Free-ranging and Feral Cats

Domestic cats (Felis catus) are a common household pet in the United States, with an estimated 25.4% of households owning cats (American Veterinary Medical Association 2018). While an increasing number of cat owners keep their pet cats exclusively indoors, a portion of society maintains that domestic cats are entitled to a free-ranging lifestyle and may even consider unowned domestic cats to be wildlife. Although wildlife managers recognize the beliefs of many concerned stakeholders, including advocates who use strong emotional appeals on behalf of cats, it remains that free-ranging and feral domestic cats are an invasive species spread by humans (Lowe et al. 2000) (Figure 1). Free-ranging cats are associated with a number of sociological and ecological conflicts. They impact people directly through the spread of parasites and diseases, damage to gardens and property, and noise nuisances. Cats also cause conflict through their direct and indirect impacts on native wildlife through predation, competition, spread of disease, and impacts on species survival (e.g., nest failure, injury, behavioral changes). Removing free-ranging cats is the most effective strategy for addressing cat-caused damage. Such removals could include adoption, placement in a long-term holding facility (e.g., cat sanctuary), or euthanasia. Owned cats should be kept indoors or otherwise under their owner’s control. Up to 164 million cats reside in the United States, of which an estimated 30 to 80 million are unowned (Loss et al. 2013) (Figure 2). A large portion of owned cats are also free-ranging (Loss et al. 2013). The threat which free-ranging cats pose to native wildlife cannot be understated

The Impact of Feral Honey Bees on Endangered Seabirds in the Hawaiian Islands

The ʻaʻo (Puffinus newellii; Newell’s shearwater) and ʻuaʻu (Pterodroma sandwichensis; Hawaiian petrel) are both endangered seabirds endemic to the Hawaiian Archipelago. For the last decade, multiple colonies on the islands of Kauaʻi and Lānaʻi have been the focus of intensive management (particularly predator control) and monitoring programs. Management has been effective at reducing the number of introduced mammalian predators recorded within colonies with a resultant increase in reproductive success rates for both seabird species. However, in recent years a new threat has emerged—feral honey bees (Apis mellifera; bees)—which were deliberately introduced to the Hawaiian Islands starting in 1857 for beekeeping. Between 2011 and 2021, 17 bee swarms were recorded at seabird burrows on both islands combined, consisting of 14 Hawaiian petrel burrows and 3 Newell’s shearwater burrows. Ten (58.8%) of these incidents resulted in the bees taking over the burrow and building a hive inside. Of the 10 takeovers, all resulted in a failed breeding season in that year, and 6 resulted in a seabird mortality (including 2 instances where both adults of a breeding pair were killed). Furthermore, for burrows where bee takeovers occurred, only 30.0% of pairs reinitiated breeding in the following year, despite the hive being removed as soon as it was discovered. An analysis of microhabitat data revealed that bee swarms were more likely at burrows located at the base of cliff walls. We discuss management strategies that can be implemented, including reactive methods such as bee vacuums and proactive methods such as bee swarm traps using pheromones, to mitigate species conservation threats. Addressing this issue is critical, as climate change may increase the likelihood of these events occurring in the future

HEATR2 Plays a Conserved Role in Assembly of the Ciliary Motile Apparatus

Cilia are highly conserved microtubule-based structures that perform a variety of sensory and motility functions during development and adult homeostasis. In humans, defects specifically affecting motile cilia lead to chronic airway infections, infertility and laterality defects in the genetically heterogeneous disorder Primary Ciliary Dyskinesia (PCD). Using the comparatively simple Drosophila system, in which mechanosensory neurons possess modified motile cilia, we employed a recently elucidated cilia transcriptional RFX-FOX code to identify novel PCD candidate genes. Here, we report characterization of CG31320/HEATR2, which plays a conserved critical role in forming the axonemal dynein arms required for ciliary motility in both flies and humans. Inner and outer arm dyneins are absent from axonemes of CG31320 mutant flies and from PCD individuals with a novel splice-acceptor HEATR2 mutation. Functional conservation of closely arranged RFX-FOX binding sites upstream of HEATR2 orthologues may drive higher cytoplasmic expression of HEATR2 during early motile ciliogenesis. Immunoprecipitation reveals HEATR2 interacts with DNAI2, but not HSP70 or HSP90, distinguishing it from the client/chaperone functions described for other cytoplasmic proteins required for dynein arm assembly such as DNAAF1-4. These data implicate CG31320/HEATR2 in a growing intracellular pre-assembly and transport network that is necessary to deliver functional dynein machinery to the ciliary compartment for integration into the motile axoneme

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

Lean Six Sigma meets data science: Integrating two approaches based on three case studies

The amount of available data is rapidly increasing, which is an opportunity to the Lean Six Sigma (LSS) methodology. Starting off with a well-established definition of LSS as theoretical foundations we employ theory-generating case-study research. Three successful improvement projects from a large financial services firm in the Netherlands are analyzed. Clear differences to the definition of LSS are observed. The research leads to three recommendations for integrating data science in LSS. Concerning the structure of an improvement organization, skills of employees and, practical modifications to LSS's celebrated DMAIC roadmap to solidify its applicability in the modern age of data

High-resolution comparative analysis of great ape genomes

Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ∼17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors

Snowmass 2021 CMB-S4 White Paper

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan

Snowmass 2021 CMB-S4 White Paper

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan

Snowmass 2021 CMB-S4 White Paper

This Snowmass 2021 White Paper describes the Cosmic Microwave Background Stage 4 project CMB-S4, which is designed to cross critical thresholds in our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. We provide an overview of the science case, the technical design, and project plan