Suboptimal Host Research Articles

Divergent behavioural responses of gypsy moth (Lymantria dispar) caterpillars from three different subspecies to potential host trees

Almost all previous work on host-plant selection by insect herbivores has focused on adult behaviour; however, immature life stages can also play an active role in host discrimination. The important forest pest Lymantria dispar (gypsy moth) has three recognised subspecies: the European, Asian, and Japanese gypsy moth. Unlike the other two subspecies, the European subspecies is characterised by a loss of female flight ability, which might impose a selective pressure on larvae to actively engage in host-plant selection. We therefore explored the interactions of early-instar larvae from laboratory colonies of each subspecies with four potential hosts of differing quality: oak, beech, maple, and pine—measuring larval survival and performance, feeding preferences, responses to host-derived odour cues, and the propensity to disperse from hosts via ballooning. Compared to larvae from the Asian and Japanese subspecies, larvae from the (American-originated) European gypsy moth colony exhibited (i) significantly lower survival on the poorest quality host (pine), (ii) an ability to discriminate among hosts via olfactory cues; and (iii) higher propensity to disperse from sub-optimal hosts. These results are consistent with the hypothesis that larvae from flightless female European Gypsy moth subspecies play a more active role in host-plant selection.

Potential for Acanthoscelides obtectus to Adapt to New Hosts Seen in Laboratory Selection Experiments.

Effective pest management strategies for a targeted pest species must rely on accurate, reliable and reproducible estimates of population dynamics. Importance of such approaches is even more conspicuous when assessing pest’s potential to utilize other stored products. Using an experimental evolution approach, we have focused our attention on a common bean pest, the seed beetle (Acanthoscelides obtectus). We looked into the potential to invade and sustain population growth on two suboptimal host plants (chickpeas and mung beans). Such an approach simulates steps of the host-shift process in storages. By analyzing population dynamics during initial encountering with a new host plant, we detected a population drop for both novel hosts. However, transgenerational development in a novel environment resulted in a constant population growth in chickpeas, but not in mung bean populations. Reversal of chickpea selected populations to original host plant has led to a severe decrease in population parameters due to low viability of immatures, while the opposite trend was detected in mung bean populations. This paper highlights the importance of good practice in estimating population dynamics for economically important species. With special emphasis on storage pest species, we discuss how this approach can be useful for estimating invading potential of pest insects.

Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection

Industrial hog operation (IHO) workers are at increased risk of carrying Staphylococcus aureus in their nares, particularly strains that are livestock-associated (LA) and multidrug-resistant. The pathogenicity of LA-S. aureus strains remains unclear, with some prior studies suggesting reduced transmission and virulence in humans compared to community-associated methicillin-resistant (CA-MRSA) S. aureus. The objective of this study was to determine the degree to which LA-S. aureus strains contracted by IHO workers cause disease relative to a representative CA-MRSA strain in a mouse model of skin and soft tissue infection (SSTI). Mice infected with CC398 LA-S. aureus strains (IHW398-1 and IHW398-2) developed larger lesion sizes with higher bacterial burden than mice infected with CA-MRSA (SF8300) (p < 0.05). The greatest lesion size and bacterial burden was seen with a CC398 strain that produced a recurrent SSTI in an IHO worker. The LA-S. aureus infected mice had decreased IL-1β protein levels compared with CA-MRSA-infected mice (p < 0.05), suggesting a suboptimal host response to LA-S. aureus SSTIs. WGSA revealed heterogeneity in virulence factor and antimicrobial resistance genes carried by LA-S. aureus and CA-MRSA strains. The observed pathogenicity suggest that more attention should be placed on preventing the spread of LA-S. aureus into human populations.

Relative Performance and Impacts of the Psyllid Arytinnis hakani (Hemiptera: Psyllidae) on Nontarget Plants and the Target Weed Genista monspessulana (Fabales: Fabaceae).

No-choice tests can help select weed biological control agents with a high degree of host specificity but may exclude potentially effective agents that can develop on nontarget plants under laboratory conditions. The actual amount of damage to nontarget plants often goes unstudied, even though agents may exploit nontarget plants without inflicting significant harm. Furthermore, tests typically assess whether prospective agents can complete one generation on nontarget plants, and rarely examine whether agents are likely to persist on the nontarget plants over the long term. Pre-release assessments that occur over multiple generations of the agent could help determine whether prospective agents pose a threat to nontarget plants under field conditions. This study focused on the psyllid Arytinnis hakani Loginova (Hemiptera: Psyllidae), which is under consideration in California for release against the invasive shrub French broom, Genista monspessulana (L.) LAS Johnson. We examined the host suitability of seven nontarget Lupinus spp. (Fabales: Fabaceae) for the psyllid using no-choice tests, and assessed psyllid impacts on Lupinus arboreus Sims, which consistently supported psyllid oviposition and development. The psyllid oviposited on all of the tested Lupinus spp., and completed two generations on five of the Lupinus spp., although numbers of psyllids were highest on French broom. In an additional experiment, A. hakani did not affect growth or survival of L. arboreus, but reduced growth and dramatically reduced survival of French broom. Taken together, these results indicate that Lupinus spp. are suboptimal hosts for the psyllid and are unlikely to be significantly impacted by its feeding.

Identifying the abiotic and biotic drivers behind the elevational distribution shift of a parasitic plant.

Climate change will alter the biotic and abiotic environment and dissipate ecological barriers, reorganising maps of current distribution of parasites and their hosts. In this study, we analyse the population dynamics of the parasitic plant Viscum album subsp. austriacum and explore key biotic (host availability and seed dispersal) as well as abiotic (temperature) factors influencing elevational distribution. The study was conducted along an elevational gradient of a Mediterranean mountain, covering the distribution belts of three potential pine hosts: Pinus halepensis (1300-1500m), P.nigra (1300-1900m) and P.sylvestris var.nevadensis (1600-2000m). Along this gradient, we measured multiple variables of mistletoe population (prevalence, abundance and demographic profile) and different factors that might define the current mistletoe distribution (host suitability and availability, temperature and seed dispersal services). We found a decline in mistletoe prevalence and abundance with increasing elevation, detecting larger values of both variables at lower elevations of the most suitable host (Pinus nigra). Pinus sylvestris var.nevadensis was a suboptimal but suitable host for the parasite at high elevations. Mistletoe found suitable temperatures and seed dispersal services all along the gradient, being able to recruit at any site. With warming temperatures, the presence of suitable vectors for parasite dispersion, and the presence of a sub-optimal host (P.sylvestris var.nevadensis) at the mountain top, mistletoe currently has a window of opportunity to expand its present geographic distribution to the summits.

Adaptation to sub-optimal hosts is a driver of viral diversification in the ocean

Cyanophages of the Myoviridae family include generalist viruses capable of infecting a wide range of hosts including those from different cyanobacterial genera. While the influence of phages on host evolution has been studied previously, it is not known how the infection of distinct hosts influences the evolution of cyanophage populations. Here, using an experimental evolution approach, we investigated the adaptation of multiple cyanophage populations to distinct cyanobacterial hosts. We show that when infecting an “optimal” host, whose infection is the most efficient, phage populations accumulated only a few mutations. However, when infecting “sub-optimal” hosts, different mutations spread in the phage populations, leading to rapid diversification into distinct subpopulations. Based on our results, we propose a model demonstrating how shifts in microbial abundance, which lead to infection of “sub-optimal” hosts, act as a driver for rapid diversification of viral populations.

Hepatocellular carcinoma: Prospects for natural killer cell immunotherapy.

Liver disease is a growing cause of death in the United Kingdom and the incidence of hepatocellular carcinoma (HCC) is rising (http://www.cancerresearchuk.org/). The combination of an immunosuppressive environment within the liver and suboptimal host anti-tumour immune responses may account for the poor survival outcome of HCC. Understanding how tumours evade immune recognition coupled with new insights into the unique immunological environment within the liver will be critical to developing liver-specific immunotherapies.

Oviposition Preference and Larval Host Range of the Sugarbeet Root Maggot (Diptera: Ulidiidae).

The sugarbeet root maggot, Tetanops myopaeformis Röder (Diptera: Ulidiidae), is native to North America. However, its primary crop host, sugarbeet, Beta vulgaris L., was introduced to the continent from Europe in the late 19th century. This field and greenhouse research was conducted to compare the relative attractiveness of eight cultivated and wild plant species for oviposition by T. myopaeformis, and the suitability of these potential host plants for larval development to elucidate the potential native and current host range of this pest. Results indicated that females preferred ovipositing in soil immediately adjacent to or on the following plant species: sugarbeet; spinach, Spinacia olerocea L.; common lambsquarters, Chenopodium album L.; redroot pigweed, Amaranthus retroflexus L.; Palmer amaranth, Amaranthus palmeri S. Wats.; and to a lesser extent, spear saltbush, Atriplex patula L. Larval survival was greatest on spinach, sugarbeet, and spear saltbush, which all belong to the family Chenopodiaceae. Larval survival on these plants suggests that T. myopaeformis could have exploited wild chenopodiaceous plants or others within the order Caryophyllales before sugarbeet was introduced to North America. Low larval survival on common lambsquarters, redroot pigweed, and Palmer amaranth suggests that these species are suboptimal hosts, despite demonstrated attractiveness for oviposition. A general lack of oviposition preference by T. myopaeformis females was observed for sunflower, Helianthus annuus L., and common ragweed, Ambrosia artemisiifolia L. These results provide insights regarding the successful and somewhat rapid host preference shift by this insect to sugarbeet after cultivation of the crop began in the continent.

Prognostic value of neutrophil-to-lymphocyte ratio (NLR) on overall survival (OS), progression free survival (PFS) and disease control rate (DCR) in patients with metastatic colorectal cancer (mCRC) from the RECOURSE study.

744 Background: Elevated neutrophil-to-lymphocyte (NLR) ratios may represent markers of a suboptimal host immune response to cancer and have been shown to correlate with prognosis in multiple tumor types. Trifluridine/tipiracil (FTD/TPI also known as TAS-102) compared with placebo significantly improved OS (median: 7.1 vs.5.3 months, hazard ratio (HR) = 0.68, 95% confidence interval (CI) [0.58;0.81], p &lt; 0.0001), PFS, and DCR in the phase 3 RECOURSE study, conducted in patients with refractory mCRC. A post-hoc analysis was conducted to assess correlation between clinical outcomes and baseline NLR (in blood) in RECOURSE. Methods: A retrospective review on 782/800 patients, with available NLR, was performed on OS, PFS, and DCR in two subgroups of patients with low ( &lt; 3) or high (≥ 3) NLR at baseline. Based on literature, the cutoff value of 3 was chosen as the number of patients was similar in each NLR subgroup. Between-group comparison was performed using a stratified Cox’s proportional hazard model for OS and PFS, and Fisher’s Exact test for DCR. Results: The median value of NLR at baseline was similar in each group, FTD/TPI (N = 519): 4.4 ± 6.3, placebo (N = 263): 4.7 ± 6.5. Almost 60% of patients in each group had high NLR. In the low NLR vs. high NLR subgroup, there were differences at baseline for ethnic origin (Asian: 45% vs.29%), ECOG PS 0 (69% vs. 49%), and number of metastatic sites ≥ 3 (32% vs. 46%). The median OS [95 % CI] was statistically significantly higher in the low vs. high NLR subgroup: 8.4 [7.8;9.5] vs. 5.3 [4.7;5.7] months, HR = 0.49, 95% CI [0.41;0.59], p &lt; 0.0001. Irrespective of NLR, all patients benefited from FTD/TPI vs. placebo. The results of PFS and DCR were statistically significantly better in the low NLR vs. high NLR subgroup. The multivariate Cox analysis for OS with the interaction test between treatment groups and NLR showed that NLR is not a predictive factor (p = 0.15). Conclusions: In this retrospectively analyzed mCRC population, NLR was shown to be an independent prognostic factor. Further research is warranted to assess if NLR can be a stratification factor in mCRC clinical trials. Clinical trial information: NCT01607957.

The performance of Dactylopius opuntiae as a biological control agent on two invasive Opuntia cactus species in South Africa

Many biological control projects targeting weeds in the Cactaceae have been noteworthy successes. Recently, populations of a prickly pear, Opuntia humifusa, have spread across South Africa, endangering both grazing lands and natural biodiversity. A biotype of the cochineal insect, Dactylopius opuntiae ‘stricta’, which has been successfully used in South Africa to control Opuntia stricta, has been observed to use O. humifusa as a host. However, it does not appear to effectively control O. humifusa infestations. To investigate the possible reasons for this, we tested two hypotheses: firstly, that O. humifusa is a sub-optimal host of D. opuntiae ‘stricta’ compared to O. stricta; and, secondly, that the underground tubers characteristic of O. humifusa enable it to regenerate after sustaining cochineal damage. We compared the survival, fecundity and development of D. opuntiae on the two host plant species under controlled conditions. Host plant had no significant effect on the survival rates and development of the insects. In addition, O. stricta plants generated more new growth after sustaining damage from D. opuntiae than O. humifusa under the same conditions. These results show that O. humifusa and O. stricta are equally suitable hosts for D. opuntiae ‘stricta’ and that the underground tubers of O. humifusa do not increase its resistance to D. opuntiae damage. Further ecological observations may elucidate other possible reasons for the failure of cochineal insects to control invasive O. humifusa populations in South Africa.

Refuges and host shift pathways of host-specialized aphids Aphis gossypii

Polyphagous cotton-melon aphid populations usually comprise cotton- and cucurbit-specialized biotypes. Host-specialized aphids are prone to food shortages. Cucumber, the favourite food of cucurbit-specialized aphids, is usually absent during autumn and winter in Nanjing, China. Therefore, suboptimal host plants act as refuges and govern the population dynamics of this aphid. The species, growth stages and leaf ages of host plants that cotton- and cucurbit-specialized aphids potentially could use were explored in this study. Cotton-specialized aphids were found to use wild chrysanthemum, potato, zucchini, pumpkin and flowering cucumber besides cotton, whilst cucurbit-specialized aphids were able to utilize potato, zucchini, pumpkin and mature cotton besides cucumber. The population dynamics and genotype frequencies of aphids on hibiscus, cotton, zucchini, cucumber and pumpkin showed that cotton-melon aphids on cucumber could transfer onto mature cotton. Aphids on zucchini shared microsatellite genotypes with aphids on cotton and cucumber. The predominant genotype of aphids on cotton was found on hibiscus, but the predominant genotype on cucumber was not found on hibiscus. Host-specialized aphids clearly have refuges during food shortages. Hibiscus is an overwintering host for cotton-specialized aphids but not for cucurbit-aphids. Removing refuges or managing aphids on refuges could potentially be an effective method to control cotton-melon aphids.

Susceptibility of Aronia (Aronia melanocarpa) toDrosophila suzukii(Diptera: Drosophilidae)

Drosophila suzukii is an invasive pest of cultivated fruit crops in Europe, Asia, and the Americas. However, more information is needed to understand the extent of D. suzukii utilization of wild fruit and specialty crops as suitable hosts, such as aronia (Aronia melanocarpa), for which risk assessment has not yet been established. Both laboratory bioassays and field monitoring were conducted to assess the susceptibly of aronia to D. suzukii. No-choice bioassays were conducted on damaged, destemmed, and undamaged aronia fruit. Field infestation was assessed using yeast-sugar traps for adults and fruit samples for larvae during the 2015 growing season at three farms in south-central Wisconsin. In bioassays, D. suzukii successfully completed its life cycle in damaged and destemmed aronia, while undamaged aronia did not support larval or adult development. Adult flies which emerged from damaged aronia took longer to develop and weighed less compared to adults emerging from raspberry. In the field, adults were abundant throughout the growing season (late June–late September) and larvae were detected in low numbers in ripe fruit samples collected from late August through late September. After harvest, fruit sampled from the processing and packing line revealed low numbers of drosophila larvae. Overall, these findings suggest that damaged or destemmed aronia is susceptible to D. suzukii infestation, while intact fruit is resistant to D. suzukii. In addition, the bioassays suggest that aronia may serve as a suboptimal host compared to raspberry. These findings suggest the importance of preventing fruit damage before harvest and add to a growing understanding of how wild and specialty crops, such as aronia, may affect population dynamics of this invasive fly.

Exploring the Effects of Plant Odors, from Tree Species of Differing Host Quality, on the Response of Lymantria disparMales to Female Sex Pheromones.

A widely accepted hypothesis for host-plant selection in herbivorous insects is that ovipositing females select host-plants that maximize the survival and performance of their offspring. However, numerous studies indicate that this is not always the case for polyphagous species. Lymantria dispar is a highly polyphagous forest defoliator and has flightless females in some subspecies, resulting in a limited capacity to make host-choices. Males of other Lepidopteran species utilize a combination of sexual pheromones and plant volatiles in their mating choices and exhibit preferences among plant species. We explored the behavior of L. dispar males towards sexual pheromone in the presence and absence of plant volatiles and their ability to discriminate between two plant species with different degrees of suitability for their offspring: a suboptimal host (Pinus sylvestris), and an optimal host (Quercus robur). In no-choice wind tunnel assays, we found that rates of male success in locating a pheromone source were not altered by the presence of plant odors; however, the time spent by males searching for the pheromone source after reaching the full length of the tunnel was reduced by more than 50% in the presence of plant volatiles. In dual choice assays, males exhibited a clear preference for a combination of pheromones and plant volatiles over the pheromone alone. However, we did not find evidence of an innate ability to discriminate between the odors of optimal and suboptimal host plants. We discuss possible ecological and evolutionary explanations for these observations.

Parasitological and transcriptomic comparison of Strongyloides ratti infections in natural and in suboptimal permissive hosts

The nematode genus Strongyloides consists of fairly species-specific small intestinal parasites of various vertebrates, among them the human pathogen S. stercoralis. Between the parthenogenetic parasitic generations these worms can also form single facultative sexual free-living generations. In addition to their primary hosts, several species can also live more or less well in other permissive hosts, which are sometimes not very closely related with the normal host. For example, S. stercoralis can also infect dogs and non-human primates.Here we compare the infection and reproductive success over time and the gene expression profiles as determined by quantitative sequencing of S. ratti parasitizing in its natural host rat and in the permissive host gerbil. We show that in gerbils fewer infective larvae successfully establish in the host, but those that do accomplish this survive and reproduce for longer and produced a higher proportion of males during the first two month of infection. Globally, the gene expression profiles in the two hosts are very similar. Among the relatively few differentially expressed genes, astacin-like and acetylcholinesterase genes are prominently represented. In the future it will be interesting to see if these changes in the suboptimal host are indeed ecologically sensible responses to the different host.

Host size and spatiotemporal patterns mediate the coexistence of specialist parasitoids.

Many insect parasitoids are highly specialized and thus develop on only one or a few related host species, yet some hosts are attacked by many different parasitoid species in nature. For this reason, they have been often used to examine the consequences of competitive interactions. Hosts represent limited resources for larval parasitoid development and thus one competitor usually excludes all others. Although parasitoid competition has been debated and studied over the past several decades, understanding the factors that allow for coexistence among species sharing the same host in the field remains elusive. Parasitoids may be able to coexist on the same host species if they partition host resources according to size, age, or stage, or if their dynamics vary at spatial and temporal scales. One area that has thus far received little experimental attention is if competition can alter host usage strategies in parasitoids that in the absence of competitors attack hosts of the same size in the field. Here, we test this hypothesis with two parasitoid species in the genus Aphytis, both of which are specialized on the citrus pest California red scale Aonidiella aurantii. These parasitoids prefer large scales as hosts and yet coexist in sympatry in eastern parts of Spain. Parasitoids and hosts were sampled in 12 replicated orange groves. When host exploitation by the stronger competitor, A. melinus, was high the poorer competitor, A. chrysomphali, changed its foraging strategy to prefer alternative plant substrates where it parasitized hosts of smaller size. Consequently, the inferior parasitoid species shifted both its habitat and host size as a result of competition. Our results suggest that density-dependent size-mediated asymmetric competition is the likely mechanism allowing for the coexistence of these two species, and that the use of suboptimal (small) hosts can be advantageous under conditions imposed by competition where survival in higher quality larger hosts may be greatly reduced.

Host Plant Effects on Halyomorpha halys (Hemiptera: Pentatomidae) Nymphal Development and Survivorship.

Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is a highly polyphagous invasive species and an important pest of orchard crops in the United States. In the Mid-Atlantic region, wild hosts of H. halys are common in woodlands that often border orchards, and H. halys movement from them into orchards poses ongoing management issues. To improve our understanding of host plant effects on H. halys populations at the orchard-woodland interface, nymphal survivorship, developmental duration, and adult fitness (size and fresh weight) on apple (Malus domestica Borkh.), peach (Prunus persica (L.) Batsch), Tree of Heaven (Ailanthus altissima (Mill.) Swingle), and northern catalpa (Catalpa speciosa (Warder)) were examined in laboratory studies. Specifically, we investigated nymphal performance on the foliage and fruiting structures of those hosts and on single- versus mixed-host diets, as well as the effects of host phenology on their suitability. Nymphal performance was poor on a diet of foliage alone, regardless of host. When fruiting structures were combined with foliage, peach was highly suitable for nymphal development and survivorship, whereas apple, Tree of Heaven, and catalpa were less so, although nymphal survival on Tree of Heaven was much greater later in the season than earlier. Mixed-host diets yielded increased nymphal survivorship and decreased developmental duration compared with diets of suboptimal single hosts. Adult size and weight were generally greater when they developed from nymphs reared on mixed diets. The implications of our results to the dispersal behavior, establishment, and management of H. halys are discussed.

Host preference and host colonization of the Asian long-horned beetle, Anoplophora glabripennis (Coleoptera Cerambycidae), in Southern Europe.

The Asian long-horned beetle (ALB), Anoplophora glabripennis (Motschulsky), is a highly polyphagous invasive pest with a broad range of host species, but showing relevant differences between infestation areas. Host preference and host colonization (female fecundity, egg and larval survival) were assessed in a population in Northern Italy by choice and no-choice experiments conducted in both field and laboratory conditions. During 5 years of field observations, ALB was found to infest seven genera of trees: Acer, Aesculus, Betula, Populus, Prunus, Salix and Ulmus. However, Acer, Betula, Ulmus and Salix resulted to be the preferred hosts corresponding to 97.5% (1112) of the 1140 infested trees. In both laboratory and field trials carried out on these four host genera, no-choice experiments recorded the highest host colonization of A. glabripennis on Acer trees, with the highest number of laid eggs and the lowest egg and larval mortality. Ulmus and Salix showed a lower number of laid eggs during laboratory choice test, but egg and larval mortality had mean values similar to Acer. On the contrary, despite the high number of Betula trees felled during the eradication plan carried out in the infestation area, this tree species showed the lowest beetle suitability in terms of number of laid eggs and insect survival. An overestimation of the number of infested Betula occurring during the tree survey may explain the discordance between high number of infested Betula and low beetle suitability. Instead, the large number of infested Acer recorded in the field was probably due to the high abundance of these trees occurring in parks and gardens within the infestation area and to the low adult dispersal of A. glabripennis. Overall, results from this study confirm that host species affects both beetle colonization and breeding performance. The study shows ALB host preference and host suitability varying between tree species, suggesting an ALB acceptance even of sub-optimal hosts.

Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients treated with selective internal radiation therapy.

Elevated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) may represent markers of a suboptimal host immune response to cancer and have been shown to correlate with prognosis in multiple tumor types across different treatment modalities, including radiation therapy. Limited data suggest that NLR may predict for survival and disease control in patients receiving selective internal radiation therapy (SIRT). The correlation between clinical outcomes and change in NLR and PLR after SIRT has not been evaluated. We retrospectively reviewed 339 consecutive patients with primary (n=37) or metastatic (n=79) liver cancer treated with SIRT from 2006 to 2014. Complete blood counts with differential were available for 116 patients both before and after (median, 29 and 20 days, respectively) SIRT. Survival and progression were calculated from date of initial SIRT. Patient and tumor characteristics evaluated for ability to predict overall survival (OS) and progression free survival (PFS) included pre- and post-treatment neutrophil, platelet, and lymphocyte counts (LCs), as well as NLR, PLR, and relative change in NLR and PLR. Cutoff values were determined for variables that were significant on multivariate analysis (MVA) for OS and/or PFS. Median follow-up of surviving patients was 12 months. Median OS was 8 months from SIRT and 20 months from date of liver metastasis diagnosis. Significant factors on univariate analysis (UVA) for both lower OS and PFS included higher post-treatment neutrophil count (NC), higher post-treatment NLR, higher liver tumor volume, higher percentage liver tumor burden, and worse Eastern Cooperative Oncology Group (ECOG) performance status. Significant factors on MVA for lower OS and PFS were ECOG performance status ≥2, higher liver tumor volume, higher pretreatment PLR, and increase in PLR after SIRT. Post-treatment increase in PLR >3-fold was the most predictive early marker for increased risk of death when compared with those whose PLR did not increase or increased <3-fold. Pretreatment PLR >78 was the most predictive serum marker associated with improved OS prior to therapy. This is the largest study to evaluate the association between NLR and PLR with clinical outcomes in patients receiving SIRT, with results that confirm that pre- and/or post-treatment NLR and/or PLR are predictive of clinical outcomes. The largest increase in risk of death as well as local and extrahepatic disease progression was related to change in PLR, a datum not well reported in the literature. The impact of SIRT on blood count changes and the underlying implications of these ratios should be further characterized in a prospective study.

Understanding Host-Switching by Ecological Fitting.

Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness space. The capacity for host colonization is strongly influenced by propagule pressure early in the process and by the size of the fitness space later. The simulations suggest that co-adaptation may be initiated by the temporary loss of less fit phenotypes. Further, parasites can persist for extended periods in sub-optimal hosts, and thus may colonize distantly related hosts by a "stepping-stone" process.

Functionalized composite scaffolds improve the engraftment of transplanted dopaminergic progenitors in a mouse model of Parkinson's disease

With the brain's limited capacity for repair there is a need for new and innovative therapies to promote regeneration. Stem/progenitor cell transplantation has received increasing attention, and whilst clinical trials demonstrating functional integration exist, inherent variability between patients has hindered development of this therapy. Variable outcomes have largely been attributed to poor survival and insufficient reinnervation of target tissues due in part to the suboptimal host environment. Here we examined whether improving the physical properties of the host milieu, by way of bioengineered scaffolds, may enhance engraftment. We developed a composite scaffold, incorporating electrospun poly(l-lactic acid) short nanofibers embedded within a thermo-responsive xyloglucan hydrogel, which could be easily injected into the injured brain. Furthermore, to improve the trophic properties of the host brain, glial derived neurotrophic factor (GDNF), a protein known to promote cell survival and axonal growth, was blended into and/or covalently attached onto the composite scaffolds to provide controlled delivery. In vitro we confirmed the ability of the scaffolds to support ventral midbrain (VM) dopamine progenitors, and provide sustained delivery of GDNF – capable of eliciting effects on cell survival and dopaminergic axon growth. In Parkinsonian mice, we show that these composite scaffolds, whilst having no deleterious impact on the host immune response, enhanced the survival of VM grafts and reinnervation of the striatum, an effect that was augmented through the scaffold delivery of GDNF. Taken together, these functionalized composite scaffolds provide a means to significantly improve the milieu of the injured brain, enabling enhanced survival and integration of grafted neurons.