Empirical evidence suggests that co-flowering species can facilitate each other through shared pollinators. However, the extent to which one co-flowering species can relieve pollination limitation of another while simultaneously competing for abiotic resource has rarely been examined. Using a deterministic model we explored the demographic outcome for one ("focal") species of its co-occurrence with a species that shares pollinators and competes for both pollinator visitation and abiotic resources. In this paper we showed how the overall impact can be positive or negative, depending on the balance between enhanced fertilization versus increased competition. Our model could predict the density of co-flowering species that will maximize the pollination rate of the focal species by attracting pollinators. Because that density will also give rise to competitive effects, a lower density of co-flowering species is required for optimizing the trade-off between enhanced fertilization and competition so as to give the maximum possible facilitation of reproduction in the focal species. Results were qualitatively different when we considered attractiveness of the co-flowering species, as opposed to its density, because attractiveness, unlike density, had no effect on competition for abiotic resources. Whereas unattractive neighbours would not bring in pollinators, very attractive neighbours would captivate pollinators, not sharing them with the focal species. Thus optimal benefit to the focal species came at intermediate levels of attractiveness in the co-flowering species. This intermediate level of attractiveness in co-flowering species simultaneously maximized pollination and overall facilitation of reproduction for the focal species. The likelihood of facilitation was predicted to decline with the selfing rate of the focal species, revealing an indirect cost for an inbreeding mating system. Whether a co-flowering species can be facilitative depends on the way pollinators respond to the plant density: only a Type III functional response for visitation rate can result in facilitation. Our model provided both a conceptual framework and precise quantitative measures for determining the impacts of a neighbouring co-flowering species on reproduction.

Neuromuscular and neurodegenerative diseases are conditions that affect both motor neurons and the underlying skeletal muscle tissue. At present, the majority of neuromuscular research utilizes animal models and there is a growing need to develop novel methodologies that can be used to help understand and develop treatments for these diseases. Skeletal muscle tissue-engineered constructs exhibit many of the characteristics of the native tissue such as accurate fascicular structure and generation of active contractions. However, to date, there has been little consideration toward the integration of engineered skeletal muscle with motor neurons with the aim of neuromuscular junction (NMJ) formation, which would provide a model to investigate neuromuscular diseases and basic biology. In the present work we isolated primary embryonic motor neurons and neonatal myoblasts from Sprague-Dawley rats, and cocultured the two cell types in three-dimensional tissue-engineered fibrin hydrogels with the aim of NMJ formation. Immunohistochemistry revealed myotube formation in a fascicular arrangement and neurite outgrowth from motor neuron cell bodies toward the aligned myotubes. Furthermore, colocalization of pre- and postsynaptic proteins and chemical inhibition of spontaneous myotube twitch indicated the presence of NMJs in the innervated constructs. When electrical field stimulation was employed to evoke isometric contractions, maximal twitch and tetanic force were higher in the constructs cocultured with motor neurons, which may, in part, be explained by improved myotube cytoskeletal organization in these constructs. The fabrication of such constructs may be useful tools for investigating neuromuscular pharmaceuticals and improving the understanding of neuromuscular pathologies.

Abstract: Toxic cyanobacterial blooms (CBs) are becoming more frequent globally, posing a threat to freshwater ecosystems. While making long‐range forecasts is overly challenging, predicting imminent CBs is possible from precise monitoring data of the underlying covariates. It is, however, infeasibly costly to conduct precise monitoring on a large scale, leaving most lakes unmonitored or only partially monitored. The challenge is hence to build a predictive model that can use the incomplete, partially‐monitored data to make near‐future CB predictions. By using 30 years of monitoring data for 78 water bodies in Alberta, Canada, combined with data of watershed characteristics (including natural land cover and anthropogenic land use) and meteorological conditions, we train a Bayesian network that predicts future 2‐week CB with an area under the curve (AUC) of 0.83. The only monitoring data that the model needs to reach this level of accuracy are whether the cell count and Secchi depth are low, medium, or high, which can be estimated by advanced high‐resolution imaging technology or trained local citizens. The model is robust against missing values as in the absence of any single covariate, it performs with an AUC of at least 0.78. While taking a major step toward reduced‐cost, less data‐intensive CB forecasting, our results identify those key covariates that are worth the monitoring investment for highly accurate predictions.

The founding population in most new species introductions, or at the leading edge of an ongoing invasion, is likely to be small. Severe Allee effects-reductions in individual fitness at low population density-may then result in a failure of the species to colonize, even if the habitat could support a much larger population. Using a simulation model for plant populations that incorporates demography, mating systems, quantitative genetics, and pollinators, we show that Allee effects can potentially be overcome by transient hybridization with a resident species or an earlier colonizer. This mechanism does not require the invocation of adaptive changes usually attributed to invasions following hybridization. We verify our result in a case study of sequential invasions by two plant species where the outcrosser Cakile maritima has replaced an earlier, inbreeding, colonizer Cakile edentula (Brassicaceae). Observed historical rates of replacement are consistent with model predictions from hybrid-alleviated Allee effects in outcrossers, although other causes cannot be ruled out.

Background

Few adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014).

Methods

Using AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics.

Results

Overall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively).

Conclusion

Not only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed.

Objective

Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126.

Design

Animals were administered PGT126 at three different doses before challenged either vaginally or rectally with a single dose of SHIVSF163P3.

Methods

Viral loads, PGT126 serum concentrations, and serum neutralizing titers were monitored.

Results

In vaginally challenged animals, sterilizing immunity was achieved in all animals administered 10 mg/kg, in two of five animals administered 2 mg/kg and in one of five animals administered 0.4 mg/kg PGT126. Comparable protection was observed for the corresponding groups challenged rectally as sterilizing immunity was achieved in three of four animals administered 10 mg/kg, in two of four animals administered 2 mg/kg and in none of four animals administered 0.4 mg/kg PGT126. Serological analysis showed similar serum concentrations of PGT126 and serum neutralization titers in animals administered the same antibody dose.

Conclusion

Our data suggest that broadly neutralizing antibody-mediated protection is not strongly dependent on the mucosal route of challenge, which indicates that a vaccine aimed to induce a neutralizing antibody response would have broadly similar efficacy against both primary transmission routes for HIV.

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT.