low-gradient habitat and increased in higher-gradient habitat, although their absolute density increased in all stream gradient categories. Variation in habitat use was consistent with ideal free theory for age-1 juveniles in high-gradient habitat, but not in low-gradient habitat. Age-2+ individuals appeared not to modify their distribution among habitats, even though increasing competition changes the relative benefit of low-gradient habitat in terms of resource acquisition. In contrast, age-1 individuals responded to increased competition by modifying their distribution along the habitat gradient, even though this may have slightly reduced an individual's potential for growth.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hubley, P. B., Amiro, P. G., Gibson, A. J. F., Lacroix, G. L., and Redden, A. M. 2008. Survival and behaviour of migrating Atlantic salmon (Salmo salar L.) kelts in river, estuarine, and coastal ...habitat. – ICES Journal of Marine Science, 65: 1626–1634. The downstream migration of 30 Atlantic salmon (Salmo salar) kelts tagged with acoustic transmitters was monitored using 26 underwater receivers at eight locations from April to October 2006 in the LaHave River and Estuary. In all, 27 tags were detected as they left the coastal environment by the middle of May, 5 weeks after release, indicating a possible 90% kelt survival to coastal departure. Two missing tags and one dropped tag were assumed to be attributable to natural mortality in the estuary. Migration time from release to the outermost coastal receivers 24 km below the tide limit took an average of 14 d, but varied from 3 to 32 d. Some 40% of the kelts lingered and were active in the lower estuary. Five kelts monitored with depth transmitters migrated mostly at the surface in all habitats, with occasional brief descent to the bottom. A consecutive spawning salmon returned after 79 d outside the outermost array. The low rate of returns is consistent with the historical repeat spawning schedule for this river, and more precisely documents the temporal and spatial habitat use of migrating kelts.
Quantifying functional relationships between abundance and land use is critical during recovery planning for endangered freshwater and diadromous fishes. However, there is little practical guidance ...on how much abundance might be expected to change from specific types or magnitudes of land use, making it difficult to identify specific sites for restoration or to prioritize among remediation actions. To address these needs for endangered Atlantic Salmon Salmo salar inhabiting the Southern Upland region of Nova Scotia, Canada, we developed a suite of hierarchical models to evaluate the functional form and magnitude of response of populations to land use at two spatial scales. Juvenile distribution patterns showed a strong longitudinal gradient throughout the stream network, with higher densities occurring in headwaters, which suggests that maintaining connectivity as well as unmodified landscapes in the upper reaches of rivers should be prioritized to aid recovery. Relative to threats, there was no single type of land use that was primarily associated with changes in juvenile abundance. Instead, responses to the combined suite of land‐use types were nonlinear and did not appear dependent on spatial scale. When the proportion of natural forest cover was high, populations appeared to benefit from low levels of anthropogenic land use, declining with increasing human activity only once the average proportion of natural forest cover was low. To use threat relationships in recovery planning, we propose a simple quantitative index based on the extent of development in the vicinity of rivers to identify sites for remediation or protection. To aid future monitoring, we demonstrate why site‐specific electrofishing catchability must be estimated when evaluating population responses to landscape change.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Typically, juvenile survey data are not used explicitly to determine status, trends, or abundance designations for Atlantic salmon Salmo salar , even though they can be the only source of information ...for many populations. To determine whether juvenile data can be informative about adult abundance and status in Atlantic salmon, we evaluated the similarities in trends among age-classes for two data-rich populations using a nested log-linear model. We found relatively consistent and significant trends for the age-0, adult and egg time series, but the trends in juvenile density data for older age-classes were less consistent with adult abundance trends. A threshold-based analysis demonstrated that relatively low misclassification rates for adult status relative to a set reference level could be obtained from juvenile density estimates. Together, these results suggest that juvenile density data can be an informative proxy for adult abundance and may be useful as an indicator for large changes in population status relative to reference points. This would make data collection via electrofishing an appropriate monitoring method for fisheries management or conservation programs. However, the validity of the idea that dramatic changes in adult abundance will be mirrored in juvenile data partially depends on the specific age-classes monitored, the survey design, and the timing of density dependence in the population. Using juvenile data as an index would necessitate some prior knowledge of the underlying population dynamics before the method could be applied more generally. Received May 9, 2012; accepted August 8, 2012
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We review and evaluate methods of estimating reference fishing mortality rates from spawnerrecruit (SR) data to obtain maximum sustainable yield. Using Monte Carlo simulations, we found that a ...reference fishing mortality rate derived from the maximum likelihood estimates of the SR parameters was less biased than reference fishing mortality rates obtained using the mode of the marginal probability distribution for the maximum rate that spawners produce recruits or by finding the fishing mortality rate that maximizes the expected yield. However, the maximum likelihood method produced the most variable estimates, at times leading to substantial under- or over-exploitation of the population. In contrast, the decision theoretic method of maximizing the expected yield exhibited less variability, produced higher yields, and substantially reduced the risk of overexploiting the population. We show how these methods can be extended to include information from other populations. Bayesian priors for the SR parameters, obtained through meta-analyses of population dynamics at some higher organizational level (e.g., the species), may be used to assess the plausibility of parameter estimates obtained for a single population or combined with the data for the population of interest. Reference fishing mortality rates are then estimated from the resulting joint posterior distribution.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Poecilogony is the production of more than one type of young within a single species of marine invertebrate. We chose a poecilogonous polychaete to investigate potential differences in morphogenesis ...among offspring that are polymorphic in dispersal potentials (planktonic, benthic) and trophic modes (planktotrophy, adelphophagy). Differences in morphogenesis occur and are strongly influenced by maternal type. Females that provide extra‐embryonic nutrition (as nurse eggs; type III females) also produce offspring with an accelerated onset of juvenile traits, relative to planktotrophic offspring of females that do not provide extra‐embryonic nutrition (type I females). Thus, progeny of some females appear morphologically preadapted for a benthic lifestyle. Surprisingly, differences in phenotype among offspring do not parallel offspring ecotype, as offspring with early onset of juvenile traits (III) are ecologically bimodal. Some Type III offspring eat the nurse eggs (adelphophagy), have accelerated development, and hatch as benthic juveniles. In contrast, their siblings hatch as small, planktotrophic, dispersive larvae that are morphologically similar to their type III siblings, but ecologically similar to Type I planktotrophic larvae. We propose that poecilogony evolved through sequence heterochrony in morphogenesis with accelerated onset of juvenile traits in type III offspring. In addition, we suggest that heterochrony in life‐history events (hatching, metamorphosis) also occurs, thereby generating offspring that are dimorphic in both phenotype and ecotype. Over time, selection acting on different levels of ontogeny (morphogenesis vs. dispersal) may balance this polymorphism and allow poecilogony to persist.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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