Simulating the effects of long‐distance dispersal and landscape heterogeneity on the eco‐evolutionary outcomes of range expansion in an invasive riverine fish, Tench (Tinca tinca)

Predicting how quickly populations expand their range and whether they will retain genetic diversity when they are introduced to new regions or track environmental conditions suited to their survival is an important applied and theoretical challenge. The literature suggests that long-distance dispersal, landscape heterogeneity and the evolution of dispersal influence populations' expansion rates and genetic diversity. We used individual-based spatially explicit simulations to examine these relationships for Tench (Tinca tinca), an invasive fish expanding its geographical range in eastern North America since the 1990s. Simulated populations varied greatly in expansion rates (1.1–28.6 patches year−1) and genetic diversity metrics, including changes in observed heterozygosity (−19 to +0.8%) and effective number of alleles (−0.32 to −0.01). Populations with greater dispersal distances expanded faster than those with smaller dispersal distances but exhibited considerable variation in expansion rate among local populations, implying less predictable expansions. However, they tended to retain genetic diversity as they expanded, suggesting more predictable evolutionary trajectories. In contrast, populations with smaller dispersal distances spread predictably more slowly but exhibited more variability among local populations in genetic diversity losses. Consistent with empirical data, populations spreading in a longer, narrower dispersal corridor lost more neutral genetic variation to the stochastic fixation of alleles. Given the unprecedented pace of anthropogenic environmental change and the increasing need to manage range-expanding populations, our results have conservation ramifications as they imply that the evolutionary trajectories of populations characterised by shorter dispersal distances spreading in narrower landscapes are more variable and, therefore, less predictable

A missing link in the estuarine nitrogen cycle?: coupled nitrification-denitrification mediated by suspended particulate matter

In estuarine and coastal ecosystems, the majority of previous studies have considered coupled nitrification-denitrification (CND) processes to be exclusively sediment based, with little focus onsuspended particulate matter (SPM) in the water column. Here, we present evidence of CND processes in the water column of Hangzhou Bay, one of the largest macrotidal embayments in the world

Geographic variation in the trophic ecology of an avian rocky shore predator, the African black oystercatcher, along the southern African coastline

International audienceThe reflection of baseline isotopic signals along marine food chains up to higher trophic levels has been widely used in the study of oceanic top predators but rarely for intertidal predators. We investigated variation in the δ13C and δ15N ratios of a sedentary, rocky shore predator, the African black oystercatcher Haematopus moquini, over ~2000 km of the southern African coastline, which is characterized by strong biogeographic patterns in primary productivity and intertidal communities. Blood and feathers from breeding adults and chicks and muscle tissues from primary prey items (mussels and limpets) were sampled between southern Namibia and the southeast coast of South Africa. 15N enrichment was observed between the southeast and west coasts in oystercatcher tissues and their prey, mirroring an isotope shift between the oligotrophic Agulhas Current on the east coast and the eutrophic Benguela upwelling system on the west coast. Oystercatcher blood showed δ13C values that varied between those of the carbon-depleted mussels and the carbon-enriched limpets along the coastline, which reflected changes in the proportion of grazers and filter feeders in the oystercatcher diet across the sampling range. The geographic shift in diet, dominated by mussels on the west coast and composed of mixed proportions of mussels and limpets on the southeast coasts, strongly reflected regionally high abundances of the invasive Mediterranean mussel Mytilus galloprovincialis. Finally, isotope signatures of blood and feathers displayed a strong correlation throughout the study area, indicating seasonal stability in environmental conditions and feeding habits of the adults. There were, however, local discrepancies on the south coast that indicated movement of adults occurred outside the breeding season possibly in response to a lower abundance of food in this region. Overall, the results indicate that the influence of regional oceanic conditions on the base of the food web can penetrate to the predator level, but that local effects can be incorporated within this pattern

Genetic diversity and structure of a recent fish invasion: Tench (Tinca tinca) in eastern North America

Introduced and geographically expanding populations experience similar eco-evolutionary challenges, including founder events, genetic bottlenecks, and novel environments. Theory predicts that reduced genetic diversity resulting from such phenomena limits the success of introduced populations. Using 1900 SNPs obtained from restriction-site-associated DNA sequencing, we evaluated hypotheses related to the invasion history and connectivity of an invasive population of Tench (Tinca tinca), a Eurasian freshwater fish that has been expanding geographically in eastern North America for three decades. Consistent with the reported history of a single introduction event, our findings suggest that multiple introductions from distinct genetic sources are unlikely as Tench had a small effective population size (~114 [95% CI = 106–123] individuals), no strong population subdivision across time and space, and evidence of a recent genetic bottleneck. The large genetic neighbourhood size (220 km) and weak within-population genetic substructure suggested high connectivity across the invaded range, despite the relatively large area occupied. There was some evidence for a small decay in genetic diversity as the species expanded northward, but not southward, into new habitats. As eradicating the species within a ~112 km radius would be necessary to prevent recolonization, eradicating Tench is likely not feasible at watershed—and possibly local—scales. Management should instead focus on reducing abundance in priority conservation areas to mitigate adverse impacts. Our study indicates that introduced populations can thrive and exhibit relatively high levels of genetic diversity despite severe bottlenecks (<1.5% of the ancestral effective population size) and suggests that landscape heterogeneity and population demographics can generate variability in spatial patterns of genetic diversity within a single range expansion

Temporal and spatial variability in stable isotope ratios of SPM link to local hydrography and longer term SPM averages suggest heavy dependence of mussels on nearshore production

Temporal changes in hydrography affect suspended particulate matter (SPM) composition and distribution in coastal systems, potentially influencing the diets of suspension feeders. Temporal variation in SPM and in the diet of the mussel Perna perna, were investigated using stable isotope analysis. The δ13C and δ15 N ratios of SPM, mussels and macroalgae were determined monthly, with SPM samples collected along a 10 km onshore–offshore transect, over 14 months at Kenton-on-Sea, on the south coast of South Africa. Clear nearshore (0 km) to offshore (10 km) carbon depletion gradients were seen in SPM during all months and extended for 50 km offshore on one occasion. Carbon enrichment of coastal SPM in winter (June–August 2004 and May 2005) indicated temporal changes in the nearshore detrital pool, presumably reflecting changes in macroalgal detritus, linked to local changes in coastal hydrography and algal seasonality. Nitrogen patterns were less clear, with SPM enrichment seen between July and October 2004 from 0 to 10 km. Nearshore SPM demonstrated cyclical patterns in carbon over 24-h periods that correlated closely with tidal cycles and mussel carbon signatures, sampled monthly, demonstrated fluctuations that could not be correlated to seasonal or monthly changes in SPM. Macroalgae showed extreme variability in isotopic signatures, with no discernable patterns. IsoSource mixing models indicated over 50% reliance of mussel tissue on nearshore carbon, highlighting the importance of nearshore SPM in mussel diet. Overall, carbon variation in SPM at both large and small temporal scales can be related to hydrographic processes, but is masked in mussels by long-term isotope integration

Retreatment for hepatitis C virus direct-acting antiviral therapy virological failure in primary and tertiary settings: The REACH-C cohort

Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n = 10,843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n = 56) and tertiary (n = 157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p = 1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11–0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64–11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15–0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralized models may increase retreatment uptake and reduce HCV-related mortality

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Baseline isotopic data for Wolffia spp.: another option for tracing N-loading in freshwater systems?

δ15N values of aquatic plants can reflect anthropogenic N loading. Recent work suggests the duckweed Spirodela spp. effectively maps N loading in freshwater ecosystems, but its use may be complicated by a cyanobacterium–duckweed symbiosis that could reduce its utility in low-nutrient environments. I aimed to evaluate the potential of a 2nd duckweed species Wolffia spp., which lacks a cyanobacterial symbiosis, for use in pollution monitoring in freshwater ecosystems. I used a series of laboratory experiments to investigate δ15N equilibration rates and concentration-level effects of single-source N solutions in plant tissue over 16 d to provide baseline data for sewage-plume mapping with Wolffia spp. I also tested concentration-level effects in multisource solutions to investigate the effects of mixed-source inputs. Wolffia reflected environmental N sources with a 12- to 16-d isotopic equilibration time and showed enriched and depleted δ15N ratios for manure and KNO3 solutions, respectively, but distinguished poorly between lower concentrations of manure. Fractionations at isotopic equilibrium were opposite to expectations and decreased with increasing [N]. Wolffia showed a consistent preference for NH3 in mixed-source treatments, regardless of the proportion or concentration of NH3 or NO3– available, and a capacity for N storage, which may complicate mapping of N-loading in natural environments. Wolffia is likely to be a less useful bioindicator than the previously tested Spirodela. Future research should focus on field applications of Spirodela spp. to test its capacity for sewage-plume mapping of freshwater ecosystems in a natural environment

Baseline isotopic data for Wolffia spp.: another option for tracing N-loading in freshwater systems?

δ15N values of aquatic plants can reflect anthropogenic N loading. Recent work suggests the duckweed Spirodela spp. effectively maps N loading in freshwater ecosystems, but its use may be complicated by a cyanobacterium–duckweed symbiosis that could reduce its utility in low-nutrient environments. I aimed to evaluate the potential of a 2nd duckweed species Wolffia spp., which lacks a cyanobacterial symbiosis, for use in pollution monitoring in freshwater ecosystems. I used a series of laboratory experiments to investigate δ15N equilibration rates and concentration-level effects of single-source N solutions in plant tissue over 16 d to provide baseline data for sewage-plume mapping with Wolffia spp. I also tested concentration-level effects in multisource solutions to investigate the effects of mixed-source inputs. Wolffia reflected environmental N sources with a 12- to 16-d isotopic equilibration time and showed enriched and depleted δ15N ratios for manure and KNO3 solutions, respectively, but distinguished poorly between lower concentrations of manure. Fractionations at isotopic equilibrium were opposite to expectations and decreased with increasing [N]. Wolffia showed a consistent preference for NH3 in mixed-source treatments, regardless of the proportion or concentration of NH3 or NO3– available, and a capacity for N storage, which may complicate mapping of N-loading in natural environments. Wolffia is likely to be a less useful bioindicator than the previously tested Spirodela. Future research should focus on field applications of Spirodela spp. to test its capacity for sewage-plume mapping of freshwater ecosystems in a natural environment

Biogeographic and nearshore–offshore trends in isotope ratios of intertidal mussels and their food sources around the coast of southern Africa

There are broad differences in oceanography and primary production around the southern African coast that are likely to give rise to major differences in trophic pathways. Stable isotope ratios provide integrated information on trophic relationships, yet there has been limited research on geographic variation in isotopic composition of marine consumers and their food. In this study, δ13C and δ15N of suspended particulate matter (SPM), intertidal mussels and common macroalgae along the southern African coastline were explored. Nearshore–offshore isotope trends as well as biogeographic and temporal patterns in isotopic ratios of mussel tissue, macroalgae and SPM were investigated at 12 sites along the coast from Namibia to the Mozambique border. SPM exhibited overall trends of nearshore 13C depletion from south-west to north-east along the coastline and from nearshore (0 km) to offshore (10 km) waters, in both cases suggesting a shift from a nearshore signature strongly influenced by macroalgal detritus to one more representative of oceanic phytoplankton. With one exception it was possible, using discriminant analysis, to categorize mussel populations into 4 geographic groups, on the basis of both carbon and nitrogen signatures: the east coast, the south-east coast, the south-west coast and the west coast. Macroalgae showed no consistent biogeographic trends and need to be examined in greater detail to relate nearshore SPM values to living macroalgal signatures. A linear mixing model indicated that mussels along the entire coastline generally demonstrated more than 50% dependence on nearshore carbon and nitrogen, emphasizing the importance of nearshore primary production to intertidal consumers